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).

Shorter History of Hypertension as a Predictor of Hypertension Remission after 3-years of Bariatric Surgery: Data from the GATEWAY Trial.

BACKGROUND: Previous evidence explored predictors of hypertension (HTN) remission after bariatric but data are limited to observational studies and lack of ambulatory blood pressure monitoring (ABPM). This study was aimed to evaluate the rate of HTN remission after bariatric surgery using ABPM and to define predictors of mid-term HTN remission. METHODS: We included patients enrolled in the surgical arm of the GATEWAY randomized trial. HTN remission was defined as controlled blood pressure (< 130 × 80 mmHg) evaluated by 24-h ABPM while no need of anti-hypertensive medications after 36 months. A multivariable logistic regression model was used to assess the predictors of HTN remission after 36 months. RESULTS: 46 patients submitted Roux-en-Y gastric bypass (RYGB). HTN remission occurred in 39% (n = 14 out of 36 patients with complete data at 36 months). Patients with HTN remission had shorter HTN history than no remission group (5.9 ± 5.5 vs. 12.5 ± 8.1 years; p = 0.01). The baseline insulin levels were lower in patients who presented HTN remission, although not statistically significant (OR: 0.90; CI 95%: 0.80-0.99; p = 0.07). In the multivariate analysis, the HTN history (years) was the only independent predictor of HTN remission (OR: 0.85; 95% CI: 0.70-0.97; p = 0.04). Therefore, for each additional year of HTN history, the chance of HTN remission decreases by approximately 15% after RYGB. CONCLUSION: After 3 years of RYGB, HTN remission defined by ABPM was common and independently associated with a shorter HTN history. These data underscore the need of early effective approach of obesity aiming greater impact in its comorbidities.

Pre-clinical evaluation of new dibucaine formulations for preventive analgesia.

We have previously developed ammonium sulphate gradient loaded liposomes to encapsulate dibucaine. Thus, the purpose of this study was to evaluate the pre-clinical safety and effectiveness of this novel ionic liposomal formulation of dibucaine (DBC), as described in previous work. Effectiveness was evaluated in vivo on Wistar rats (n = 8) that received plain DBC or liposomal DBC (DBCLUV). Control empty liposomes (without DBC) or saline were also used as control. Sciatic nerve block was performed using the formulations or controls (0.4 mL). A hindpaw incision-based postoperative pain model was used to evaluate mechanical hypersensitivity with von Frey filaments. To verify antiinflamatory activity protein levels of TNF-α, IL-1ß, substance P and CGRP were measured by ELISA in the hindpaw tissue after 1 and 6 hours of the incision. To corroborate drug safety, sciatic nerve Schwann cell cultures were treated with the aforementioned formulations and assessed for cell viability (MTT assay) and death (flow cytometry assay). Histopathology of the tissues surrounding the sciatic nerve region was also assessed 2 and 7 days after treatment. All animals presented post incisional hypersensitivity and DBCLUV showed longer analgesic effect (p < 0.001). DBCLUV reduced TNF-α and CGRP levels (p < 0.05). Histopathological evaluation showed greater inflammatory reaction after the administration of control liposomes when compared to DBC (p < 0.05). There was no difference in Schwann cell viability and death between plain and encapsulated DBC. DBCLUV was safe and enhanced anaesthesia duration due to slow release of dibucaine from ammonium sulphate gradient loaded liposomes.

Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension: A Randomized Clinical Trial

Hypertension is a leading cause of cardiovascular mortality (1). Its unfavorable impact is potentially explained by several factors, including the asymptomatic nature of this condition, poor medication adherence, and high burden of comorbid conditions, including obesity (1, 2). Hypertension occurs mostly in persons with excess weight and is often poorly controlled in patients with obesity (3, 4), and pharmacologic treatment of obesity has modest impact on blood pressure (BP) reduction (5). Bariatric surgery is the most effective method to treat obesity (6 ­ 8). Although recent research efforts have focused on metabolic improvement and diabetes resolution (9 ­12), growing interest has been devoted to evaluating the effects of this surgery on hypertension (13­15). The GATEWAY (Gastric Bypass to Treat Obese Patients With Steady Hypertension) trial focused on hypertension and included patients with mild obesity (body mass index [BMI], 30 to 34.9 kg/m2 ) and those with a BMI greater than 35 kg/m2 per current guidelines. The 1-year results showed that patients with coexisting obesity and hypertension were able to reduce or completely discontinue their antihypertensive medications after surgery, while maintaining a controlled BP and a similar 24-hour BP profile (16, 17). However, midterm effects of bariatric surgery on office and 24-hour BP measurements in a broad population of patients with obesity and hypertension remain uncertain. Here, we present the 3-year results from the GATEWAY trial. METHODS The GATEWAY trial is a randomized, nonblinded, single-center, investigator-initiated clinical trial performed at Heart Hospital in Sa˜ o Paulo, Brazil. Study design (18) and 1-year results (16) were previously pub lished; the full protocol, approved by the Research Ethics Board at the Heart Hospital (HCor), and the statistical analysis plan are available in Supplements 1 and 2 (available at Annals.org). The follow-up period for the primary end point was 12 months, but we prespecified that all patients would be scheduled for a 3-year and 5-year extension study. Here, we present the 3-year outcomes.

Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension : A Randomized Clinical Trial.

BACKGROUND: Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain. OBJECTIVE: To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared with medical therapy (MT) alone. DESIGN: Randomized clinical trial. (ClinicalTrials.gov: NCT01784848). SETTING: Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil. PARTICIPANTS: Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m2 were randomly assigned (1:1 ratio). INTERVENTION: RYGB plus MT or MT alone. MEASUREMENTS: The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg). RESULTS: Among 100 patients (76% female; mean BMI, 36.9 kg/m2 [SD, 2.7]), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 [95% CI, 2.50 to 17.03]; P < 0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (P < 0.001). Total weight loss was 27.8% and -0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B12 and 2 patients required reoperation. LIMITATION: Single-center, nonblinded trial. CONCLUSION: RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity. PRIMARY FUNDING SOURCE: Ethicon, represented in Brazil by Johnson & Johnson do Brasil.

Implementation of a Brazilian Cardioprotective Nutritional (BALANCE) Program for improvement on quality of diet and secondary prevention of cardiovascular events: A randomized, multicenter trial

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

Implementation of a Brazilian Cardioprotective Nutritional (BALANCE) Program for improvement on quality of diet and secondary prevention of cardiovascular events: A randomized, multicenter trial.

BACKGROUND: Appropriate dietary recommendations represent a key part of secondary prevention in cardiovascular disease (CVD). We evaluated the effectiveness of the implementation of a nutritional program on quality of diet, cardiovascular events, and death in patients with established CVD. METHODS: In this open-label, multicenter trial conducted in 35 sites in Brazil, we randomly assigned (1:1) patients aged 45 years or older to receive either the BALANCE Program (experimental group) or conventional nutrition advice (control group). The BALANCE Program included a unique nutritional education strategy to implement recommendations from guidelines, adapted to the use of affordable and regional foods. Adherence to diet was evaluated by the modified Alternative Healthy Eating Index. The primary end point was a composite of all-cause mortality, cardiovascular death, cardiac arrest, myocardial infarction, stroke, myocardial revascularization, amputation, or hospitalization for unstable angina. Secondary end points included biochemical and anthropometric data, and blood pressure levels. RESULTS: From March 5, 2013, to Abril 7, 2015, a total of 2534 eligible patients were randomly assigned to either the BALANCE Program group (n = 1,266) or the control group (n = 1,268) and were followed up for a median of 3.5 years. In total, 235 (9.3%) participants had been lost to follow-up. After 3 years of follow-up, mean modified Alternative Healthy Eating Index (scale 0-70) was only slightly higher in the BALANCE group versus the control group (26.2 ±â€¯8.4 vs 24.7 ±â€¯8.6, P < .01), mainly due to a 0.5-serving/d greater intake of fruits and of vegetables in the BALANCE group. Primary end point events occurred in 236 participants (18.8%) in the BALANCE group and in 207 participants (16.4%) in the control group (hazard ratio, 1.15; 95% CI 0.95-1.38; P = .15). Secondary end points did not differ between groups after follow-up. CONCLUSIONS: The BALANCE Program only slightly improved adherence to a healthy diet in patients with established CVD and had no significant effect on the incidence of cardiovascular events or death.

Effects of bariatric surgery versus medical therapy on the 24-hour ambulatory blood pressure and the prevalence of resistant hypertension

Bariatric surgery is an effective strategy for blood pressure (BP) reduction, but most of the evidence relies on office BP measurements. In this study, we evaluated the impact of bariatric surgery on 24-hour BP profile, BP variability, and resistant hypertension prevalence. This is a randomized trial including obese patients with grade 1 and 2 using at least 2 antihypertensive drugs at maximal doses or >2 at moderate doses. Patients were allocated to either Roux-en-Y Gastric Bypass (RYGB) combined with medical therapy or medical therapy alone for 12 months. The primary outcome was the 24-hour BP profile and variability (average real variability of daytime and night time BP). We evaluated the nondipping status and prevalence of resistant hypertension as secondary end points. We included 100 patients (76% female, body mass index, 36.9±2.7 kg/m2). The 24-hour BP profile (including nondipping status) was similar after 12 months, but the RYGB group required less antihypertensive classes as compared to the medical therapy alone (0 [0­1] versus 3 [2.5­4] classes; P<0.01). The average real variability of systolic nighttime BP was lower after RYGB as compared to medical therapy (between-group difference, −1.63; 95% CI, −2.91 to −0.36; P=0.01). Prevalence of resistant hypertension was similar at baseline (RYGB, 10% versus MT, 16%; P=0.38), but it was significantly lower in the RYGB at 12 months (0% versus 14.9%; P<0.001). In conclusion, RYGB significantly reduced antihypertensive medications while promoting similar 24-hour BP profile and nondipping status. Interestingly, bariatric surgery improved BP variability and may decrease the burden of resistant hypertension associated with obesity. (AU)

Effects of Bariatric Surgery Versus Medical Therapy on the 24-Hour Ambulatory Blood Pressure and the Prevalence of Resistant Hypertension.

Bariatric surgery is an effective strategy for blood pressure (BP) reduction, but most of the evidence relies on office BP measurements. In this study, we evaluated the impact of bariatric surgery on 24-hour BP profile, BP variability, and resistant hypertension prevalence. This is a randomized trial including obese patients with grade 1 and 2 using at least 2 antihypertensive drugs at maximal doses or >2 at moderate doses. Patients were allocated to either Roux-en-Y Gastric Bypass (RYGB) combined with medical therapy or medical therapy alone for 12 months. The primary outcome was the 24-hour BP profile and variability (average real variability of daytime and night time BP). We evaluated the nondipping status and prevalence of resistant hypertension as secondary end points. We included 100 patients (76% female, body mass index, 36.9±2.7 kg/m2). The 24-hour BP profile (including nondipping status) was similar after 12 months, but the RYGB group required less antihypertensive classes as compared to the medical therapy alone (0 [0-1] versus 3 [2.5-4] classes; P<0.01). The average real variability of systolic nighttime BP was lower after RYGB as compared to medical therapy (between-group difference, -1.63; 95% CI, -2.91 to -0.36; P=0.01). Prevalence of resistant hypertension was similar at baseline (RYGB, 10% versus MT, 16%; P=0.38), but it was significantly lower in the RYGB at 12 months (0% versus 14.9%; P<0.001). In conclusion, RYGB significantly reduced antihypertensive medications while promoting similar 24-hour BP profile and nondipping status. Interestingly, bariatric surgery improved BP variability and may decrease the burden of resistant hypertension associated with obesity. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01784848.

An Open-Label Clinical Trial of Hypothalamic Deep Brain Stimulation for Human Morbid Obesity: BLESS Study Protocol.

BACKGROUND: Human morbid obesity is increasing worldwide in an alarming way. The hypothalamus is known to mediate its mechanisms. Deep brain stimulation (DBS) of the ventromedial hypothalamus (VMH) may be an alternative to treat patients refractory to standard medical and surgical therapies. OBJECTIVE: To assess the safety, identify possible side effects, and to optimize stimulation parameters of continuous VMH-DBS. Additionally, this study aims to determine if continuous VMH-DBS will lead to weight loss by causing changes in body composition, basal metabolism, or food intake control. METHODS: The BLESS study is a feasibility study, single-center open-label trial. Six patients (body mass index > 40) will undergo low-frequency VMH-DBS. Data concerning timing, duration, frequency, severity, causal relationships, and associated electrical stimulation patterns regarding side effects or weight changes will be recorded. EXPECTED OUTCOMES: We expect to demonstrate the safety, identify possible side effects, and to optimize electrophysiological parameters related to VMH-DBS. No clinical or behavioral adverse changes are expected. Weight loss ≥ 3% of the basal weight after 3 mo of electrical stimulation will be considered adequate. Changes in body composition and increase in basal metabolism are expected. The amount of food intake is likely to remain unchanged. DISCUSSION: The design of this study protocol is to define the safety of the procedure, the surgical parameters important for target localization, and additionally the safety of long-term stimulation of the VMH in morbidly obese patients. Novel neurosurgical approaches to treat metabolic and autonomic diseases can be developed based on the data made available by this investigation.

Prevalência de neoplasias em 415 pacientes com trombose venosa profunda avaliados em hospital escola / Prevalence of neoplasms in 415 patients with deep venous thrombosis evaluated in a university hospital

Objetivo: Os objetivos do presente estudo foram identificar os tipos de neoplasias e avaliar sua prevalência em 415 pacientes com trombose venosa profunda.Método: Foi investigada a presença de neoplasias, em estudo prospectivo, em 415 pacientes com trombose venosa profunda em membras inferiores, com idades entre 11 e 92 anos; média de 55,2 anos. O diagnóstico de trombose foi realizado com dúplex em todos pacientes e nos casos de dúvida foi confirmado pela flebografia. Procederam-sea história clínica e o exame físico, além de exames bioquímicas, por imagem, biópsias e cirurgias quando indicadas. Entre os principais exames laboratoriais, nos casos de suspeita clínica, realizaram-se asradiografias de tórax, endoscopia, ultra-som de abdômen, tomografia computadorizada e a ressonância magnética. Foram incluídos todos os pacientes que apresentaram trombose venosa profunda e excluídos os pacientes que já tinham diagnóstico prévio de neoplasia.Resultados: Detectou-se a presença de neoplasias em 58 (415)pacientes, representando 13,9 por cento, sendo que 27,5 por cento envolveu o trato gastrointestinal, 17,2 por cento o sistema ginecológico, 17,2 por cento o sistema nervaso central, 15,5 por cento o sistema urológico, 8,6 por cento o sistema respiratório,6,8 por cento o sistema tegumentar, 3,4 por cento o esquelético, 1,7 por cento o retroperitôneo e 1,7 por cento o reticuloendotelial.Conclusão: Conclui-se que pacientes com trombose venosa profunda apresentam uma alta prevalência de neoplasias, sendo sugerido o seu rastreamento.

Aminaftona no tratamento da epistaxe / Amnaphtone in the treatment of nosebleed

Nasal haemorrhage or nosebleed, is the most common of haemorrhages due to the intense vasculization of the nose, the fragility of the nasal mucous membrane and its vulnerability to traumas and irritant agents. The aim of this study is to report on a reduction of episodes of nosebleed in two patients with the use of amnophtone. A 34-year-old male patient and a 44- year-old female patient presented with histories of two or more nosebleeds per week, despite treatment during the acute phase. They both sought medical assistance for other vascular complaints, which were suggestive of vascular insufficiency as, during the physical examination petechia lesions in the lower limbs were detected. They were treated with 75 mg of amnaphtone three times daily. One week after, at the follow-up, they reported an improvement of the vascular symptoms, however, more markedly was the significant improvement in relation to the nosebleeds which were frequent but had not been reported in the first consultation. In conclusion, amnaphtone demonstrated to be efficient in the prevention of recurrence of nosebleed in these patients