Ultrastructural discrimination between malignant melanomas and benign nevocytic nevi using high-resolution image and multivariate analyses

Prompted by the well-known difficulties of reliable and objective histologic differentiation between initial malignant melanoma (MM) and benign nevocytic nevi (NN), ultrastructural high-resolution image and multivariate analyses were evaluated for their diagnostic efficiency. Thirty-seven different features describing morphometry (area, circumference, and shape factor), amount of heterochromatin and euchromatin, chromatin homogeneity, and presence of smaller dark chromatin aggregations were determined by a MICROVAX 3500 computer in each of 1840 intraepidermal melanocytic nuclei of 17 MM and 20 NN. A strategy for the classification of cases based on the identification of markedly atypical melanocytic cells (MACS) was developed. MACS, selected in multivariate analysis with a linear combination of the eight most important features for cell classification, were found in 39.4% of the melanoma cells, but only in 0.3% of nevocytic nevus cells. The presence of MACS allowed a clear differentiation between MM and NN. All cases of MM had more than four MACS, whereas 17 cases of nevocytic nevi were MACS negative, and in each of the remaining three cases only one MAC was present. The percentage of MACS detected within intraepidermal parts of MM by using computerized high-resolution image analysis was found to be a highly efficient diagnostic marker. The new classification strategy has the potential of saving considerable time in subsequent studies, because preselected sampling and the calculation of only a few criteria have proven sufficient for correct classification of malignant melanomas.     

Electrophysiological consequence of adipose-derived stem cell transplantation in infarcted porcine myocardium.

AIMS: Aim of this study was to investigate the effect of intracoronary administration of freshly isolated adipose-derived mononuclear cells (ADMCs) on myocardial vulnerability to arrhythmia induction after infarction. METHODS AND RESULTS: A transmural myocardial infarction in an experimental porcine model was induced by occlusion of the mid-left anterior descending artery with an angioplasty balloon for 3 h. Upon reperfusion, a cellular suspension with freshly isolated ADMCs (1.5 x 10(6) cells/kg BW) or vehicle alone was injected into the infarct artery. All animals underwent a programmed ventricular stimulation at 8 weeks follow-up for possible induction of ventricular arrhythmias using a train of 8 S1 stimuli. Cell injections did not cause acute ventricular arrhythmia, bradycardia, or conduction block. The cycle length of the ventricular arrhythmia was compared at 1 and 10 s following its induction. Despite comparable infarct size in both groups, we found that the cycle length of the induced ventricular arrhythmia in the ADMC-treated group was significantly longer compared with control animals (P < 0.05). We also found that extra-stimuli were required for arrhythmia induction in the ADMC-treated group compared with control animals. CONCLUSION: Freshly isolated autologous stem cell therapy is not proarrhythmic in pigs.     

Predictors and early and late outcomes of respiratory failure in contemporary cardiac surgery

BACKGROUND: Respiratory failure (RF) is a serious complication following heart surgery. The profile of patients referred for cardiac surgery has changed during the last decade, making prior investigations of RF after cardiac surgery less relevant to the current population. This study was designed to analyze the incidence, predictors of RF, and early and late outcomes following this complication in a large contemporary cardiac surgery population. METHODS: We retrospectively analyzed prospectively collected data from the New York State Department of Health database including 5,798 patients undergoing cardiac surgery between January 1998 and December 2005. Patients with RF (intubation time > or = 72 h) were compared to patients without RF. RESULTS: The incidence of RF was 9.1% (n = 529). The highest incidence of RF was observed following combined valve/coronary artery bypass graft (14.8%) and aortic procedures (13.5%). Multivariate analysis revealed preoperative and operative predictors of RF such as renal failure (odds ratio [OR], 2.3), aortic procedures (OR, 2.6), hemodynamic instability (OR, 3.2), and intraaortic balloon pump (OR, 2.6). The mortality rate following RF was 15.5% (n = 82), compared to 2.4% (n = 126) in the no-RF group (p < 0.001). Kaplan-Meier survival curves showed significantly poorer survival among RF patients (p < 0.001) compared to the no-RF group. CONCLUSION: RF remains a serious and common complication following cardiac surgery, particularly in patients undergoing complex procedures. RF is associated with significant comorbidity, increased hospital mortality, and reduced long-term survival. Future research efforts should focus on a more precise identification of patients at risk and the development of new treatment modalities that would potentially prevent the occurrence of this complication.     

Prognostic value of preoperative cardiac troponin I in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery

STUDY OBJECTIVES: Elevated levels of cardiac troponin I (cTnI) have been associated with adverse short-term and long-term outcomes in acute coronary syndrome (ACS) patients and in patients who underwent coronary artery bypass grafting (CABG); however, the prognostic implications of preoperative cTnI determination have not been investigated so far. DESIGN AND SETTING: Retrospective study in a department of cardiothoracic surgery of a university hospital. PATIENTS AND METHODS: A possible correlation between preoperative cTnI levels and major adverse cardiac events (MACE) and in-hospital mortality in CABG patients with non-ST-segment elevation ACS (NSTE-ACS) was investigated. cTnI was determined in 1,978 of 3,124 consecutive CABG patients. Among these, 1,592 patients had preoperative cTnI levels < 0.1 ng/mL and therefore served as control subjects (group 1), 265 patients had NSTE-ACS with cTnI levels from 0.11 to 1.5 ng/mL (group 2), and 121 patients had NSTE-ACS with cTnI levels > 1.5 ng/mL (group 3). cTnI levels, clinical data, MACE, and in-hospital mortality were recorded prospectively. Logistic regression and receiver operating characteristic analyses were applied to determine prognostic cutoff values of cTnI. RESULTS: Perioperative myocardial infarction was found in 5.8% of the patients in group 1, 8.3% of the patients in group 2 (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9 to 2.5), and 18.2% patients in group 3 (OR, 3.6; 95% CI, 2.1 to 6.2; p < 0.0001, Cochran-Armitage trend test). Low cardiac output syndrome occurred in 1.5% of patients in group 1, 4.2% of patients in group 2 (OR, 2.8; 95% CI, 1.3 to 6.1), and 10.9% patients in group 3 (OR, 6.5; 95% CI, 2.9 to 14.4; p < 0.0001). In-hospital mortality was 1.5% in group 1, 3.0% in group 2 (OR, 2.0; 95% CI, 0.8 to 4.8), but 6.6% in group 3 (OR, 4.6; 95% CI, 1.9 to 11.1; p < 0.0001). Univariate and multivariate logistic regression analyses identified cTnI as the strongest preoperative predictor for MACE and in-hospital mortality, respectively. CONCLUSIONS: Preoperative cTnI measurement before CABG appears as a powerful and independent determinant of short-term surgical risk in patients with NSTE-ACS.     

Administration of C1-esterase inhibitor during emergency coronary artery bypass surgery in acute ST-elevation myocardial infarction.

OBJECTIVE: Myocardial inflammatory response including complement activation was demonstrated as an important mechanism of ischemia-reperfusion injury and complement inhibition by C1-esterase inhibitor (C1-INH) has recently shown to have cardioprotective effects in experimental and clinical settings. METHODS: The effects of C1-INH on complement activation, myocardial cell injury, and clinical outcome were studied in patients undergoing emergency CABG due to acute ST-elevation myocardial infarction (STEMI) with (group 1, CABG+STEMI+C1-INH, n=28) and without (group 2, CABG+STEMI, n=29) bolus administration of C1-INH (40 IU kg(-1)) during reperfusion and 6 h postoperatively (20 IU kg(-1)) besides the same study protocol. C1-INH activity, C3c and C4 complement activation fragments, and cardiac troponin I (cTnI) were measured preoperatively and up to 48 h postoperatively and compared to another elective set of CABG patients without STEMI as controls (group 3, CABG-STEMI, n=10). Clinical data, adverse events, and patient outcome were recorded prospectively. RESULTS: Patient characteristics were not different between groups 1 and 2. No drug-related adverse events were observed. Constant plasma levels of C1-INH were found in group 1, but not in groups 2 and 3. Plasma levels of C3c and C4 complement fragments were reduced in all three groups after surgery throughout the observation time, but tended to be lower in groups 1 and 2 compared with group 3. Preoperative cTnI levels were elevated but not different between the groups 1 and 2. The area under curve (AUC), as well as the postoperative cTnI serum levels, was significantly lower (P<0.05) in group 1 with a treatment delay < or = 6 h between reperfusion and symptom onset compared to group 2 at 36 h (47.9+/-11.1 ng/ml vs 97.7+/-17.2 ng/ml; mean+/-SEM), and 48 h (33.5+/-5.8 ng/ml vs 86.5+/-19.2 ng/ml) after surgery, but remained unchanged between groups among patients with a treatment delay of more than 6-24 h. In-hospital adverse events and postoperative complications, ICU and hospital stay, as well as in-hospital mortality (14.3% vs 13.8%; P=NS) were not different between groups 1 and 2. CONCLUSIONS: C1-INH administration in emergency CABG with acute STEMI is safe and effective to inhibit complement activation and may reduce myocardial ischemia-reperfusion injury as measured by cTnI.     

Sodium nitroprusside during coronary artery bypass grafting: evidence for an antiinflammatory action.

BACKGROUND: It was the aim of the present study to investigate whether a nitric oxide donor can reduce systemic inflammation and the cardiac inflammatory response during coronary artery bypass grafting with cardiopulmonary bypass. METHODS: Patients undergoing elective coronary artery bypass grafting (n = 22) were randomly assigned to treatment with either sodium nitroprusside (0.5 microg x kg(-1) x min(-1)) or placebo (controls), both for the first 20 minutes of reperfusion. Interleukin-6 and interleukin-8 levels, the adhesion molecules CD41 and CD62 on platelets and CD41 on monocytes and PMN (as markers for coaggregate formation), CD11b on monocytes and PMN, as well as platelet and leukocyte counts were determined in radial artery and coronary sinus blood before cardiopulmonary bypass and during reperfusion (1, 5, 10, 25, and 35 minutes). RESULTS: A reduction of systemic interleukin-6 levels (15.4+/-3.5 pg/mL, 36.7+/-5.9 pg/mL, and 46.8+/-8.0 pg/mL versus 33.4+/-7.7 pg/mL, 76.7+/-13.2 pg/mL, and 106.0+/-26.5 pg/mL, respectively, at 1, 25, and 35 minutes of reperfusion) and interleukin-8 (29.6+/-4.5 pg/mL versus 54.0+/-9.4, pg/mL, resp., at 35 minutes of reperfusion) resulted from treatment with sodium nitroprusside. No intracardiac production of interleukin-8 in sodium nitroprusside-treated patients (-1.1+/-0.4 pg/mL and -2.8+/-2.2 pg/mL, resp., for the coronary sinus-radial artery difference at 5 and 25 minutes of reperfusion) was observed, whereas cardiac production of interleukin-8 was present in controls (2.5+/-1.5 pg/mL and 5.5+/-2.8 pg/mL, resp.). Retention of platelet/leukocyte coaggregates occurred during coronary passage in controls (coronary sinus-radial artery difference for CD41-positive monocytes at 1 and 10 minutes of reperfusion, -16.3%+/-8.5% and -8.8%+/-2.6%, resp.). This was reduced in sodium nitroprusside-treated patients (with 5.8%+/-5.2% and 0.0%+/-3.2%). Retention of platelets in controls (ratio of coronary sinus to radial artery platelet count at 5 and 10 minutes of reperfusion, 88%+/-6% and 91%+/-5%) was compared to washout in treated patients (108%+/-6% and 113%+/-7%). CONCLUSIONS: In patients undergoing routine coronary artery bypass grafting, administration of sodium nitroprusside during early reperfusion alleviates systemic inflammation and the cardiac inflammatory response.     

Results and predictors of early and late outcomes of coronary artery bypass graft surgery in octogenarians

OBJECTIVES: The aim of this study was to investigate early and late outcomes of coronary artery bypass graft (CABG) surgery in a large cohort of octogenarian patients. The results were compared with 2 other age groups including septuagenarians and patients <70 years old. DESIGN: A retrospective study of consecutive patients undergoing CABG surgery using a computerized database based on the New York State Department of Health registry. Data collection was performed prospectively. Setting: A university hospital (single institution). PARTICIPANTS: Two thousand nine hundred eighty-five patients undergoing CABG surgery including 282 (9.4%) octogenarians, 852 (28.6%) septuagenarians, and 1851 (62%) patients younger than 70 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, hospital mortality, morbidity, length of stay, and long-term survival were analyzed. Octogenarians were more likely female and presented significantly more often with comorbidities such as heart failure, an ejection fraction <30%, peripheral vascular disease, and aortic calcification. Crude hospital mortality was 4.6% (n = 13) in octogenarians compared with 2.2% (n = 19) in septuagenarians and 2.4% (n = 44) in patients <70 years old (p = 0.067). Respiratory failure and gastrointestinal complications occurred more frequently in octogenarians. The stroke rate was 1.6% and similar in the 3 age groups. In multivariate logistic regression analysis, age >80 years was not a predictor of hospital mortality. The length of stay was significantly higher in octogenarians compared with nonoctogenarians (16 +/- 24 days v 10 +/- 13 days, p < 0.001). Five-year survival was 63% +/- 4% in octogenarians and was similar to that of an age- and sex-matched general US population. CONCLUSIONS: Excellent results after CABG surgery can be expected in octogenarians, with a minimal increase in postoperative mortality and acceptable postoperative morbidity. Respiratory failure is the main postoperative complication in octogenarians. Recent advances in operative techniques and perioperative management have contributed in improving surgical outcome in these patients compared with historic reports.     

Paradigmenwechsel in der Chirurgie der komplexen thorakalen Aortenerkrankung

One of the main issues in complex thoracic aortic disease, requiring the replacement of the ascending aorta, the entire aortic arch and the descending aorta, is the vast amount of surgery necessary to cure the patient. Though one-stage repair is feasible by a clamshell thoracotomy, the associated surgical trauma and perioperative morbidity limit this approach to younger patients only. Classic surgical repair consist of a two-stage strategy, whereby, in the first step, the ascending aorta and the aortic arch are replaced via a midline sternotomy. In the second step, via a lateral thoracotomy, the descending aorta is replaced. The two stages may sum up to a mortality of 20%; furthermore, the waiting period between the stages is associated with a mortality rate of 10% of its own. Additionally, the two-stage strategy has an inherent limitation, due to the comorbidity and advanced age of the majority of patients. Therefore, the second stage cannot be offered to up to 30% of patients. New developments and improvements in aortic surgery were introduced to overcome these shortcomings and to simplify the surgical repair. The "elephant trunk" principle, introduced by Borst et al. in 1983, was an important step to facilitate surgical repair, but still required the second step. With the introduction of endovascular repair of thoracic aortic disease with stent grafts implanted retrograde via the femoral artery, new therapeutic concepts emerged. In the late 1990s, two Japanese groups reported first trials to stabilize the free-floating "elephant trunk" prosthesis by implantation of nitinol stent grafts into the vascular graft. The applied devices were purely custom-made and nonstandardized. The availability of industrially made and CE-marked stent-graft devices raised the possibility to apply them in open aortic arch surgery. The experience with stent-graft devices implanted antegrade into the descending aorta (Medtronic Talent) was reported first by the Essen and the Vienna group. The experience gained with these devices revealed the limitations of the devices designed for pure retrograde aortic delivery. This required a complete redesign and new construction of the stent graft itself as well as the introducer system. In a preliminary series of 14 patients the required stent-graft properties were presented in detail and resulted in the first industrially manufactured standardized and CE-marked Hybrid stent graft (Essen 1 prosthesis, E-vita Open, Jotec), especially made for antegrade open stent grafting of the descending aorta. This device consists of a stent graft with an integrated Dacron vascular prosthesis, enabling for direct and continuous aortic arch replacement after stent grafting of the descending aorta. From 01/2005 to 03/2006, this hybrid prosthesis was implanted in 16 patients (one aneurysm and 15 aortic dissections). In all cases, the underlying pathology within the thoracic aspect of the aorta could be excluded in a one-stage approach. In case of aortic dissection, thrombosis of the false lumen was detectable by transesophageal echocardiography already at the end of surgery. Though long-term results using this new method are not yet available, the initial promising results postoperatively are encouraging toward true one-stage repair by combining classic aortic surgery with open antegrade stent grafting utilizing the newly designed hybrid prosthesis. While surgical trauma is markedly reduced, this treatment option can be offered to elderly patients as well.     

Origin of shoulder pain after "neck dissection". Importance of the cervical plexus

BACKGROUND: The role of sensitive parts of the cervical plexus for the development of neuropathic pain is not yet clear. Our study investigated the correlation between shoulder pain and cervical plexus damage after different types of neck dissection (ND). MATERIAL AND METHODS: The sensitivity for warm/cold and sharp/blunt was tested in the dermatomes of C2, C3, C4, and the minor occipital nerve. Shoulder pain was measured semiquantitatively by a rating scale. RESULTS: Motion-dependent shoulder pain was observed 6 months postoperatively in 50% after resection and in 29.2% after preservation of these structures. Pain occurred more frequently following radical ND than after modified radical types 1 and 3 ND. DISCUSSION: Our investigations showed that the superficial cervical plexus function is assessable by cutaneous sensitivity tests. The minor occipital nerve seemed to be less affected. Fewer pain symptoms in cases with preserved cervical plexus could be demonstrated. We can conclude that preservation of the superficial cervical plexus is important to diminish postoperative shoulder pain.