M. De Feo

Deep sternal wound infection: the role of early debridement surgery

OBJECTIVE This retrospective chart review study aimed to evaluate whether a more aggressive staged approach can reduce morbidity and mortality following post-cardiotomy deep sternal wound infection. METHODS Between 1979 and 2000, 14620 patients underwent open heart surgery: mediastinitis developed in 124 patients (0.85%). Patients were divided in two groups: in 62 patients (Group A) (1979-1994) an initial attempt of conservative antibiotic therapy was the rule followed by surgical approach in case of failure; in 62 patients (Group B) (1995-2000) the treatment was staged in three phases: (1) wound debridement, removal of wires and sutures, closed irrigation for 10 days; (2) in case of failure open dressing with sugar and hyperbaric therapy (11 patients, 17%); (3) delayed healing and negative wound cultures mandated plastic reconstruction (three patients, 4%). Categorical values were compared using the Chi-square test, continuous data were compared by unpaired t-test. RESULTS Incidence of mediastinitis was higher in Group B (62 out of 5535; 1.3%) than in Group A (62 out of 9085; 0.7%) (P=0.007). Mean interval between diagnosis and treatment was shorter in Group B (18+/-6 days) than in group A (38+/-7 days) (P=0.001). Hospital mortality was higher in Group A (19/62; 31%) than in Group B (1 out of 62; 1.6%) (P<0.001). Hospital stay was shorter in Group B (30.5+/-3 days) than in group A (44+/-9 days) (P=0.001). In Group B complete healing was observed in all the 61 survivors: 47 cases (76%) after Stage 1; 11 (18%) after Stage 2; three (4.8%) after Stage 3. CONCLUSIONS Although partially biased by the fact that the two compared groups draw back to different decades, this study showed that an aggressive therapeutic protocol can significantly reduce morbidity and mortality of deep sternal wound infection.

Molecular analysis of arterial stenosis in rat carotids

A new model of surgical injury for the induction and development of stenosis in common rat carotids is described. This model differs from balloon angioplasty or vein graft systems currently applied on animals to develop stenosis, since it involves the entire vessel wall layers and mimics the injury occurring during arterial grafts, endarterectomy or organ transplantation. At different times following arterial damage, the pattern of expression of genes already known to be involved in the proliferation, differentiation, and apoptosis of smooth muscle cells (c‐myc, Angiotensin II receptor 1, Bcl‐2 and Bax α), as well as of Rb and Rb2 genes, whose pattern of expression after arterial injury has not yet been reported, was analyzed by semi‐quantitative reverse transcription‐polymerase chain reaction technique. Histological and histochemical analysis on carotid sections shows the morphological changes which occurred 30 days after surgical injury in the vessel wall. Molecular and histological data demonstrate that this model of surgical injury induces neointimal proliferation in about 30% of rats. In about 70% of the remaining rats, it induces the processes responsible for negative remodelling, namely the significant accumulation of extracellular matrix and fibers and disorganization of arterial tunics. This model is therefore available for further studies on the expression of genes involved in the arterial stenotic process, as well as for testing drugs aimed at limiting this recurrent pathophysiological phenomenon. J. Cell. Physiol. 186:307–313, 2001.

Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE).

Diabetic foot (DF) is a chronic and highly disabling complication of diabetes. The prevalence of peripheral arterial disease (PAD) is high in diabetic patients and, associated or not with peripheral neuropathy (PN), can be found in 50% of cases of DF. It is worth pointing out that the number of major amputations in diabetic patients is still very high. Many PAD diabetic patients are not revascularised due to lack of technical expertise or, even worse, negative beliefs because of poor experience. This despite the progress obtained in the techniques of distal revascularisation that nowadays allow to reopen distal arteries of the leg and foot. Italy has one of the lowest prevalence rates of major amputations in Europe, and has a long tradition in the field of limb salvage by means of an aggressive approach in debridement, antibiotic therapy and distal revascularisation. Therefore, we believe it is appropriate to produce a consensus document concerning the treatment of PAD and limb salvage in diabetic patients, based on the Italian experience in this field, to share with the scientific community.

c-Myc Antisense Oligonucleotides Preserve Smooth Muscle Differentiation and Reduce Negative Remodelling following Rat Carotid Arteriotomy

Objectives: The vascular biology of restenosis is complex and not fully understood, thus explaining the lack of effective therapy for its prevention in clinical settings. The role of c-Myc in arteriotomy-induced stenosis, smooth muscle cell (SMC) differentiation and apoptosis was investigated in rat carotids applying full phosphorothioate antisense (AS) oligonucleotides (ODNs). Methods: Carotid arteries from WKY rats were submitted to arteriotomy and to local application of ODNs through pluronic gel. Apoptosis (deoxynucleotidyl transferase-mediated dUTP nick end-labelling), SMC differentiation (SM22 immunofluorescence) and vessel morphology and morphometry (image analysis) were determined 2, 5 and 30 days after injury, respectively. Results: AS ODNs induced a 60% decrease of target c-Myc mRNA 4 h after surgery in comparison to control sense (S) and scrambled ODN-treated carotids (p < 0.05). A significant 37 and 50% decrease in SM22 protein in the media of S ODN-treated and untreated carotids was detected when compared to uninjured contralateral arteries (p < 0.05). This reduction in SM22 expression was prevented in AS ODN-treated carotids. Stenosis was mainly due to adventitial constrictive remodelling. Lumen area in AS ODN-treated carotids was 35% greater than in control arteries 30 days after surgery (p < 0.05). TUNEL assay revealed increased apoptosis in AS ODN-treated carotids (p < 0.05). Conclusions: c-Myc AS ODNs reduce arteriotomy-induced negative remodelling. This is accompanied by maintained SMC differentiation and greater apoptosis. The combination of reduced c-Myc-induced proliferation and increased apoptosis may thus underlie the less severe remodelling upon treatment with c-Myc mRNA AS ODN.

Expression profiles in surgically-induced carotid stenosis: a combined transcriptomic and proteomic investigation.

Vascular injury aimed at stenosis removal induces local reactions often leading to restenosis. The aim of this study was a concerted transcriptomic‐proteomics analysis of molecular variations in a model of rat carotid arteriotomy, to dissect the molecular pathways triggered by vascular surgical injury and to identify new potential anti‐restenosis targets. RNA and proteins extracted from inbred Wistar Kyoro (WKY) rat carotids harvested 4 hrs, 48 hrs and 7 days after arteriotomy were analysed by Affymetrix rat microarrays and by bidi‐mensional electrophoresis followed by liquid chromatography and tandem mass spectrometry, using as reference the RNA and the proteins extracted from uninjured rat carotids. Results were classified according to their biological function, and the most significant Kyoro Encyclopedia of Genes and Genomes (KEGG) pathways were identified. A total of 1163 mRNAs were differentially regulated in arteriotomy‐injured carotids 4 hrs, 48 hrs and 7 days after injury (P < 0.0001, fold‐change ≥2), while 48 spots exhibited significant changes after carotid arteriotomy (P < 0.05, fold‐change ≥2). Among them, 16 spots were successfully identified and resulted to correspond to a set of 19 proteins. mRNAs were mainly involved in signal transduction, oxidative stress/inflammation and remodelling, including many new potential targets for limitation of surgically induced (re)stenosis (e.g. Arginase I, Kruppel like factors). Proteome analysis confirmed and extended the microrarray data, revealing time‐dependent post‐translational modifications of Hsp27, haptoglobin and contrapsin‐like protease inhibitor 6, and the differential expression of proteins mainly involved in contractility. Transcriptomic and proteomic methods revealed functional categories with different preferences, related to the experimental sensitivity and to mechanisms of regulation. The comparative analysis revealed correlation between transcriptional and translational expression for 47% of identified proteins. Exceptions from this correlation confirm the complementarities of these approaches.

Prediction of severe bleeding after coronary surgery: the WILL-BLEED Risk Score.

Severe perioperative bleeding after coronary artery bypass grafting (CABG) is associated with poor outcome. An additive score for prediction of severe bleeding was derived (n=2494) and validated (n=1250) in patients from the E-CABG registry. Severe bleeding was defined as E-CABG bleeding grades 2-3 (transfusion of >4 units of red blood cells or reoperation for bleeding). The overall incidence of severe bleeding was 6.4 %. Preoperative anaemia (3 points), female gender (2 points), eGFR <45 ml/min/1.73 m2 (3 points), potent antiplatelet drugs discontinued less than five days (2 points), critical preoperative state (5 points), acute coronary syndrome (2 points), use of low-molecular-weight heparin/fondaparinux/unfractionated heparin (1 point) were independent predictors of severe bleeding. The WILL-BLEED score was associated with increasing rates of severe bleeding in both the derivation and validation cohorts (scores 0-3: 2.9 % vs 3.4 %; scores 4-6: 6.8 % vs 7.5 %; scores>6: 24.6 % vs 24.2 %, both p<0.0001). The WILL-BLEED score had a better discriminatory ability (AUC 0.725) for prediction of severe bleeding compared to the ACTION (AUC 0.671), CRUSADE (AUC 0.642), Papworth (AUC 0.605), TRUST (AUC 0.660) and TRACK (AUC 0.640) bleeding scores. The net reclassification index and integrated discrimination improvement using the WILL-BLEED score as opposed to the other bleeding scores were significant (p<0.0001). The decision curve analysis demonstrated a net benefit with the WILL-BLEED score compared to the other bleeding scores. In conclusion, the WILL-BLEED risk score is a simple risk stratification method which allows the identification of patients at high risk of severe bleeding after CABG.

Does priming implementation with low-dose albumin reduce postoperative bleeding following cardiopulmonary bypass?

This study aimed to assess whether low doses of albumin in the priming solution for cardiopulmonary bypass (CPB) reduce postoperative bleeding. Three-hundred and seventy-seven patients undergoing CPB were retrospectively assigned to group A (154 patients, CPB primed with 20 ml/kg Ringer Lactate solution + 0.75mg/kg albumin 20%) and group B (223 patients with 20 ml/kg Ringer Lactate). A significant difference was found in terms of reoperations for bleeding (group A 0/154 versus group B 9/223; P=0.033). The mean number of blood derivatives transfused per patient was higher in group B than in group A (p <0.001). Platelet count after CPB was higher in group A than in group B (175±52×103/μl versus 131±70×103/μl; P=0.045). The amount of postoperative bleeding was 525ml versus 680ml at 24hrs (p <0.001), 819ml versus 1102ml at 48hrs, (p <0.001), 963ml versus 1294ml at 72hrs, (p <0.045) (group A versus group B respectively). Crystalloid priming with low-dose albumin reduces postoperative bleeding.

Gene Expression and Morphological Changes in Surgically Injured Carotids of Spontaneously Hypertensive Rats

The expression profiles of genes involved in cell proliferation, differentiation and programmed death were investigated in carotids of spontaneously hypertensive rats (SHR) treated with a model of surgical injury that mimics events occurring during arterial grafts, endarterectomy and organ transplantation. The mRNA level of the c-myc, angiotensin II receptor 1 (AT1), Rb/p105, Rb2/p130, Bcl-2 and Bax-α genes was assessed by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique at different times up to 48 h after injury, while the morphological changes were evaluated 30 days after injury. The proliferation marker c-myc increases almost immediately, peaks after 4 h and returns to basal levels after 24 h; the AT1 receptor mRNA reaches its maximal level 48 h after injury. The level of cell cycle exit markers Rb/p105 and Rb2/p130 gradually decreases after injury. The apoptosis marker Bcl-2/Bax-α ratio shows a significant reduction only 4 h after injury, resuming the initial value after 24 and 48 h. Morphological analysis reveals that surgical injury in SHR induces adventitial and medial constrictive remodeling changes rather than intima proliferation as in balloon angioplasty. Both molecular and histological data show substantial differences with respect to normotensive rats.

Is Aortic Valve Replacement with Bileaflet Prostheses Still Contraindicated in the Elderly

Background: Prolonged survival in the Western world has increased the number of elderly patients referred for open-heart surgery during the last decade. Aortic valve disease is the most common heart valve disease in aged patients. Which aortic valve substitute is best employed in the elderly is still a debated matter. The main concern is about the thromboembolic and hemorrhagic risks related to mechanical valves and anticoagulation. Objective: The study aimed at reviewing clinical results after isolated aortic valve replacement with bileaflet prostheses in patients over 70 years and at retrospectively comparing them with those of a group of otherwise comparable patients under 50 years of age who underwent isolated aortic valve replacement with a mechanical device. Methods: The study population included 118 consecutive elderly patients (group A) operated on between January 1988 and January 1999 and 122 young patients (group B) who underwent aortic valve replacement during the same time period. Patients with associated coronary artery disease, mitral stenosis or regurgitation, type A aortic dissection, and infective endocarditis were excluded from the study. Preoperative clinical data, early and late postoperative mortality, all valve-related complications, and all data concerning the anticoagulation status – including the mean international normalized ratio (INR) and the mean time interval between each INR assay – were compared between the two groups. Results: The hospital mortality was significantly lower in group B (2.45%) than in group A (9.3%; p = 0.022). The mean follow-up period was 50.98 ± 2.23 months. The 12-year actuarial survival was significantly lower (69.6 ± 0.08%) in group A than in group B (94.4 ± 0.02%; p < 0.001). No significant difference was found in terms of valve-related and anticoagulation-related complication rates and actuarial freedom as well as mean interval between consecutive INR checks (p = 0.219) and mean INR value (p = 0.914). Conclusions: Bileaflet prostheses in elderly patients can achieve excellent early and late clinical results, with a low incidence of anticoagulation-related complications and an extremely low risk of a reoperation. Older age can no longer be considered a contraindication to bileaflet prosthesis implantation in the aortic position.

Long-term follow-up of open commissurotomy versus bileaflet valve replacement for rheumatic mitral stenosis.

OBJECTIVE Despite the achievements of third generation mechanical cardiac valve prostheses, conservative procedures are still considered the best surgical option for rheumatic mitral valve stenosis. To compare long-term results of open mitral commissurotomy (Group A) and mitral valve replacement with bileaflet prostheses (Group B) a 15-year follow-up study was carried out. METHODS From January 1981 to May 1996, 540 consecutive patients with pure isolated rheumatic mitral stenosis underwent mitral valve surgery: 300 had mitral commissurotomy and 240 valve replacement. The follow-up was 99.05% complete and ranged between 1 and 185 months in Group A and from 1 to 171 months in Group B. RESULTS Hospital mortality was 2% in Group A and 2.08% in Group B. Late mortality was 1% in Group A and 3% in Group B. The 10-year survival rates were 98.7% +/- 1% in Group A and 93.7% +/- 3% in Group B. There was a statistically significant difference of freedom from reoperation in Group B (97.7% +/- 1%) versus Group A (88.1% +/- 2%) (P = 0.04). In group A 14 embolic events occurred (93.7% +/- 2%), and 15 (6.52%) in Group B (83.9% +/- 7%). Haemorrhagic events were observed in 2 patients (0.68%) of Group A (99.3% +/- 0.5%) and in 3 patients (1.3%) of Group B (98.4% +/- 1%). CONCLUSIONS Long term results of mitral commissurotomy were more satisfactory than those obtained with bileaflet valves. Reoperation rate was higher in mitral commissurotomy.