Prolonged effects of dexamethasone following total knee arthroplasty: A pre-planned sub-study of the DEX-2-TKA trial.

OBJECTIVES: The DEX-2-TKA trial demonstrated that one and two doses of 24 mg intravenous dexamethasone reduced opioid consumption and pain after total knee arthroplasty (TKA). We aimed to investigate the prolonged effects of dexamethasone after the 48-h intervention period. DESIGN: This was a prospective, pre-planned questionnaire follow-up on postoperative days 3-7 of patients in the DEX-2-TKA trial that randomly received: DX1 (dexamethasone 24 mg + placebo), DX2 (dexamethasone 24 mg + dexamethasone 24 mg), and placebo (placebo + placebo) perioperatively and 24 h later. SETTING: A multicenter trial performed at five Danish hospitals. PARTICIPANTS: We analyzed 434 of 485 adult participants enrolled in the DEX-2-TKA trial. OUTCOME MEASURES: Primary outcome was difference between groups in average of all numerical rating scale (NRS) pain scores reported in the morning, at bedtime, and the daily average pain on postoperative days 3-7. Secondary outcomes were sleep quality and patient satisfaction. RESULTS: The median (interquartile range) pain intensity levels for postoperative days 3-7 were: DX2 3.2 (2.1-4.3); DX1 3.3 (2.3-4.1); and placebo 3.3 (2.5-4.7). Hodges-Lehmann median differences between groups were: 0 (95% confidence interval - 0.54 to 0.2), P = 0.38 between DX1 and placebo; 0.1 (-0.47 to 0.33), p = .87 between DX1 and DX2; and 0.1 (-0.6 to 0.13), p = .20 between DX2 and placebo. We found no relevant differences between groups on sleep quality on postoperative days 3-7 nor for patient satisfaction with the analgesic treatment. CONCLUSIONS: We found that neither one nor two doses of 24 mg intravenous dexamethasone demonstrated prolonged effects on overall pain or sleep quality on postoperative days 3-7 after total knee arthroplasty. We also found that dexamethasone had no effect on patient satisfaction. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03506789 (main result trial).

Effect of dexamethasone as an analgesic adjuvant to multimodal pain treatment after total knee arthroplasty: randomised clinical trial.

OBJECTIVE: To investigate the effects of one and two doses of intravenous dexamethasone in patients after total knee arthroplasty. DESIGN: Randomised, blinded, placebo controlled trial with follow-up at 90 days. SETTING: Five Danish hospitals, September 2018 to March 2020. PARTICIPANTS: 485 adult participants undergoing total knee arthroplasty. INTERVENTION: A computer generated randomised sequence stratified for site was used to allocate participants to one of three groups: DX1 (dexamethasone (24 mg)+placebo); DX2 (dexamethasone (24 mg)+dexamethasone (24 mg)); or placebo (placebo+placebo). The intervention was given preoperatively and after 24 hours. Participants, investigators, and outcome assessors were blinded. All participants received paracetamol, ibuprofen, and local infiltration analgesia. MAIN OUTCOME MEASURES: The primary outcome was total intravenous morphine consumption 0 to 48 hours postoperatively. Multiplicity adjusted threshold for statistical significance was P<0.017 and minimal important difference was 10 mg morphine. Secondary outcomes included postoperative pain. RESULTS: 485 participants were randomised: 161 to DX1, 162 to DX2, and 162 to placebo. Data from 472 participants (97.3%) were included in the primary outcome analysis. The median (interquartile range) morphine consumptions at 0-48 hours were: DX1 37.9 mg (20.7 to 56.7); DX2 35.0 mg (20.6 to 52.0); and placebo 43.0 mg (28.7 to 64.0). Hodges-Lehmann median differences between groups were: -2.7 mg (98.3% confidence interval -9.3 to 3.7), P=0.30 between DX1 and DX2; 7.8 mg (0.7 to 14.7), P=0.008 between DX1 and placebo; and 10.7 mg (4.0 to 17.3), P<0.001 between DX2 and placebo. Postoperative pain was reduced at 24 hours with one dose, and at 48 hours with two doses, of dexamethasone. CONCLUSION: Two doses of dexamethasone reduced morphine consumption during 48 hours after total knee arthroplasty and reduced postoperative pain. TRIAL REGISTRATION: Clinicaltrials.gov NCT03506789.

Fast-track revision knee arthroplasty.

BACKGROUND: Limited data exist on fast-track protocols in relation to revision knee arthroplasty. Hence, the aim of this study was to report length of stay (LOS), risk of LOS > 5 days and readmission ≤ 90 days after revision knee arthroplasty in centers with a well-established fast-track protocol in both primary and revision surgery. METHODS: An observational cohort study from the Centre for Fast-track Hip and Knee Replacement and the Danish Knee Arthroplasty Register. We included elective aseptic major component revision knee arthroplasties consecutively from 6 dedicated fast-track centers from 2010 to 2018. RESULTS: 1439 revision knee arthroplasties were analyzed, including 900 total revisions, 171 large partial revisions (revision of either femoral or tibia component) and 368 revisions of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA). Mean age was 65 years (SD 10.9) and 66% were females. Mean LOS was 3.7 days (SD 3.9) in the study period, but decreased to 2.4 days (SD 1.3) in 2018. Risk factors for LOS > 5 days was ≥ 1 previous revision, use of walking aid, BMI > 35, ages < 50, 70-79 and ≥ 80 years, whereas revision of UKA to TKA and large partial revision were negatively associated. The 90-day readmission and mortality risk was 9.1% and 0.5%. Cardiac disease and use of walking aid were associated with increased risk of readmission ≤ 90 days. CONCLUSION: Elective aseptic major component revision knee arthroplasty using similar fast-track protocols as in primary TKA is safe with short and decreasing LOS.

DEX-2-TKA - DEXamethasone twice for pain treatment after Total Knee Arthroplasty: Detailed statistical analysis plan for a randomized, blinded, three-group multicentre clinical trial.

BACKGROUND: Optimization of post-operative pain treatment is of upmost importance. Multimodal analgesia is the main post-operative pain treatment principle, but the evidence on optimal analgesic combinations is unclear. With the "DEXamethasone twice for pain treatment after TKA" trial, we aim to investigate the role of one or two doses of glucocorticoid for post-operative pain treatment after total knee arthroplasty. To ensure transparency and minimization of bias, we present this article with a detailed statistical analysis plan, to be published before the last participant is enrolled. METHODS: "DEXamethasone twice for pain treatment after TKA" (DEX-2-TKA) is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three intervention groups: single dose of iv dexamethasone 24 mg, two consecutive doses of iv dexamethasone 24 mg or matching iv placebo. All three intervention groups will receive paracetamol, NSAID (ibuprofen) and local infiltration analgesia. Participants, treatment providers, outcome assessors, data managers, statisticians and conclusion drawers will be blinded to the allocated intervention. The primary outcome is total opioid consumption (iv morphine milligram equivalents) 0-48 hours post-operatively. Secondary outcomes are (1) visual analogue scale pain levels: (a) during active 45 degrees flexion of the knee at 24 and 48 hours post-operatively, (b) at rest at 24 and 48 hours post-operatively, and (c) during 0-24 hours (highest score) and 24-48 hours post-operatively (highest score); and (2) the proportion of participants with one or more adverse events within 48 hours post-operatively. DISCUSSION: The DEX-2-TKA trial will provide high quality data regarding benefits and harms of adding one or two high-doses of dexamethasone to a multimodal analgesic regimen. TRIAL REGISTRATION: EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019).

DEX-2-TKA-DEXamethasone twice for pain treatment after Total Knee Arthroplasty: A protocol for a randomized, blinded, three-group multicentre clinical trial.

BACKGROUND: Multimodal analgesia is considered the leading principle for post-operative pain treatment, but no gold standard after total knee arthroplasty (TKA) exists. AIM: To investigate the beneficial and harmful effects of one or two doses of 24 mg intravenous dexamethasone (DXM) as part of a multimodal analgesic regimen (paracetamol, NSAID and perioperative local infiltration analgesia) after TKA. We hypothesize that addition of DXM will reduce post-operative opioid consumption. METHODS: DEXamethasone twice for pain treatment after TKA is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three groups: placebo, single dose of DXM or two consecutive doses of DXM. Participants, treatment providers and investigators will be blinded to the allocated intervention. The primary outcome is total opioid consumption (units of morphine equivalents) 0-48 hours post-operatively. INCLUSION CRITERIA: unilateral, primary TKA; age ≥18 years; American Society of Anesthesiologists-Score 1-3; Body Mass Index ≥18 and ≤40; for women-not pregnant; and written informed consent. EXCLUSION CRITERIA: allergy or contraindications against trial medication; daily use of high dose opioid and/or use of methadone/transdermal opioids; daily use of systemic glucocorticoids; dysregulated diabetes; and patients suffering from alcohol and/or drug abuse. Four-hundred-and-eighty-six eligible participants are needed to detect or discard a difference of 10 mg morphine equivalents 0-48 hours post-operatively maintaining a familywise error rate of 0.05 and a power of 90% for the three possible pairwise comparisons. DISCUSSION: Recruiting is planned to commence September 2018 and expected to finish March 2020. TRIAL REGISTRATION: EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019). Editorial Comment This is the protocol for the largest randomized clinical trial investigating the effect of one or two doses of dexamethasones on pain treatment after total knee arthroplasty. Due to the pragmatic and rigerous design this study will deliver results of high quality and external validity.

Preoperative High-Dose Methylprednisolone and Glycemic Control Early After Total Hip and Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: To evaluate the effect of a single preoperative dose of 125 mg methylprednisolone (MP) on glycemic homeostasis early after fast-track total hip and knee arthroplasty. METHODS: One-hundred thirty-four patients undergoing elective unilateral total hip arthroplasty and total knee arthroplasty were randomized (1:1) to preoperative intravenous MP 125 mg (group MP) or isotonic saline intravenous (group C). All procedures were performed under spinal anesthesia, using a standardized multimodal analgesic regime. The primary outcome was the change in plasma glucose 2 hours postoperatively, and secondary outcomes included plasma C-peptide concentrations, homeostatic model assessment (HOMA), HOMA-IR (insulin resistance), and HOMA-B (ß-cell function). Fasting blood samples were collected at baseline and 2, 6 (nonfasting), 24, and 48 hours after surgery with complete samples from 122 patients (group MP = 62, group C = 60) for analyses. RESULTS: MP patients had increased plasma glucose levels at 2 hours (adjusted mean [95% CI], 7.4 mmol·L [7.2-7.5] vs 6.0 mmol·L [5.9-6.2]; P = .023) and 6 hours (13.9 mmol·L [13.3-14.5] vs 8.4 mmol·L [7.8-9.0]; P < .001), and in plasma C-peptide 24 hours postoperatively (1675 pmol·L [1573-1778] vs 1248 pmol·L [1145-1351]; P < .001). An impaired insulin response was also observed in group MP as reflected by HOMA-B (P < .001). Additionally, HOMA-IR increased 24 hours postoperatively in group MP compared to group C (P < .001). Parameters were normalized 48 hours postoperatively. CONCLUSIONS: Preoperative administration of MP 125 mg resulted in a transient postoperative increase in plasma glucose and insulin resistance and impaired insulin secretion in response to hyperglycemia.

Microbiological diagnosis in revision of infected knee arthroplasties in Denmark.

BACKGROUND: Revision of infected knee arthroplasties is associated with high failure rates (30-40%). An understanding of the microbiology is important to optimize treatment and outcome. We describe microbiological diagnostic practice and diagnosis in revision of infected knee arthroplasties. METHODS: One hundred and two partial revisions (open debridement and exchange of tibial insert) and 213 two-stage procedures performed due to infection in 275 patients from 1 July 2011 to 30 June 2013 were included and analysed by linkage to data from a nationwide registry on microbiological test results. RESULTS: 78 (24.8%) revisions were culture negative, 192 (60.9%) showed monomicrobial growth and 43 (14.3%) polymicrobial growth. Staphylococcus aureus was the most frequent isolate in mono-culture in 70 (22.2%) revisions and in polymicrobial culture in 15 revisions with a total frequency of 27.0%. Only one case (1.4%) of methicillin-resistance was registered. Coagulase-negative staphylococci (CoNS) were frequent, sole pathogen in 65 revisions and in polymicrobial cultures in 28 revisions with a total frequency of 29.5%. A pre-operative knee aspiration was performed in 50% and preoperative blood cultures were performed in 22% of cases. In 73% of the preoperative knee-aspirations bacteriological findings were fully or partially in accordance with intraoperative cultures. In 54% of the later re-revisions due to infection (treatment-failures) the cultured species differed from or was not detected at index revision surgery. CONCLUSIONS: The 25% culture negative cases in combination with only 50% preoperative knee aspirations and prevailing high failure rates confirm the need for improvement of diagnostic practice and treatment of infected knee arthroplasties.

Preoperative methylprednisolone does not reduce loss of knee-extension strength after total knee arthroplastyA randomized, double-blind, placebo-controlled trial of 61 patients.

Background and purpose - Patients undergoing total knee arthroplasty (TKA) face challenges related to postoperative reduction in knee-extension strength. We evaluated whether inhibition of the inflammatory response by a single preoperative dose of methylprednisolone (MP) reduces the pronounced loss of knee-extension strength at discharge after fast-track TKA. Patients and methods - 70 patients undergoing elective unilateral TKA were randomized (1:1) to preoperative intravenous (IV) MP 125 mg (group MP) or isotonic saline IV (group C). All procedures were performed under spinal anesthesia without tourniquet, and with a standardized multimodal analgesic regime. The primary outcome was change in knee-extension strength from baseline to 48 hours postoperatively. Secondary outcomes were knee joint circumference, functional performance using the Timed Up and Go (TUG) test, pain during the aforementioned tests, rescue analgesic requirements, and plasma C-reactive protein (CRP) changes. Results - 61 patients completed the follow-up. The loss in quadriceps muscle strength was similar between groups; group MP 1.04 (0.22-1.91) Nm/kg (-89%) vs. group C 1.02 (0.22-1.57) Nm/kg (-88%). Also between-group differences were similar for knee circumference, TUG test, and pain scores. MP reduced the inflammatory response (CRP) at 24 hours postoperatively; group MP 33 (IQR 21-50) mg/L vs. group C 72 (IQR 58-92) mg/L (p < 0.001), and 48 hours postoperatively; group MP 83 (IQR 56-125) mg/L vs. group C 192 (IQR 147-265) mg/L (p < 0.001), respectively. Interpretation - Preoperative systemic administration of MP 125 mg did not reduce the pronounced loss of knee-extension strength or other functional outcomes at discharge after fast-track TKA despite a reduced systemic inflammatory response.

Revision of infected knee arthroplasties in Denmark.

Background and purpose - The surgical treatment of periprosthetic knee infection is generally either a partial revision procedure (open debridement and exchange of the tibial insert) or a 2-stage exchange arthroplasty procedure. We describe the failure rates of these procedures on a nationwide basis. Patients and methods - 105 partial revisions (100 patients) and 215 potential 2-stage revision procedures (205 patients) performed due to infection from July 1, 2011 to June 30, 2013 were identified from the Danish Knee Arthroplasty Register (DKR). Failure was defined as surgically related death ≤ 90 days postoperatively, re-revision due to infection, or not reaching the second stage for a planned 2-stage procedure within a median follow-up period of 3.2 (2.2-4.2) years. Results - The failure rate of the partial revisions was 43%. 71 of the partial revisions (67%) were revisions of a primary prosthesis with a re-revision rate due to infection of 34%, as compared to 55% in revisions of a revision prosthesis (p = 0.05). The failure rate of the 2-stage revisions was 30%. Median time interval between stages was 84 (9-597) days. 117 (54%) of the 2-stage revisions were revisions of a primary prosthesis with a re-revision rate due to infection of 21%, as compared to 29% in revisions of a previously revised prosthesis (p = 0.1). Overall postoperative mortality was 0.6% in high-volume centers (> 30 procedures within 2 years) as opposed to 7% in the remaining centers (p = 0.003). Interpretation - The failure rates of 43% after the partial revision procedures and 30% after the 2-stage revisions in combination with the higher mortality outside high-volume centers call for centralization and reconsideration of surgical strategies.

Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial.

OBJECTIVES: The purpose of this study was to compare the safety and efficacy of percutaneous coronary intervention (PCI) with stenting against coronary artery bypass grafting (CABG) in patients with diabetes and symptomatic multivessel coronary artery disease. BACKGROUND: CABG is the established method of revascularization in patients with diabetes and multivessel coronary disease, but with advances in PCI, there is uncertainty whether CABG remains the preferred method of revascularization. METHODS: The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), and stroke, and the main secondary outcome included the addition of repeat revascularization to the primary outcome events. A total of 510 diabetic patients with multivessel or complex single-vessel coronary disease from 24 centers were randomized to PCI plus stenting (and routine abciximab) or CABG. The primary comparison used a noninferiority method with the upper boundary of the 95% confidence interval (CI) not to exceed 1.3 to declare PCI noninferior. Bare-metal stents were used initially, but a switch to Cypher (sirolimus drug-eluting) stents (Cordis, Johnson & Johnson, Bridgewater, New Jersey) was made when these became available. RESULTS: At 1 year of follow-up, the composite rate of death, MI, and stroke was 10.5% in the CABG group and 13.0% in the PCI group (hazard ratio [HR]: 1.25, 95% CI: 0.75 to 2.09; p=0.39), all-cause mortality rates were 3.2% and 3.2%, and the rates of death, MI, stroke, or repeat revascularization were 11.3% and 19.3% (HR: 1.77, 95% CI: 1.11 to 2.82; p=0.02), respectively. When the patients who underwent CABG were compared with the subset of patients who received drug-eluting stents (69% of patients), the primary outcome rates were 12.4% and 11.6% (HR: 0.93, 95% CI: 0.51 to 1.71; p=0.82), respectively. CONCLUSIONS: The CARDia (Coronary Artery Revascularization in Diabetes) trial is the first randomized trial of coronary revascularization in diabetic patients, but the 1-year results did not show that PCI is noninferior to CABG. However, the CARDia trial did show that multivessel PCI is feasible in patients with diabetes, but longer-term follow-up and data from other trials will be needed to provide a more precise comparison of the efficacy of these 2 revascularization strategies. (The Coronary Artery Revascularisation in Diabetes trial; ISRCTN19872154).

Diagnosing displaced four-part fractures of the proximal humerus: a review of observer studies.

Displaced four-part fractures comprise 2-10 % of all proximal humeral fractures. The optimal treatment is unclear and randomised trials are needed. The conduct and interpretation of such trials is facilitated by a reproducible fracture classification. We aimed at quantifying observer agreement on the classification of displaced four-part fractures according to the Neer system. Published and unpublished data from five observer studies were reviewed. Observers agreed less on displaced four-part fractures than on the overall Neer classification. Mean kappa values for interobserver agreement ranged from 0.16 to 0.48. Specialists agreed slightly more than fellows and residents. Advanced imaging modalities (CT and 3D CT) seemed to contribute more to classification of displaced four-part patterns than in less complex fracture patterns. Low observer agreement may challenge the clinical approach to displaced four-part fractures and poses a problem for the interpretation and generalisation of results from future randomised trials.

The effect of patient origin and relevance of contact on patient and caregiver satisfaction in the emergency room.

AIMS: This study examined (1) whether patient and caregiver satisfaction in the emergency room (ER) varies according to patient origin, and (2) whether relevance of visit can explain any variation. METHODS: Data were obtained from a questionnaire survey of walk-in patients and their caregivers at four ERs in Copenhagen. The patient questionnaire was available in nine languages, and addressed patient satisfaction. The caregiver questionnaire addressed caregiver satisfaction and relevance of the patient contact in the ER. A total of 3,809 patients and 3,905 caregivers responded. The response rate among patients was 54%. Only data with both patient and caregiver responses and with patient country of birth were included in the analyses (n=3,426). The effect of patient origin was examined using bivariate, stratified analyses and tested for independence. RESULTS: Patients and caregivers had lower satisfaction rates when patients were of Middle Eastern compared with Danish origin. Satisfaction of both groups was associated with the relevance of the visit as assessed by the caregiver. Visits by patients of Middle Eastern origin were less often assessed as being relevant, but caregivers were less satisfied with visits by these patients even after controlling for relevance. Differences in patient satisfaction by patient origin were no longer significant when stratifying by relevance. CONCLUSIONS: Patient and caregiver satisfaction among patients of foreign origin can be improved by lowering the number of irrelevant visits among patients of foreign origin, e.g. by improving access to general practitioners. Training of caregivers in dealing with patients of different origins might reduce differences in caregiver satisfaction according to patient origin.

Motivation and relevance of emergency room visits among immigrants and patients of Danish origin.

BACKGROUND: We investigated the extent to which immigrants and patients of Danish origin have different motivations for seeking emergency room (ER) treatment, and differences in the relevance of their claims. METHODS: Data were obtained from a questionnaire survey of walk-in patients and their caregivers at four Copenhagen ERs. The patient survey was available in nine languages, and addressed patient-identified reasons for using the ER. Caregivers were asked if the claim was appropriate to the ER. 3809 patients and 3905 caregivers responded. The response rate among patients was 54%. Only questionnaires in which both patient and caregiver had responded, and in which data on the patient's nationality were available, were included in the analyses (n = 3426). The effect of region of origin was examined using bivariate, stratified analyses and tested for independence. RESULTS: More among immigrant patients than among patients of Danish origin had considered contacting a primary caregiver before visiting the ER, and more immigrants reported going to the ER because they could not contact a general practitioner, or could not explain their problem on the telephone. Compared to immigrants, more patients of Danish origin explained that the ER was most relevant to their need. A higher proportion of claims among immigrants were seen by caregivers as not being appropriate to the ER. CONCLUSION: Migrants have more irrelevant ER claims, presumably because of barriers in access to primary care. Access to primary care should be facilitated for these groups. Alternatively, ERs could include primary care activities as part of their services.

Enhanced external counterpulsation for treatment of refractory angina pectoris.

OBJECTIVE: Enhanced external counterpulsation (EECP) is a noninvasive, well-tolerated treatment, effective for managing patients with refractory angina pectoris. The aim of this study was to evaluate the efficacy of EECP to relieve symptoms, to decrease myocardial ischaemia and to improve cardiac performance in patients with intractable angina, refractory to surgical and medical treatment. METHODS: Twenty-five patients (24 men and one woman, mean age 65 years) with persistent ischaemia notwithstanding optimal medical therapy or after interventional or surgical procedure, received EECP sessions for 35 h. Each patient underwent dobutamine stress echocardiography before and after treatment. We evaluated modifications in either cardiac systolic or diastolic function, and in wall motion score index. RESULTS: Eighty-four percent of patients showed an increase in at least one functional angina class. We did not observe any significant changes in fractional shortening and diastolic function. Thirty-six percent of patients had a reduction in the area of inducible ischaemia at dobutamine stress echocardiography after treatment. Unfortunately, because of the small sample size, we did not find any statistically significant difference. There was a trend showing that patients who benefited the most were those with the worst systolic function and with severely compromised segmental kinesis (P = NS). CONCLUSIONS: EECP is effective in relieving symptoms in patients with refractory angina and may reduce inducible ischaemia at dobutamine stress echocardiography, especially in patients with reduced systolic function and compromised segmental kinesis.

Coronary artery size and disease in UK South Asian and Caucasian men.

OBJECTIVE: South Asian patients in the UK have a higher mortality rate after coronary artery bypass grafting (CABG) than Caucasian patients. As coronary artery size has been shown to correlate to outcome from bypass grafting, it has been suggested that smaller coronary arteries in South Asians as compared to Caucasians could contribute to a poorer outcome in the Asian population. We aimed to measure coronary artery size and disease in matched South Asian and Caucasian men undergoing first time coronary artery bypass grafting. METHODS: Coronary arteriograms from 53 matched first generation South Asian and Caucasian men were examined. The patients had no history of myocardial infarction, coronary revascularisation, familial dyslipidaemia, diabetes or renal disease. They were individually matched for age, height, weight, body mass index and body surface area. Thereafter, coronary artery diameters and significant (> or =50%) diameter stenoses were measured in a blinded fashion using quantitative coronary angiography (QCA). RESULTS: In South Asian men, diameters of the left main stem (LMS) and the proximal left anterior descending, the circumflex and the right coronary arteries were 4.6+/-0.9 mm, 3.5+/-0.8 mm, 3.4+/-0.8 mm and 3.5+/-0.8 mm, respectively. The corresponding arterial diameters among Caucasian men (4.5+/-0.9 mm, 3.5+/-0.7 mm, 3.5+/-0.8 mm and 3.8+/-0.8 mm) did not differ from those in South Asians. There was no difference in the number of significant coronary artery stenoses between the two groups and no difference in bypass and cross-clamp times or in adverse outcome (one from each group died after coronary artery bypass grafting). CONCLUSION: Proximal coronary artery size and number of significant coronary stenoses did not differ between matched pairs of South Asian and Caucasian men using strict inclusion/exclusion criteria.

Arterial concentration of 99mTc-sestamibi at rest, during peak exercise and after dipyridamole infusion.

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial (99m)Tc-sestamibi (MIBI) time-activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one-vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by (99m)Tc-sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5-30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.

Insulin increases glycolysis without further vasodilation in porcine coronary arteries exposed to hypoxia.

In acute ischaemia, glucose-insulin-potassium administration reduces mortality and beta-adrenoceptor antagonists have favourable effects on the outcome of ischaemic heart disease. The present study was designed to investigate whether insulin (1.4x10(-7) M) and the beta-adrenoceptor antagonist, propranolol (10(-5) M), increase hypoxic vasodilation in correspondence with changes in glycolysis. Porcine coronary arteries, precontracted with 10(-5) M prostaglandin F(2alpha), were mounted in a pressure myograph and a microdialysis catheter was inserted in the tunica media. Hypoxic vasodilation, interstitial lactate/pyruvate ratio and interstitial glucose were measured at low (2 mM) and high (20 mM) glucose concentrations. Hypoxia (60 min) caused vasodilation and doubled the lactate/pyruvate ratio. Treatment with insulin quadrupled the lactate/pyruvate ratio during hypoxia, but did not change hypoxic vasodilation. Propranolol blocked isoprenaline-evoked vasodilation, but hypoxic increases in lactate/pyruvate ratio and vasodilation did not change. The combination of insulin and propranolol did not cause further changes compared with each drug added alone, although the combination increased vasoconstriction during reoxygenation. Interstitial glucose fell during hypoxia at an organ bath glucose concentration of 2 mM, and rose at a glucose concentration of 20 mM. Addition of insulin and propranolol alone or in combination had no effect on interstitial glucose concentration. Accordingly, arteries were found to contain only minute amounts of the glucose transporter isoform GLUT4. Our findings suggest that insulin increases arterial glycolysis, but treatment with insulin, propranolol, or both, is not associated with enhanced coronary vasodilation during hypoxia.

Postoperative infection with meticillin-resistant Staphylococcus aureus and socioeconomic background.

Infectious disease can be linked to social deprivation. We investigated whether postoperative infection with meticillin-resistant Staphylococcus aureus (MRSA) is related to socioeconomic background. Patients were stratified by social deprivation according to postcode. In a consecutive series of 1739 UK residents undergoing isolated coronary artery bypass grafting, 23 (1.3%) were infected with MRSA. We noted a graded relation between incidence of infection and social deprivation. Patients from the most deprived areas had a seven-fold higher infection rate (13 of 579 [2.2%]) than those from the least deprived areas (two of 580 [0.3%]; p=0.0040). Patients with MRSA infection had a six-fold higher mortality rate and a longer hospital stay than patients with no such infection. Our findings suggest that patients from deprived areas might be especially susceptible to postoperative infection with MRSA.

Effect of enhanced external counterpulsation on dobutamine-induced left ventricular wall motion abnormalities in severe chronic angina pectoris.

We studied the effect of enhanced external counterpulsation (EECP) in 23 consecutive patients with stable angina pectoris who had a positive dobutamine stress echocardiogram. After EECP, stress-induced wall motion score (WMS) improved by > or =2 grades in 43% of the patients (n = 10); the average improvement was 5.3 +/- 3.8 compared with -0.6 +/- 3.0 in the remaining 13 patients (p = 0.007). The diastolic/systolic augmentation ratio increased by 217% in response to the full course of EECP (p = 0.0002) among patients with improved WMS, and by 71% (p = 0.004) among the other patients; the increase was greater among patients with improved WMS than among patients with no improvement (p = 0.01). After EECP, Canadian Cardiovascular Society angina class improved from 3.1 +/- 0.6 to 2.2 +/- 0.7 (p <0.0001) in the entire group and exercise capacity increased by 73 seconds (p = 0.0002) in patients who were able to exercise (n = 18).