Vacuum-assisted wound closure is superior to primary rewiring in patients with deep sternal wound infection.

OBJECTIVE: Deep sternal wound infections are serious complications after cardiac surgery. The aim of the present study is to compare the outcome after vacuum-assisted wound closure to that after primary rewiring with disinfectant irrigation. The study additionally focuses on defining predictors for the failure of primary rewiring and its impact on postoperative outcome. METHODS: Retrospective analysis was performed in 5232 patients who underwent cardiac surgery with a median sternotomy. 192 patients postoperatively developed deep sternal wound infections and were distributed into 2 therapy groups: a vacuum-assisted wound closure (= VAC) group and a primary rewiring (= RW) group, which was subdivided into healing after rewiring (= RW-h) and failure of rewiring (= RW-f). These groups were compared statistically to reveal coincidental pre-, intra- and postoperative parameters. RESULTS: Compared to the VAC group, the RW group showed a poorer outcome, although RW baseline characteristics were apparently beneficial. Primary rewiring failed in 45.8 % of all cases, which led to even worse outcomes. Important predictors for failure of primary rewiring were morbid obesity, diabetes mellitus type II, chronic obstructive pulmonary disease, preoperatively impaired left ventricular function, postoperatively positive blood and wound cultures, bilateral harvesting of internal thoracic arteries and the need for surgical reexploration. CONCLUSIONS: In spite of patients being in a worse condition, vacuum-assisted wound closure therapy resulted in improved outcomes and thus should be preferred to primary rewiring. Moreover we report on predictors which may indicate whether there is a high risk of rewiring failure.

Early reintubation after cardiac operations: impact of nasal continuous positive airway pressure (nCPAP) and noninvasive positive pressure ventilation (NPPV).

BACKGROUND: Due to an increasing number of comorbidities there is still a significant incidence of respiratory failure after primary postoperative extubation in patients who undergo cardiosurgery. We wanted to study whether nCPAP could improve pulmonary oxygen transfer and avoid the necessity for reintubation after cardiac surgery. Additionally, we compared this protocol to noninvasive positive pressure ventilation (NPPV). PATIENTS AND METHODS: Over a period of 3 years we analyzed all patients who were extubated within 12 hours after cardiac surgery, and in whom pulmonary oxygen transfer (PaO2/FIO2) deteriorated without hypercapnia so that all these patients met predefined criteria for reintubation. There were three groups of patients: A = patients required immediate reintubation (n = 125); B = patients had nCPAP with intermittent mask CPAP (n = 264); and C = patients had NPPV (n = 36). RESULTS: 25.8 % of patients in Group B and 22.2 % of patients in Group C were also intubated after a period of CPAP or NPPV. All other patients of Groups B and C could be weaned from these devices (B: 33.4 ± 5.8 hours, C: 26.2 ± 4.2 h; P < 0.05) and were well oxygenated using a face mask at ambient pressures (PaO2/FIO2: B: 136 ± 12, C: 141 ± 12). In Group A, we found a higher mortality (8.8 %) than in Group B (4.2 %) and Group C (5.6 %). The ICU stay and in-hospital stay were significantly prolonged in Group A. The incidence of pulmonary infections (A: 24 %, B: 10.6 %, C: 13.8 %; P < 0.05) and the need for catecholamines were significantly increased in Group A, whereas nCPAP patients suffered significantly more often from impaired sternal wound healing (A: 4.8 %, B: 8.3 %; P < 0.05). CONCLUSIONS: We conclude that reintubation after cardiac operations should be avoided since nCPAP and NPPV are safe and effectively improve arterial oxygenation in the majority of patients with nonhypercapnic oxygenation failure. However, it is of great importance to pay special care to sternal wound complications in these patients.

Heparin-induced thrombocytopenia type II after cardiac surgery: predictors and outcome.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious complication after cardiac surgery. The aim of the present study was to identify pre- and intraoperative predictors for the postoperative occurrence of HIT. The study additionally focused on the impact of HIT on postoperative outcome. METHODS: Retrospective analysis was performed for 5073 patients who had required extracorporeal circulation during cardiac surgery. Patients were divided into 3 groups: 1) patients who had postoperative HIT (HIT+); 2) patients with postoperative thrombocytopenia but without HIT (HIT-); and 3) patients with normal platelet count (C). The groups were statistically compared with regard to pre-, intra- and postoperative parameters. RESULTS: Statistically significant predictors were renal insufficiency, intravenous application of heparin for more than 3 days, previous percutaneous coronary intervention within the last 4 weeks, urgency/emergency operation, combined surgery, prolonged extracorporeal circulation or cross-clamping time, and low cardiac output syndrome. Postoperative HIT was associated with an enhanced risk of renal failure, infectious and thromboembolic complications and in-hospital mortality. CONCLUSION: Postoperative HIT increases morbidity and mortality. The predictors presented in this study can be used to identify patients at risk of developing HIT.

Predictors of postoperative complications in octogenarians undergoing cardiac surgery.

OBJECTIVE: Aim of the study was to clarify the impact of different pre- and perioperative conditions on outcome in octogenarians undergoing cardiac surgery. METHODS: We retrospectively analyzed preoperative risk factors and intraoperative adverse events and studied in-hospital morbidity and mortality in 646 patients > or = 80 years of age (82.5 +/- 3.5 years) and in 6081 younger patients (70.3 +/- 3.4 years) who underwent cardiac surgery between 1/2001 and 12/2006. RESULTS: Preoperatively, octogenarians suffered significantly more from arterial hypertension, renal failure, previous neurological problems, unstable angina and NYHA class IV than younger subjects. The incidence of combined valve and coronary procedures and of urgent operations was also significantly higher in patients > or = 80 years (27.7 % vs. 18.2 %, P < 0.05, and 7.3 % vs. 4.2 %, P < 0.05, respectively). In-hospital mortality was higher (7.4 % vs. 3.7 %, P < 0.05), and average ICU and total in-hospital stay was longer in the older age group. Postoperative complications occurred in 15 % of patients > or = 80 years compared to 7.6 % of patients < or = 79 years ( P < 0.05). NYHA class IV, female sex and preoperative renal failure correlated with perioperative morbidity. Multivariate analysis could identify urgent procedures, redo surgery, mitral valve surgery and prolonged cross-clamping times as predictors of mortality. CONCLUSIONS: Cardiac surgery in octogenarians can be performed with an acceptable risk but an increased mortality and morbidity compared to younger patients. High-risk octogenarians, who require intensive perioperative management, should be identified to reduce the incidence of postoperative complications.

Cardiac valve replacement in patients with end-stage renal failure: impact of prosthesis type on the early postoperative course.

BACKGROUND: It is still unclear whether biological or mechanical valves should be preferred in patients on chronic dialysis therapy. PATIENTS AND METHODS: We retrospectively analyzed data from 104 patients (66.5 +/- 8.6 years) with end-stage renal failure (RF) who underwent aortic or mitral valve replacement between 2002 and 4/2008. Mechanical valves were implanted in 44 (42 %) patients and bioprostheses in 60 (58 %). The two groups were comparable with regard to preoperative data, age and incidence of additional CABG procedures. We studied in-hospital morbidity and mortality, major postoperative complications and length of ICU and hospital stay. Additionally, parameters predicting a poor outcome were analyzed with multivariate regression analysis. RESULTS: The overall hospital mortality was 12.5 % and did not differ between the two groups (mechanical: 13.6 %, biological: 11.7 %, n. s.). In the postoperative course, duration of ventilation and ICU stay were similar, whereas hospital stay was significantly longer for patients with mechanical prostheses (19.5 +/- 5.4 vs. 15.6 +/- 4.1 days, P < 0.05). Mechanical valve patients had a significantly higher rate of postoperative cerebrovascular incidents (18.2 vs. 8.3 %, P < 0.05) and bleeding complications (15.9 vs. 11.7 %, P < 0.05). Reoperation, obesity, left ventricular ejection fraction < 30 % and previous neurological complications were independent predictors of hospital mortality. CONCLUSIONS: Our results demonstrate that in patients with end-stage RF, the use of mechanical valves is associated with a significant risk of complications. Because of the poor overall survival of patients on dialysis, bioprosthesis degeneration will not be a limiting factor. Therefore, preference should be given to biological valves in these patients.

[Intrathoracic lesions in association with germ cell tumor of the testis]. / Bihiläre Lymphome bei nichtseminomatösem Keimzelltumor.

Intrathoracic enlarged lymph nodes in patients with malignant diseases always arouse suspicion of lymphatic metastases. Despite modern diagnostic investigation, surprising findings sometimes emerge. The present case of a young man with intrathoracic lesions in association with a germ-cell tumor of the testis turned out to have sarcoidosis mimicking testicular cancer relapse.

Quality control of endoscopic ultrasound in preoperative staging of esophageal cancer.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is generally established as the most sensitive diagnostic tool for the assessment of locoregional tumor stage in esophageal carcinoma. It therefore has a crucial impact on the decision whether patients should undergo surgery as primary treatment or should receive neoadjuvant therapy. This study retrospectively evaluates the accuracy of EUS in tumor and nodal staging of prospectively evaluated patients with esophageal carcinoma in relation to tumor type, tumor grading, tumor site, and the influence of dilation. PATIENTS AND METHODS: All 214 patients included in the study underwent surgery without neoadjuvant therapy and had tumor-free resection margins with no evidence of distant metastasis. EUS investigations were done at our Department of Interdisciplinary Endoscopy. EUS results were compared with the pathological findings. RESULTS: EUS correctly identified T status in 141 patients (65.9 %). The sensitivity and specificity in relation to T status were 68.1 % and 98.2 % respectively for T1, 40.9 % and 83.4 % for T2, 84.3 % and 64.6 % for T3, and 14.3 % and 98.8 % for T4. The overall diagnostic accuracy of EUS in relation to N status was 64.5 % (n = 138); sensitivity and specificity for the diagnosis of N1 were 93.8 % and 20 %, respectively. Sixty-eight (80 %) of 85 pN0-staged tumors were overstaged as uN1. Dilation had a significant influence on the accuracy of EUS staging in advanced tumors ( P = 0.02), whereas tumor grading impacted on EUS staging in early tumors ( P = 0.01). Tumor site and tumor type did not show any influence. CONCLUSIONS: Endosonographic staging of esophageal carcinoma is still unsatisfactory. An improvement in staging accuracy may be achieved by adding fine-needle aspiration biopsy (FNA) to EUS, because FNA improves N-stage accuracy, but it has no bearing on T-stage accuracy.

Laparoscopic gastric tailoring for huge subcardial gastrointestinal stromal tumor.

BACKGROUND: A 67-year-old woman with a gastrointestinal stromal tumor (GIST) of the stomach presented to our outpatient clinic. Preoperative computed tomographic scans and endoscopic examination revealed a spherical submucosal tumor (7.7 x 6.1 x 6 cm) in the posterior wall of the stomach less than 1cm away from the cardia, on the small curvature side. METHODS: The tumor, which endosonographically had a volume of 282 cm(3), was completely resected by a full-thickness laparoscopic wedge excision without discontinuous gastric resection. The whole procedure was performed using 4 working ports (one 12-mm and three 5-mm ports) and 1 camera port (12 mm). Because the resection margins were tumor free on frozen sections and the distance between the resection margin and cardia was wide enough not to compromise food passage, there was no need for total gastrectomy or upper discontinuous gastric resection. The patient was discharged on the fourth postoperative day after an uneventful clinical course. RESULTS: Histological examination revealed a malignant gastrointestinal stroma tumor of the stomach. The patient was therefore enrolled for Imatinib adjuvant therapy. Careful and long-term follow-up of 21 months showed no signs of local or distant tumor recurrence. However, further follow-up is needed to monitor for signs of possible recurrence or distant metastases. CONCLUSION: The described technique prevented proximal gastric resection and a risk of anastomosis without compromising the food passage and radicality.

Which cases are found and missed by neuroblastoma screening at 1 year? Results from the 1992 to 1995 study in three Federal States of Germany.

PURPOSE: Neuroblastoma screening during the first half-year of life is associated with a two- to three-fold overdiagnosis. Because regression processes seem to be confined to infancy, we investigated whether screening at 1 year would be associated with fewer overdiagnoses, and we investigated the characteristics of thus-detected and not-detected patients. PATIENTS AND METHODS: Thin-layer chromatography was used for semiquantitative assessment of urine samples dried on filter paper and obtained when patients were 10 to 14 months old (sample 1) and 17 to 19 months old (sample 2). Abnormal results were reanalyzed quantitatively from the same specimen by high-performance liquid chromatography and/or gas chromatography-mass spectrometry. RESULTS: A total of 200,054 children of the German federal states Lower Saxony, Northern Rhine-Westphalia, and Bremen were screened from May 1992 to April 1995. Of 229,078 investigated samples (100%), 228,245 (99.6%) were first, 657 (0.3%) were second, and 176 (0.08%) were third urine specimens. The compliance rate was 27.8%, but it continued to increase throughout the study period and in the last year it was 43. 3%. The second screening offered at 18 months was accepted by only 12.1% (24,259) of the children. Thirty children underwent clinical examination, and nine asymptomatic neuroblastoma cases were detected (stage 1, n = 4; stage 2, n = 2; stage 3, n = 2; stage 4, n = 1; detection rate, 1:22,228). The results of 21 tests were false-positive. Ten children with false-negative test results presented 8 to 35 months later with neuroblastoma (stage 1 tumor, n = 1; stage 2, n = 1; stage 3, n = 1; stage 4, n = 7; five of nine tumors were N-myc-amplified tumors). Three children were nonsecretors at the time of diagnosis. Fifty-two patients were "missed" (not screened), and 37 children developed neuroblastoma before the age of screening (early cases). During the same period, a total of 23.6 cases per million children within the screening area and 24.0 cases per million children outside the screening area were diagnosed as neuroblastoma cases (not significant [NS]). In prescreening times in the area of the later screening states, 20.7 cases per million children were found (NS). CONCLUSION: Screening at 1 year of age demonstrated a lower detection rate than earlier screening programs and did not produce a "halo effect." The good prognostic features of early-detected cases and the poor characteristics of not-detected-but-late-presenting cases corresponded to those of the related age groups.

Evaluation of timefurone, a new anti-atherosclerotic drug, for its effects on lipoprotein cholesterol in male SEA Japanese quail and rats.

Timefurone was evaluated in several animal models for cholesterol-lowering and anti-atherosclerotic activity. In normal male rats, a dose-response study with timefurone (3, 10, 30, 50 and 100 mg/kg/day) was conducted for 7 days. Significant activity was observed only at 50 and 100 mg/kg/day, where very low and low density lipoprotein cholesterol [(VLDL + LDL)-C] and total-C levels were reduced (mean 27 and 20%). High density lipoprotein cholesterol (HDL-C) was lowered 24% by the high timefurone dose. Timefurone (10, 20, 50 and 100 mg/kg/day in the diet) was then examined in normocholesterolemic SEA japanese quail. beta-lipoprotein cholesterol (VLDL + LDL)-C was reduced at all doses (mean 58%), while alpha-lipoprotein cholesterol (HDL-C) was elevated by all doses of timefurone (mean 45%). Male weanling rats made moderately hypercholesterolemic represented a 3rd phase of timefurone (2.5, 5, 10, 20, 50, 100 mg/kg/day) testing. After 4 days of drug treatment, marked hypocholesterolemic activity was observed for (VLDL + LDL)-C (mean decrease 49%) and total-C (mean 33%). HDL-C levels were increased with 10 and 100 mg/kg/day doses. Timefurone (25 and 100 mg/kg/day in the diet) also caused a significant reduction in atherosclerotic development in hypercholesterolemic SEA japanese quail. Atherosclerotic involvement (determined by visual assessment of plaque), arterial weight, and arterial cholesterol (total and mg/g artery) were clearly lowered by both doses of timefurone. There was no evidence of significant drug toxicity in any of these experiments. On the basis of these data, timefurone has excellent therapeutic potential and additional study of the drug's hypocholesterolemic and anti-atherosclerotic properties appears warranted.

Activity of ethyl 5-(p-chlorophenoxy)-3-hydroxy-3-methylpentanoate, a new hypocholesterolemic compound, in male rats and SEA Japanese quail.

Ethyl 5-(p-chlorophenoxy)-3-hydroxy-3-methylpentanoate (HMP), a new hypocholesterolemic compound, was evaluated in male rats at dosage levels ranging from 25-800 mg/kg/day and in SEA Japanese quail at approximately 200 mg/kg/day. In the rat, the atherogenic lipoprotein cholesterol, that is, the combination of very low density plus low density lipoprotein cholesterol (VLDL-C + LDL-C), was reduced 20-27% at dosage levels over 100 mg/kg/day, while high density lipoprotein cholesterol (HDL-C) and total serum cholesterol (TSC) were significantly decreased 25-46%, respectively, at all dose levels of HMP. Liver weights with HMP treatment were significantly elevated (11-26%) in the rat. HMP was not active in the SEA Japanese quail, since an initial reduction in artery cholesterol could not be confirmed in subsequent tests.

Hypo-beta-lipoproteinemic agents. 1. Bicyclo[2.2.2]octyloxyaniline and its derivatives.

A new assay for agents which normalize beta-lipoproteins in cholesterol-cholic acid fed rats is described. Both lowering of serum cholesterol and of serum heparin precipitable lipoproteins (HPL) were measured at the end of the treatment period. Compounds which shifted the ratio of the decrease in favor of HPL are considered hypo-beta-lipoproteinemic. p-(1-Bicyclo[2.2.2]octyloxy)aniline and several of its derivatives proved active in this assay. The synthesis of these compounds is described.

Hypobetalipoproteinemic agents. 2. Compounds related to 4-(1-adamantyloxy)aniline.

While the previously used displacement reaction of sodim 1-adamantyl oxide on 4-fluoronitrobenzene was applicable to the preparation of 4-(1-adamantyloxy)aniline and several related compounds, certain derivatives were not easily accessible by this route. Thus the recently reported ortho alkylation of anilines and the dicyclohexylcarbodiimide-promoted coupling of 1-adamantanol with phenols were useful in the preparation of aromatic-substituted derivatives. Furthermore, addition of phenylmagnesium bromide to 1-cyanoadamantane provided entry to the 4-(1-adamantylmethyl)aniline series. 4-(1-Adamantyloxy)aniline (3) is herein reported to be a more potent hypobetalipoproteinemic agent than the previously reported bicyclooctyloxy analogue. Replacement of the oxygen atom of 3 with sulfur (74) or methylene (62), but not nitrogen (71), results in active compounds. In the oxygen series derived from 3, the widest scope of substitution on nitrogen resulting in activity is found. The N-ethoxycarbonyl (5), acetyl (6), methyl (12), ethyl (13), N-methyl-N-(2-hydroxyethyl) (19), N-methyl-N-formyl (22), N,N-dimethyl (26), pyrrolidine (14), and piperidine (15) derivatives are active. Aromatic ring substitution also provided the active 3-chloro (44b), 2-fluoro (41b, 42, and 43), and 2-methylthiomethyl (48) compounds. Thus these active compounds are identified for further development as hypobetalipoproteinemic agents.

Expression and clinical relevance of NY-ESO-1, MAGE-1 and MAGE-3 in neuroblastoma.

Human genes NY-ESO-1, MAGE-1 and MAGE-3 code for antigens which are expressed in malignancies of various histological types but not in normal tissues except testis. These antigens might therefore represent potential targets for specific immunotherapy. We studied the expression of genes NY-ESO-1, MAGE-1 and MAGE-3 in 98 neuroblastoma tumors by reverse transcription-polymerase chain reaction (RT-PCR). MAGE-1 was expressed in 66%, NY-ESO-1 in 36% and MAGE-3 in 33% of the tumors. NY-ESO-1 gene expression was associated with age older than one year (p = 0.017), more differentiated tumor histology (p = 0.044), elevated urinary vanillylmandelic acid (VMA, p = 0.018) and normal serum ferritin levels (p = 0.023). MAGE-1 expression correlated significantly with normal serum ferritin levels (p = 0.009) and absence of MycN amplification (p = 0.007) while MAGE-3 expression was associated with absence of metastasis (p = 0.027). We conclude that approximately 70% of the neuroblastoma tumors express at least one of the genes coding for NY-ESO-1, MAGE-1 or -3, respectively.

Response to the hypobetalipoproteinemic agent adamantyloxyphenyl piperidine in hyperlipemic rats.

The hypobetalipoproteinemic activity of U-41,792 (1-[p-(1-adamantyloxy)-phenyl]-piperidine) is a marked and selective reduction of heparin precipitating lipoproteins (low density plus very low density lipoproteins) in cholesterol-cholic acid induced hypercholesterolemic rats. This activity consists of both a reduction in heparin precipitating lipoproteins (HPL) and an increase in high density lipoproteins that are not precipitated by heparin. The increase in high density lipoproteins is routinely noted by decreases in HPL/cholesterol ratios. The pattern of response following single 100 mg/kg doses of U-418792 was determined. After an I.V. dose was administered in a cottonseed oil emulsion, serum cholesterol levels were reduced, beginning at 8 hr after administration and persisting for 96 hr. Similar results, though delayed somewhat, were obtained after a single oral dose. Activity was accompanied by increases in weight and cholesterol content of livers. After multiple, daily, oral doses, liver weights, total lipids, and cholesterol contents were reduced. Hypobetalipopreteinmeic activity was enhanced by prolonged treatments as demonstrated by analyses of serum obtained weekly throughout 7 wk.

High volume screening procedures for hypobetalipoproteinemic activity in rats.

We describe high volume screening tests for hypobetalipoproteinemic agents in which compounds are administered orally to cholesterol-cholic acid fed (hypercholesterolemic( or normally fed weanling rats for 4 days. In these tests total serum cholesterol levels and heparin precipitating lipoproteins (HPL) are determined by automated analyses interfaced with a computer which eliminates all manual data reduction and provides necessary reports. The hypercholesterolemic rat test detects compounds which specifically reduce HPL (beta and pre beta lipoproteins) causing a decrease in the HPL: cholesterol ratio. Such activity is called hypobetalipoproteinemia. This activity is exhibited by bicyclo (2.2.2)-octyloxyaniline (U-26328) but not by any of the familiar hypocholesterolemic agents including clofibrats, lifibrats, nicotinic acid, probucol, triparanol, lentysine, D-throxine or the estrogens estrone and diethylstilbestrol.

Biological activity of a hypobetalipoproteinemic agent.

A new -ind of pharmacologic activity called hypobetalipoproteinemia is described. Iperationally the activity consists of a marked reduction of heparin precipitating lipoproteins (beta and/or pre-beta electrophoretic mobility) in hypercholesterolemic animals with a simultaneous decrease in the heparin precipitating lipoprotein: cholesterol ratio. As determined by ultracentrifugal fractionation of the lipoproteins from hypercholesterolemic rat serum, this activity consists of both a reduction in heparin precipitating lipoproteins and an increase high density lipoproteins that are not precipitated by heparin. Changes in composition were also induced in both lipoprotein fractions. The greatest changes were observed for free and esterified cholesterol, which were markedly reduced in the heparin precipitating lipoproteins and concomitantly increased in the high density lipoproteins. The hypobetalipoproteinemic agent exhibiting this activity is 1-[p-(1'-adamantyloxy) phenyl]-piperidine (U-41792). This agent is active in hypercholesterolemic rats, mice, quail, and pigeons.

Selected animal models for systematic antiatherosclerotic drug development.

We have developed an integrated system for antiatherosclerosis drug development utilizing rats, SEA quail, and cynomolgus monkeys as animal models. In general, the way the system is presently functioning is that thousands of compounds per year are randomly screened for hypobeta- or hyperalphalipoproteinemic activity in rats, and hundreds of compounds per year are screened in SEA quail for antiatherosclerotic and hypocholesterolaric activity. A few selected compounds that have activity in both rats and quail are then tested for lipoprotein modifying activity in cynomolgus monkeys. Nontoxic compounds having very good lipoprotein modifying activity in the monkey will then be recommended for clinical trials in man. We do not anticipate that this battery of testing will guarantee activity in man, but are hoping that it will at least increase the probability for finding a truly effective antiatherosclerotic drug to control the human disease.