Lars N. Jorgensen

Less collagen production in smokers

BACKGROUND An association between smoking and impaired wound healing has been reported in retrospective studies. The smoking status of a surgical patient may be confounded by social and medical parameters. We have evaluated the effect of smoking in a test wound in volunteers, with special reference to a reliable scientific match between smokers and nonsmokers. METHODS In a prospective open study with blinded assessment, 19 smoking (20 cigarettes/day) and 18 nonsmoking healthy volunteers were matched with respect to baseline characteristics. The deposition of total protein and mature collagen (expressed as hydroxyproline) was assessed in an expanded polytetrafluoroethylene wound healing model implanted subcutaneously for 10 days. RESULTS The nonsmokers had a 1.8 times higher median amount of hydroxyproline than the smokers (p < 0.01). The deposition of hydroxyproline was negatively correlated with the consumption of tobacco both before (r = -0.44; p < 0.01) and during the study (r = -0.48; p < 0.005). The impairment was specific for the production of collagenous proteins and not other proteins. CONCLUSIONS The synthesis of subcutaneous collagen in smokers is specifically impeded, indicating an impaired wound-healing process. Because mature collagen is the main determinator of strength of an operative wound, the results support the view that patients should be advised to stop smoking before an operation.

Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial.

CONTEXT Use of 80% oxygen during surgery has been suggested to reduce the risk of surgical wound infections, but this effect has not been consistently identified. The effect of 80% oxygen on pulmonary complications has not been well defined. OBJECTIVE To assess whether use of 80% oxygen reduces the frequency of surgical site infection without increasing the frequency of pulmonary complications in patients undergoing abdominal surgery. DESIGN, SETTING, AND PATIENTS The PROXI trial, a patient- and observer-blinded randomized clinical trial conducted in 14 Danish hospitals between October 2006 and October 2008 among 1400 patients undergoing acute or elective laparotomy. INTERVENTIONS Patients were randomly assigned to receive either 80% or 30% oxygen during and for 2 hours after surgery. MAIN OUTCOME MEASURES Surgical site infection within 14 days, defined according to the Centers for Disease Control and Prevention. Secondary outcomes included atelectasis, pneumonia, respiratory failure, and mortality. RESULTS Surgical site infection occurred in 131 of 685 patients (19.1%) assigned to receive 80% oxygen vs 141 of 701 (20.1%) assigned to receive 30% oxygen (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.72-1.22; P = .64). Atelectasis occurred in 54 of 685 patients (7.9%) assigned to receive 80% oxygen vs 50 of 701 (7.1%) assigned to receive 30% oxygen (OR, 1.11; 95% CI, 0.75-1.66; P = .60), pneumonia in 41 (6.0%) vs 44 (6.3%) (OR, 0.95; 95% CI, 0.61-1.48; P = .82), respiratory failure in 38 (5.5%) vs 31 (4.4%) (OR, 1.27; 95% CI, 0.78-2.07; P = .34), and mortality within 30 days in 30 (4.4%) vs 20 (2.9%) (OR, 1.56; 95% CI, 0.88-2.77; P = .13). CONCLUSION Administration of 80% oxygen compared with 30% oxygen did not result in a difference in risk of surgical site infection after abdominal surgery. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00364741.

Update with level 1 studies of the European Hernia Society guidelines on the treatment of inguinal hernia in adult patients

Purpose In 2009, the European Hernia Society published the EHS Guidelines for the Treatment of Inguinal Hernia in Adult Patients. The Guidelines contain recommendations for the treatment of inguinal hernia from diagnosis till aftercare. The guidelines expired January 1, 2012. To keep them updated, a revision of the guidelines was planned including new level 1 evidence.MethodsThe original Oxford Centre for Evidence-Based Medicine ranking was used. All relevant level 1A and level 1B literature from May 2008 to June 2010 was searched (Medline and Cochrane) by the Working Group members. All chapters were attributed to the two responsible authors in the initial guidelines document. One new chapter on fixation techniques was added. The quality was assessed by the Working Group members during a 2-day meeting and the data were analysed, especially with respect to any change in the level and/or text of any of the conclusions or recommendations of the initial guidelines. In the end, all relevant references published until January 1, 2013 were included. The final text was approved by all Working Group members.ResultsFor the following topics, the conclusions and/or recommendations have been changed: indications for treatment, treatment of inguinal hernia, day surgery, antibiotic prophylaxis, training, postoperative pain control and chronic pain. The addendum contains all current level 1 conclusions, Grade A recommendations and new Grade B recommendations based on new level 1 evidence (with the changes in bold).ConclusionsDespite the fact that the Working Group responsible for it tried to represent most kinds of surgeons treating inguinal hernias, such general guidelines inevitably must be fitted to the daily practice of every individual surgeon treating his/her patients. There is no doubt that the future of guideline implementation will strongly depend on the development of easy to use decision support algorithms tailored to the individual patient and on evaluating the effect of guideline implementation on surgical outcome. At the 35th International Congress of the EHS in Gdansk, Poland (May 12–15, 2013), it was decided that the EHS, IEHS and EAES will collaborate from now on with the final goal to publish new joint guidelines, most likely in 2015.

Epidemiology of Sprains in the Lateral Ankle and Foot

The epidemiology of sprains in the lateral ankle and foot was investigated in a prospective study at the casualty ward at Hillerad County Hospital. During one year, 766 patients were registered. The overall sprain incidence was 7/1000 person-years. The incidence was highest for young males. After the age of 40 years, the incidence was higher for women than for men. Most sprains were sustained during sport, but, with increasing age, other activities became dominant. Sixty-one percent of the lesions were located around the lateral ankle, and 24% were located on the lateral midfoot.

Nationwide Prospective Study of Outcomes after Elective Incisional Hernia Repair

BACKGROUND Incisional hernia repair is a frequent surgical procedure, but perioperative risk factors and outcomes have not been prospectively assessed in large-scale studies. The aim of this nationwide study was to analyze surgical risk factors for early and late outcomes after incisional hernia repair. STUDY DESIGN We conducted a prospective nationwide study on all elective incisional hernia repairs registered in the Danish Ventral Hernia Database between January 1, 2007 and December 31, 2010. Main outcomes measures were surgical risk factors for 30-day readmission, reoperation (excluding recurrence), and mortality after incisional hernia repair. Late outcomes included reoperation for recurrence during the follow-up period. Follow-up was obtained by merging the Danish Ventral Hernia Database with the Danish National Patient Register. Results were evaluated by multivariate analyses. RESULT The study included 3,258 incisional hernia repairs. Median follow-up was 21 months (interquartile range 10 to 35 months). The 30-day readmission, reoperation, and mortality rates were 13.3%, 2.2%, and 0.5%, respectively. Advanced age, open repair, large hernia defect, and vertical incision at the primary laparotomy were significant independent risk factors for poor early outcomes (p < 0.05). The cumulated risk of recurrence repair after open and laparoscopic repair was 21.1% and 15.5%, respectively (p = 0.03). Younger age, open repair, hernia defects >7 cm, and onlay or intraperitoneal mesh positioning in open repair were significant risk factors for poor late outcomes (p < 0.05). CONCLUSIONS Elective incisional hernia repair were beset with high rates of readmission and reoperation for recurrence. Readmission and reoperation for recurrence were most pronounced after open repair and repair for hernia defects up to 20 cm. Additionally, sublay mesh position reduced the risk of reoperation for recurrence after open repairs.

A nationwide study on anastomotic leakage after colonic cancer surgery

Aim  Anastomotic leakage (AL) is a major challenge in colorectal cancer surgery due to increased morbidity and mortality. Possible risk factors should be investigated differentially, distinguishing between rectal and colonic surgery in large‐scale studies to avoid selection bias and confounding.

Subunit-specific agonist activity at NR2A, NR2B, NR2C, and NR2D containing N-methyl-D-aspartate glutamate receptors

The four N-methyl-d-aspartate (NMDA) receptor NR2 subunits (NR2A-D) have different developmental, anatomical, and functional profiles that allow them to serve different roles in normal and neuropathological situations. Identification of subunit-selective NMDA receptor agonists, antagonists, or modulators could prove to be both valuable pharmacological tools as well as potential new therapeutic agents. We evaluated the potency and efficacy of a wide range of glutamate-like compounds at NR1/NR2A, NR1/NR2B, NR1/NR2C, and NR1/NR2D receptors. Twenty-five of 53 compounds examined exhibited agonist activity at the glutamate binding site of NMDA receptors. Concentration-response relationships were determined for these agonists at each NR2 subunit. We find consistently higher potency at the NR2D subunit for a wide range of dissimilar structures, with (2S,4R)-4-methylglutamate (SYM2081) showing the greatest differential potency between NR2A- and NR2D-containing receptors (46-fold). Analysis of chimeric NR2A/D receptors suggests that enhanced agonist potency for NR2D is controlled by residues in both of the domains (Domain1 and Domain2) that compose the bilobed agonist binding domain. Molecular dynamics (MD) simulations comparing a crystallography-based hydrated NR1/NR2A model with a homology-based NR1/NR2D hydrated model of the agonist binding domains suggest that glutamate exhibits a different binding mode in NR2D compared with NR2A that accommodates a 4-methyl substitution in SYM2081. Mutagenesis of functionally divergent residues supports the conclusions drawn based on the modeling studies. Despite high homology and conserved atomic contact residues within the agonist binding pocket of NR2A and NR2D, glutamate adopts a different binding orientation that could be exploited for the development of subunit selective agonists and competitive antagonists.

Anastomotic leak increases distant recurrence and long-term mortality after curative resection for colonic cancer: a nationwide cohort study.

Objective:To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer. Background:There is no solid data as to whether AL after colonic cancer surgery increases the risk of disease recurrence. Methods:This was a nationwide cohort study of 9333 patients, prospectively registered in the database of the Danish Colorectal Cancer Group and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable Cox regression analysis was used to adjust for confounding. Results:The incidence of AL was 6.4%, 744 patients died within 120 days. Of the remaining 8589 patients, 861 (10.0%) developed local recurrence with no association to AL [adjusted hazard ratio (HR) = 0.78; 95% confidence interval (CI): 0.55–1.12; P = 0.184]. Distant recurrence developed in 1281 (14.9%) patients and more frequently after AL (adjusted HR = 1.42; 95% CI: 1.13–1.78; P = 0.003). AL was also associated with increased long-term mortality (adjusted HR = 1.20; 95% CI: 1.01–1.44; P = 0.042). In 2841 patients with stage III cancer, AL was associated with both decreased likelihood of receiving adjuvant chemotherapy (adjusted HR = 0.58; 95% CI: 0.45–0.74; P < 0.001) and a delay to initial administration (16 days; 95% CI: 12–20 days; P < 0.001). Conclusions:AL was significantly associated with increased rates of distant recurrence and long-term all-cause mortality. Cancelled or delayed administration of adjuvant chemotherapy may partly account for these findings.

Asymptomatic postoperative deep vein thrombosis and the development of postthrombotic syndrome: A systematic review and meta-analysis

Perioperative antithrombotic clinical regimens have reduced the incidence of postoperative deep venous thrombosis (DVT). Long-term effects of asymptomatic postoperative DVT have been studied in a number of clinical trials and the present review describes the clinical significance of asymptomatic postoperative DVT regarding the possible development of postthrombotic syndrome (PTS). We performed a systematic review of reference databases focusing upon studies including patients suspected of having postoperative DVT and reporting subsequent cases of PTS at the end of a well-defined follow-up period. The included studies were stratified according to type of screening method and applied statistics. Over-all evaluation included meta-analyses based upon the Cochrane software package. The overall relative risk of developing PTS was 1.58 (95% confidence intervals: 1.24-2.02) in patients suffering from asymptomatic DVT as compared to patients without DVT (p<0.0005). In conclusion, asymptomatic postoperative DVT is associated with an increased risk of late development of PTS. The finding emphasizes that postoperative DVT, diagnosed by means of well-defined objective measures, remains the correct scientific endpoint in trials evaluating the efficacy of preoperative antithrombotic treatment regimens.

Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis

OBJECTIVE To study the incidence of late deep venous thrombosis (DVT), and to evaluate a regimen of prolonged thromboprophylaxis after general surgery. DESIGN Randomised, controlled, open trial, with blinded evaluation. SETTING University hospital, Denmark. SUBJECTS 176 consecutive patients undergoing major elective abdominal or non-cardiac thoracic operations, of whom 118 were eligible for evaluation. INTERVENTIONS Thromboprophylaxis with a low-molecular-weight heparin, tinzaparin, given for four weeks (n = 58), compared with one week (control group, n = 60). MAIN OUTCOME MEASURES Presence of DVT established by bilateral venography four weeks after the operation. RESULTS The incidence of late DVT in the control group was 6/60 (10%, 95% confidence interval (CI) 4% to 21%). In the prophylaxis group it was 3/58 (5.2%, 95% CI 1% to 14%) (p = 0.49). CONCLUSION Prolonged thromboprophylaxis had no significant effect on the incidence of DVT occurring late after general surgery.