Perioperative outcome, long-term mortality and time trends in elderly patients undergoing low-, intermediate- or major non-cardiac surgery.

BACKGROUND: Decision-making whether older patients benefit from surgery can be a difficult task. This report investigates characteristics and outcomes of a large cohort of inpatients, aged 80 years and over, undergoing non-cardiac surgery. METHODS: This observational study was performed at a tertiary university medical centre in the Netherlands. Patients of 80 years or older undergoing elective or urgent surgery from January 2004 to June 2017 were included. Outcomes were length of stay, discharge destination, 30-day and long-term mortality. Patients were divided into low-, intermediate and high-risk surgery subgroups. Univariable and multivariable logistic regression were used to evaluate the association of risk factors and outcomes. Secondary outcomes were time trends, assessed with Mantel-Haenszel chi-square test. RESULTS: Data of 8251 patients, undergoing 19,027 surgical interventions were collected from the patients' medical record. 7032 primary procedures were suitable for analyses. Median LOS was 3 days in the low-risk group, compared to six in the intermediate- and ten in the high-risk group. Median LOS of the total cohort decreased from 5.8 days (IQR 1.9-14.5) in 2004-2007 to 4.6 days (IQR 1.9-9.0) in 2016-2017. Three quarters of patients were discharged to their home. Postoperative 30-day mortality in the low-risk group was 2.3%. In the overall population 30-day mortality was high and constant during the study period (6.7%, ranging from 4.2 to 8.4%). CONCLUSION: Patients should not be withheld surgery solely based on their age. However, even for low-risk surgery, the mortality rate of more than 2% is substantial. Deciding whether older patients benefit from surgery should be based on the understanding of individual risks, patients' wishes and a patient-centred plan.

Prognostic factors for chronic post-surgical pain after lung and pleural surgery: a systematic review with meta-analysis, meta-regression and trial sequential analysis.

Chronic post-surgical pain is known to be a common complication of thoracic surgery and has been associated with a lower quality of life, increased healthcare utilisation, substantial direct and indirect costs, and increased long-term use of opioids. This systematic review with meta-analysis aimed to identify and summarise the evidence of all prognostic factors for chronic post-surgical pain after lung and pleural surgery. Electronic databases were searched for retrospective and prospective observational studies as well as randomised controlled trials that included patients undergoing lung or pleural surgery and reported on prognostic factors for chronic post-surgical pain. We included 56 studies resulting in 45 identified prognostic factors, of which 16 were pooled with a meta-analysis. Prognostic factors that increased chronic post-surgical pain risk were as follows: higher postoperative pain intensity (day 1, 0-10 score), mean difference (95%CI) 1.29 (0.62-1.95), p < 0.001; pre-operative pain, odds ratio (95%CI) 2.86 (1.94-4.21), p < 0.001; and longer surgery duration (in minutes), mean difference (95%CI) 12.07 (4.99-19.16), p < 0.001. Prognostic factors that decreased chronic post-surgical pain risk were as follows: intercostal nerve block, odds ratio (95%CI) 0.76 (0.61-0.95) p = 0.018 and video-assisted thoracic surgery, 0.54 (0.43-0.66) p < 0.001. Trial sequential analysis was used to adjust for type 1 and type 2 errors of statistical analysis and confirmed adequate power for these prognostic factors. In contrast to other studies, we found that age had no significant effect on chronic post-surgical pain and there was not enough evidence to conclude on sex. Meta-regression did not reveal significant effects of any of the study covariates on the prognostic factors with a significant effect on chronic post-surgical pain. Expressed as grading of recommendations, assessment, development and evaluations criteria, the certainty of evidence was high for pre-operative pain and video-assisted thoracic surgery, moderate for intercostal nerve block and surgery duration and low for postoperative pain intensity. We thus identified actionable factors which can be addressed to attempt to reduce the risk of chronic post-surgical pain after lung surgery.

In-depth assessment of health-related quality of life after in-hospital cardiac arrest.

INTRODUCTION: Evidence on physical and psychological well-being of in-hospital cardiac arrest (IHCA) survivors is scarce. The aim of this study is to describe long-term health-related quality of life (HRQoL), functional independence and psychological distress 3 and 12 months post-IHCA. METHODS: A multicenter prospective cohort study in 25 hospitals between January 2017 - May 2018. Adult IHCA survivors were included. HRQoL (EQ-5D-5L, SF-12), psychological distress (HADS, CSI) and functional independence (mRS) were assessed at 3 and 12 months post-IHCA. RESULTS: At 3-month follow-up 136 of 212 survivors responded to the questionnaire and at 12 months 110 of 198 responded. The median (IQR) EQ-utility Index score was 0.77 (0.65-0.87) at 3 months and 0.81 (0.70-0.91) at 12 months. At 3 months, patients reported a median SF-12 (IQR) physical component scale (PCS) of 38.9 (32.8-46.5) and mental component scale (MCS) of 43.5 (34.0-39.7) and at 12 months a PCS of 43.1 (34.6-52.3) and MCS 46.9 (38.5-54.5). DISCUSSION: Using various tools most IHCA survivors report an acceptable HRQoL and a substantial part experiences lower HRQoL compared to population norms. Our data suggest that younger (male) patients and those with poor functional status prior to admission are at highest risk of impaired HRQoL.

Between-centre differences in care for in-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Survival after in-hospital cardiac arrest is poor, but current literature shows substantial heterogeneity in reported survival rates. This study aims to evaluate care for patients suffering in-hospital cardiac arrest (IHCA) in the Netherlands by assessing between-hospital heterogeneity in outcomes and to explain this heterogeneity stemming from differences in case-mix or differences in quality of care. METHODS: A prospective multicentre study was conducted comprising 14 centres. All IHCA patients were included. The adjusted variation in structure and process indicators of quality of care and outcomes (in-hospital mortality and cerebral performance category [CPC] scale) was assessed with mixed effects regression with centre as random intercept. Variation was quantified using the median odds ratio (MOR), representing the expected odds ratio for poor outcome between two randomly picked centres. RESULTS: After excluding centres with less than 10 inclusions (2 centres), 701 patients were included of whom, 218 (32%) survived to hospital discharge. The unadjusted and case-mix adjusted MOR for mortality was 1.19 and 1.05, respectively. The unadjusted and adjusted MOR for CPC score was 1.24 and 1.19, respectively. In hospitals where personnel received cardiopulmonary resuscitation (CPR) training twice per year, 183 (64.7%) versus 290 (71.4%) patients died or were in a vegetative state, and 59 (20.8%) versus 68 (16.7%) patients showed full recovery (p < 0.001). CONCLUSION: In the Netherlands, survival after IHCA is relatively high and between-centre differences in outcomes are small. The existing differences in survival are mainly attributable to differences in case-mix. Variation in neurological outcome is less attributable to case-mix.

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals.

BACKGROUND: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. AIM: To determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. METHODS: This was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. RESULTS: A total of 1136 patients completed the questionnaire. Patients' CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. CONCLUSIONS: The average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.

Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review and meta-analysis.

The Impella percutaneous mechanical circulatory support device is designed to augment cardiac output and reduce left ventricular wall stress and aims to improve survival in cases of cardiogenic shock. In this meta-analysis we investigated the haemodynamic effects of the Impella device in a clinical setting. We systematically searched all articles in PubMed/Medline and Embase up to July 2019. The primary outcomes were cardiac power (CP) and cardiac power index (CPI). Survival rates and other haemodynamic data were included as secondary outcomes. For the critical appraisal, we used a modified version of the U.S. Department of Health and Human Services quality assessment form. The systematic review included 12 studies with a total of 596 patients. In 258 patients the CP and/or CPI could be extracted. Our meta-analysis showed an increase of 0.39 W [95% confidence interval (CI): 0.24, 0.54], (p = 0.01) and 0.22 W/m2 (95% CI: 0.18, 0.26), (p < 0.01) for the CP and CPI, respectively. The overall survival rate was 56% (95% CI: 0.50, 0.62), (p = 0.09). The quality of the studies was moderate, mostly due to the presence of confounders. Our study suggests that in patients with cardiogenic shock, Impella support seems effective in augmenting CP(I). This study merely investigates the haemodynamic effectiveness of the Impella device and does not reflect the complete clinical impact for the patient.

Prospective observational cohort study of the association between antiplatelet therapy, bleeding and thrombosis in patients with coronary stents undergoing noncardiac surgery.

BACKGROUND: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). METHODS: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. RESULTS: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93-3.88), P=0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31-3.46), P=0.96. Bleeding was more frequent with DAPT 6.55 (2.3-17.96) P=0.0002. In a propensity matched analysis of 177 patients who received DAPT and 177 monotherapy patients, the risk ratio for MACE with DAPT was 1.83 (0.69-4.85), P=0.32. The risk of bleeding was significantly greater in the DAPT group 4.00 (1.15-13.93), P=0.031. CONCLUSIONS: OBTAIN showed an increased risk of bleeding with DAPT and found no evidence for protective effects of DAPT from perioperative MACE in patients who have undergone previous PCI.

Postoperative troponin release is associated with major adverse cardiovascular events in the first year after noncardiac surgery.

INTRODUCTION: Troponin elevations after intermediate-to-high risk noncardiac surgery are common and can predict mortality. However, the prognostic value for early and late major adverse cardiovascular events (MACE) is less well investigated. The authors evaluated the relationship between postoperative troponin release and MACE in the first year after noncardiac surgery. METHODS: This observational cohort registry comprised data of patients aged ≥60 years undergoing intermediate-to-high risk noncardiac surgery between July 2012 and 2015, at the Erasmus University Medical Center, Rotterdam, the Netherlands. High-sensitivity troponin T was measured on day 1 to 3 after surgery. Peak troponin values were divided into four categories: <14 ng·L-1, 14-49 ng·L-1, 50-149 ng·L-1 and ≥150 ng·L-1. The primary endpoint MACE was defined as the occurrence of myocardial infarction, angina, revascularization therapy or cerebrovascular accident in the first year after surgery. The incidence of MACE and all-cause mortality was calculated using Kaplan-Meier estimates. Cox regression was used to estimate risks for both endpoints. RESULTS: In total, 3085 patients were included for analyses and peak troponin elevation above 14 ng·L-1 was present in 1678 (54.4%) patients. The overall incidence for one-year MACE was 5.8% (3.4%, 6.1%, 10.4% and 40.6% per increasing troponin category) with adjusted HR (95% CI) 1.32 (0.85-2.06), 2.53 (1.42-4.53) and 10.24 (5.91-17.75) for the consecutive increasing categories. One-year mortality occurred in 14.6% and showed a similar stepwise increase with adjusted HR (95% CI) 1.25 (0.98-1.60), 2.39 (1.72-3.32) and 3.79 (2.60-5.54). CONCLUSION: Our dataset demonstrates a graded relationship between postoperative troponin release and occurrence of MACE in the first year after intermediate-to-high risk noncardiac surgery.

Prognostic value of postoperative high-sensitivity troponin T in patients with different stages of kidney disease undergoing noncardiac surgery.

BACKGROUND: Emerging evidence suggests that postoperative troponin release is a strong and independent predictor of short-term mortality. However, evaluating elevated troponins in patients with chronic kidney disease (CKD) is still controversial and is often disregarded. This study examines morbidity along with short- and long-term mortality risk associated with elevated high-sensitivity troponin T (hsTnT) in patients with different stages CKD undergoing noncardiac surgery. METHODS: This observational cohort comprised 3262 patients aged ≥60 yr who underwent noncardiac surgery. Postoperative hsTnT concentrations were divided into normal [<14 ng l-1 (reference)], low (14-49 ng l-1), moderate (50-149 ng l-1), and high (≥150 ng l-1) groups. A threshold of 50 ng l-1 was used to dichotomize hsTnT. The study endpoints were 30-day and long-term all-cause mortality, and postoperative myocardial infarction. RESULTS: Postoperative hsTnT was associated with a stepwise increase in 30-day and long-term mortality risk: low hsTnT adjusted hazard ratio (HR) 1.4 [95% confidence interval (CI): 1.1-1.7], moderate hsTnT adjusted HR 3.1 (95% CI: 2.3-4.3), high hsTnT adjusted HR 5.5 (95% CI: 3.6-8.4). Postoperative hsTnT ≥50 ng l-1 was associated with 30-day and long-term mortality risk for each stage of CKD. Elevated troponin concentrations in severe CKD (estimated glomerular filtration rate <30 mL min-1 1.73 m-2), however, did not predict short-term death. CONCLUSIONS: Elevated postoperative hsTnT is associated with a dose-dependent increase in 30-day and long-term mortality risk in each stage of CKD with an estimated glomerular filtration rate ≥30 ml min-1 1.73 m-2.

Association between postoperative mean arterial blood pressure and myocardial injury after noncardiac surgery.

BACKGROUND: Myocardial injury after noncardiac surgery is common, although the exact pathophysiology is unknown. It is plausible that hypotension after surgery is relevant for the development of myocardial injury. The authors evaluated whether low mean arterial pressures (MAPs) after surgery are related to an increased incidence in postoperative cardiac-troponin elevation. METHODS: A prospective cohort of 2211 patients aged ≥60 yr, undergoing major or moderate noncardiac surgery in The Netherlands, was retrospectively analysed for the occurrence of postoperative cardiac-troponin elevation [high-sensitive troponin T (hsTnT) >14 ng L-1]. Blood pressures after surgery were recorded and divided into quartiles based on the lowest MAP prior to peak troponin recording. The association between MAP and extent of postoperative cardiac-troponin elevation was analysed. RESULTS: The patients were divided into quartiles based on their lowest MAP in the period preceding the peak hsTnT, ranging from a median of 62 in the lowest quartile to 94 in the highest quartile. Postoperative hsTnT elevation was present in 53.2% of the population. An association between MAP quartile and postoperative peak hsTnT was predominantly observed in the lowest quartile (P<0.001): median hsTnT 17.6 (10.3-37.3), 14.9 (9.4-24.6), 13.8 (9.1-22.5), and 14.0 (9.2-22.4). The multivariable logistic-regression analysis showed an increased risk for postoperative cardiac-troponin elevation with decreasing MAP thresholds. CONCLUSIONS: Lower postoperative blood pressure is associated with an increased incidence of postoperative cardiac hsTnT elevation, irrespective of pre- and intraoperative variables.

Co-administration of dexamethasone with peripheral nerve block: intravenous vs perineural application: systematic review, meta-analysis, meta-regression and trial-sequential analysis.

BACKGROUND: I.V. and perineural dexamethasone have both been found to prolong loco-regional analgesia compared with controls without dexamethasone. It is unclear whether perineural administration offers advantages when compared with i.v. dexamethasone. METHODS: A systematic literature search was performed to identify randomized controlled double-blind trials that compared i.v. with perineural dexamethasone in patients undergoing surgery. Using the random effects model, risk ratio (for binary variables), weighted mean difference (for continuous variables) and 95% confidence intervals were calculated. We applied trial sequential analysis to assess the risks of type I and II error, meta-regression for the study of the doseresponsive relationship, and the Grading of Recommendations Assessment, Development, and Evaluation system. RESULTS: We identified 10 randomized controlled double-blind trials (783 patients). When using conventional meta-analysis of nine low risk of bias trials, we found a statistically significantly longer duration of analgesia, our primary outcome with perineural dexamethasone (241 min, 95%CI, 87, 394 min). When trial sequential analysis was applied, this result was confirmed. Meta-regression did not show a dose-response relationship. Despite the precision in the results, using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE), we assessed the quality of the evidence for our primary outcome as low. CONCLUSIONS: There is evidence that perineural dexamethasone prolongs the duration of analgesia compared with i.v. dexamethasone. Using GRADE, this evidence is low quality.

The preoperative cardiology consultation: indications and risk modification.

BACKGROUND: The cardiologist is regularly consulted preoperatively by anaesthesiologists. However, insights into the efficiency and usefulness of these consultations are unclear. METHODS: This is a retrospective study of 24,174 preoperatively screened patients ≥18 years scheduled for elective non-cardiac surgery, which resulted in 273 (1%) referrals to the cardiologist for further preoperative evaluation. Medical charts were reviewed for patient characteristics, main reason for referring, requested diagnostic tests, interventions, adjustment in medical therapy, 30-day mortality and major adverse cardiac events. RESULTS: The most common reason for consultation was the evaluation of a cardiac murmur (95 patients, 35%). In 167 (61%) patients, no change in therapy was initiated by the cardiologist. Six consultations (2%) led to invasive interventions (electrical cardioversion, percutaneous coronary intervention or coronary artery bypass surgery). On average, consultation delayed clearance for surgery by two weeks. CONCLUSION: In most patients referred to the cardiologist after being screened at an outpatient anaesthesiology clinic, echocardiography is performed for ruling out specific conditions and to be sure that no further improvement can be made in the patient's health. In the majority, no change in therapy was initiated by the cardiologist. A more careful consideration about the potential benefits of consulting must be made for every patient.

Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR.

OBJECTIVES: To determine the influence of a positive family history for aneurysms on clinical success and mortality after endovascular aneurysm repair (EVAR). METHODS: From 2009 to 2011, 1262 patients with abdominal aortic aneurysms (AAA) treated by EVAR were enrolled in a prospective, industry sponsored clinical registry ENGAGE. Patients were classified into familial and sporadic AAA patients according to baseline clinical reports. Clinical characteristics, aneurysm morphology, and follow-up were registered. The primary endpoint was clinical success after EVAR, a composite of technical success and freedom from the following complications: AAA increase >5 mm, type I and III endoleak, rupture, conversion, secondary procedures, migration, and occlusion. Secondary endpoints were the individual components of clinical success, 30 day mortality, and aneurysm related and all cause mortality. RESULTS: Of the 1262 AAA patients (89.5% male and mean age 73.1 years), 86 patients (6.8%) reported a positive family history and were classified as familial AAA. Duration of follow-up was 4.4 ± 1.7 years. Patients with familial AAA were more often female (18.6% vs. 9.9%, p = .012). No difference was observed in aneurysm morphology. There was no significant difference in clinical success between patients with familial and sporadic AAA (72.1% vs. 79.3%, p=.116). Familial AAA patients had a higher 30 day mortality after EVAR (4.7% vs. 1.0%, adjusted HR 5.7, 1.8-17.9, p = .003) as well as aneurysm related mortality (5.8% vs. 1.3%, adjusted HR 5.4, 1.9-14.9, p = .001), while no difference was observed in all cause mortality (19.8% vs. 24.3%, adjusted HR 0.8, 0.5-1.4, p = .501). CONCLUSIONS: The current study shows a higher 30 day mortality after EVAR in familial AAA patients. Future studies should determine the role of family history in AAA treatment, suitability for endovascular or open repair, and on adaptation of post-operative surveillance. For the time being, patients with familial forms of AAA should be considered at higher risk for EVAR and warrant extra vigilance.

Iliac Seal Zone Dynamics and Clinical Consequences After Endovascular Aneurysm Repair.

OBJECTIVE: To evaluate the dynamics of the iliac attachment zone after EVAR, and the association with clinical events. METHODS: A tertiary institution's prospective EVAR database was searched to identify common iliac arteries at risk. Internally validated measurements were made, using centre lumen line reconstructions. Iliac dilatation and endograft limb retraction were the main endpoints. Associations between dilatation, retraction, oversizing, and distal seal length were investigated. Association with clinical events (sealing or occlusion) was also explored. RESULTS: Of 452 primary EVAR patients treated from 2004 to 2012, 341 were included (mean age 72 years, 12% female, 597 common iliac arteries). Median follow-up was 4.7 years. At 30 days, the mean iliac diameter increased from 14 mm to 15 mm (p < .001). Over follow-up, it increased to 18 mm (p < .001). Iliac dilatation ≥20% occurred in 295 cases (49.4%) and exceeded the implanted endograft diameter in 170 (28.7%). Limb retraction ≥5 mm was identified in 54 patients (9.1%) and was associated with iliac seal complications (p < 0.001). Iliac endograft extension diameter ≥24 mm (OR 3.3, 95% CI 1.7-6.4) and iliac artery dilatation beyond the endograft (OR 2.1, 95% CI 1.2-3.8) were independent risk factors. Overall, there were 34 (5.7%) iliac seal complications. Retraction of the iliac endograft (OR 1.17 per mm, 95% CI 1.10-1.24) and baseline AAA diameter (1.04 per mm, 95% CI 1.01-1.07) were independent risk factors for seal related complications. Greater initial post-operative iliac seal length was protective (OR 0.94 per mm, 95% CI 0.90-0.97). CONCLUSIONS: Iliac dilatation and endograft retraction are common findings during follow-up, potentially leading to adverse clinical events. Optimisation of the iliac seal zone providing a long distal seal length and added attention to patients with large aneurysms or receiving ≥24 mm diameter iliac extensions are recommended. Also, long-term surveillance including CTA is advised to reveal and correct loss of seal at the iliac attachments before adverse clinical events occur.

Intelligence quotient scores at the age of 6 years in children anaesthetised before the age of 5 years.

We analysed the association of independent variables with non-verbal cognition at 6 years in children with complete data (3441 from a cohort of 9901), of whom 415 were anaesthetised before the age of 5 years. Using multivariable regression, cognition was reduced by a mean (95% CI) score for children: anaesthetised before the age of 5 years, 2.1 (0.7-3.5), p = 0.004; born prematurely, 9.8 (4.1-15.4), p = 0.001; whose mothers smoked while pregnant, 2.3 (0.8-3.8), p = 0.004; whose mothers had lower IQ scores, 0.3 (0.2-0.3) for each unit reduction in maternal IQ, p < 0.0001. The association of child IQ with exposure to anaesthetic drugs was sensitive to missing data.

Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-ß Signaling.

Aneurysm-osteoarthritis syndrome characterized by unpredictable aortic aneurysm formation, is caused by SMAD3 mutations. SMAD3 is part of the SMAD2/3/4 transcription factor, essential for TGF-ß-activated transcription. Although TGF-ß-related gene mutations result in aneurysms, the underlying mechanism is unknown. Here, we examined aneurysm formation and progression in Smad3-/- animals. Smad3-/- animals developed aortic aneurysms rapidly, resulting in premature death. Aortic wall immunohistochemistry showed no increase in extracellular matrix and collagen accumulation, nor loss of vascular smooth muscle cells (VSMCs) but instead revealed medial elastin disruption and adventitial inflammation. Remarkably, matrix metalloproteases (MMPs) were not activated in VSMCs, but rather specifically in inflammatory areas. Although Smad3-/- aortas showed increased nuclear pSmad2 and pErk, indicating TGF-ß receptor activation, downstream TGF-ß-activated target genes were not upregulated. Increased pSmad2 and pErk staining in pre-aneurysmal Smad3-/- aortas implied that aortic damage and TGF-ß receptor-activated signaling precede aortic inflammation. Finally, impaired downstream TGF-ß activated transcription resulted in increased Smad3-/- VSMC proliferation. Smad3 deficiency leads to imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and immune responses resulting in rapid aortic wall dilatation and rupture. Our findings uncover new possibilities for treatment of SMAD3 patients; instead of targeting TGF-ß signaling, immune suppression may be more beneficial.

Perioperative Complications are Associated With Adverse Long-Term Prognosis and Affect the Cause of Death After General Surgery.

BACKGROUND: It is unclear how mortality and causes of death vary between patients and surgical procedures and how occurrence of postoperative complications is associated with prognosis. This study describes long-term mortality rates and causes of death in a general surgical population. Furthermore, we explore the effect of postoperative complications on mortality. METHODS: A single-centre analysis of postoperative complications, with mortality as primary endpoint, was conducted in 4479 patients undergoing surgery. We applied univariate and multivariable regression models to analyse the effect of risk factors, including surgical risk and postoperative complications, on mortality. Causes of death were also explored. RESULTS: 75 patients (1.7 %) died within 30 days after surgery and 730 patients (16.3 %) died during a median follow-up of 6.3 years (IQR 5.8-6.8). Significant differences in long-term mortality were observed with worst outcome for patients undergoing high-risk vascular surgery (HR 1.5; 95 % CI 1.2-1.9). When looking at causes of death, high-risk surgery was associated with a twofold higher risk of cardiovascular death (HR 1.9; 95 % CI 1.2-3.1), whereas the intermediate-risk group had a higher risk of dying from cancer-related causes (HR 1.5; 95 % CI 1.1-2.0). Occurrence of complications-particularly of cardiovascular nature- was associated with worse survival (HR 1.9; 95 % CI 1.3-2.7). CONCLUSION: High-risk vascular surgery and occurrence of postoperative complications are important predictors of late mortality. Further focus on these groups of patients can contribute to reduced morbidity. Improvement in quality of care should be aimed at preventing postoperative complications and thus a better outcome in a general surgical population.

Review: Quality of life in lower limb peripheral vascular surgery.

PURPOSE: Vascular intervention studies generally consider patency and limb salvage as primary outcomes. However, quality of life is increasingly considered an important patient-oriented outcome measurement of vascular interventions. Existing literature was analyzed to determine the effect of different treatments on quality of life for patients suffering from either claudication or critical limb ischemia. BASIC METHODS: A review of the literature was undertaken in the Medline library. A search was performed on quality of life in peripheral arterial disease. Results were stratified according to treatment groups. PRINCIPAL FINDINGS: Twenty-one articles described quality of life in approximately 4600 patients suffering from peripheral arterial disease. Invasive treatment generally results in better quality of life scores (at a maximum of 2 years of follow-up), compared with non-invasive treatment. In patients with critical limb ischemia, successful revascularization improves quality of life scores. Only one study reported long-term results. CONCLUSIONS: Increase in quality of life scores can be found for any intervention performed for peripheral arterial disease. However, there is scarce information on long-term quality of life after vascular intervention.