Higher Baseline Body Mass Index Research Articles

Efficacy and safety of relugolix in men with advanced prostate cancer based on baseline body mass index (BMI): A subgroup analysis from the randomized, phase 3 HERO study versus leuprolide (LEU).

5073 Background: BMI has been correlated with adverse prostate cancer outcomes, such as risk of biochemical failure, mortality and androgen deprivation therapy complications. Relugolix is a FDA-approved, once-daily oral GnRH receptor antagonist that has demonstrated superior continuous suppression of testosterone (T) to castrate levels through Week 48 compared to LEU (96.7% vs 88.8%, respectively; Shore N, NEJM 2020;382:2187) in men with advanced prostate cancer (APC). This HERO subgroup analysis looks at the impact of baseline BMI on efficacy and safety. Methods: HERO was a phase 3 randomized, open-label study to evaluate relugolix vs LEU in 930 men with APC. This analysis looked at all men enrolled and treated in the HERO study divided by baseline BMI (BMI subgroups: <25.0 [underweight and healthy weight]; 25.0 – 29.9 [overweight]; and >29.9 [obese]). Assessments included sustained T suppression to castrate levels (<50 ng/dL) from Day 29 through 48 weeks, early T suppression to castrate levels (Day 4 and Day 15), prostate specific antigen (PSA) response (>50% decrease from baseline) at Day 15 with confirmation at Day 29, and profound castration rate (<20 ng/dL) at Day 15. T recovery subset analysis was not included due to low patient numbers. All analyses performed were descriptive. Results: Of the 930 men (relugolix:622; LEU:308) treated in HERO, 287 (30.9%) men had BMI <25, 424 (45.6%) were 25 – 29.9, 219 (23.5%) were >29.9. Sustained castration rates through 48 weeks were higher for the relugolix group than the LEU group and results for select key secondary endpoints were generally consistent across BMI categories, although PSA response proportions were lower in obese patients (table). No differences were noted in the incidence or types of adverse events within treatment groups in the subgroups analyzed. Conclusions: In this HERO study subgroup analysis, relugolix demonstrated greater continuous T suppression than LEU regardless of baseline BMI. Although higher BMI has been associated with poorer outcomes, we did not observe a similar trend with T responses. A numerically lower PSA response was seen in obese patients. Additional research with longer follow-up is warranted. Clinical trial information: NCT03085095. [Table: see text]

0387 Weight Changes During Treatment With Lower-Sodium Oxybate in a Phase 3 Clinical Study in Patients With Idiopathic Hypersomnia

Abstract Introduction Treatment with sodium oxybate (SXB) has been associated with weight loss in patients with narcolepsy. Lower-sodium oxybate (LXB) contains the same active moiety as SXB, with 92% less sodium, and is approved in the United States for the treatment of idiopathic hypersomnia in adults. This analysis assessed weight changes during LXB treatment in a phase 3 clinical study (NCT03533114). Methods Participants 18–75 years of age with idiopathic hypersomnia (treatment naive or taking an alerting agent [with or without SXB] at study entry) began LXB treatment in a 10- to 14-week, open-label, optimized treatment and titration period. After a 2-week stable-dose period (SDP) on their optimized dose of LXB, participants were randomized (1:1) to LXB or placebo for a 2-week, double-blind, randomized withdrawal period, followed by a 24-week open-label extension (OLE). Results Study participants (N=154) had a mean (SD) age of 40.3 (13.7) years; baseline mean (SD) weight was 76.9 (18.6) kg, and baseline mean (SD) body mass index (BMI) was 27.1 (5.9) kg/m2. At baseline, 1.3% (2/154) of participants were underweight (BMI <18.5 kg/m2), 40.3% (62/154) of participants had a normal weight (BMI 18.5 to <25 kg/m2), 33.8% (52/154) were overweight (BMI 25 to <30 kg/m2), and 24.7% (38/154) were obese (BMI ≥30 kg/m2). At the end of the SDP, 28.7% (31/108) of participants had weight loss ≥5%. Mean (SD) change in weight at the end of the SDP (n=108) was −2.5 (4.1) kg. Mean (SD) decreases in weight at the end of SDP were numerically greater in participants with higher baseline BMI (normal baseline BMI, −1.8 [3.0] kg; overweight baseline BMI, −2.8 [3.1] kg; obese baseline BMI, −3.2 [5.9] kg). Conclusion In this phase 3 clinical trial, adults with idiopathic hypersomnia treated with LXB experienced weight loss, including weight loss ≥5% in 28.7% of participants. Mean weight loss was greater in participants with a higher baseline BMI. Support (If Any) Jazz Pharmaceuticals.

Meta-analysis of seven heterogeneous studies on liraglutide add-on therapy in patients with type 2 diabetes mellitus treated with insulin

Background and aimsClinical trials indicate the efficacy of add-on therapy using incretin-related drugs to treat type 2 diabetes mellitus (DM) inadequately controlled by insulin. However, heterogeneity exists among these studies. Baseline body mass index (BMI) accounts for the heterogeneity of add-on therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors and the associated higher BMI with a lower efficacy. The efficacy of add-on therapy with glucagon-like peptide-1 (GLP-1) receptor agonists remains unclear. MethodsWe performed a meta-analysis of randomized controlled trials of ≥12 weeks reporting the endpoint of adjusted mean change in hemoglobin A1c levels (AMΔHbA1c) or hypoglycemia incidence. Patients with type 2 DM treated with insulin alone or with metformin for at least 8 weeks before the study treatment were included. The intervention group received liraglutide co-administered with insulin or a fixed-dose combination. The control group received a placebo or insulin. Covariates included five baseline parameters (HbA1c, fasting plasma glucose, BMI, type 2 DM duration, and treatment duration). ResultsSeven studies (2067 patients) were selected. AMΔHbA1c was −1.00% (95% confidence interval [CI]: −1.21 to −0.78, I2 = 74.7%). The odds ratio for hypoglycemia incidence was 0.97 (95% CI: 0.50–1.87, I2 = 81.9%). Covariates did not account for the heterogeneity in AMΔHbA1c or hypoglycemia incidence. ConclusionsLiraglutide add-on therapy reduced HbA1c levels without increasing hypoglycemia incidence, independent of BMI, in insulin non-responders with type 2 DM. GLP-1 receptor agonists may be more suitable than DPP-4 inhibitors for add-on therapy in patients with high BMI. Registration number. PROSPERO #CRD42021178888.

Abstract EP19: Obesity And Diabetes Risk According To Age Groups; An Analysis Of The National Health Screening Program For The People In Transition In Korea

Objective: The prevalence of type 2 diabetes mellitus (DM) and obesity is increasing among young population. However, the effect of obesity on the development of diabetes in different age groups is unclear. Therefore, we assessed the risk of development of future DM in two different age groups without diabetes at baseline, according to baseline body mass index (BMI) and waist circumference (WC). Research Design and Methods: The Korean National Health Insurance Service record, a nationwide population-based cohort was used to retrospectively analyze 4,145,321 Korean adults without DM, who had national health screening in Korea between 2009 and 2014. We included participants with mean age of 40 (n=2,905,752) and 66 (n=1,239,569) years old. Participants were categorized into 5, and 6 groups based on their BMI and WC, respectively. Each participant was followed either until 2017 or until the new diagnosis of DM was made. We assessed the risk of developing DM based on BMI and WC. Obesity (O) was defined as BMI≥25. Abdominal obesity (AO) was defined as WC ≥ 90cm for men, and ≥85cm for women. Multiple confounding factors were adjusted for multivariable analysis. Results: The median duration of follow-up was 5.6 years. In a multivariable analysis, higher BMI and WC among subjects with a mean age of 40 were associated with a higher risk of developing DM in the future. There was a linear association between BMI, WC, and the risk of DM (BMI<18.5, ref; BMI≥30, HR 10.35, P trend <0.001; WC 75-80 cm, ref; WC≥100 cm, HR 3.23, P trend <0.001). A similar pattern was observed among patients with mean age 66 years old (BMI<18.5, ref; BMI≥30, HR 3.16, P trend <0.001; WC 75-80cm, ref; WC≥100, HR 1.98, P trend <0.001). When participants were categorized based on the presence of O and AO, AO had a stronger impact on the development of DM than O in the 66 years old group (O(-)/AO(-), ref; O(-)/AO(+), HR 1.55; O(+)/AO(-), HR 1.45; O(+)/AO(+), HR 2.09). At the same time, O had a stronger impact on DM development than AO in the 40 years old group. (O(-)/AO(-), ref; O(-)/AO(+), HR 2.18; O(+)/AO(-), HR 2.62; O(+)/AO(+), HR 4.94). Conclusions: Regardless of age, both obesity and abdominal obesity increase the risk of DM. Among younger people, obesity was associated with a higher impact on the risk of DM. In older adults, the presence of abdominal obesity might have a greater effect on the development of DM in the future.

Abstract 051: Association Between Body Mass Index Trajectories From Early To Middle Childhood And Biomarkers Of Cardiometabolic Risk Among Children Living In Low-income And Racially/ethnically Diverse Households

Introduction: Substantial cross-sectional evidence exists supporting an association between high body mass index (BMI) during childhood and increased cardiometabolic risk factors. However, less is known about longitudinal associations of child BMI trajectories with biomarkers of cardiometabolic risk. The objective of this study was to (1) identify distinct BMI trajectories during childhood from ages 2-11 years and (2) evaluate the association of these BMI trajectories with biomarkers of cardiometabolic risk at ages 7-11 years. Methods: The analytic sample included 338 children living in low-income and racially/ethnically diverse households who participated in the NET-Works randomized intervention trial and the NET-Works 2 prospective follow-up study. BMI was measured at baseline (when children were 2-4 years of age) and again at 1-, 2-, 3- and 5-year follow-up visits. Percent of the 95 th percentile of BMI (%BMIp95) was the BMI metric calculated at each time point. At the 5-year follow-up visit, children (aged 7 to 11 years) completed assessments for carotid to anterior tibial artery pulse wave velocity (PWV), C-reactive protein (CRP), leptin, adiponectin, and oxidized low-density lipoprotein (oxLDL). Group-based trajectory modeling was used to identify child %BMIp95 trajectory groups. Adjusted linear regressions evaluated the associations between %BMIp95 trajectory groups and PWV, CRP, leptin, adiponectin, and oxLDL. Results: We identified two trajectory groups: (1) 75% of children had a moderate-decreasing trajectory (baseline BMI was below the 95th percentile of BMI and followed a moderate-decreasing trajectory over time), and (2) 25% had a marked-increasing trajectory (baseline BMI was above the 95th percentile of BMI and followed a steep increase over time). Relative to children in the moderate-decrease trajectory group, children in the marked-increase trajectory group had higher mean adjusted CRP (3.3 mg/L, 95% CI [1.6, 4.9]) and leptin (62.5 ng/mL, 95% CI [44.0, 80.9]), and lower levels of adiponectin (-1.4 μg/mL, 95% CI [-2.5, -0.1]). Differences in PWV and oxLDL were small and not statistically significant. Conclusions: Two unique BMI trajectories were observed among children living in low-income and racially/ethnically diverse households. Compared to children with steady BMI decrease over time, those with steady BMI increase over time had a higher baseline BMI and adverse inflammatory and adipokine profiles later in childhood. However, we found no evidence of differences in arterial stiffness, which could develop later in adolescence or adulthood. This study provides additional objective evidence supporting the importance of early-life tracking of BMI using the %BMIp95 metric and lifestyle interventions to reduce the risk of obesity and emerging cardiometabolic risk during childhood.

Reduction in Gout Attacks Post Sleeve Gastrectomy in Al-Ahsa Hospital, KSA

Objective: The objective of this study was to assess the improvements in patients following sleeve gastrecto-my as measured by a subsequent reduction in the incidence of gout attacks. Methods: This retrospective study was conducted at the Bariatric Surgery Department, Al-Moosa Hospital, Al Mubarraz, Saudi Arabia, in 2018. Data for this study were extracted from the records of 3247 patients who had undergone sleeve gastrectomy. The data were analyzed using SPSS version 20. Result: The study included 36 patients who fulfilled the study’s inclusion criteria, with mean age of 39.6 ± 11.6 years, and 26 (72.2%) of them were male. A significant reduction (p = 0.002) in weight was observed in both male and female patients after sleeve gastrectomy; similarly, a significant reduction (p = 0.003) in uric acid levels was also found in both genders. Post-surgery acute gout attack was observed in five (45.5%) cases in the 1 month following surgery and in only one (9.1%) case after 9 months. Various factors were analyzed for their association with postoperative acute gout attack, but only higher baseline body mass index showed a sig-nificant association (p = 0.001). Conclusion: The outcome of the study is that sleeve gastronomy significantly reduces gout attacks in obese patients. Along with this conclusion, it was also observed that age, gender, preoperative uric acid levels, and a higher body mass index are risk factors associated with the incidence of gout attacks. Keywords: sleeve gastrectomy; acute gout attack; uric acid

The Influence of Treatment with Ledipasvir/Sofosbuvir on Growth Parameters in Children and Adolescents with Chronic Hepatitis C.

Background: There are limited data available on the influence of direct-acting antivirals used to treat chronic hepatitis C (CHC) on growth in children. In this study, we aimed to analyze the growth parameters in children treated with ledipasvir/sofosbuvir (LDV/SOF). Methods: We included 38 patients (16 girls and 22 boys) aged 10–17 years treated with LDV/SOF for CHC (33 infected with genotype 1 and 5 with genotype 4; 36 were treated for 12 weeks, and 2 for 24 weeks according to the current guidelines). Patient weight and height were measured at baseline, after 4 weeks of treatment, at the end of the treatment (EOT), and 12 weeks and one year after the EOT. Body mass index (BMI), BMI z and height-for-age (HA) z scores were calculated according to the WHO Child Growth Standards and Growth reference data using the WHO anthropometric calculator AnthroPlus v. 1.0.4. In addition, correlations between BMI z scores and liver fibrosis (liver stiffness measurement, LSM), the aspartate transaminase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4) and liver steatosis (controlled attenuation parameter, CAP) were analyzed. Results: At baseline, 5/38 (13%) patients were obese (BMI z score > 2 SD), 4/38 (11%) were overweight, and 29 (76%) were normal. A significant increase was observed in mean weight, height and BMI both 12 weeks and one year after the treatment compared to the baseline, whereas no differences were observed for BMI z scores and HA z scores. Baseline BMI z scores correlated with alanine aminotransferase levels (r = 0.33, 95% CI 0.01–0.58, p = 0.04), LSM (r = 0.40, 95% CI 0.09–0.65, p = 0.01), the APRI (r = 0.33, 95% CI 0.02–0.59, p = 0.03), and the CAP (r = 0.40, 95% CI 0.08–0.64, p = 0.01). No similar correlations were reported at 12 weeks posttreatment. Conclusions: Treatment with LDV/SOF in children with CHC (genotypes 1 and 4) did not negatively influence the patients’ growth. However, higher baseline BMI z scores correlated with more advanced liver fibrosis and steatosis in children with CHC.

Abstract GS4-01: Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: Results of a prospective screening study

Abstract GS4-01: Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: Results of a prospective screening study

Trajectories of body weight change and survival among mCRC patients treated with systemic therapy: Pooled analysis from the ARCAD database.

80 Background: Higher baseline body mass index is associated with improved survival in metastatic CRC (mCRC). Whether weight gain or loss after mCRC diagnosis is associated with survival remains largely unknown. Methods: We analyzed individual patient data from 3504 patients with previously untreated mCRC enrolled in five phase III randomized trials (AVF2017g, AVF2192g, CRYSTAL, N9741, OPUS) conducted between 2000 and 2006. Weight measurements were prospectively collected at 3 months after diagnosis and then up to 5 years. Patients were categorized into three groups based on the percent weight change at 3 months: stable weight or gain, weight loss up to 5% of baseline weight, and ≥5% weight loss of baseline weight. Cox models were used to assess the prognostic associations of weight change at 3 months with overall survival (OS) and progression-free survival (PFS), adjusting for baseline BMI, age, sex, performance score, chemotherapy backbone (oxaliplatin vs. irinotecan), and biologics type (cetuximab vs. bevacizumab). Sub-analyses included Cox models adjusted for additional clinical-pathological factors (primary tumor sidedness [right colon vs. left colon-rectum], and BRAF status; N=1,511). Results: Median percent weight change at 3 months was -0.5% (IQR -4.0 to+1.6%). OS was better in patients with weight stability or gain than in those with weight loss (up to 5% or ≥5%; (Table). Results were consistent for PFS for patients with ≥5% weight loss of baseline weight, as well as for sub-analyses. Conclusions: Patients losing weight during the first 3 months of systemic therapy for metastatic colorectal cancer have significantly shorter overall survival than those with stable or increasing weight. Degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight and obese individuals. Further studies examining possible usefulness of on-treatment early weight loss as a novel intermediary end-point are needed.[Table: see text]

Association between reproductive lifespan and risk of incident type 2 diabetes and hypertension in postmenopausal women: Findings from a 20-year prospective study

BackgroundThis study examined the association between reproductive lifespan and incident type 2 diabetes mellitus (T2DM) and hypertension in mid-age women. Also, the combined effect of reproductive lifespan and body mass index (BMI) on the risks of T2DM and hypertension were explored. MethodsReproductive lifespan was defined as the difference between age at menopause and age at menarche, and categorized as <35, 35–37, 38–40, and ≥41 years based on the quartile distribution. A multivariable Cox proportional hazard regression was used, adjusting for socio-demographic, lifestyle, and reproductive factors. ResultsOf 6357 postmenopausal women included (mean [SD] age at last follow-up, 66.3[3.3] years), a total of 655 developed incident T2DM (10.3%) and 1741 developed hypertension (30.0%) during 20 years of follow-up. The total sample had a mean (SD) reproductive lifespan of 37.9 (4.5). Compared with the women who had a reproductive lifespan of 38–40 years, those with a short reproductive lifespan (<35 years) had a 30% increased risk of T2DM and twice the risk of hypertension. Under the combined model, women who had a short reproductive lifespan (<35 years) and who had a BMI ≥30 kg/m2 at baseline showed a higher risk of T2DM (HR: 6.30, 95% CI: 4.41–8.99) and hypertension (HR: 6.06, 4.86–7.55) compared with women who had a reproductive lifespan of 38–40 years and a BMI < 25 kg/m2. ConclusionsA higher risk of both incident T2DM and hypertension at midlife was found among women experiencing a shorter reproductive lifespan, with pronounced risk for women experiencing both a short reproductive lifespan (<35 years) and a higher baseline BMI (≥30 kg/m2). Women with a short reproductive lifespan may benefit from maintaining healthy body weight in midlife.

Health-related Quality of Life Increases After First-time Acute Myocardial Infarction: a Population-based Study.

IntroductionAcute myocardial infarction (AMI) affects patients’ health-related quality of life (HRQOL). AMI may decrease HRQOL, thus negatively affecting QOL. However, the improvements in interventional treatment and early rehabilitation after AMI may have a positive effect on HRQOL.AimWe evaluated HRQOL in patients after the first AMI treated in a reference cardiology centre in Poland and assessed which clinical variables affect HRQOL after AMI.Material and methodsWe prospectively evaluated HRQOL in 60 consecutive patients suffering after their first AMI during the index hospitalisation and again after 6 months, using: (i) MacNew, (ii) World Health Organization Quality of Life (WHOQOL) BREF, and (iii) Short Form (SF) 36.ResultsAs measured by the MacNew questionnaire, global, social, and physical functioning did not change (p≥0.063), whereas emotional functioning improved 6 months after AMI, compared to index hospitalisation (p=0.002). As measured by WHOQOL BREF, physical health, psychological health, and environmental functioning did not change (p≥0.321), whereas social relationships improved 6 months after AMI (p=0.042). As assessed by SF-36, the global HRQOL improved after AMI (p=0.044). Patients with improved HRQOL in SF-36 often had a higher baseline body mass index (p=0.046), dyslipidaemia (p=0.046), and lower left ventricle ejection fraction (LVEF; p=0.013). LVEF<50% was the only variable associated with improved HRQOL in multivariate analysis (OR 4.463, 95% CI 1.045 - 19.059, p=0.043).ConclusionsHRQOL increased 6 months after the first AMI, especially in terms of emotional functioning and social relationships. Patients with LVEF<50% were likely to have improved HRQOL.

Значение N-концевого пропептида натрийуретического гормона B-типа в развитии диастолической дисфункции левого желудочка при сахарном диабете типа 2

Introduction. Left ventricular diastolic dysfunction (LV DD) is associated with the development of chronic heart failure (CHF) with preserved ejection fraction. This CHF phenotype is most common in patients with type 2 diabetes mellitus (T2DM). It is relevant to study the relationship between LV DD in patients with T2DM and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), as a CHF biomarker, and other clinical, laboratory and echocardiographic parameters. Aim. To determine the significance of NT-proBNP and other factors in the development of LV DD in T2DM in the long-term follow-up period. Materials and methods. The study included 94 patients with T2DM aged 40 to 65 years (65% women). All patients had arterial hypertension (AH), obese or overweight and had no signs of NYHA class III–IV CHF, LV ejection fraction (EF) &lt; 50%. 37 patients had stable coronary artery disease (SCAD). Patients underwent clinical and laboratory examination, echocardiography. The concentration of NT-proBNP was determined. After 8.8 ± 0.72 years, 41 patients with T2DM were examined again with an assessment of clinical, biochemical and echocardiographic parameters. At baseline the 2009 National Guidelines of the Society of Cardiology of the Russian Federation and the Society of Heart Failure Specialists for the diagnosis and treatment of CHF were used for the diagnosis of LV DD. After 8.8 ± 0.72 years, the 2020 Clinical Guidelines of the Russian Society of Cardiology (RSC) for CHF were used for the diagnosis of LV DD. The search for factors that determine the presence of LV DD in the long-term period was carried out using logistic regression and ROC analysis. Results. At baseline LV DD was detected in 81.9% of cases in patients with T2DM and correlated with the presence of SCAD and the duration of AH. T2DM patients with LV DD compared with patients without LV DD did not differ in the level of NT-proBNP (30.6 pg/ml [20; 83.4] vs 36.7 pg/ml [20; 71.1]), p = 0.7). After 8.8 ± 0.72 years, LV DD was detected in 51.2% of patients with T2DM according to the 2020 Clinical Guidelines of the RSC. Patients with T2DM were divided into 2 groups: with LV DD (group 1) and without LV DD (group 2). Patients of the first and second groups differed in duration of diabetes (20 years [16; 25] vs 17.5 years [14.5; 20.5], р = 0.04), body mass index (BMI) (33.9 kg/m2 [31.2; 37.4] vs 32.2 kg/m2 [27.4; 34.7], р = 0.03), left ventricular mass index (LVMI) (94.8 g/m2 [82.5; 107] vs 73.9 g/m2 [71; 82.7], p &lt; 0.01) and were comparable in terms of carbohydrate, lipid metabolism, and kidney function. Compared to the second group, the first group had the higher baseline level of NT-proBNP (47.3 pg/ml [23.4; 111] vs 20 pg/ml [20; 20.3], p &lt; 0.01), higher baseline BMI (34.6 kg/m2 [30; 38] vs 31.2 kg/m2 [29.6; 33.7], р = 0.04) and higher baseline LVMI (101.1 ± 1 g/m2 vs 86.3 ± 14.1 g/m2, р = 0.02). The logistic regression revealed that in patients with T2DM the presence of LV DD in the long-term period is associated with the level of NT-proBNP (p = 0.03), baseline BMI (p = 0.04), baseline LVMI (p = 0.01). The baseline level of NT-proBNP &gt; 31.2 pg/ml showed a sensitivity of 66.7% and a specificity of 100% for the presence of LV DD in patients with T2DM after 8.8 ± 0.72 years of follow-up. Conclusion. In the long-term follow-up period the presence of LV DD in patients with type 2 diabetes mellitus is associated with the increased baseline level of NT-proBNP, especially in combination with the increased baseline LVMI and BMI values, while the level of NT-proBNP &gt; 31.2 pg/ml can be considered as a prognostic marker of LV DD in patients with T2DM after 8.8 ± 0.72 years of follow-up with a sensitivity of 66.7% and a specificity of 100%.

Meta-analysis of randomized controlled trials of the effects of probiotics on type 2 diabetes in adults

Despite advancements in preventive medicine and pharmacotherapy, diabetes remains an overwhelming health problem. Evidence from randomized controlled trials (RCTs) suggests that probiotics may offer beneficial effects on glycemic control. Our objective was to perform a systematic review and meta-analysis of RCTs to quantify the effect of probiotic administration on glycemic homeostasis in type 2 diabetes. Medline, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for relevant trials published until October 12, 2021. RCTs that lasted ≥3 weeks and assessed the effects of probiotics on the markers of glycemic homeostasis in type 2 diabetes were included. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q statistic and quantified using the I2 statistic. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. A total of 33 eligible trial comparisons (n=1927) were included in this meta-analysis. Our results revealed that compared with placebo, a median probiotic dose of ∼109cfu/day significantly reduced the glycated hemoglobin (HbA1c) levels (MD:-0.19% [95% CI:-0.32,-0.07]; P=0.003), fasting blood glucose levels (MD:-1.00mmol/L [95% CI:-1.45,-0.56]; P<0.0001), fasting insulin levels (MD:-5.73pmol/L [95% CI:-12.17, 0.72]; P=0.08), and HOMA-insulin resistance (IR) (MD:-1.00 [95% CI:-1.32,-0.68]; P<0.00001). The certainty of evidence was graded low for HbA1c and fasting glucose, moderate for fasting insulin, and high for HOMA-IR. Probiotic supplements do not induce clinically significant reductions in HbA1c levels, but lead to marginally clinically significant reductions in fasting glucose and fasting insulin levels in patients with type 2 diabetes. Compared with single-strain and low-dose probiotics, multi-strain and high-dose probiotics have a greater beneficial effect on glycemic homeostasis. In addition, probiotic treatment may be more effective in patients with a high baseline body mass index and age.

Effect of BMI on Prolonged Abstinence after Smoking Cessation Treatment: A Retrospective Cohort Study.

Despite the well-documented relationship between weight gain and poorer cessation outcomes among smokers, the role of the former (baseline) weight in smoking cessation is insufficiently investigated. We hypothesized that patients with higher baseline body mass index( BMI) have a worse prognosis in tobacco cessation. This retrospective clinical cohort study aimed to investigate the role of the baseline BMI on abstinence over 12 months after participation in smoking cessation treatment conducted in a middle-income country (n = 664). Data from a 6-week smoking cessation protocol performed in a Psychosocial Care Unit (CAPS) were used. The protocol included four medical consultations and six Cognitive-Behavioral Therapy (CBT) group sessions. Initially, 1,213 participants were evaluated for the study, but only the participants whose telephone contact was successful were included in the outcome analyses. The attrition rate was 45.3%. Continuous and categorical (normal, overweight, and obesity) BMI values were computed. Survival regression models were used to test the associations between BMI and the 12-month abstinence outcome. Self-report 4-week abstinence at the end of treatment was also investigated using logistic regression models. Baseline BMI had no significant effect on both short (4-week-point abstinence) and long (12-month prolonged abstinence) treatment outcomes. The possible influence of the baseline BMI on smoking cessation outcomes, especially considering prolonged abstinence, was not corroborated by our results. Regardless of our results, the detrimental health outcomes due to the combination of obesity/overweight and smoking justify that these subgroups of individuals be continuously targeted for adequate smoking prevention and treatment.

Bariatric surgery short-term outcomes in patients with obstructive sleep apnoea: the Severe Obesity Outcome Network prospective cohort.

Although the benefits of bariatric surgery have been clearly established, it is not known whether they are as important in patients with obstructive sleep apnoea (OSA). Primary aim: to evaluate whether patients with moderate-to-severe OSA (apnoea-hypopnea index (AHI) ≥ 15 events/h) treated by continuous positive airway pressure/non-invasive ventilation (median [IQR] adherence 6.5 h/night [5; 7.9] at baseline) lose the same amount of body weight 1 year after bariatric surgery as patients with no or mild OSA. Secondary objectives: to compare the evolution of type 2 diabetes and hypertension after bariatric surgery, and surgical complication rates between groups. Analyses were performed in 371 patients included in a prospective cohort of bariatric surgery, the Severe Obesity Outcome Network cohort. Subjects having moderate-to-severe OSA (n = 210) at baseline were compared with other subjects (n = 161). Excess weight loss (%EWL) at 1 year was lower in patients with moderate-to-severe OSA than in patients without (64.9%EWL [46.9; 79.5] vs. 73.8%EWL [56.6; 89.3], p < 0.01). Multivariable analysis showed that age, initial body mass index and type of surgery, but not OSA status, were associated with 1-year %EWL. Diabetes remitted in 25 (41%) patients with moderate-to-severe OSA and 16 (48%) patients with no or mild OSA (p = 0.48). Hypertension remitted in 28 (32.9%) patients with moderate-to-severe OSA and 9 (40.9%) with no or mild (p = 0.48). Complication rates were 28 (13.3%) in patients with moderate-to-severe OSA and 12 (7.5%) in patients with no or mild OSA (p = 0.07). Patients with OSA lose less body weight after bariatric surgery. This was related to older age and a higher baseline body mass index. However, the improvements of diabetes and hypertension were similar to that of patients without OSA, and the risk of surgical complications was not higher.

Abstract LB081: Systemic inflammation is associated with increased risk of mortality after invasive breast cancer among Hispanic women from New Mexico

Abstract Introduction: Soluble tumor necrosis factor receptor-II (sTNF-R2), a circulating pro-inflammatory biomarker, has been found to associated with obesity and increased risk of breast cancer. No studies to date have examined the association between sTNF-R2 and risk of mortality among Hispanic breast cancer survivors, an at-risk population due to their high prevalence of obesity and poor prognosis. The current study examined the long-term effects of sTNF-R2 on risk of mortality among Hispanic and non-Hispanic white (NHW) breast cancer survivors from the New Mexico Health Eating Activity and Lifestyle Study. Methods: A total of 397 invasive breast cancer survivors (96 Hispanic, 301 NHW) contributed data for the present study. Women with breast cancer diagnosed between July 1996 and March 1999 were ascertained through the National Cancer Institute's Surveillance Epidemiology and End Results registry in New Mexico. Baseline demographic characteristics, anthropometric measures, and blood samples were collected approximately 5 months post diagnosis by trained interviewers. Plasma levels of sTNF-R2 were assayed and measures were log-transformed to conform to normality. The main predictor of low (referent) vs high sTNF-R2 levels was based on the median value. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the associations between sTNF-R2 and all-cause mortality were calculated using Cox proportional hazards regression models overall and by ethnicity. Models were adjusted for age at diagnosis, education, breast cancer stage, treatment, and body mass index (BMI). Results: A total of 133 deaths (53 breast cancer-specific deaths) were observed after a median follow-up time of 13 years. While Hispanic women had higher baseline BMI (mean= 27.21, standard deviation (SD)= 5.83) compared to NHW women (mean= 25.68, SD= 5.36) (p&amp;lt; 0.001), significant differences by ethnicity for sTNF-R2 levels were not observed. In models adjusted for ethnicity and other covariates, the association between high vs low levels of plasma sTNF-R2 and risk of mortality was not statistically significant among all women (HR, 1.36; 95% CI 0.90-2.03). However, in models stratified by ethnicity, Hispanic women had increased risk of mortality of almost 3-fold (HR, 2.83; 95% CI 1.21-6.63), while the association among NHW women was attenuated and was not statistically significant (HR, 0.99; 95% CI 0.61-1.61). The statistical interaction between sTNF-R2 and ethnicity with risk of mortality was not statistically significant (p= 0.10). Conclusion: Our study results suggest Hispanic breast cancer survivors with high levels of systemic inflammation measured by sTNF-R2 are at increased risk of mortality. These results could inform targeted intervention studies to decrease inflammation and reduce risk of mortality among this at-risk population. Citation Format: Avonne E. Connor, Stephanie D. Boone, Kathy B. Baumgartner, Richard N. Baumgartner. Systemic inflammation is associated with increased risk of mortality after invasive breast cancer among Hispanic women from New Mexico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB081.

Soluble Suppression of Tumorigenicity-2 Associates With Ventilator Dependence in Coronavirus Disease 2019 Respiratory Failure.

We hypothesize that elevated soluble suppression of tumorigenicity-2 concentrations, a marker of pulmonary epithelial injury, reflect ongoing lung injury in acute hypoxemic respiratory failure due to coronavirus disease 2019 and associate with continued ventilator dependence. We associated serial plasma soluble suppression of tumorigenicity-2 levels and markers of systemic inflammation including d-dimer, C-reactive protein, and erythrocyte sedimentation rate with 30-day mortality and ventilator dependence. Adult medical ICUs and general medicine wards at an academic teaching hospital in Boston, MA. Adult patients with severe acute respiratory syndrome coronavirus 2 infection and acute hypoxemic respiratory failure admitted to the ICU (n = 72) and non-ICU patients managed with supplemental oxygen (n = 77). Observational study from April 25 to June 25, 2020. ICU patients had a higher baseline body mass index and median soluble suppression of tumorigenicity-2, d-dimer, and C-reactive protein concentrations compared with non-ICU patients. Among ICU patients, elevated baseline modified Sequential Organ Failure Assessment score and log (soluble suppression of tumorigenicity-2) were associated with 30-day mortality, whereas initial Pao2/Fio2 and markers of systemic inflammation were similar between groups. Only log (soluble suppression of tumorigenicity-2) associated with ventilator dependence over time, with the last measured log (soluble suppression of tumorigenicity-2) concentration obtained on ICU day 11.5 (interquartile range [7-17]) higher in patients who required reintubation or tracheostomy placement compared with patients who were successfully extubated (2.10 [1.89-2.26] vs 1.87 ng/mL [1.72-2.13 ng/mL]; p = 0.03). Last measured systemic inflammatory markers, modified Sequential Organ Failure Assessment score, and Pao2/Fio2 were not different between patients who were successfully extubated compared with those with continued ventilator dependence. Plasma soluble suppression of tumorigenicity-2 is a biomarker readily measured in blood that can provide dynamic information about the degree of a patient's lung injury and real-time assessment of the likelihood of extubation success. Measures of systemic inflammation, illness severity, and oxygenation did not associate with ventilator outcomes.

Effectiveness of IL-12/23 inhibition (ustekinumab) versus tumour necrosis factor inhibition in psoriatic arthritis: observational PsABio study results

ObjectivesTo evaluate 6-month effectiveness of ustekinumab versus tumour necrosis factor inhibitor (TNFi), analysing predictors of low disease activity (LDA)/remission.MethodsPsABio is a prospective, observational cohort study of patients with psoriatic arthritis...

Predictors of Improvement in Quality of Life When Treating Hypothyroidism.

Background Primary hypothyroidism is characterized by reduced quality of life (QoL). Although thyrotropin (TSH) is utilized as the primary indicator of thyroid disease and treatment adequacy, no simple correlation between QoL and TSH has been shown. This study aimed to investigate changes in clinically relevant predictors during initiation of levothyroxine (L-T4) therapy and their ability to predict improvement in QoL. Method Quality of life was measured in patients with newly diagnosed hypothyroidism, during the initial 12 months of L-T4 therapy, by the thyroid-related patient-reported outcome questionnaire, ThyPRO-39. The main outcome measures were the Composite QoL scale and the Tiredness and Emotional Susceptibility subscales (0–100, higher scores worse). Clinical variables (resting energy expenditure (REE), body composition, thyroid function, L-T4 dose, and cognitive function tests) were evaluated as predictors of improvement in QoL by univariate and multiple regression analysis. Results Thirty-seven hypothyroid patients with a baseline median TSH of 30 mU/l and a median QoL score of 29 were included. After twelve months of L-T4 treatment, the ThyPRO-39 QoL score had significantly improved to a median score of 14, while REE per kg fat-free mass (FFM) increased significantly from a mean of 26.5 to 28.7 kcal/day/kg (p < 0.001). Change in ThyPRO-39 was not associated with a change in REE/FFM (unstandardized coefficient (USC): 0.09 with confidence interval (CI): −1.93 to 2.11, p=0.93) but was positively predicted by baseline body mass index (BMI) (USC: 1.54 with CI: 0.59 to 2.49, (p=0.002), without association with weight loss (USC: 0.33 with CI: −1.21 to 1.27, p=0.96). Conclusion Improvement in QoL as measured by ThyPRO-39 after initiation of L-T4 therapy for hypothyroidism was not associated with changes in REE. High baseline BMI, but not weight loss during therapy, was associated with improvement in QoL. This trail is registered with www.Clinicaltrials.gov (registration no. https://clinicaltrials.gov/ct2/show/NCT02891668).

Impact of Body Composition Indices on Ten-year Mortality After Revascularization of Complex Coronary Artery Disease (From the Syntax Extended Survival Trial)

Numerous studies have demonstrated a paradoxical association between higher baseline body mass index (BMI) and lower long-term mortality risk after coronary revascularization, known as the "obesity paradox", possibly relying on the single use of BMI. The current study is a post-hoc analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the SYNTAX trial comparing percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in patients with left-main coronary artery disease (LMCAD) or three-vessel disease (3VD). Patients were stratified according to baseline BMI and/or waist circumference (WC). Out of 1,800 patients, 1,799 (99.9%) and 1,587 (88.2%) had available baseline BMI and WC data, respectively. Of those, 1,327 (73.8%) patients had High BMI (≥25 kg/m2), whereas 705 (44.4%) patients had High WC (>102 cm for men or >88 cm for women). When stratified by both BMI and WC, 10-year mortality risk was significantly higher in patients with Low BMI/Low WC (adjusted hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 1.09 to 2.51), Low BMI/ High WC (adjusted HR: 2.74; 95% CI: 1.12 to 6.69), or High BMI/High WC (adjusted HR: 1.59; 95% CI: 1.11 to 2.27) compared to those with High BMI/Low WC. In conclusion, the "obesity paradox" following coronary revascularization would be driven by low long-term mortality risk of the High BMI/Low WC group. Body composition should be assessed by the combination of BMI and WC in the appropriate evaluation of the long-term risk of obesity in patients with LMCAD or 3VD.