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The aim of this study was to compare the accuracy of measurements of body composition made using dual x-ray absorptiometry (DXA), analysis of computed tomography (CT) scans at the L3 vertebral level, and bioelectrical impedance analysis (BIA). DXA, CT, and BIA were performed in 47 patients recruited from two clinical trials investigating metabolic changes associated with major abdominal surgery or neoadjuvant chemotherapy for esophagogastric cancer. DXA was performed the week before surgery and before and after commencement of neoadjuvant chemotherapy. BIA was performed at the same time points and used with standard equations to calculate fat-free mass (FFM). Analysis of CT scans performed within 3 mo of the study was used to estimate FFM and fat mass (FM). There was good correlation between FM on DXA and CT (r2 = 0.6632; P < 0.0001) and FFM on DXA and CT (r2 = 0.7634; P < 0.0001), as well as FFM on DXA and BIA (r2 = 0.6275; P < 0.0001). Correlation between FFM on CT and BIA also was significant (r2 = 0.2742; P < 0.0001). On Bland–Altman analysis, average bias for FM on DXA and CT was 0.2564 with 95% limits of agreement (LOA) of –9.451 to 9.964. For FFM on DXA and CT, average bias was –0.1477, with LOA of –8.621 to 8.325. For FFM on DXA and BIA, average bias was –3.792, with LOA of –15.52 to 7.936. For FFM on CT and BIA, average bias was –2.661, with LOA of –22.71 to 17.39. Although a systematic error underestimating FFM was demonstrated with BIA, it may be a useful modality to quantify body composition in the clinical situation. •The present study compared the accuracy of measurements of body composition made using dual x-ray absorptiometry (DXA), analysis of computed tomography (CT) scans, and bioelectrical impedance analysis (BIA).•DXA, CT, and BIA were performed in 47 patients recruited from two clinical trials.•Although a systematic error underestimating fat-free mass was demonstrated with BIA, it may be a useful modality to quantify body composition in a clinical situation.

Polymeric immunoglobulin receptor (PIGR) has a major role in mucosal immunity as a transporter of polymeric immunoglobulin across the epithelial cells. The aim of this study was to determine the effect of PIGR on cellular behaviours and chemo-sensitivity of MCF7 and MDA-MB468 breast cancer cell lines. Basal levels of PIGR mRNA and protein expression in MCF7 and MDA-MB468 cells were evaluated by real time quantitative polymerase chain reaction and Western blotting, respectively. MCF7/PIGR and MDA-MB468/PIGR stable cell lines, overexpressing the PIGR gene, were generated using a lentiviral vector with tetracycline dependent induction of expression. Cell viability, cell proliferation and chemo-sensitivity of PIGR transfected cells were evaluated and compared with un-transfected cells to determine the effect of PIGR overexpression on cell phenotype. The levels of PIGR mRNA and protein expression were significantly higher in MDA-MB468 cells than in MCF7 cells (380-fold, p  < 0.0001). However, the differential expression of PIGR in these two cell lines did not lead to significant differences in chemosensitivity. Viral overexpression of PIGR was also not found to change any of the parameters measured in either cell line. PIGR per se did not affect cellular behaviours and chemosensitivity of these breast cancer cell lines.

High expression of polymeric immunoglobulin receptor (PIGR) in breast cancer is associated with increased 5-year survival rate. However, the factors influencing PIGR expression in breast cancer have not been elucidated. The aim of this study was to determine the role of macrophages and cytokines affecting expression of PIGR in two breast cancer cell lines. M1, M2 macrophage conditioned media (CM) and recombinant human cytokines were used to determine factors which increased PIGR expression in MCF7 (HTB-22) and MDA-MB468 (HTB-132) breast cancer cell lines. The level of PIGR expression in the cells and PIGR secretory component were evaluated by real-time quantitative polymerase chain reaction and Western blotting. M1 macrophage CM induced a dose-dependent increase in PIGR mRNA expression in MDA-MB468 cells, up to 20-fold. The level of PIGR expression in MCF7 cells was very low and not affected by M1 and M2 CM. Interferon gamma (IFN-γ) and interleukin (IL)-1β also increased PIGR expression in MDA-MB468 and MCF7 cells. However, IL-1β was demonstrated to increase in M1 macrophages, while IFN-γ was not. The role of IL-1β secreted from M1 macrophages in increasing expression of PIGR was confirmed by IL-1 receptor blockade, indicating that IL-1β was the major M1 macrophage-derived cytokine that enhanced PIGR expression. Elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumor-associated immune cells.

Background Protocols for enhanced recovery provide comprehensive and evidence-based guidelines for best perioperative care. Protocol implementation may reduce complication rates and enhance functional recovery and, as a result of this, also reduce length-of-stay in hospital. There is no comprehensive framework available for pancreaticoduodenectomy. Methods An international working group constructed within the Enhanced Recovery After Surgery (ERAS ® ) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group. The quality of evidence was rated “high”, “moderate”, “low” or “very low”. Recommendations were graded as “strong” or “weak”. Results Comprehensive guidelines are presented. Available evidence is summarised and recommendations given for 27 care items. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. Conclusions The present evidence-based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy. A unified protocol allows for comparison between centres and across national borders. It facilitates multi-institutional prospective cohort registries and adequately powered randomised trials.

The aim of this study was to determine, from the methodologic standpoint, the effect of the presence or absence of intravenous contrast on body composition variables obtained by analysis of computed tomography (CT) images. Triphasic abdominal (noncontrast, arterial phase, and portovenous phase contrast) CT scans from 111 patients were analyzed by two independent assessors at the third lumbar vertebral level using SliceOmatic software (version 5.0, TomoVision, Montreal, Canada). Variables included skeletal muscle index (SMI), fat and fat-free mass (FM and FFM, respectively), and mean skeletal muscle Hounsfield units (SMHU). Mean SMHU was lowest in the noncontrast phase (29.4, standard deviation [SD] 8.9 HU), followed by arterial (32.4, SD 9.3 HU) then portovenous phases (34.9, SD 9.4 HU). The mean skeletal muscle attenuation was significantly different depending on the phase of the scan in which the images were obtained. Calculated FM was significantly lower in both arterial (28.6, SD 8.8 kg, P < 0.0001) and portovenous phase scans (28.5, SD 8.9 kg, P < 0.0001) when compared with noncontrast (29.2, SD 8.9 kg). The mean FFM was not significantly different as measured on noncontrast, arterial, or portovenous phase CT scans (48, SD 11.2; 48.1, SD 9.8; and 48.6, SD 10.2 kg, respectively). No difference was seen in SMI. Interobserver reliability was high. The definition of myosteatosis should include a standardized phase of CT for analysis and this should be incorporated within its definition. However, as the magnitudes of the differences were relatively small, the effect of the phase of the scan on predicting outcome needs to be determined. •In this study, we clarified the effect of intravenous contrast on body composition analysis of computed tomography (CT) scans.•Triphasic abdominal CT scans from 111 patients were analyzed.•Skeletal muscle attenuation (myosteatosis) was dependent on the phase of the scan.•No difference was seen in fat-free mass or skeletal muscle index.•The definition of myosteatosis should include a standardized phase of CT for analysis.

Disease-related malnutrition in adult patients who have been admitted to hospital is a syndrome associated with substantially increased morbidity, disability, short-term and long-term mortality, impaired recovery from illness, and cost of care. There is uncertainty regarding optimal diagnostic criteria, definitions for malnutrition, and how to identify patients who would benefit from nutritional intervention. Malnutrition has become the focus of research aimed at translating current knowledge of its pathophysiology into improved diagnosis and treatment. Researchers are particularly interested in developing nutritional interventions that reverse the negative effects of disease-related malnutrition in the hospital setting. High-quality randomised trials have provided evidence that nutritional therapy can reduce morbidity and other complications associated with malnutrition in some patients. Screening of patients for risk of malnutrition at hospital admission, followed by nutritional assessment and individualised nutritional interventions for malnourished patients, should become part of routine clinical care and multimodal treatment in hospitals worldwide.

The high chloride content of 0.9% saline leads to adverse pathophysiological effects in both animals and healthy human volunteers, changes not seen after balanced crystalloids. Small randomized trials confirm that the hyperchloremic acidosis induced by saline also occurs in patients, but no clinical outcome benefit was demonstrable when compared with balanced crystalloids, perhaps due to a type II error. A strong signal is emerging from recent large propensity-matched and cohort studies for the adverse effects that 0.9% saline has on the clinical outcome in surgical and critically ill patients when compared with balanced crystalloids. Major complications are the increased incidence of acute kidney injury and the need for renal replacement therapy, and that pathological hyperchloremia may increase postoperative mortality. However, there are no large-scale randomized trials comparing 0.9% saline with balanced crystalloids. Some balanced crystalloids are hypo-osmolar and may not be suitable for neurosurgical patients because of their propensity to cause brain edema. Saline may be the solution of choice used for the resuscitation of patients with alkalosis and hypochloremia. Nevertheless, there is evidence to suggest that balanced crystalloids cause less detriment to renal function than 0.9% saline, with perhaps better clinical outcome. Hence, we argue that chloride-rich crystalloids such as 0.9% saline should be replaced with balanced crystalloids as the mainstay of fluid resuscitation to prevent ‘pre-renal’ acute kidney injury.

Background Enhanced recovery may be viewed as a comprehensive approach to improving meaningful outcomes in patients undergoing major surgery. Evidence to support enhanced recovery pathways (ERPs) is strong in patients undergoing colorectal surgery. There is some controversy about the adoption of specific elements in enhanced recovery “bundles” because the relative importance of different components of ERPs is hard to discern (a consequence of multiple simultaneous changes in clinical practice when ERPs are initiated). There is evidence that specific approaches to fluid management are better than alternatives in patients undergoing colorectal surgery; however, several specific questions remain. Methods In the “Perioperative Quality Initiative (POQI) Fluids” workgroup, we developed a framework broadly applicable to the perioperative management of intravenous fluid therapy in patients undergoing elective colorectal surgery within an ERP. Discussion We discussed aspects of ERPs that impact fluid management and made recommendations or suggestions on topics such as bowel preparation; preoperative oral hydration; intraoperative fluid therapy with and without devices for goal-directed fluid therapy; and type of fluid.

Background Antibiotic treatment has been shown to be effective in treating selected patients with acute appendicitis, and three randomized controlled trials (RCTs) have compared the efficacy of antibiotic therapy alone with that of surgery for acute appendicitis. The purpose of this meta-analysis of RCTs was to assess the outcomes with these two therapeutic modalities. Methods All RCTs comparing antibiotic therapy alone with surgery in patients over 18 years of age with suspected acute appendicitis were included. Patients with suspected perforated appendix or peritonitis, and those with an allergy to antibiotics had been excluded in the RCTs. The outcome measures studied were complications, length of hospital stay, and readmissions. Results Meta-analysis of RCTs of antibiotic therapy versus surgery showed a trend toward a reduced risk of complications in the antibiotic-treated group [RR (95%CI): 0.43 (0.16, 1.18) p  = 0.10], without prolonging the length of hospital stay [mean difference (inverse variance, random, 95% CI): 0.11 (−0.22, 0.43) p  = 0.53]. Of the 350 patients randomized to the antibiotic group, 238 (68%) were treated successfully with antibiotics alone and 38 (15%) were readmitted. The remaining 112 (32%) patients randomized to antibiotic therapy crossed over to surgery for a variety of reasons. At 1 year, 200 patients in the antibiotic group remained asymptomatic. Conclusions This meta-analysis suggests that although antibiotics may be used as primary treatment for selected patients with suspected uncomplicated appendicitis, this is unlikely to supersede appendectomy at present. Selection bias and crossover to surgery in the RCTs suggest that appendectomy is still the gold standard therapy for acute appendicitis.

Background Bed rest (BR) reduces whole‐body insulin‐stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance. Methods Healthy males (n = 10, 24.0 ± 1.3 years), maintained in energy balance, underwent 3‐day BR (acute BR). A second cohort matched for sex and body mass index (n = 20, 34.2 ± 1.8 years) underwent 56‐day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp (60 mU/m2/min) was performed to determine rates of whole‐body insulin‐stimulated GD before and after BR (normalized to lean body mass). Indirect calorimetry was performed before and during steady state of each clamp to calculate rates of whole‐body fuel oxidation. Muscle biopsies were taken to determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, and the expression of 191 mRNA targets before and after BR. Two‐way repeated measures analysis of variance was used to detect differences in endpoint measures. Results Acute BR reduced insulin‐mediated GD (Pre 11.5 ± 0.7 vs. Post 9.3 ± 0.6 mg/kg/min, P < 0.001), which was unchanged in magnitude following chronic BR (Pre 10.2 ± 0.4 vs. Post 7.9 ± 0.3 mg/kg/min, P < 0.05). This reduction in GD was paralleled by the elimination of the 35% increase in insulin‐stimulated muscle glycogen storage following both acute and chronic BR. Acute BR had no impact on insulin‐stimulated carbohydrate (CHO; Pre 3.69 ± 0.39 vs. Post 4.34 ± 0.22 mg/kg/min) and lipid (Pre 1.13 ± 0.14 vs. Post 0.59 ± 0.11 mg/kg/min) oxidation, but chronic BR reduced CHO oxidation (Pre 3.34 ± 0.18 vs. Post 2.72 ± 0.13 mg/kg/min, P < 0.05) and blunted the magnitude of insulin‐mediated inhibition of lipid oxidation (Pre 0.60 ± 0.07 vs. Post 0.85 ± 0.06 mg/kg/min, P < 0.05). Neither acute nor chronic BR increased muscle IMCL content. Plentiful mRNA abundance changes were detected following acute BR, which waned following chronic BR and reflected changes in fuel oxidation and muscle glycogen storage at this time point. Conclusions Acute BR suppressed insulin‐stimulated GD and storage, but the extent of this suppression increased no further in chronic BR. However, insulin‐mediated inhibition of fat oxidation after chronic BR was less than acute BR and was accompanied by blunted CHO oxidation. The juxtaposition of these responses shows that the regulation of GD and storage can be dissociated from substrate oxidation. Additionally, the shift in substrate oxidation after chronic BR was not explained by IMCL accumulation but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein abundance changes, pointing to lack of muscle contraction per se as the primary signal for muscle adaptation.