EuroSCORE predicts mid-term outcome after combined valve and coronary bypass surgery

BACKGROUND AND AIM OF THE STUDY: EuroSCORE is widely used to assess operative risk. Combined cardiac procedures carry increased perioperative mortality, but the influence of preoperative factors on mid-term outcome is not well known for these patients. The study aim was to determine if EuroSCORE risk influences mid-term survival after combined coronary artery bypass grafting (CABG) and valve surgery. METHODS: Follow up (mean 23.7 months) was obtained in 258 consecutive hospital survivors (148 males, 110 females; median age 72.29 years; mean EuroSCORE 7 points) operated on between January 1998 and March 2001. CABG + aortic valve replacement (AVR) was performed in 171 patients, CABG + mitral surgery in 72, and CABG + double valve surgery in 15. Kaplan-Meier estimates were calculated for survival and combined freedom from death and NYHA class III/IV. The Cox regression model was applied to prove the influence of EuroSCORE risk and a number of preoperative and operative variables on mid-term outcome. RESULTS: Thirty patients (11.63%) died during follow up, and 34 (13.17%) were in NYHA class III/IV. Freedom from death and NYHA class III/IV was 89.3%, 74.7% and 55.2% at 12, 24 and 36 months, respectively. The significant predictor for combined death and NYHA class III/IV was EuroSCORE risk (p = 0.0004). In the subgroup of patients with CABG + mitral valve surgery, age was identified as a significant risk factor for death (p = 0.0346), whereas in the subgroup of patients with CABG + AVR EuroSCORE was detected as significant risk factor for combined death and NYHA class III/IV. CONCLUSION: EuroSCORE is an important predictor for poor mid-term outcome after combined CABG and valve surgery.     

An algorithm to screen long-term care residents at risk for accidental falls

BACKGROUND AND AIMS: The process applied to identify fall risks in frail elderly persons remains a matter of debate. We intended to develop a fall screening instrument for clinically defined subgroups of long-term care residents, to be administered by nursing staff. METHODS: Fall risk indicators were selected by multiple logistic regression in three pre-defined subgroups. The first consisted of residents who were not able to transfer, defined as a change from sit-to-stand position, without physical assistance (NAT). The second subgroup comprised residents who were able to transfer, but who had had a recent fall during the last 6 months (AT-F). Residents who were able to transfer but had had no recent fall (AT-NF) were in the third subgroup. The prospective observational study included 472 long-stay residents (mean age 84 years, 79% female) from three community nursing homes, with a follow-up period of 12 months. RESULTS: Fall incidence was highest in the AT-F subgroup: 6066 per 1000 resident years. The risk indicators identified included a positive fall history and restraint use in the NAT group, transfer assistance in the AT-F group, and urinary incontinence and visual impairment in the AT-NF group. CONCLUSIONS: The identification of different risk indicators in the subgroups indicates that specific strategies may be more appropriate to improve the effectiveness of fall prevention in long-term care, than the application of one strategy to all residents. The identification of incontinence, visual impairment, and restraints as risk indicators stresses the need for intervention studies which specifically address these items.     

Beta-blocker treatment of chronic systolic heart failure improves prognosis even in patients meeting one or more exclusion criteria of the MERIT-HF study.

AIMS: Improved prognosis of patients with chronic systolic heart failure by treatment with beta-blockers has been shown in several randomized controlled multicentre trials. However, in clinical practice only a part of heart failure patients meet the inclusion criteria of these trials. The present study evaluates whether reduction of mortality by beta-blockers also can be achieved in patients presenting one or more exclusion criteria of the MERIT-HF trial. METHODS AND RESULTS: From the Ludwigshafen Heart Failure Registry 675 patients with chronic systolic heart failure consecutively enrolled between January 1995 and June 2004 were divided in two groups either meeting the inclusion criteria of the MERIT-HF trial ('trial patients': n = 278, 60% treated with beta-blockers) or not ('non-trial patients': n = 397; 51% treated with beta-blockers). The distribution of the MERIT-HF exclusion criteria in the group of 'non-trial patients' was as follows: acute myocardial infarction 9.6%; systolic blood pressure <100 mmHg 7.5%; chronic obstructive lung disease 33.2%; other serious diseases potentially limiting prognosis 16.9%; acutely performed or planned ICD, bypass surgery, PCI, heart transplantation: 17.1, 15.9, 7.8, and 4.8%, respectively. Median follow-up was 31.3 months (upper/lower quartile 16.3/50.0 months). All-cause mortality was significantly reduced by beta-blocker treatment not only in 'trial patients' (adjusted hazard ratio 0.57, 95% CI 0.38-0.86) but also in 'non-trial patients' (adjusted hazard ratio 0.72, 95% CI 0.53-0.97). CONCLUSION: In clinical practice only the smaller part of the population to be treated for chronic systolic heart failure meets the inclusion criteria of the MERIT-HF study. However, beta-blocker treatment is associated with a significantly reduced long-term mortality even in patients meeting one or more exclusion criteria of the MERIT-HF study.     

Loss of heterozygosity at 11p15 and p53 alterations in malignant gliomas

Purpose: Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with prognostic implications. In the later steps of tumor-progression, deletions on chromosome 11p15 and mutations of the tumor suppressor gene p53 were determined for different malignancies. To elucidate the involvement of 11p15 deletions in the tumorigenesis of malignant gliomas, we analyzed a series of 50 glioblastomas for loss of heterozygosity (LOH). Methods: Paired tissue and blood samples from 50 patients with glioblastoma multiforme were included. Microsatellite markers located on 11p15.1–11p15.5 were used for LOH analysis. Additionally, mutation analysis of the tumor suppressor gene p53 was performed, which might correlate with favorable survival in glioblastomas. Results: The region 11p15.4–5 was deleted heterozygously in 28% of cases representing 15 cM. Twenty-six glioblastomas did not show allelic loss for any locus. Our data revealed close association of LOH 11p15 with p53 mutations, and survival analysis showed a trend indicating better prognosis in glioblastomas characterized by LOH 11p15. Conclusion: In the tumorigenesis of malignant gliomas, p53 mutations and 11p15 deletions seem to indicate a genetic subset of tumors with favorable prognostic value. Received: 13 June 2000 / Accepted: 2 October 2000     

Influence of the needle bore size on platelet count and routine coagulation testing.

The phlebotomy technique, particularly the use of small-bore needles, may influence the reliability of coagulation testing and platelet count. Routine coagulation tests were assayed in blood specimens collected from 22 consecutive patients in three separate, sequential phlebotomies, using butterfly devices with different needle sizes. Test results of samples collected with 23 and 25 G needles were compared with those obtained with the currently recommended 21 G needle. Although both the prothrombin time and activated partial thromboplastin time displayed a trend towards lower values employing the smaller 23 and 25 G needles, results did not differ significantly from the reference 21 G needle specimen, with the exceptions of D-dimer (25 G versus 21 G needle, 186 +/- 70 versus 178 +/- 66/ml, P < 0.01) and platelet count (23 G versus 21 G needle, 246 +/- 55 versus 254 +/- 56 x 10(-3)/l, P < 0.01; 25 G versus 21 G needle, 240 +/- 55 versus 254 +/- 56 x 10(-3)/l, P < 0.01). None of the mean biases recorded for the parameters was clinically meaningful, nor did they exceed the current desirable analytical quality specifications for desirable bias. Results of the present investigation suggest that, when a proper technique is used and within certain limitations, butterfly devices with small-bore needles may be a reliable alternative to draw venous blood for platelet count and coagulation testing.     

Increased renovascular response to angiotensin II in persons genetically predisposed to arterial hypertension disappears after chronic angiotensin-converting enzyme inhibition

OBJECTIVE AND METHODS: Functional changes in the kidneys of healthy men with (FH+) (n = 15) and without (FH-) (n = 15) family history of primary arterial hypertension were examined during administration of low-dose exogenous angiotensin II (A2) (1 ng/kg per min) before and after acute (1 mg intravenous enalaprilat) and chronic (7 days oral enalapril, 30 mg/day) angiotensin-converting enzyme (ACE) inhibition. RESULTS: Before chronic ACE inhibition, A2 increased mean arterial blood pressure (FH+, 8.7 +/- 0.8 mmHg; FH-, 8.9 +/- 0.9 mmHg), plasma immunoreactive A2 (FH+, 21 +/- 2 pg/ml; FH-, 18 +/- 3 pg/ml) and plasma aldosterone (FH+, 64 +/- 7 pg/ml; FH-, 56 +/- 6 pg/ml) to a similar degree in both groups. Chronic ACE inhibition had no impact on A2 blood pressure, plasma A2, or plasma aldosterone effects. A2 significantly increased renal vascular resistance in both groups (FH+, 3956 +/- 462 dyne s cm(-5); FH-, 2219 +/- 550 dyne s cm(-5)), but the effect was more pronounced in FH+ (P = 0.02). Glomerular hemodynamics, estimated by a modified Gomez model, revealed increased afferent and efferent responsiveness to A2 in FH+ subjects. These differences disappeared after chronic ACE inhibition when total, afferent and efferent sensitivities to A2 were similar in both groups. CONCLUSIONS: Systemic blood pressure and plasma aldosterone responses to A2 were similar in men with or without a genetic disposition to primary arterial hypertension. However, our data demonstrate that men with a family history of hypertension have increased renovascular sensitivity to A2, and that chronic ACE inhibition normalizes their sensitivity.     

Rapid suppression of hematopoiesis by standard or pegylated interferon-alpha

BACKGROUND & AIMS: Treatment of chronic hepatitis C with interferon (IFN)-alpha often has hematotoxic effects. We evaluated the effects of acute vs. chronic and standard vs. pegylated IFN-alpha on hematopoiesis. METHODS: We studied hematopoiesis in 46 patients with chronic hepatitis C receiving single high-dose IN-Falpha2b followed by daily dose standard or weekly pegylated IFN before combination antiviral therapy. RESULTS: Single high-dose therapy resulted in a significant drop in hemoglobin (HB), leukocytes, and platelet count. Although platelets, stimulated by a significant increase in thrombopoietin (TPO), and leukocytes recovered quickly, HB remained below baseline for 7 days. Daily standard or weekly pegylated IFN-alpha leads to a more pronounced drop in all 3 lineages with concomitant increases in TPO and erythropoietin (EPO). No difference was observed between standard and pegylated IFN, except for HB, which fell more during pegylated IFN therapy. Consecutive combination antiviral therapy aggravated the anemia but not the drop in leukocytes or thrombocytes. CONCLUSIONS: The drop in all 3 hematopoietic lineages through IFN-alpha treatment, high-dose standard, standard daily dose, or pegylated, is caused by a combination of bone marrow inhibition and probably some other rapid acting mechanisms. Hematopoietic growth factors are increased as a consequence but cannot overcome the bone marrow suppression.     

Accuracy and 'range of uncertainty' of oscillometric blood pressure monitors around the upper arm and the wrist

BACKGROUND: Although they have been marketed widely, few data about the diagnostic accuracy of blood pressure monitors are available. METHODS: Repeated measurements of blood pressures in 85 patients were performed in random sequence with two oscillometric blood pressure monitors around the upper arm (Visomat OZ2) and the wrist (Omron R3( and with a standard sphygmomanometer. The oscillometric blood pressure monitors were validated according to protocols of the British Hypertension Society (BHS) and the American Association for the Advancement of Medical Instrumentation (AAMI). Subsequently, sensitivity and specificity of these monitors for the diagnosis of hypertension or exclusion of the possibility of its presence in a general medical outpatient population were calculated. RESULTS: Sphygmomanometric readings exceeded oscillometric blood pressure measurements by 3.7+/-7.5/4.8+/-5.6 mmHg (systolic/diastolic) for the upper arm and 5.7+/-6.2/6.8+/-6.8 mmHg for the wrist. Deviations occurred in both directions and were higher for blood pressures in the hypertensive range. Oscillometric blood pressure measurements at the upper arm, but not at the wrist, satisfied validation criteria of BHS and AAMI protocols. Optimal sensitivity and specificity for the diagnosis of hypertension, defined as blood pressure > 140/90 mmHg with a standard sphygmomanometer, was achieved with blood pressure limits of 133/82 mmHg for the Visomat OZ and 131/80 mmHg for the Omron R3. CONCLUSIONS: Average sphygmomanometer values exceed oscillometrically measured blood pressure values but individual disagreements cannot be predicted. Measurements at the upper arm are more accurate than are those at the wrist according to the validation protocols of the BHS and AAMI. Additional appraisal of sensitivities and specificities and of a 'range of uncertainty' for the diagnosis of hypertension may allow better judgement of accuracy of individual oscillometric blood pressure measurements.     

Geldanamycin-induced Lyn dissociation from aberrant Hsp90-stabilized cytosolic complex is an early event in apoptotic mechanisms in B-chronic lymphocytic leukemia

Lyn, a tyrosine kinase belonging to the Src family, plays a key role as a switch molecule that couples the B-cell receptor to downstream signaling. In B-CLL cells, Lyn is overexpressed, anomalously present in the cytosol, and displays a high constitutive activity, compared with normal B lymphocytes. The aim of this work was to gain insights into the molecular mechanisms underlying these aberrant properties of Lyn, which have already been demonstrated to be related to defective apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Herein, Lyn is described to be in an active conformation as integral component of an aberrant cytosolic 600-kDa multiprotein complex in B-CLL cells, associated with several proteins, such as Hsp90 through its catalytic domain, and HS1 and SHP-1L through its SH3 domain. In particular, Hsp90 appears tightly bound to cytosolic Lyn (CL), thus stabilizing the aberrant complex and converting individual transient interactions into stable ones. We also demonstrate that treatment of B-CLL cells with geldanamycin, an Hsp90 inhibitor already reported to induce cell death, is capable of dissociating the CL complex in the early phases of apoptosis and thus inactivating CL itself. These data identify the CL complex as a potential target for therapy in B-CLL.