Long-term survival and health-related quality of life after in-hospital cardiac arrest.

INTRODUCTION: In-hospital cardiac arrest (IHCA) is an adverse event associated with high mortality. Because of the impact of IHCA more data is needed on incidence, outcomes and associated factors that are present prior to cardiac arrest. The aim was to assess one-year survival, patient-centred outcomes after IHCA and their associated pre-arrest factors. METHODS: A multicentre prospective cohort study in 25 hospitals between January 1st 2017 and May 31st 2018. Patients ≥ 18 years receiving cardiopulmonary resuscitation (CPR) for IHCA were included. Data were collected using Utstein and COSCA-criteria, supplemented by pre-arrest Modified Rankin Scale (MRS, functional status) and morbidity through the Charlson Comorbidity Index (CCI). Main outcomes were survival, health-related quality of life (HRQoL, EuroQoL) and functional status (MRS) after one-year. RESULTS: A total of 713 patients were included, 64.5% was male, median age was 63 years (IQR 52-72) and 72.8% had a non-shockable rhythm, 394 (55.3%) achieved ROSC, 231 (32.4%) survived to hospital discharge and 198 (27.8%) survived one year after cardiac arrest. Higher pre-arrest MRS, age and CCI were associated with mortality. At one year, patients rated HRQoL 72/100 points on the EQ-VAS and 69.7% was functionally independent. CONCLUSION: One-year survival after IHCA in this study is 27.8%, which is relatively high compared to previous studies. Survival is associated with a patient's pre-arrest functional status and morbidity. HRQoL appears acceptable, however functional rehabilitation warrants attention. These findings provide a comprehensive insight in in-hospital cardiac arrest prognosis.

Effects of very low calorie diet induced body weight loss with or without human pegylated recombinant leptin treatment on changes in ghrelin and adiponectin concentrations.

The aim of the study was to investigate the effects of energy restriction with or without pegylated recombinant leptin (PEG-leptin) treatment on ghrelin, adiponectin, insulin and glucose concentrations. A randomized double-blind placebo-controlled trial was performed in 24 moderately overweight/obese men. PEG-leptin or placebo was administered weekly for 6 weeks, combined with a restricted energy intake of 2.1 MJ/d. At days 1, 25, and 46 a blood sample was taken and body-weight (BW) was measured. Days 1-25 was named phase 1, and days 25-46 phase 2. During phase 1 the rate of BW loss was significantly higher in the PEG-leptin compared to the placebo group (0.38+/-0.07 vs 0.32+/-0.06 kg/d, p<0.05). The rate of BW loss during phase 2 was 0.24+/-0.08 and 0.18+/-0.09 kg/d, respectively (p=0.07). In both groups the rate of BW loss during phase 1 was significantly higher than during phase 2 (p<0.001). Energy balance (EB) was significantly more negative during phase 1 than during phase 2 in both groups (p<0.0005). During phase 1 insulin, glucose and adiponectin decreased significantly in both groups. Adiponectin and ghrelin concentrations changed in the opposite direction between phase 1 and phase 2 (p<0.05). Initial BW loss due to a considerable negative EB induced decreased ghrelin, adiponectin, insulin and glucose levels. However, when EB became less negative and the rate of BW loss decreased, these changes were reversed for adiponectin and ghrelin. The PEG-leptin injections did not have an effect on the changes in insulin, glucose and adiponectin, but had an effect on the changes in ghrelin concentrations.

Leptin and energy expenditure.

PURPOSE OF REVIEW: A fundamental advance in our understanding of endocrine control of energy balance and body weight came with the discovery of the adipocyte-derived hormone leptin. The leptin pathway appeared to be the long-sought peripheral signal pathway from the adipose tissue to the brain involved in the regulation of feeding and energy balance. RECENT FINDINGS: Initially, leptin was considered to function as the long-sought antiobesity hormone. According to this hypothesis, rising concentrations of leptin with increasing adiposity would generate a signal to reduce food intake and increase energy expenditure in order to limit further weight gain. However, widespread resistance to the proposed antiobesity action of leptin is observed in humans, which might reflect the fact that the inability to store energy efficiently at times of abundance is evolutionarily disadvantageous. According to this alternative view, falling leptin concentrations observed during fasting act as a peripheral signal of starvation, which serves to conserve energy in the face of limited reserves. However, leptin administration failed to blunt the changes in energy expenditure during severe energy restrictions in several clinical studies. In addition, leptin therapy in several different human low-leptin states failed to affect energy expenditure in recent studies. SUMMARY: Increasing evidence from human studies suggests that leptin predominantly influences the human energy balance through appetite but appears not to be involved in regulating energy expenditure. None of the expected factors such as resting metabolic rate, total diurnal energy expenditure or dietary induced thermogenesis was related to blood leptin concentrations.

Leptin and the proinflammatory state associated with human obesity.

It has been suggested that elevated leptin levels underlie the low grade proinflammatory state in human obesity. We reasoned that if elevated leptin levels are an important factor in the proinflammatory state in obesity, then exogenous leptin administration during weight loss should counteract the concurrent beneficial effects of weight loss on the proinflammatory state. We therefore determined whether long-acting pegylated recombinant leptin (PEG-OB) prevents the decrease in cellular and humoral inflammation parameters during a very low calorie diet in healthy overweight young men. Except for B cells, PEG-OB treatment did not influence the decline in total leukocyte count and mononuclear subfractions during the diet. Weight loss decreased the humoral inflammation parameters TNFalpha, tissue plasminogen activator, and von Willebrand factor (P < 0.05), but in combination with PEG-OB treatment, a significant decrease was shown for inflammation markers as a whole (P < 0.014) and that of the individual parameters tissue plasminogen activator, von Willebrand factor, plasminogen activator inhibitor type 1, and intercellular adhesion molecule-1 (P < 0.05). The increase in C-reactive protein levels (P < 0.05) was the sole indication for a humoral proinflammatory action of leptin. Although PEG-OB treatment significantly increased weight loss (P < 0.03), the data do not support a proinflammatory role of leptin in human obesity.

The effect of pegylated human recombinant leptin (PEG-OB) on neuroendocrine adaptations to semi-starvation in overweight men.

OBJECTIVE: Starvation induces a complex neuroendocrine response in humans thought to have evolved to defend against reduced energy intake. The drop in leptin levels observed during fasting has been implicated as a factor that triggers this adaptive response. To explore this hypothesis, we executed a randomized, double-blind, placebo-controlled study to investigate whether elevated leptin levels using long-acting pegylated human recombinant leptin (PEG-OB) influenced the neuroendocrine responses to semi-starvation in human subjects. DESIGN: Twenty-four overweight male subjects (mean+/-s.e.m.; 34.8+/-1.3 yrs; 28.8+/-0.5 kg/m(2)) were prescribed a very low energy diet (2.1 MJ/day) to induce a state of semi-starvation for the next 46 days. In addition, all subjects received a weekly treatment of 80 mg PEG-OB or matching placebo. Hormone measurements were performed throughout the study period and included 5-h frequent hormone samplings and 24-h urine collections. RESULTS: Weekly subcutaneous administration of PEG-OB led to significant additional weight loss (2.8 kg) but it did not reverse the fasting-induced changes in the thyroid, corticotropic, somatotropic axes and sympathetic nervous system activity. However, after adjustment for weight loss, the drop in mean luteinizing hormone levels was attenuated in the PEG-OB group compared with the placebo group. CONCLUSIONS: These results suggest that a reduced level of leptin accompanying food restriction might be a component of the fasting-induced neuroendocrine inhibition of the human reproductive axis.

Pegylated human recombinant leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men.

BACKGROUND: Increasing evidence suggests that falling leptin concentrations observed during fasting act as a peripheral signal of starvation, which serves to conserve energy in the face of limited reserves. An extension of this hypothesis is that exogenous leptin should affect energy regulation during severe energy restriction. OBJECTIVE: To explore this hypothesis, we assessed whether elevated leptin concentrations achieved with the use of long-acting pegylated human recombinant leptin [polyethylene glycol-OB protein (PEG-OB)] affected weight loss and changes in body composition, energy expenditure, appetite, and metabolic variables during semistarvation in healthy overweight men. DESIGN: A randomized, double-blind, placebo-controlled study was executed in overweight men with a mean (+/- SEM) age of 34.8 +/- 1.3 y and body mass index (in kg/m2) of 28.8 +/- 0.5. All subjects received weekly treatment with 80 mg PEG-OB (n = 12) or matching placebo (n = 10) for 46 d while their energy intake was reduced to 2.1 MJ/d by means of a very-low-energy diet. Body composition (hydrodensitometry and deuterium dilution), energy expenditure (ventilated hood), and appetite (visual analogue scales) were evaluated at the start and the end of the study. Metabolic variables were measured throughout the study period. RESULTS: Compared with placebo treatment, treatment with PEG-OB led to significant (P < 0.03) additional weight loss (14.6 +/- 0.8 compared with 11.8 +/- 0.9 kg) and a reduction in appetite (P < 0.05) after 46 d, but the 2 treatment groups did not differ significantly in changes in body composition, energy expenditure, and metabolic variables. CONCLUSION: Our observations support the hypothesis that the decrease in leptin concentrations during starvation increases appetite in humans.