Enhanced Recovery After Surgery (ERAS®) Society Consensus Guidelines for Emergency Laparotomy Part 3: Organizational Aspects and General Considerations for Management of the Emergency Laparotomy Patient.

BACKGROUND: This is Part 3 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy using an enhanced recovery after surgery (ERAS) approach. This paper addresses organizational aspects of care. METHODS: Experts in management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and MEDLINE database searches were performed for ERAS elements and relevant specific topics. Studies were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. RESULTS: Components of organizational aspects of care were considered. Consensus was reached after three rounds of a modified Delphi process. CONCLUSIONS: These guidelines are based on best current available evidence for organizational aspects of an ERAS® approach to patients undergoing emergency laparotomy and include discussion of less common aspects of care for the surgical patient, including end-of-life issues. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.

Consensus Guidelines for Perioperative Care for Emergency Laparotomy Enhanced Recovery After Surgery (ERAS®) Society Recommendations Part 2-Emergency Laparotomy: Intra- and Postoperative Care.

BACKGROUND: This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra- and postoperative aspects of care. METHODS: Experts in aspects of management of high-risk and emergency general surgical patients were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL. RESULTS: Twenty-three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process. CONCLUSIONS: These guidelines are based on best available evidence for an ERAS® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.

Horse-riding hazards: an observational cohort study mapping equestrian related injuries at a Scandinavian trauma centre.

INTRODUCTION: Horse-riding is practiced on a regular basis by 500,000 people in Sweden. It is reputed to be one of the most dangerous sports. On average, there were 1756 acute injuries and three fatalities each year between 1997 and 2014 in Sweden related to horses. The primary aim of this study was to outline the injury spectrum related to equestrian activities cared for at a large Swedish trauma centre. The secondary aim was to identify trends in clinical outcomes and to investigate the association between age and such outcomes. MATERIAL AND METHODS: The electronic medical records system at Karolinska University Hospital was queried for patients cared for due to equestrian related trauma between July 2010 and July 2020. Complementary data were gathered using the hospital's Trauma Registry. No exclusion criteria were applied. Descriptive statistics were used to outline the injury spectrum. Age was split into four categories which were compared using the Kruskal-Wallis H test or the Chi-squared test. Logistic regression was used to analyse correlations between age and outcomes. RESULTS: A total of 3036 patients were included with 3325 injuries identified as equestrian related. The hospital admission rate was 24.9%. The cohort had one death. Regression analysis showed significant associations between decreasing risk of upper extremity injury (p < 0.001), increasing risk of vertebral fractures (p = 0.001) and increasing risk of thoracic injury (p < 0.001) with increasing age. CONCLUSIONS: Equestrian activities are not without risks. The morbidity is high, and injuries are taken seriously by the medical profession, reflected by the high admission rate. There are age-related variations in the injury spectrum. Older age appears to predispose to vertebral fractures and thoracic injuries. Other factors than age appear more important in determining the need for surgery or admission to ICU.

Guidelines for Perioperative Care for Emergency Laparotomy Enhanced Recovery After Surgery (ERAS) Society Recommendations: Part 1-Preoperative: Diagnosis, Rapid Assessment and Optimization.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols reduce length of stay, complications and costs for a large number of elective surgical procedures. A similar, structured approach appears to improve outcomes, including mortality, for patients undergoing high-risk emergency general surgery, and specifically emergency laparotomy. These are the first consensus guidelines for optimal care of these patients using an ERAS approach. METHODS: Experts in aspects of management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. Pubmed, Cochrane, Embase, and MEDLINE database searches on English language publications were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized controlled trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on non-emergency patients when appropriate. The Delphi method was used to validate final recommendations. The guideline has been divided into two parts: Part 1-Preoperative Care and Part 2-Intraoperative and Postoperative management. This paper provides guidelines for Part 1. RESULTS: Twelve components of preoperative care were considered. Consensus was reached after three rounds. CONCLUSIONS: These guidelines are based on the best available evidence for an ERAS approach to patients undergoing emergency laparotomy. Initial management is particularly important for patients with sepsis and physiological derangement. These guidelines should be used to improve outcomes for these high-risk patients.

Body composition, muscle function and biochemical values in patients after pancreatic surgery: An observational study.

BACKGROUND & AIMS: The complex nature of pancreatic operation makes it a high-risk and technically demanding major abdominal procedure, resulting in early pathophysiological alterations. This study aims to observe changes in body composition, muscle function and biochemical values in patients during the early postoperative days (PODs) following pancreaticoduodenectomy or total pancreatectomy. METHODS: Assessment of body composition by bioimpedance spectroscopy, muscle function by peak expiratory flow rate (PEFR) and maximum handgrip strength (HGS), and biochemical values were measured in patients the day before surgery and on PODs 3, 6 and 9. RESULTS: Significant changes occurred among 34 patients on POD 3 in body weight +2.3 (0.8-3.6) kg, total body water +2.8 (1.1-5.9) L, extracellular water +2.5 (1.2-3.7) L, intracellular water +1.1 (-0.4-1.9) L, phase angle -1.0 (-1.2 to -0.7)°, PEFR -250.0 (-407.5 to -125.0) L/m and HGS -4.8 (-7.3 to -3.0) kg, C-reactive protein +78.0 (41.0-102.8) mg/L, haemoglobin -34.5 (-45.8 to -26.0) g/L, albumin -12 (-16.5 to -10.0) g/L. CONCLUSIONS: Changes in water distribution, phase angle, initial reduced muscle function and altered biochemical values were observed during the first 9 PODs.

No association between preoperative impaired glucose control and postoperative adverse events following hip fracture surgery - A single-centre observational cohort study.

RATIONALE: Observational studies have shown an association between hyperglycaemia and increased complications in orthopaedic patients. The aim of the study was to investigate if impaired preoperative glycaemic control, reflected by elevated HbA1c, was associated with adverse postoperative events in hip fracture patients. METHODS: 160 patients (116 women and 44 men; age 80 ± 10 and BMI 24 ± 4; mean ± SD) with hip fractures were included in a prospective observational cohort study. The patients were divided into two groups, normal glycaemic control (NGC) and impaired glycaemic control (IGC) HbA1c ≥ 42 mmol/mol. The patients were also characterized according to BMI and nutritional status using MNA-SF (Minimal Nutritional Assessment Short Form). Complications within 30 days of surgery were classified according to Clavien-Dindo and 1-year mortality was compared between the groups. RESULTS: Out of 160 patients, 18 had diabetes and 4 more had likely occult diabetes (HbA1c ≥ 48). Impaired glycaemic control (IGC) was seen in 29 patients (18.1%) and normal glycaemic control (NGC) in 131 (81.9%). In patients with NGC and IGC, no postoperative complications (Clavien-Dindo Grade 0) were seen in 64/131 vs. 14/29 (48.9 vs. 48.3%), Grade 1-3a in 54/131 vs. 14/29 (41.2 vs. 48.3%) and Grade 3b-5 in 13/131 vs. 1/29 (9.9 vs. 3.4%) respectively, p = NS. There were no differences in 30-day complications (p = 0.55) or 1-year mortality (p = 0.35) between the groups. CONCLUSION: Elevated HbA1c at admission is not associated with increased complications or mortality after hip fracture surgery.

Antibiotic prophylaxis in acute cholecystectomy revisited: results of a double-blind randomised controlled trial.

PURPOSE: Evidence supporting the value of preoperative antibiotic prophylaxis (PAP) in surgery for acute cholecystitis is lacking. This study aimed to shed light on whether PAP in acute cholecystectomy for cholecystitis reduces the postoperative infectious complication (PIC) rate. Secondary outcomes were the prevalence of bacteriobilia, CRP values and leucocyte counts. METHODS: The study was performed as a single-centre, double-blinded, placebo-controlled, randomised study. Patients with acute cholecystitis amenable for acute laparoscopic cholecystectomy were randomly assigned to either PAP (piperacillin/ tazobactam) or placebo, and the subsequent clinical course was followed. RESULTS: A total of 106 patients were enrolled, 16 of whom were excluded due to protocol violation. PIC developed in 22 of the 90 patients included with no significant difference between the PAP and placebo groups (8 patients in the PAP group and 14 in the placebo arm, p = 0.193). The PIC rate was significantly higher in patients with a raised CRP at randomisation and on the day of surgery and in cases of conversion to an open procedure (p = 0.008, 0.004 and 0.017, respectively) but with no differences between the study groups. CONCLUSION: PAP does not affect the risk for PIC in patients with acute cholecystitis. The major risk factors determining PIC in these patients need defining, in particular, the impact of bacteriobilia. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov (NCT02619149) December 2, 2015.

Index versus delayed cholecystectomy in mild gallstone pancreatitis: results of a randomized controlled trial.

BACKGROUND: Delayed cholecystectomy is associated with increased risk of biliary events. The objectives of the study were to confirm the superiority of index cholecystectomy over delayed operation in mild gallstone pancreatitis. METHODS: Patients with mild gallstone pancreatitis were randomized into index-or delayed cholecystectomy (IC vs. DC). IC was performed within 48 h from randomization provided a stable or improved clinical condition. The primary outcome was gallstone-related events. Secondary outcomes were rates of cholecystectomy complications, common bile duct stones (CBDS) detected at cholecystectomy and patient reported quality-of-life and pain. RESULTS: Sixty-six patients were randomized into IC (n = 32) or DC (n = 34) between May 2009 and July 2017. There were significantly higher rates of gallstone-related events in the DC compared with the IC group (nine patients vs. one patient, p = 0.013). No statistically significant differences could be demonstrated in cholecystectomy complications (p = 0.605) and CBDS discovered during cholecystectomy (p = 0.302) between the groups. Pain and emotional well-being measured by SF-36 were improved significantly in the IC group at follow-up. CONCLUSIONS: Delayed cholecystectomy in mild gallstone pancreatitis can no longer be recommended since it is associated with an increased risk for recurrent gallstone-related events and impaired patient's reported outcomes. TRIAL REGISTRATION NUMBER: clinicaltrials.gov (ID: NCT02630433).

Patient-Related Risk Factors for Postoperative Infection After Cholecystectomy.

BACKGROUND: The impact of patient-related risk factors on the incidence of postoperative infection after cholecystectomy is relatively unknown. AIM: The aim of this study was to explore potential patient-related risk factors for surgical site infection (SSI) and septicaemia following cholecystectomy. MATERIALS AND METHODS: All cholecystectomies registered in the Swedish national population-based register for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) 2006-2014 were identified. The study cohort was cross-matched with the Swedish National Patient Register in order to obtain data on patient history and postoperative infections. Simple and multiple logistic regression analyses were performed in order to assess the impact of various comorbidities on the risk for SSI and septicaemia. RESULTS: A total of 94,557 procedures were registered. A SSI was seen following 5300 procedures (5.6%), and septicaemia following 661 procedures (0.7%). There was a significantly increased risk for SSI in patients with connective tissue disease (odds ratio [OR] 1.404, 95% confidence interval [CI] 1.208-1.633), complicated diabetes (OR 1.435, CI 1.205-1.708), uncomplicated diabetes (OR 1.391, CI 1.264-1.530), chronic kidney disease (OR 1.788, CI 1.458-2.192), cirrhosis (OR 1.764, CI 1.268-2.454) and obesity (OR 1.630, CI 1.475-1.802). There was a significantly higher risk for septicaemia in patients with chronic kidney disease (OR 3.065, CI 2.120-4.430) or cirrhosis (OR 5.016, CI 3.019-8.336). CONCLUSION AND DISCUSSION: Certain comorbidities have an impact on the risk for postoperative infection after cholecystectomy, especially SSI. This should be taken into account when planning the procedure and when deciding on prophylactic antibiotic treatment.

Approximation of Resting Energy Expenditure in Intensive Care Unit Patients Using the SenseWear Bracelet: A Comparison With Indirect Calorimetry.

BACKGROUND AND AIMS: Indirect calorimetry (IC) is the gold standard for determining energy expenditure in patients requiring mechanical ventilation. Metabolic armbands using data derived from dermal measurements have been proposed as an alternative to IC in healthy subjects, but their utility during critical illness is unclear. The aim of this study was to determine the level of agreement between the SenseWear armband and the Deltatrac Metabolic Monitor in mechanically ventilated intensive care unit (ICU) patients. METHODS: Adult ICU patients requiring invasive ventilator therapy were eligible for inclusion. Simultaneous measurements were performed with the SenseWear Armband and Deltatrac under stable conditions. Resting energy expenditure (REE) values were registered for both instruments and compared with Bland-Altman plots. RESULTS: Forty-two measurements were performed in 30 patients. The SenseWear Armband measured significantly higher REE values as compared with IC (mean bias, 85 kcal/24 h; P = .027). Less variability was noted between individual SenseWear measurements and REE as predicted by the Harris-Benedict equation (2 SD, ±327 kcal/24 h) than when IC was compared with SenseWear and Harris-Benedict (2 SD, ±473 and ±543 kcal/24 h, respectively). CONCLUSIONS: The systematic bias and large variability of the SenseWear armband when compared with gas exchange measurements confer limited benefits over the Harris Benedict equation in determining caloric requirements of ICU patients.

Simultaneous assessment of the synthesis rate and transcapillary escape rate of albumin in inflammation and surgery.

BACKGROUND: Better knowledge of albumin kinetics is needed to define the indications for albumin use in clinical practice. This study involved two approaches: the synthesis rate and transcapillary escape rate of albumin were measured simultaneously at different levels of plasma albumin concentration in relation to acute inflammation and surgery; and two different tracers were compared to determine plasma volume and the transcapillary escape rate. METHODS: Healthy volunteers (n = 10), patients with acute inflammatory abdominal disease (n = 10), and patients undergoing elective pancreatic resection (n = 10) were studied. The albumin synthesis rate was measured by the incorporation of deuterium-labeled phenylalanine. Plasma volume and the transcapillary escape rate were assessed using 123I-labeled and 125I-labeled albumin. RESULTS: A 50 % elevated de-novo albumin synthesis rate was seen in patients with acute inflammation and marked hypoalbuminemia, while patients with marginal hypoalbuminemia before the start of surgery had a normal albumin synthesis rate. The transcapillary escape rate was elevated intraoperatively during the reconstructive phase of pancreatic surgery, when plasma albumin was decreased but stable. In acute inflammation with marked hypoalbuminemia, the transcapillary escape rate was no different from normal. 123I-labeled and 125I-labeled albumin were found exchangeable for plasma volume determinations, but could be used only in groups of patients for the transcapillary escape rate. CONCLUSIONS: This observational study illustrates the limited information contained in albumin plasma concentrations to reflect albumin kinetics. On the contrary, single measurements of the synthesis rate and/or transcapillary escape rate of albumin obviously cannot explain the plasma level of albumin or the changes seen in plasma albumin concentration. TRIAL REGISTRATION: www.clinicaltrials.gov , study number NCT01686776 . Registered 13 September 2012.

Cholecystectomy in Patients with Liver Cirrhosis.

Background. The aim of this population-based study was to describe characteristics of patients with liver cirrhosis undergoing cholecystectomy and evaluate the risk for perioperative and postoperative complications during the 30-day postoperative period. Method. All laparoscopic and open cholecystectomy procedures registered between 2006 and 2011 in the Swedish Registry for Gallstone Surgery and ERCP (GallRiks) were included. Patients with liver cirrhosis were identified by linking data to the Swedish National Patient Registry (NPR). Results. Of 62,488 patients undergoing cholecystectomy, 77 (0.12%) had cirrhosis, of which 29 patients (37.7%) had decompensated cirrhosis. Patients with cirrhosis were older and had more often gallstone complications at the time for surgery. Postoperative complications were registered in 13 (16.9%) patients with liver cirrhosis and in 5,738 (9.2%) patients in the noncirrhotic group (P < 0.05). Univariable analysis showed that patients with liver cirrhosis are more likely to receive postoperative blood transfusion (OR = 4.4, CI 1.08-18.0, P < 0.05) and antibiotic treatment >1 day (OR = 2.3, CI 1.11-4.84, P < 0.05) than noncirrhotic patients. Conclusion. Patients with cirrhosis undergoing cholecystectomy have a higher incidence of postoperative complications than patients without cirrhosis. However, cholecystectomy is safe and if presented with adequate indication, surgery should not be delayed due to fears of surgical complications.

Vasodilatory effects of the selective GPER agonist G-1 is maximal in arteries of postmenopausal women.

G-protein-coupled estrogen receptors (GPERs) have been proposed to mediate estrogen-mediated vasodilation. The presence of GPER-dependent vasodilation in human resistance-sized arteries (HRAs) or its signal transduction pathways have not been investigated. HRAs in subcutaneous fat tissues (biopsies from postmenopausal women (PMW), age-matched men (M) and pregnant women (PGW)) were mounted for in vitro isometric force recording. Vasodilation induced by G-1 (selective GPER-agonist, 3 µM) from HRAs pre-contracted with norepinephrine amounted to 40±5% in PMW, significantly larger than those obtained from M (20±5%) or PGW (20±5%). L-NAME (nitric oxide (NO) synthase inhibitor) abolished these relaxations in PGW, attenuated them in PMW and had no effect in M. Immunohistochemical analysis confirmed the presence of GPER in both smooth muscle and endothelial cells of HRA with maximum expression in PGW. In cultured human umbilical vein endothelial cells (HUVECs), G-1 increased NO-synthesis concentration-dependently through higher expressions of endothelial NO-synthase (eNOS) and through enhanced phosphorylation of eNOS on Ser(1177). In conclusion, GPER vasodilates human resistance arteries through various activating mechanisms of the eNOS-signaling pathway.

Elevated circulating levels and tissue expression of pentraxin 3 in uremia: a reflection of endothelial dysfunction.

Elevated systemic pentraxin 3 (PTX3) levels appear to be a powerful marker of inflammatory status and a superior outcome predictor in patients with chronic kidney disease (CKD). As previous data imply that PTX3 is involved in vascular pathology and that adipose tissue mass may influence circulating PTX3 levels, we aimed to study the importance of adipose tissue expression of PTX3 in the uremic milieu and its relation to endothelial dysfunction parameters. Plasma PTX3 and abdominal subcutaneous adipose tissue (SAT) PTX3 mRNA levels were quantified in 56 stage 5 CKD patients (median age 57 [range 25-75] years, 30 males) and 40 age and gender matched controls (median age 58 [range 20-79] years, 27 males). Associations between PTX3 measures and an extensive panel of clinical parameters, including surrogate markers of endothelial function, were assessed. Functional ex vivo studies on endothelial status and immunohistochemical staining for PTX3 were conducted in resistance subcutaneous arteries isolated from SAT. SAT PTX3 mRNA expression correlated with plasma PTX3 concentrations (rho = 0.54, p = 0.0001) and was increased (3.7 [0.4-70.3] vs. 1.2 [0.2-49.3] RQ, p = 0.02) in CKD patients with cardiovascular disease (CVD), but was not significantly different between patients and controls. The association to CVD was lost after adjustments. SAT PTX3 mRNA levels were independently correlated to asymmetric dimethylarginine and basal resistance artery tone developed after inhibition with nitric oxide synthase and cyclooxygenase (rho = -0.58, p = 0.002). Apparent positive PTX3 immunoreactivity was observed in both patient and control arteries. In conclusion, fat PTX3 mRNA levels are associated with measures of endothelial cell function in patients with CKD. PTX3 may be involved in adipose tissue-orchestrated mechanisms that are restricted to the uremic milieu and modify inflammation and vascular complications in CKD patients.

Mechanisms of endothelial dysfunction in resistance arteries from patients with end-stage renal disease.

The study focuses on the mechanisms of endothelial dysfunction in the uremic milieu. Subcutaneous resistance arteries from 35 end-stage renal disease (ESRD) patients and 28 matched controls were studied ex-vivo. Basal and receptor-dependent effects of endothelium-derived factors, expression of endothelial NO synthase (eNOS), prerequisites for myoendothelial gap junctions (MEGJ), and associations between endothelium-dependent responses and plasma levels of endothelial dysfunction markers were assessed. The contribution of endothelium-derived hyperpolarizing factor (EDHF) to endothelium-dependent relaxation was impaired in uremic arteries after stimulation with bradykinin, but not acetylcholine, reflecting the agonist-specific differences. Diminished vasodilator influences of the endothelium on basal tone and enhanced plasma levels of asymmetrical dimethyl L-arginine (ADMA) suggest impairment in NO-mediated regulation of uremic arteries. eNOS expression and contribution of MEGJs to EDHF type responses were unaltered. Plasma levels of ADMA were negatively associated with endothelium-dependent responses in uremic arteries. Preserved responses of smooth muscle to pinacidil and NO-donor indicate alterations within the endothelium and tolerance of vasodilator mechanisms to the uremic retention products at the level of smooth muscle. We conclude that both EDHF and NO pathways that control resistance artery tone are impaired in the uremic milieu. For the first time, we validate the alterations in EDHF type responses linked to kinin receptors in ESRD patients. The association between plasma ADMA concentrations and endothelial function in uremic resistance vasculature may have diagnostic and future therapeutic implications.

Impaired resistance artery function in patients with end-stage renal disease.

We investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (≈ 200 µm) isolated from subcutaneous fat biopsies obtained from 35 ESRD (end-stage renal disease) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients compared with controls. NO (nitric oxide) contribution to flow was lacking in ESRD patients, but present in the controls. ADMA (asymmetrical dimethyl L-arginine) levels were higher in the ESRD group compared with the control group. Dilatation in response to acetylcholine was reduced in ESRD patients compared with controls, but response to NO donor was similar. Expression of nitrotyrosine and heat shock proteins 70 and 27, but not 90, was increased in arteries from ESRD patients compared with controls. Arterial remodelling was absent in ESRD patients. There was no difference between the groups in myogenic tone, vascular reactivity or sensitivity to several vasoconstrictors. Arterial distensibility, reflecting passive properties of the vascular wall, was reduced in ESRD patients compared with controls. Exclusion of ESRD patients with diabetes and/or cardiovascular disease from analyses had no influence on the main findings. Thus we propose that uraemia has a strong impact on endothelial function and passive properties of the arterial wall of human peripheral resistance vasculature. The reduced contribution of NO to flow stimulus via enhanced nitrosative stress and higher plasma concentrations of ADMA may suggest potential mechanisms behind endothelial dysfunction in the resistance peripheral circulation in ESRD.

Expression of osteoprotegerin in human fat tissue; implications for chronic kidney disease.

BACKGROUND: Premature vascular calcification (or rather ossification) significantly contributes to morbidity and mortality in patients with chronic kidney disease stage 5 (CKD-5) and is linked to dysregulation of bone remodelling proteins. Recent evidence of a cross-talk between bone and fat tissue urged us to investigate whether the calcification/ossification-associated factors osteoprotegerin (OPG) and alpha-2-HS-glycoprotein (AHSG) are expressed in human uremic subcutaneous adipose tissue (SAT) and if the expression differs from nonuremic SAT. MATERIALS AND METHODS: Abdominal SAT biopsies were obtained from 38 patients with CKD-5 [16 women, 58 (22-73) years old] during the surgical insertion of a peritoneal dialysis catheter and 20 controls [11 females, 56 (40-77) years old] undergoing elective hernia repair or laparoscopic cholecystectomy. Real-time polymerase chain reaction (PCR) quantifications were performed followed by immunohistochemical staining and serum protein concentration measurements. Relative mRNA expression and protein concentrations were evaluated together with clinical parameters. An additional 59 patients with CKD-5 were included for replication of statistical analyses. RESULTS: OPG but not AHSG mRNAs were detected in SAT, which were also positively immunolabelled for OPG. OPG mRNA levels were reduced (P = ·0001) and serum OPG concentrations were elevated (P < 0·0001), both about twofold, in patients compared to controls. Circulating OPG increased in proportion to BMI. CONCLUSIONS: Human SAT expresses OPG but not AHSG, and OPG expression is reduced in patients with CKD-5 when compared to controls, despite increased circulating protein levels.

Effects of growth hormone and insulin-like growth factor-1 on postoperative muscle and substrate metabolism.

This study explored if a combined supplementation of GH and IGF-1 had an additive effect on whole body nitrogen economy, energy, substrate and skeletal muscle metabolism following surgical trauma. Patients were randomized to controls (C; n = 10), to GH (0.15 IU/kg/injection) (GH; n = 7) or GH combined with IGF-1 (40 mug/kg/injection) subcutaneously twice a day (GH-IGF-1; n = 9) together with standardized parenteral nutrition. Muscle amino acids, glutathione and the ribosomal pattern reflecting protein synthesis, and nitrogen balance were measured. GH- and GH-IGF-1 groups showed lower urea and higher plasma glucose concentrations. Energy expenditure increased in the GH-group. GH-IGF-1 prevented a decrease in muscle polyribosomes indicating a preserved muscle protein synthesis. In the GH group unaltered BCAA and AAA levels were seen in muscle indicating an unchanged protein breakdown, while the other groups showed increased muscle concentrations postoperatively. Without statistically difference GH marginally improved the nitrogen balance, in terms of higher values, and growth factors improved the nitrogen balance when the shift in urea was taken into account. To conclude, growth factors influences urea metabolism, protein degradation and protein synthesis. There was no clearcut additional effect when combining GH and IGF-1 but the study was probably underpowered to outrule this and effects on nitrogen balance.

Age-related changes of muscle and plasma amino acids in healthy children.

The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: < 1 year, n = 8; group 2: 1-4 years, n = 13 and group 3: 5-15 years, n = 15). A reference group of healthy adults (21-38 years, n = 22) was included in their comparisons and reflected specific differences between children and adults. In muscle the concentrations of 8 out of 19 amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P < 0.05). In plasma the concentrations of threonine, glutamine, valine, cysteine, methionine, leucine, lysine, tryptophane, arginine, BCAA, BAA and the essential amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.