Selkäydinstimulaatio ja angina pectoris

Selkäydinstimulaatio (SCS) on tehokas ja turvallinen hoitomuoto potilaille, joiden elämänlaatu on voimakkaasti heikentynyt vaikeiden hoitoresistenttien rintakipukohtausten vuoksi. SCS-hoidon anti-iskeeminen ja analgeettinen teho näyttää perustuvan vaikutuksiin sekä sydänlihaksen että keskushermoston tasolla.</p

The Extension of Surgery Predicts Acute Postoperative Pain, While Persistent Postoperative Pain Is Related to the Spinal Pathology in Adolescents Undergoing Posterior Spinal Fusion

Persistent pain after posterior spinal fusion affects 12 to 42% of patients with adolescent idiopathic scoliosis. The incidence of persistent pain among surgically treated children with Scheuermann kyphosis and spondylolisthesis is not known. The aim of our study was to determine the predictors and incidence of acute and chronic postoperative pain in adolescents undergoing posterior spinal fusion surgery. The study was a retrospective analysis of a prospectively collected pediatric spine register data. The study included 213 consecutive patients (158 AIS, 19 Scheuermann kyphosis, and 36 spondylolisthesis), aged 10–21 years undergoing posterior spinal fusion at a university hospital between March 2010 and March 2020. The mean (SD) daily postoperative opioid consumption per kilogram was significantly lower in the spondylolisthesis patients 0.36 mg/kg/day (0.17) compared to adolescent idiopathic scoliosis 0.51 mg/kg/day (0.25), and Scheuermann kyphosis 0.52 mg/kg/day (0.25) patients after surgery (p = 0.0004). Number of levels fused correlated with the daily opioid consumption (rs = 0.20, p = 0.0082). The SRS-24 pain domain scores showed a statistically significant improvement from preoperative levels to two-year follow-up in all three groups (p ≤ 0.03 for all comparisons). The spondylolisthesis patients had the lowest SRS pain domain scores (mean 4.04, SD 0.94), reporting more pain two years after surgery, in comparison to AIS (mean 4.31, SD 0.60) (p = 0.043) and SK (mean 4.43, SD 0.48) patients (p = 0.049). Persistent postoperative pain in adolescents undergoing posterior spinal fusion is related to disease pathology while higher acute postoperative pain is associated with a more extensive surgery. Spondylolisthesis patients report more chronic pain after surgery compared to AIS and SK patients

Predictors of postoperative urinary retention after posterior spinal fusion for adolescent idiopathic scoliosis

Purpose To determine predictors for postoperative urinary retention in adolescents undergoing posterior spinal fusion for idiopathic scoliosis. Postoperative urinary retention affects almost every third adolescent after spinal fusion for idiopathic scoliosis. There are limited data regarding the risk factors of postoperative urinary retention in this patient group.Methods A retrospective study with prospectively collected urinary retention data from paediatric spine register with 159 consecutive patients (114 females, mean age 15.6 years, range 10-21 years) undergoing pedicle screw instrumentation for adolescent idiopathic scoliosis at a university hospital between May 2010 and April 2020. Postoperative urinary retention was defined as an inability to void after catheter removal and documented residual over 300 mL as confirmed using an ultrasound or by catheterization.Results Postoperative urinary retention was diagnosed in 33% (53 of 159) of the patients during hospital stay. Opioid amount on the day of catheter removal (OR 6.74 [95% CI: 2.47, 18.36], p Conclusions Higher total opioid consumption, opioid amount on the day of catheter removal, higher weight, and male gender increases the risk of postoperative urinary retention in adolescents with idiopathic scoliosis undergoing posterior spinal fusion.</p

Trimetazidine Reduces Endogenous Free Fatty Acid Oxidation

INTRODUCTION: The metabolic modulator trimetazidine (TMZ) has been suggested to induce a metabolic shift from myocardial fatty acid oxidation (FAO) to glucose utilization, but this mechanism remains unproven in humans. The oxidation of plasma derived FA is commonly measured in humans, whereas the contribution of FA from triglycerides stored in the myocardium has been poorly characterized. AIMS: To verify the hypothesis that TMZ induces a metabolic shift, we combined positron emission tomography (PET) and magnetic resonance spectroscopy ((1)H-MRS) to measure myocardial FAO from plasma and intracellular lipids, and myocardial glucose metabolism. Nine obese subjects were studied before and after 1 month of TMZ treatment. Myocardial glucose and FA metabolism were assessed by PET with (18)F-fluorodeoxyglucose and (11)C-palmitate. (1)H-MRS was used to measure myocardial lipids, the latter being integrated into the PET data analysis to quantify myocardial triglyceride turnover. RESULTS: Myocardial FAO derived from intracellular lipids was at least equal to that of plasma FAs (P = NS). BMI and cardiac work were positively associated with the oxidation of plasma derived FA (P ≤ 0.01). TMZ halved total and triglyceride-derived myocardial FAO (32.7 ± 8.0 to 19.6 ± 4.0 μmol/min and 23.7 ± 7.5 to 10.3 ± 2.7 μmol/min, respectively; P ≤ 0.05). These changes were accompanied by increased cardiac efficiency since unchanged LV work (1.6 ± 0.2 to 1.6 ± 0.1 Watt/g × 10(2), NS) was associated with decreased work energy from the intramyocardial triglyceride oxidation (1.6 ± 0.5 to 0.4 ± 0.1 Watt/g × 10(2), P = 0.036). CONCLUSIONS: In obese subjects, we demonstrate that myocardial intracellular triglyceride oxidation significantly provides FA-derived energy for mechanical work. TMZ reduced the oxidation of triglyceride-derived myocardial FAs improving myocardial efficiency

Cannabinoid Type 1 Receptors Are Upregulated During Acute Activation of Brown Adipose Tissue

Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans. Obesity is associated with upregulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and to decrease cardiometabolic risk factors. These effects may be mediated partly via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents. To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography radioligand [F-18]FMPEP-d(2) and measured BAT activation in parallel with the glucose analog [F-18]fluorodeoxyglucose. Activation by cold exposure markedly increased CB1R density and glucose uptake in the BAT of lean men. Similarly, 3-receptor agonism increased CB1R density in the BAT of rats. In contrast, overweight men with reduced BAT activity exhibited decreased CB1R in BAT, reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose uptake and lipolysis of brown adipocytes. Our results highlight that CB1Rs are significant for human BAT activity, and the CB1Rs provide a novel therapeutic target for BAT activation in humans

Adenosine/A2B receptor signaling ameliorates the effects of ageing and counteracts obesity

The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti-obesity potential

BATLAS: Deconvoluting Brown Adipose Tissue

Recruitment and activation of thermogenic adipocytes have received increasing attention as a strategy to improve systemic metabolic control. The analysis of brown and brite adipocytes is complicated by the complexity of adipose tissue biopsies. Here, we provide an in-depth analysis of pure brown, brite, and white adipocyte transcriptomes. By combining mouse and human transcriptome data, we identify a gene signature that can classify brown and white adipocytes in mice and men. Using a machine-learning-based cell deconvolution approach, we develop an algorithm proficient in calculating the brown adipocyte content in complex human and mouse biopsies. Applying this algorithm, we can show in a human weight loss study that brown adipose tissue (BAT) content is associated with energy expenditure and the propensity to lose weight. This online available tool can be used for in-depth characterization of complex adipose tissue samples and may support the development of therapeutic strategies to increase energy expenditure in humans

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P <5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.Peer reviewe

The Extension of Surgery Predicts Acute Postoperative Pain, While Persistent Postoperative Pain Is Related to the Spinal Pathology in Adolescents Undergoing Posterior Spinal Fusion

Persistent pain after posterior spinal fusion affects 12 to 42% of patients with adolescent idiopathic scoliosis. The incidence of persistent pain among surgically treated children with Scheuermann kyphosis and spondylolisthesis is not known. The aim of our study was to determine the predictors and incidence of acute and chronic postoperative pain in adolescents undergoing posterior spinal fusion surgery. The study was a retrospective analysis of a prospectively collected pediatric spine register data. The study included 213 consecutive patients (158 AIS, 19 Scheuermann kyphosis, and 36 spondylolisthesis), aged 10&ndash;21 years undergoing posterior spinal fusion at a university hospital between March 2010 and March 2020. The mean (SD) daily postoperative opioid consumption per kilogram was significantly lower in the spondylolisthesis patients 0.36 mg/kg/day (0.17) compared to adolescent idiopathic scoliosis 0.51 mg/kg/day (0.25), and Scheuermann kyphosis 0.52 mg/kg/day (0.25) patients after surgery (p = 0.0004). Number of levels fused correlated with the daily opioid consumption (rs = 0.20, p = 0.0082). The SRS-24 pain domain scores showed a statistically significant improvement from preoperative levels to two-year follow-up in all three groups (p &le; 0.03 for all comparisons). The spondylolisthesis patients had the lowest SRS pain domain scores (mean 4.04, SD 0.94), reporting more pain two years after surgery, in comparison to AIS (mean 4.31, SD 0.60) (p = 0.043) and SK (mean 4.43, SD 0.48) patients (p = 0.049). Persistent postoperative pain in adolescents undergoing posterior spinal fusion is related to disease pathology while higher acute postoperative pain is associated with a more extensive surgery. Spondylolisthesis patients report more chronic pain after surgery compared to AIS and SK patients