Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial.

BACKGROUND: Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 µg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320). CONCLUSIONS: There was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury. TRIAL REGISTRATION NUMBER: (EudraCT 2010-019527-58, ISRCTN82061264).

Congenital sucrase-isomaltase deficiency: diagnostic challenges and response to enzyme replacement therapy.

Congenital sucrase-isomaltase (SI) deficiency is a rare genetic condition characterised by a deficiency in the brush-border SI enzyme, resulting in an inability to metabolise sucrose and starches. Six cases of congenital SI deficiency treated with Sucraid (sacrosidase, a yeast-derived enzyme that facilitates sucrose digestion) are described. Typical presenting symptoms were watery diarrhoea, abdominal pain and bloating, sometimes noticeably worse after ingestion of fruit. Diagnosis is challenging since conventional hydrogen breath testing after an oral sucrose load is impractical in young children, and many laboratories no longer look for maldigested sucrose using faecal sugar chromatography. Confirmation is by disaccharidase assay of duodenal or jejunal mucosa obtained endoscopically. All six patients showed little improvement following advice regarding dietary management, but experienced a marked reduction in symptoms with sacrosidase administration; no adverse events were reported. Sacrosidase is an effective and well-tolerated treatment for patients with congenital SI deficiency. Gene testing and clinical trial of sacrosidase may become an alternative to endoscopic biopsies for diagnosis.

Management of blunt thoracic aortic injury.

Blunt traumatic aortic transection (TAT) is an uncommon injury in clinical practice that is associated with a high morbidity and mortality. The approach to patients with such an injury is controversial with specific regard to the most effective diagnostic tools, timing of surgical intervention and mechanisms of spinal cord protection. Chest X-ray with widening of the mediastinum is unreliable as a diagnostic tool. Contrast enhanced helical CT Scan has replaced the traditional angiography as the screening diagnostic tool of choice Emergency thoracotomy and repair should be reserved for the few patients with isolated TAT without any major concomitant injuries. Delayed management approach with aggressive blood pressure control and serial radiological monitoring is a safe and recommended option for those with severe concomitant injuries or other medical co-morbidity that puts surgery at high risk. Active augmentation of the distal perfusion pressure during cross clamp offers the best protection against development of paraplegia during open surgical repair. Endovascular stenting offers a minimally invasive method of treatment but the long-term durability of the endovascular stent is still unknown. We feel that the greater feasibility of the endovascular repair in the acute phase of the thoracic injury is an advantage over the open surgery and should be the treatment of choice in patients with severe concomitant injuries.

Validation of four different risk stratification systems in patients undergoing off-pump coronary artery bypass surgery: a UK multicentre analysis of 2223 patients.

BACKGROUND: Various risk stratification systems have been developed in coronary artery bypass graft surgery (CABG), based mainly on patients undergoing procedures with cardiopulmonary bypass. OBJECTIVE: To assess the validity and applicability of the Parsonnet score, the EuroSCORE, the American College of Cardiology/American Heart Association (ACC/AHA) system, and the UK CABG Bayes model in patients undergoing off-pump coronary artery bypass surgery (OPCAB) in the UK. METHODS: Data on 2223 patients who underwent OPCAB in eight cardiac surgical centres were collected. Predicted mortality risk scores were calculated using the four systems and compared with observed mortality. Calibration was assessed by the Hosmer-Lemeshow (HL) test. Discrimination was assessed using the receiver operating characteristic (ROC) curve area. RESULTS: 30 of 2223 patients (1.3%) died in hospital. For the Parsonnet score the HL test was significant (p < 0.001) and the receiver operating characteristic curve (ROC) area was 0.74. For the EuroSCORE the HL test was also significant (p = 0.008) and the ROC area was 0.75. For the ACC/AHA system the HL test was non-significant (p = 0.7) and the ROC area was 0.75. For the UK CABG Bayes model the HL test was also non-significant (p = 0.3) and the ROC area was 0.81. CONCLUSIONS: The UK CABG Bayes model is reasonably well calibrated and provides good discrimination when applied to OPCAB patients in the UK. Among the other three systems, the ACC/AHA system is well calibrated but its discrimination power was less than for the UK CABG Bayes model. These data suggest that the UK CABG Bayes model could be an appropriate risk stratification system to use for patients undergoing OPCAB in the UK.

Iatrogenic candidal infection of a mediastinal foregut cyst following endoscopic ultrasound-guided fine-needle aspiration.

EUS-guided fine-needle aspiration (EUS-FNA) is a safe procedure with few complications. We describe the introduction of Candida into a mediastinal foregut cyst following trans-oesophageal EUS-FNA, and discuss the implications of this complication.

Bleeding from the lung surface: a unique complication of off-pump CABG operation.

A patient, with post myocardial infarction (MI) thrombolysis, underwent emergency off-pump coronary artery bypass graft. Her post-operative course was complicated by excessive bleeding. At re-exploration, the bleeding was caused by a graze on the lung surface by the needle used during the insertion of the deep pericardial retraction suture.

Juxtacardiac costal osteochondroma presenting as recurrent haemothorax.

A 21-year-old man presenting with a recurrent spontaneous haemothorax was found to have an osteochondroma arising out of the left 4th rib. This was penetrating the apical part of the heart. Surgical excision was uneventful.

Use of larger sized aortic homograft conduits in right ventricular outflow tract reconstruction.

Between 1973 and 1993 sixty aortic homograft valved conduits in fifty-six patients were used to establish continuity between the right ventricle and the pulmonary artery in congenital heart disease. Age range was one day to 23.5 years (median 3.6 years) which included twenty-six patients less than one-year-old. Conduit size ranged from 11 to 23 mm (median 17.6 mm). there were nine hospital deaths and eight late deaths. The 45 survivors have been followed for a median of 8.6 years (range 6 months to 20 years). All patients have had serial echocardiographic assessments and 35 have had post repair cardiac catheterization. Almost all patients had mild-to-moderate degrees of homograft regurgitation. There were eleven with severe homograft regurgitation and two are being considered for reoperation. The follow up homograft gradient ranged from 0 to 64 mmHg (mean 24 mmHg). Freedom from reoperation for conduit obstruction was 98.2% at five years falling to 91% (C.L. 82%-100%) at 10 years. Of the 23 homografts inserted more than 10 years ago, only one (4.3%) has been replaced because it was causing important obstruction. None have been replaced for regurgitation. Our results indicate that larger sized aortic homografts used in reconstruction of the right ventricular outflow tract give satisfactory results and there is a low incidence of reoperation for replacement at medium term follow up.