Immunologic ignorance of vascular endothelial cells expressing minor histocompatibility antigen

Endothelial cells (ECs) presenting minor histocompatibility antigen (mhAg) are major target cells for alloreactive effector CD8⁺ T cells during chronic transplant rejection and graft-versus-host disease (GVHD). The contribution of ECs to T-cell activation, however, is still a controversial issue. In this study, we have assessed the antigen-presenting capacity of ECs in vivo using a transgenic mouse model with beta-galactosidase (β-gal) expression confined to the vascular endothelium (Tie2-LacZ mice). In a GVHD-like setting with adoptive transfer of β-gal–specific T-cell receptor–transgenic T cells, β-gal expression by ECs was not sufficient to either activate or tolerize CD8⁺ T cells. Likewise, transplantation of fully vascularized heart or liver grafts from Tie2-LacZ mice into nontransgenic recipients did not suffice to activate β-gal–specific CD8⁺ T cells, indicating that CD8⁺ T-cell responses against mhAg cannot be initiated by ECs. Moreover, we could show that spontaneous activation of β-gal–specific CD8⁺ T cells in Tie2-LacZ mice was exclusively dependent on CD11c⁺ dendritic cells (DCs), demonstrating that mhAgs presented by ECs remain immunologically ignored unless presentation by DCs is granted.     

Using constraint satisfaction for designing mechanical systems

In this paper, we are studying the application of techniques to solve constraint satisfaction problems (CSP) for designing mechanical systems. After situating CSPs within the array of search and combinatorial optimisation techniques, we propose to model the design space in the form of a state graph and demonstrate the suitability of the constraint approach to solve the model. The implementation of a CSP is illustrated by an example of the dimensioning of a cluster of gear wheels in the mechanical engineering industry. Finally, we draw attention to the complementarity of CSPs with other search and solution optimisation techniques and suggest a few integration possibilities.     

Fluticasone furoate nasal spray: effective monotherapy for symptoms of perennial allergic rhinitis in adults/adolescents.

Intranasal corticosteroids are widely prescribed for the treatment of perennial allergic rhinitis (PAR). The purpose of this study was to evaluate the efficacy and tolerability of intranasal fluticasone furoate, a novel enhanced-affinity glucocorticoid, in patients > or =12 years of age with PAR in a global, randomized, double-blind, placebo-controlled, 6-week study. Patients (n = 302) received fluticasone furoate nasal spray (FFNS) 110 microg or vehicle placebo once daily (q.d.). The primary efficacy measure was mean change from baseline over the 6-week treatment period in daily reflective total nasal symptom score (TNSS). Secondary end points included mean change from baseline in total and individual reflective nasal and ocular symptom scores and in daily peak nasal inspiratory flow (PNIF). FFNS was significantly more effective than placebo in reducing daily reflective TNSS over the treatment period (least square [LS] mean difference, -1.256; p < 0.001). Significant improvements were also established in total ocular symptom score (LS mean difference, -0.506; p = 0.004 versus placebo) and in all individual nasal (p < 0.001) and ocular (p < 0.03) symptoms assessed in a reflective manner. Improvements in daily PNIF were significantly greater with FFNS than placebo (LS mean difference, 8.376 L/minute; p = 0.004). FFNS was well tolerated. In this study, FFNS 110 microg q.d. was well tolerated and effective in reducing the nasal and ocular symptoms of PAR in adult and adolescent patients > or =12 years of age.     

Impact of postoperative complications on readmission and long-term survival in patients following surgery for colorectal cancer

Purpose

It is well known that specific postoperative complications such as stroke influence readmissions and overall survival (OS) after surgery for colorectal cancer (CRC). Whether overall hospital morbidity is associated with increased risk of readmission and poorer long-term survival is unknown. New tools are available to accurately quantify overall morbidity, such as the comprehensive complication index (CCI). The aim is to evaluate the impact of complications on readmission and overall survival (OS) in patients operated for colorectal cancer.

Methods

Postoperative complications of patients undergoing surgery for CRC were assessed over a 5-year period using the Clavien-Dindo classification, and overall morbidity was assessed by using the CCI. Individual scores were analyzed regarding their association with readmission and OS by using the multivariate logistic and Cox proportional-hazards regression analysis, respectively.

Results

Two hundred eighty-four patients were operated for CRC, of which 22 (8%) were readmitted. One hundred five patients (37%) developed at least one postoperative complication during the hospital stay. While single complications or the use of severe complication only (grade ≥IIIb) was not associated with readmission, overall morbidity (CCI) predicted readmission (OR 1.02 (95% CI 1.0–1.04), p = 0.044). Similarly, morbidity assessed by the CCI had a significant negative predictive value on OS, e.g., patients with a CCI of 20 were 22% more likely to die within a 5-year follow-up, when compared to patients with a CCI of 10 (p = 0.022).

Conclusions

Overall combined morbidity as assessed by the CCI leads to more frequent readmission, and is associated with poorer long-term survival after surgery for CRC.

     

Poor level of agreement on the management of postoperative pancreatic fistula: results of an international survey

Objectives

The occurrence of postoperative pancreatic fistula (POPF) is the main cause of severe complications, including death, after pancreatic surgery. This study was conduced to evaluate current practice in the management of POPF after Whipple surgery and distal pancreatectomy (DP).

Methods

An online survey endorsed by the European–African Hepato-Pancreato-Biliary Association (E-AHPBA) was conducted among surgical departments active in pancreatic surgery. A total of 108 centres were contacted by e-mail. The survey focused on the use and timing of drainage, nutrition strategies, provision of somatostatin and antibiotic therapies, imaging strategy and indications for reoperation when POPF is diagnosed after pancreatic surgery.

Results

A total of 55 centres (51%) completed the survey. Overall, responses showed poor agreement among centres (Fleiss'' kappa: <0.40) on 89% of items after Whipple surgery and 78% of items after DP. There was very poor or no agreement (Fleiss'' kappa: <0.1) on postoperative strategies for the management of nutrition and use of somatostatin after both procedures. In the event of POPF, 42% of centres used total oral nutrition and 22% used somatostatin after Whipple surgery, and 71% used total oral nutrition and 31% used somatostatin after DP. There were significant disagreements between units conducting, respectively, more and fewer than 50 Whipple procedures per year on drain removal after DP, and imaging strategy and patient discharge after Whipple surgery and DP.

Conclusions

This survey discloses important disagreements worldwide regarding the management of POPF after both Whipple surgery and DP. The standardized management of POPF would better facilitate the comparison of outcomes in future trials.     

Are two‐stage hepatectomies associated with more complications than one‐stage procedures?

BackgroundTwo-stage liver resections with portal vein occlusion have become standard in patients with low volume future liver remnants. Whether they are associated with more complications is unclear. The aim of this study was to compare complications of one- and two-stage resections in a retrospective study.MethodsPatients with two-stage right liver resections with a previous portal vein occlusion were compared with patients with one-stage right liver resections between 2002 and 2010. Primary endpoints were the incidence of complications by severity. Secondary endpoints were mortality, post-operative liver- and kidney function tests, length of hospitalization and transfusion events. Logistic and linear regression analyses were performed to adjust for confounders.ResultsThe groups were comparable except for right trisectionectomies, pre-operative chemotherapy and underlying liver disease. Overall complications occurred in 25 out of 35 patients with two-stage and 106 out of 163 in one-stage procedures. Severe complications were observed in 47 out of 163 patients versus 9 out of 35 patients, respectively. Two-stage procedures had no increased adjusted risk for complications [relative risk (RR) 0.9, P = 0.79]. Mortality (5.7% versus 3.7%) and post-operative liver failure rates (2.9% versus 3.1%) were low. Secondary endpoints showed no adjusted differences in risk.ConclusionThis study suggests that liver resections in two stages are not associated with more post-operative complications than one-stage resections. These results should support the adoption of two-stage liver resections in selected patients.     

Blood pressure pattern in the recovery period after coronary artery bypass grafting

BACKGROUND: Data on ambulatory blood pressure profiles after coronary artery bypass grafting (CABG) are largely lacking in the literature. OBJECTIVE: To examine the ambulatory blood pressure profile and its short- and long-term variability (daytime, night-time and 24 h) 1, 6 and 14 weeks after CABG in 15 patients (14 men, one woman) who remained uncomplicated postoperatively and during the 14 weeks' follow-up. Therapy remained unchanged over the study period. METHODS: Short-term blood pressure and heart rate variability were assessed by power spectral analysis of a sample length of 256 beats of these parameters obtained with subjects supine and having stood for 30 min, using the Finapres device 1, 6 and 14 weeks after CABG. The low-frequency (0.04-0.15 Hz): high-frequency (0.15-0.40 Hz) ratio of the R-R interval variability was considered a study parameter for the autonomic balance. RESULTS: During the rehabilitation period office and mean ambulatory blood pressure parameters were within the normotensive range. There was a progressive increase in 24 h and daytime systolic and diastolic blood pressures from 1 (121+/- 11/72+/-9 and 124+/-11/74+/-9 mmHg, respectively) to 14 weeks (129+/- 11/79+/-10 and 134+/-11/82+/- 11 mmHg, respectively) after CABG. The nocturnal blood pressure dip was restored progressively but incompletely 14 weeks after CABG. In parallel there was a progressive but also incomplete restoration of the sympathicovagal balance. CONCLUSION: Our results indicate an incomplete recovery of the autonomic nervous system and 24 h blood pressure variation 14 weeks after CABG. Further studies are required to examine whether incomplete restoration of the nocturnal blood pressure dip and sympathicovagal balance have independent prognostic implications for the CABG patient.     

Prospective randomized controlled trial of simulator-based versus traditional in-surgery laparoscopic camera navigation training

Background  

Surgical residents often use a laparoscopic camera in minimally invasive surgery for the first time in the operating room (OR) with no previous education or experience. Computer-based simulator training is increasingly used in residency programs. However, no randomized controlled study has compared the effect of simulator-based versus the traditional OR-based training of camera navigation skills.