Gastric Botulinum Toxin-A Application for Weight Loss Therapy

Background/Aims: The aim of this study is to share the results of gastric botulinum toxin (BTX) application in individuals who are overweight or type 1 obese without comorbidity.Materials and Methods: In this study, 13 patients were included who were enrolled for gastric BTX application for the first time. A total of 300 U of BTX-A (Allergan Botox ^®1 vial 100 U) was diluted with 8 mL of 0.9% NaCl saline, and antrum (100 U to 8 spots), corpus (100 U to 8 spots), and fundus (100 U to 8 spots) regions were injected intramuscularly. Patients were given a 1200-calorie low-carb diet and this was followed for 6 months. Results: Gastric BTX application was applied to 13 patients with a mean age of 40.9 ± 5.2 (85% female), a mean body mass index (BMI) of 28.41 ± 1.4 kg/m² (26-31.6) and a mean excess weight of 10.1 ± 3.6 kg. As a result of the 6-month follow-up, only four patients (30.8%) were able to lose more than 50% of their excess weight (6-15 kg). Six patients (46.2%) could not lose any weight. There was an average decrease of 3.3 kg in the weight of patients before and after BTX application (P = .03). A mean decrease of BMI was detected, 1.17 kg/m² (P = .032). Conclusion: It was concluded that the application of gastric BTX for weight loss does not provide effective results.     

Body mass index and mortality in patients with severe coronary artery diseases: A cohort study from China

Background and aimsIt is still controversial whether obesity and overweight increase the risk of mortality for patients with coronary artery disease. The current study aimed to investigate the relationship between body mass index (BMI) and mortality in patients with triple-vessel disease (TVD).Methods and resultsFrom April 2004 to February 2011, 8943 patients with angiographically confirmed TVD were consecutively enrolled. Patients were divided into five groups according to BMI: underweight (<18.5 kg/m²), normal weight (18.5–23.9 kg/m²), overweight: (24–27.9 kg/m²), mild obesity (28–31.9 kg/m²), and severe obesity (≥32 kg/m²). The primary end point was all-cause death. Subgroup analysis was performed for treatment strategies: revascularization and medical treatment alone. During a median follow-up of 7.5 years, lower risks of mortality were observed in patients with overweight (adjusted HR 0.85, 95% CI 0.75–0.97) and mild obesity (adjusted HR 0.83, 95% CI 0.69–1.00) compared to those with normal weight. Polynomial Cox regression suggested a U-shape association between BMI and adjusted mortality risk. In the revascularization subgroup, there was a significantly higher mortality risk in patients with severe obesity (adjusted HR 1.57, 95% CI 1.03–2.40) than in those with normal weight. While in the medical treatment subgroup, mortality risk decreased as BMI increased, with the lowest risk being observed in patients with severe obesity.ConclusionThere is a U-shape relationship between BMI and all-cause death in patients with TVD, with increased risks among both underweight and severely obese patients. This relationship may be influenced by treatment strategies.     

A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with T4 esophageal cancer: Japan Clinical Oncology Group trial (JCOG 9908)

Background Nedaplatin is an analogue of cisplatin with less nonhematologic toxicity. The combination of nedaplatin and 5-fluorouracil showed a promising response rate in a previous phase II study for metastatic esophageal cancer. The purpose of this study was to determine a recommended dose and to evaluate the efficacy of nedaplatin and 5-fluorouracil combined with concurrent radiotherapy.Methods Eligibility criteria included squamous cell carcinoma of the thoracic esophagus; T4 disease without distant organ metastasis; age 20–70 years; performance status 0–2; and adequate organ functions. Patients received two cycles of nedaplatin (80 mg/m² or 90 mg/m²) on day 1 and continuous infusion of 5-fluorouracil 800 mg/m²/day on days 1–5, every 5 weeks with concurrent radiotherapy 60 Gy in 30 fractions.Results Between December 1999 and April 2002, 26 patients were accrued. The recommended dose of nedaplatin was 90 mg/m². Common grade ≥3 toxicities included leukopenia 9, neutropenia 5, thrombocytopenia 4, esophagitis 4, and esophageal fistula 3. Three of 26 patients achieved complete response (12%; 95% confidence interval, 2%–30%). With a minimum follow-up of 26 months for surviving patients, the median survival time was 12 months (95% confidence interval, 9–22 months), and the 2-year overall survival was 31% (95% confidence interval, 13%–49%).Conclusions This combined therapy is active with acceptable toxicity, however, the survival figure remains poor. Further investigation into more effective treatment is needed.     

Impact of being underweight or overweight on factor VIII dosing in hemophilia A patients

Since 1981, the number of factor VIII units to infuse into patients with hemophilia A in order to achieve adequate circulating factor VIII levels has been calculated using the formula: [body weight(kg)×desired factor VIII increase(%)]/2, assuming a factor VIII recovery value of 2 for all patients. This study’s aim was to evaluate the impact of several morphometric parameters and various coagulation factor concentrates on factor VIII recovery. The analysis included 201 hemophilia A adults (>18 years of age) who were carefully selected from eight pharmacokinetic clinical trials using three recombinant factor VIII concentrates (Advate^®, Kogenate^® FS, or ReFacto AF^®/Xyntha^®). Regression tree analysis was used to identify factor VIII recovery predictors. The median factor VIII recovery was 2.16 for all patients. Using regression tree analysis, patients were separated into three groups on the basis of body mass index: below 20.3 kg/m², between 20.3 and 29.5 kg/m², and 29.6 kg/m² or more. Each group had a significantly different median factor VIII recovery (P<0.001): 1.60, 2.14, and 2.70, respectively. The type of coagulation factor concentrate had no influence on recovery in the regression tree. In conclusion, factor VIII dosing should be adapted to underweight and overweight patients, as a factor VIII recovery of 2 does not apply to these patients. Ideal body weight should be considered instead of actual body weight in the dose calculations.     

Body Mass Index and Mortality from Nonrheumatic Aortic Valve Disease among Japanese Men and Women

Aim: We aimed to examine the impact of overweight and obesity on mortality from nonrheumatic aortic valve disease. Methods: In the Japan Collaborative Cohort Study, we analyzed data of 98,378 participants aged 40–79 years, with no history of coronary heart disease, stroke, or cancer at baseline (1988–1990) and who completed a lifestyle questionnaire including height and body weight; they were followed for mortality until the end of 2009. The Cox proportional hazards model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of nonrheumatic aortic valve disease mortality according to body mass index (BMI) after adjusting for potential confounding factors. Results: During the median 19.2 years follow-up, 60 deaths from nonrheumatic aortic valve disease were reported. BMI was positively associated with the risk of mortality from nonrheumatic aortic valve disease; the multivariable HRs (95% CIs) were 0.90 (0.40–2.06) for persons with BMI ＜21 kg/m², 1.71 (0.81–3.58) for BMI 23–24.9 kg/m², 1.65 (0.69–3.94) for BMI 25–26.9 kg/m², and 2.83 (1.20–6.65) for BMI ≥ 27 kg/m² (p for trend=0.006), compared with persons with BMI 21–22.9 kg/m². Similar associations were observed between men and women (p for interaction=0.56). Excluding those who died during the first ten years of follow-up or a competing risk analysis with other causes of death as competing risk events did not change the association materially. Conclusions: Overweight and obesity may be independent risk factors for nonrheumatic aortic valve disease mortality in Asian populations.     

The Association Between Body Mass Index and All-Cause Mortality in Patients With Type 2 Diabetes Mellitus: A 5.5-Year Prospective Analysis

Abundances of study in different population have noted that obese cardiovascular disease (CVD) patients have a better prognosis than leaner patients, which refer to the phenomenon of obesity paradox. However, data on the association between body mass index (BMI) and mortality among Asian patients are limited, especially in patients with type 2 diabetes mellitus (T2DM). We investigate the association between BMI and all-cause mortality in Taiwanese patients with T2DM to define the optimal body weight for health.We conducted a longitudinal cohort study of 2161 T2DM patients with a mean follow-up period of 66.7 ± 7.5 months. Using Cox regression models, BMI was related to the risk of all-cause mortality after adjusting all confounding factors.A U-shaped association between BMI and all-cause mortality was observed among all participants. Those with BMIs <22.5 kg/m² had a significantly elevated all-cause mortality as compared with those with BMIs 22.5 to 25.0 kg/m², (BMIs 17.5–20.0 kg/m²: hazard ratio 1.989, P < 0.001; BMIs 20.0–22.5 kg/m²: hazard ratio 1.286, P = 0.02), as did those with BMIs >30.0 kg/m² (BMIs 30.0–32.5 kg/m²: hazard ratio 1.670, P < 0.001; BMIs 32.5–35.0 kg/m²: hazard ratio, 2.632, P < 0.001). This U-shaped association remained when we examined the data by sex, age, smoking, and kidney function.Our study found a U-shaped relationship between all-cause mortality and BMI in Asian patients with T2DM, irrespective of age, sex, smoking, and kidney function. BMI <30 kg/m² should be regarded as a potentially important target in the weight management of T2DM.     

Beneficial impact of weight loss on respiratory function in interstitial lung disease patients with obesity

BackgroundInterstitial lung disease (ILD) patients commonly become obese or overweight due to deteriorated daily living activities and the adverse effects of prednisolone. This study aimed to clarify the effect of weight loss on pulmonary function test (PFT) in ILD patients with obesity.MethodsAmong all consecutive ILD patients with a body mass index (BMI) ≥ 27 kg/m² who received nutrition education for improving obesity between June 2014 and December 2018, we retrospectively included patients who successfully decreased their body weight by over 2 kg and underwent follow-up PFT within 6 months. The results of PFT at baseline and follow-up and the level of Krebs von den Lungen-6 (KL-6) were compared.ResultsEleven patients (5 men and 6 women; median BMI of 34.1 kg/m²), were enrolled. For PFT at baseline, the percentages of forced vital capacity (%FVC), functional residual capacity (%FRC), and diffusing capacity of the lung for carbon monoxide (%DLCO) were 69.3%, 59.9%, and 54%, respectively. The median KL-6 was 1035 U/mL. The median interval from baseline to the follow-up PFTs was 41 days. Compared to the baseline results of PFT, %FVC, %FRC, and %DLCO significantly increased (p = 0.018, 0.0006, and 0.024, respectively), and the changes in body weight and FVC were strongly correlated (p = 0.0004). In addition, the median serum level of KL-6 at follow-up tended to decrease by 206.5 U/mL (p = 0.083).ConclusionIn ILD patients with obesity, weight loss is important and potentially improves their disease course.     

Phase II trial of 5-fluorouracil,high-dose leucovorin calcium,and dipyridamole in advanced prostate cancer

Summary To examine the effect of altering intracellular folate pools on the efficacy of 5-fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300–370 mg m^–2 day^–1×5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m^–2 day^–1×5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6h×5.5 days) administered on a 28-day schedule in patients with stage D₂ disease. A group of 13 patients have been treated. The median age was 68 years (range 48–78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D₂ prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole.This study was supported, in part, by NCI Cancer Center support grant CA 33572     

Association of body mass index with risk of prediabetes in Chinese adults: A population‐based cohort study

Aims/IntroductionOverweight and obesity in adults are strongly associated with an increased risk of prediabetes, and this study set out to gain a better understanding of the optimal body mass index (BMI) range for assessing the risk of prediabetes in the Chinese population.Materials and MethodsThe cohort study included 100,309 Chinese adults who underwent health screening. Participants were divided into six groups based on the cut‐off point for BMI recommended by the World Health Organization (underweight: <18.5 kg/m², normal‐weight: 18.5–24.9 kg/m², pre‐obese: 25.0–29.9 kg/m², obese class I: 30.0–34.9 kg/m², obese class II: 35.0–39.9 kg/m², and obese class III ≥40 kg/m²). The association of BMI with prediabetes and the shape of the correlation were modeled using multivariate Cox regression and restricted cubic spline regression, respectively.ResultsIn the multivariate Cox regression model, with normal weight as the control group, underweight people had a lower risk of developing prediabetes, whereas obese and pre‐obese people had a higher risk of prediabetes. Additionally, in the restricted cubic spline model, we found that the association of BMI with prediabetes follows a positive dose–response relationship, but does not conform to the pattern of obesity paradox. Among the general population in China, a BMI of 23.03 kg/m² might be a potential intervention threshold for prediabetes.ConclusionsThe national cohort study found that the association of BMI with prediabetes follows a positive dose–response relationship, rather than a pattern of obesity paradox. For Chinese people with normal weight, more attention should be paid to glucose metabolism when BMI exceeds 23.03 kg/m².     

A phase I/II study of oral etoposide and idarubicin in elderly patients with high-risk acute myeloid leukemia unable to undergo intensive chemotherapy

Acute myeloid leukemia (AML) is a disease of mostly elderly patients who are often unable to undergo intensive intravenous chemotherapy. In an attempt to provide an all-oral regimen suitable for palliative treatment, we assessed the antileukemic efficacy of combination therapy of idarubicin 20 mg/m² (days 1, 3, and 5) and etoposide (EI) in increasing doses (75–125 mg/m²) on days 1–5. Eleven patients were included (median age 69 years, range: 56–77) with prognostically unfavorable characteristics (myelodysplastic syndrome, relapse, or unfavorable karyotypes). No complete remission and five partial remissions were observed whereas four patients had persistent leukemia. There were two patients who succumbed to early death. Median overall survival was 100 days (range: 8–493 days). Nonhematological toxicities were acceptable with nausea/vomiting being the predominant side effect. Hematological toxicity with grade III/IV aplasia was seen in all patients. In this study EI did not show convincing antileukemic efficacy and was unable to induce clinically useful complete remissions, with a substantial risk profile. In contrast to the situation of elderly patients with standard-risk AML in which similar oral treatment has shown promising activity, EI cannot be recommended for elderly patients with high-risk AML.     

Change in patients’ body weight after 12 months of treatment with glimepiride or glibenclamide in Type 2 diabetes: a multicentre retrolective cohort study

Aims/hypothesis Our study compared the effects of glimepiride or glibenclamide treatment on body weight over 12 months of treatment in patients with Type 2 diabetes in routine outpatient practice.Methods This new retrospective study design used data from physicians in a restricted manner (retrolective). Data from case report forms from 520 patients from 91 randomly selected centres were assessed and covariance analysis performed.Results The influence of practice and patient characteristics on treatment assignment was low, reflecting the design of randomised controlled trials. Mean weight loss and reduction in body mass index from baseline to study endpoint were greater with glimepiride than with glibenclamide (–2.04±3.99 kg vs –0.58±3.65 kg, p<0.001; –0.71±1.38 kg/m² vs –0.20±1.28 kg/m², p<0.001). Duration of treatment at baseline influenced treatment outcome, but propensity score, sex, age and fasting blood glucose at baseline did not. Both glimepiride and glibenclamide led to decreases in fasting blood glucose (–2.43±0.24 mmol/l vs –3.03±0.24 mmol/l; p<0.001 vs baseline) and HbA_1c (–1.23±0.09% vs –1.26±0.09%; p<0.001 vs baseline). Both treatments were associated with a decrease in serum total cholesterol and low density lipoprotein cholesterol. Triglycerides were lower in the glibenclamide group and high density lipoprotein cholesterol was higher in the glimepiride group only.Conclusions/interpretation Initial treatment of Type 2 diabetes with glimepiride was associated with a significantly greater decrease in body weight and body mass index than treatment with glibenclamide, while providing equivalent glycaemic control.Abbreviations FBG Fasting blood glucose - SU sulphonylurea - UKPDS United Kingdom Prospective Diabetes Study     

Does “Obesity Paradox” Apply for Patients Undergoing Transcatheter Aortic Valve Replacement?

BackgroundData is controversial regarding the existence of an “obesity paradox” in patients undergoing Transcatheter Aortic Valve Replacement (TAVR). We sought to investigate the prognostic value of the body mass index (BMI) on outcomes following TAVR.MethodsThis is an observational, single-center study involving all patients who underwent TAVR from 2009 to 2019. BMI was calculated in all patients before TAVR. The cohort was subdivided into four groups: underweight (<20 kg/m²), normal weight (≥20 to <25 kg/m²), overweight (≥25 to <30 kg/m²) and obese (≥30 kg/m²). The main endpoint was all-cause 30-day and one-year mortality.ResultsA total of 412 patients (mean age 79.6 ± 7.8 years, mean STS score 5.3 ± 3.6) were included. Patients were grouped as follows: underweight (n = 35, 8.5%), normal weight (n = 121, 29.4%), overweight (n = 140, 34%) and obese (n = 116, 28.1%). Obese patients were younger, included more females and had lower STS score than the rest of the cohort whereas underweight patients were older, had higher STS score, more chronic kidney disease, more left ventricular dysfunction and more often underwent non-transfemoral TAVR. BMI predicted 30-day survival (AUC:0.692 [95%CI 0.522–0.862]; p = 0.030) with an optimal cut-off of 24.4 (sensitivity = 66.6%, specificity = 63.6%). On multivariate analysis, higher BMI trended toward lower 30-day mortality (HR = 0.87 [95%CI 0.75–1.01]; p = 0.071).Thirty-day mortality was higher in the underweight group (8.3%) in comparison with other BMI subgroups (normal weight 2.5%, overweight 1.4%, obese 0.9%; p = 0.045). However, no significant difference was found after adjustment of confounders (all p = NS). BMI did not predict one-year mortality. No significant difference in one-year survival was observed between the four BMI subgroups (log rank p = 0.925).ConclusionBMI could represent an interesting prognostic tool for short-term mortality in patients undergoing TAVR. BMI < 20 kg/m² was associated with higher 30-day mortality. Symptoms improved similarly in obese patients compared to lower BMI patients. For 30-day survivors, no evidence of the existence of an obesity paradox was observed in this cohort.     

Evaluation of Body Mass Index and Survival of Nasopharyngeal Carcinoma by Propensity-Matched Analysis: An Observational Case-Control Study

The effect of pretreatment body mass index on survival of nasopharyngeal carcinoma remains contradictory.All patients (N = 1778) underwent intensity-modulated radiotherapy with or without chemotherapy. Body mass index was categorized as underweight (<18.5 kg/m²), normal weight (18.5–22.9 kg/m²), overweight (22.9–27.5 kg/m²), and obesity (≥27.5 kg/m²). Propensity score matching method was used to identify patients with balanced characteristics and treatment regimen. Disease-specific survival (DSS), overall survival (OS), distant metastasis–free survival (DMFS), and locoregional relapse–free survival were estimated by Kaplan–Meier method and Cox regression.Following propensity matching, 115 (underweight vs normal), 399 (overweight vs normal), and 93 (obese vs normal) pairs of patients were selected, respectively. In univariate analysis, underweight patients had inferior DSS/OS (P = 0.042) and DMFS (P = 0.025) while both overweight and obese patients showed similar survival across all the endpoints (P ≥ 0.098) to those with normal weight. In multivariate analysis, underweight remained predictive of poor DSS/OS (P = 0.044) and DMFS (P = 0.040), whereas overweight (P ≥ 0.124) or obesity (P ≥ 0.179) was not associated with any type of survival.Underweight increased the risk of death and distant metastasis, whereas overweight or obese did not affect the survival of nasopharyngeal carcinoma. This provides support for early nutritional intervention during the long waiting time before treatment.     

Morbid obesity in liver transplant recipients adversely affects longterm graft and patient survival in a single-institution analysis

Objective

The effects of obesity in liver transplantation remain controversial. Earlier institutional data demonstrated no significant difference in postoperative complications or 1-year mortality. This study was conducted to test the hypothesis that obesity alone has minimal effect on longterm graft and overall survival.

Methods

A retrospective, single-institution analysis of outcomes in patients submitted to primary adult orthotopic liver transplantation was conducted using data for the period from 1 January 2002 to 31 December 2012. Recipients were divided into six groups by pre-transplant body mass index (BMI), comprising those with BMIs of <18.0 kg/m², 18.0–24.9 kg/m², 25.0–29.9 kg/m², 30.0–35.0 kg/m², 35.1–40.0 kg/m² and >40 kg/m², respectively. Pre- and post-transplant parameters were compared. A P-value of <0.05 was considered to indicate statistical significance. Independent predictors of patient and graft survival were determined using multivariate analysis.

Results

A total of 785 patients met the study inclusion criteria. A BMI of >35 kg/m² was associated with non-alcoholic steatohepatitis (NASH) cirrhosis (P < 0.0001), higher Model for End-stage Liver Disease (MELD) score, and longer wait times for transplant (P = 0.002). There were no differences in operative time, intensive care unit or hospital length of stay, or perioperative complications. Graft and patient survival at intervals up to 3 years were similar between groups. Compared with non-obese recipients, recipients with a BMI of >40 kg/m² showed significantly reduced 5-year graft (49.0% versus 75.8%; P < 0.02) and patient (51.3% versus 78.8%; P < 0.01) survival.

Conclusions

Obesity increasingly impacts outcomes in liver transplantation. Although the present data are limited by the fact that they were sourced from a single institution, they suggest that morbid obesity adversely affects longterm outcomes despite providing similar short-term results. Further analysis is indicated to identify risk factors for poor outcomes in morbidly obese patients.     

Obesity and the prediction of minimal disease activity: A prospective study in psoriatic arthritis

Objective

We prospectively evaluated whether obesity impacts achievement of minimal disease activity (MDA) in subjects with psoriatic arthritis (PsA).

Methods

Among PsA subjects with an active disease and who were starting a treatment with tumor necrosis factor α blockers, 135 obese (body mass index [BMI] >30 kg/m²) patients and 135 patients of normal weight (controls) were followed up for 24 months. At baseline and at the 12‐ and 24‐month followup, all subjects underwent a clinical, rheumatologic, and laboratory assessment.

Results

With the exception of the prevalence of hypercholesterolemia and hypertriglyceridemia, case and control subjects were similar for all the clinical and demographic characteristics analyzed. At the 12‐month followup, in both cases and controls, no significant changes in body weight were found (P > 0.05 for all). MDA was achieved by 98 (36.3%) of the 270 PsA individuals. The prevalence of obesity was higher in those that did not achieve MDA than in those that did (64.0% versus 25.5%; P < 0.001). After adjusting for all the other variables, obesity was associated with a higher risk of not achieving MDA (hazard ratio [HR] 4.90, 95% confidence interval [95% CI] 3.04–7.87; P < 0.001). The HR of not achieving MDA was 3.98 (95% CI 1.96–8.06, P < 0.001) and 5.40 (95% CI 3.09–9.43, P < 0.001) in subjects with first‐degree (BMI <30 kg/m²) and second‐degree (BMI 30–35 kg/m²) obesity, respectively. Among the 98 subjects who had achieved MDA at the 12‐month followup, the presence of obesity was associated with a poor probability of sustained MDA at the 24‐month followup (HR 2.04, 95% CI 1.015–3.61; P = 0.014).

Conclusion

Obesity is a negative predictor of achieving and maintaining MDA.     

The Role of Botox in Colorectal Disorders

Purpose of review

To overview the current medical literature on the efficacy of botulism toxin treatment (BTX-A) for lower gastrointestinal disorders (GIT).

Recent findings

BTX-A was found to have a short-term efficacy for the treatment of dyssynergic defecation. Surgical treatment was found to be more effective than BTX-A for the healing of chronic anal fissures, and BTX-A can be considered when surgery is undesirable. Data regarding the effects of BTX-A injection for the treatment of chronic anal pain is limited. Beneficial effects were observed only in a minority of patients. BTX-A treatment was found to be effective for the treatment of obstructive symptoms after surgery for Hirsprung’s disease as well as for the treatment of internal anal sphincter achalasia.

Summary

BTX-A treatment has a short-term efficacy and is safe. Further research is still needed in order to establish the exact place of BTX-A treatment of lower GIT disorders.

     

The association between obesity and outcomes in critically ill patients

BACKGROUND:

Obesity rates are increasing worldwide, particularly in North America. The impact of obesity on the outcome of critically ill patients is unclear.

METHODS:

A prospective observational cohort study of consecutive patients admitted to a tertiary critical care unit in Canada between January 10, 2008 and March 31, 2009 was conducted. Exclusion criteria were age <18 years, admission <24 h, planned cardiac surgery, pregnancy, significant ascites, unclosed surgical abdomen and brain death on admission. Height, weight and abdominal circumference were measured at the time of intensive care unit (ICU) admission. Coprimary end points were ICU mortality and a composite of ICU mortality, reintubation, ventilator-associated pneumonia, line sepsis and ICU readmission. Subjects were stratified as obese or nonobese, using two separate metrics: body mass index (BMI) ≥30 kg/m² and a novel measurement of 75th percentile for waist-to-height ratio (WHR).

RESULTS:

Among 449 subjects with a BMI ≥18.5 kg/m², both BMI and WHR were available for comparative analysis in 348 (77.5%). Neither measure of obesity was associated with the primary end points. BMI ≥30 kg/m² was associated with a lower odds of six-month mortality than the BMI <30 kg/m² group (adjusted OR 0.59 [95% CI 0.36 to 0.97]; P=0.04) but longer intubation times (adjusted RR 1.56 [95% CI 1.17 to 2.07]; P=0.003) and longer ICU length of stay (adjusted RR 1.67 [95% CI 1.21 to 2.31]; P=0.002). Conversely, measurement of 75th percentile for WHR was associated only with decreased ICU readmission (OR 0.23 [95% CI 0.07 to 0.79]; P=0.02).

CONCLUSIONS:

Obesity was not necessarily associated with worse outcomes in critically ill patients.     

Resting energy expenditure and body composition in morbidly obese,obese and control subjects

Resting energy expenditure (REE) was investigated by indirect calorimetry in relation to body composition and to different degrees of obesity in order to assess if a defective energy expenditure contributes to extra body fat accumulation. Differences were found between control subjects (group C; BMI 23±0.5 kg/m², REE 5890±218 kJ/day; mean±SEM) and obese subjects (group O; BMI 34.2±0.9 kg/m², REE 7447±360 kJ/day;P<0.0001) and between group C and morbidly obese subjects (group MO; BMI 49.9±1.6 kg/m², REE 8330±360 kJ/day;P<0.0001); REE was not significantly different between groups O and MO. Body composition data were obtained by means of body impedance analysis. Even though group MO had a fat mass higher than group O, body cell mass, the metabolically active body compartment, was similar in groups O and MO, and this fact may have contributed to the similar REE in the two groups. Multiple regression analysis gave the following equation as the best predictor of REE: REE (kJ/day)+1591±49_BW+74_BCM–737 _G (R ²=0.88), where BW is body weight, BCM is body cell mass andG is a dummy variable coding group membership (group C=1; group O=2; group MO=3). Thus the analysis showed a negative impact of obesity on REE beyond body composition variables.     

Just‐in‐time rescue plerixafor in combination with chemotherapy and granulocyte‐colony stimulating factor for peripheral blood progenitor cell mobilization

Plerixafor, a recently approved peripheral blood progenitor cell mobilizing agent, is often added to granulocyte‐colony stimulating factor (G‐CSF) to mobilize peripheral blood progenitor cells in patients with lymphoma or myeloma who cannot mobilize enough CD34+ cells with G‐CSF alone to undergo autologous stem cell transplantation. However, data are lacking regarding the feasibility and efficacy of just‐in‐time plerixafor in combination with chemotherapy and G‐CSF. We reviewed the peripheral blood stem cell collection data of 38 consecutive patients with lymphoma (Hodgkin's and non‐Hodgkin's) and multiple myeloma who underwent chemomobilization and high‐dose G‐CSF and just‐in‐time plerixafor to evaluate the efficacy of this treatment combination. All patients with multiple myeloma and all but one patient with lymphoma collected the minimum required number of CD34+ cells to proceed with autologous stem cell transplantation (>2 × 10⁶/kg of body weight). The median CD34+ cell dose collected in patients with non‐Hodgkin lymphoma was 4.93 × 10⁶/kg of body weight. The median CD34+ cell dose collected for patients with multiple myeloma was 8.81 × 10⁶/kg of body weight. Plerixafor was well tolerated; no grade 2 or higher non‐hematologic toxic effects were observed. Am. J. Hematol. 88:754–757, 2013. © 2013 Wiley Periodicals, Inc.     

Prognostic relevance of gradual weight changes on long-term mortality in chronic heart failure

Background and aimsWhile obesity has been linked to better ouctomes (the obesity paradox), cachexia is associated with higher mortality in patients with heart failure with reduced ejection fraction (HFrEF). As opposed to overt cachexia, little is known about the prognostic impact of gradual, long-term weight changes in stable HFrEF.Methods and resultsWe included ambulatory patients with clinically stable chronic HFrEF on individually optimized treatment. Next to other clinical and functional parameters, changes in body weight over the past one (n = 733, group 1) or two (n = 636, group 2) years were recorded. Four-year mortality was analysed with respect to baseline BMI and changes in body weight or BMI using fractional polynomials. In addition, outcome was stratified by BMI categories (18.5–25 kg/m²: normal weight, >25–30 kg/m²: overweight, >30 kg/m²: obesity).An obesity paradox was present in both groups, with overweight and obese patients having the best prognosis. In both groups, a gradual weight gain of 5% was associated with the lowest mortality, whereas mortality steadily increases with increasing weight loss. Excessive weight gain >10% was also related to higher mortality. Stratification by baseline BMI categories revealed that weight loss was most detrimental in normal weight patients, whereas the prognostic impact of weight change was weaker in obese patients.ConclusionIn patients with chronic HFrEF, gradual weight loss is associated with steadily increasing mortality, whereas a weight gain of 5% is related to the best prognosis. Prevention of any inappropriate weight loss might be a therapeutic goal in HFrEF patient care.