Patient blood management knowledge and practice among clinicians from seven European university hospitals: a multicentre survey.

BACKGROUND AND OBJECTIVES: The aim of this survey was to evaluate the knowledge about Patient Blood Management (PBM) principles and practices amongst clinicians working in seven European hospitals participating in a European Blood Alliance (EBA) project. MATERIALS AND METHODS: A web-based questionnaire was sent to 4952 clinicians working in medical, surgery and anaesthesiology disciplines. The responses were analysed, and the overall results as well as a comparison between hospitals are presented. RESULTS: A total of 788 responses (16%) were obtained. About 24% of respondents were not aware of a correlation between preoperative anaemia (POA) and perioperative morbidity and mortality. For 22%, treatment of POA was unlikely to favourably influence morbidity and mortality even before surgery with expected blood loss. More than half of clinicians did not routinely treat POA. 29%, when asked which is the best way to treat deficiency anaemia preoperatively, answered that they did not have sufficient knowledge and 5% chose to 'do nothing'. Amongst those who treated POA, 38% proposed red cell transfusion prior to surgery as treatment. Restrictive haemoglobin triggers for red blood cell transfusion, single unit policy and reduction of number and volumes of blood samples for diagnostic purposes were only marginally implemented. CONCLUSION: Overall, the responses indicated poor knowledge about PBM. Processes to diagnose and treat POA were not generally and homogeneously implemented. This survey should provide further impetus to implement programmes to improve knowledge and practice of PBM.

Mechanism of insulin resistance in human liver cirrhosis. Evidence of a combined receptor and postreceptor defect.

Insulin resistance in liver cirrhosis may depend on either reduced sensitivity (receptor defect) and/or reduced response to insulin (postreceptor defect). To clarify the mechanism of such resistance, a [3H]glucose infusion (0.2 microCi/min) was performed for 120 min before and during a euglycemic clamp at approximately 100, 1,000, and 10,000 microU/ml steady state plasma insulin concentration in 18 compensated cirrhotics with portal hypertension and impaired glucose tolerance, and 18 healthy volunteers with no family history of diabetes, matched for sex, age, and weight. Mean fasting plasma insulin (29.2 +/- 3.4 SEM vs. 14.8 +/- 1.1 microU/ml) was significantly higher (P less than 0.001) in cirrhotics, while fasting plasma glucose was much the same in the two groups. Glucose use (milligrams per kilogram per minute) was significantly lower in cirrhotics at all three steady state plasma insulin levels: 3.04 +/- 0.34 vs. 7.72 +/- 0.61 (P less than 0.001) at approximately 100; 6.05 +/- 1.07 vs. 11.45 +/- 1.24 (P less than 0.001) at approximately 1,000; and 11.69 +/- 0.69 vs. 14.13 +/- 0.74 (P less than 0.05) at approximately 10,000 microU/ml. Mean plasma C-peptide was significantly higher in cirrhotics both basally and during the steady states (P less than 0.001); it was completely suppressed at approximately 10,000 microU/ml in controls and only 57.5% of the baseline in cirrhotics. Endogenous glucose production (milligrams per kilogram per minute) was much the same in the two groups in the fasting state and almost entirely suppressed in the controls (0.10 +/- 0.05 vs. 0.48 +/- 0.11, P less than 0.001) at approximately 100 microU/ml; at approximately 1,000 microU/ml a residual glucose production, 0.07 +/- 0.05, was observed in the cirrhotics only. In addition, insulin binding and 3-ortho-methyl-glucose transport were studied in vitro in six cirrhotics and six controls. Insulin binding to circulating monocytes and isolated adipocytes was significantly lower (P less than 0.025) in cirrhotics in all insulin concentration studies. Glucose transport values on isolated adipocytes were significantly lower in cirrhotics both basally (P less than 0.001) and at maximal insulin concentration (P less than 0.05). These results suggest that insulin resistance in human cirrhosis is more dependent on depressed peripheral glucose use than on increased endogenous glucose production, and that a combined receptor and postreceptor defect in insulin action on target cells seems to be present.

An in vivo and in vitro study of the mechanism of prednisone-induced insulin resistance in healthy subjects.

Prednisone-induced insulin resistance may depend on either reduced sensitivity (receptor defect) or reduced response to insulin (postreceptor defect). To clarify the mechanism of prednisone-induced insulin resistance, a [3H]glucose infusion (1 microCi/min) was performed for 120 min before and during a euglycemic clamp repeated at approximately 100, approximately 1,000, and approximately 10,000 microU/ml steady state plasma insulin concentration in 10 healthy, normal weight subjects, aged 35 +/- 7 yr. Each test was repeated after 7-d administration of placebo or prednisone (15 plus 15 mg/d per subject), in a randomized sequence with an interval of 1 mo between the two tests. Mean fasting blood glucose (89.5 +/- 2.1 vs. 83.7 +/- 1.9 mg/dl) and mean fasting plasma insulin values (17.8 +/- 1.2 vs. 14.3 +/- 0.8 microU/ml) were significantly higher (P less than 0.01) after prednisone. The insulin sensitivity index (glucose metabolic clearance rate in ml/kg per min) was significantly lower (P less than 0.001) after prednisone at all three steady state plasma insulin levels: 2.8 +/- 0.3 vs. 7.4 +/- 1.1 at approximately 100 microU/ml; 6.0 +/- 0.5 vs. 12.2 +/- 1.1 at approximately 1,000 microU/ml; 7.4 +/- 0.6 vs. 14.4 +/- 0.5 at approximately 10,000 microU/ml. Fasting glucose production (in mg/kg per min) was significantly higher after prednisone: 3.7 +/- 0.2 vs. 2.9 +/- 0.2, P less than 0.001. Suppression of glucose production at steady state plasma insulin level of approximately 100 microU/ml was less after prednisone (1.01 +/- 0.35 vs. 0.14 +/- 0.13, NS), and total at approximately 1,000 and approximately 10,000 microU/ml after both prednisone and placebo. The metabolic kinetic parameters of insulin after prednisone were not significantly different from those after placebo. In addition, insulin binding and 3-ortho-methyl-glucose transport were studied in vitro on fat cells from 16 normal-weight surgical candidates aged 40 +/- 8 yr (10 treated with placebo and 6 with prednisone as above). No significant difference was observed with regard to specific insulin binding (tested with 1 ng/ml hormone only), whereas significant transport differences were noted at the basal level (0.40 +/- 0.10 vs. 0.54 +/- 0.12 pmol/10(5) cells, P less than 0.05), and at increasing concentrations up to the maximum stimulation values (5 ng/ml): 0.59 +/- 0.04 vs. 0.92 +/- 0.12 pmol/10(5) cells, P less than 0.005. These results suggest that (a) administration of an anti-inflammatory dose of prednisone for 7 d induces insulin resistance in man; (b) this is more dependent on depressed peripheral glucose utilization than on increased endogenous production; (c) total insulin binding on isolated adipocytes is not significantly affected; (d) insulin resistance is primarily the outcome of postreceptor defect (impaired glucose transport).

Genetic, immunologic, and environmental heterogeneity of IDDM. Incidence and 12-mo follow-up of an Italian population.

The 1-yr incidence of insulin-dependent diabetes mellitus (IDDM) in a population of the Piedmont and Aosta Valley area of Italy was recorded. Anti-virus antibodies (e.g., Coxsackie B1-6, mumps, cytomegalovirus), islet cell antibodies (ICAs), and HLA-A, -B, -C, and -DR were determined in 74 IDDM patients (38 males, 36 females) and in controls. Total IDDM incidence was 5.0/100,000, and the incidence for those less than 20 yr of age was 11.6/100,000. Anti-virus antibody frequency was not different in IDDM patients and controls. ICAs were present in 58% of IDDM patients at onset and in 30% after 12 mo, and complement-fixing ICAs were found in 39 and 17%, respectively. IDDM was significantly and positively associated with DR3/DR4 and negatively associated with DR2 and DR5. ICA frequency was significantly higher in DR3/DR4 heterozygote patients than in patients without DR3 and DR4. These results suggest that in this IDDM population viral etiology is not evident, ICAs offer only a partial pathogenetic explanation, and genetic and immunologic heterogeneity is evident.

Angiotensin I-converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an italian population.

To evaluate the role of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in the progression of immunoglobulin A glomerulonephritis (IgA-GN), genotype distribution in 81 biopsy-proven cases of IgA-GN was studied. A logistic regression model showed that the risk for homozygous DD was not significantly elevated in patients with IgA-GN compared with healthy subjects (odds ratio = 1.16; confidence interval [CI], 0.4 to 3.3). However, the 5-year (78% v 90%) and 10-year (52% v 82%) renal survival rates for 47 patients with serum creatine (Cr) levels of 1.5 mg/dL or less at biopsy was significantly less in DD patients (n = 18; chi2 = 5.41; P = 0.02). The hazard ratio (HR) for DD (multivariate analysis from Cox proportional model after adjustment for known factors of progression, such as hypertension [HPT] and proteinuria [PTO]) was 3.07 (CI, 1.1 to 9.4). The HR for heavy PTO was 6.1 (CI, 1.9 to 19). The association of DD genotype with progression was even more striking when patients with other risk factors (heavy proteinuria) were excluded, as shown by DD-related risk in the absence (HR = 3.6; CI, 1.1 to 12) and presence (HR = 2; CI, 0.4 to 10) of PTO. The risk ratio was further increased by the coexistence of DD + PTO (HR = 9.16; CI, 1.8 to 15.7). Furthermore, in a cross-sectional study among patients with IgA-GN, a logistic regression model showed that the risk for homozygous DD was greater, although not at a statistically significant level in the end-stage renal failure subgroup compared with the normal renal function subgroup (odds ratio = 3.16; CI, 0.7 to 13.7) after adjustment by sex, age at biopsy, HPT, PTO, and therapy. Last, DD was significantly more frequent in those patients who started hemodialysis at an earlier age (chi2 for trend = 6.81; P = 0.009). Our study further supports that ACE genotype is a risk factor not for the development, but for the worsening of IgA-GN clinical course. However, on the basis of current knowledge, we cannot exclude that I/D polymorphism may simply serve as a prognostic marker, eventually linked with other discrete loci involved in the progression of renal damage.

Pregnancy in heart transplant recipients.

The aim of this report is to present data from Italian cardiac transplant centers assessing pregnancy after cardiac transplantation. Our retrospective survey included 10 pregnancies occurring in 7 patients during January 1991 to February 2002. Eight pregnancies were completed successfully and 2 abortions were reported (frequency rate 20%). No complications were observed during pregnancy or after delivery. Of 8 infants studied, 6 (75%) were born at term and 2 (25%) pre-term. One baby presented congenital talipes valgus. Pediatric development was uneventful. The data from the literature and our series show that a multidisciplinary approach is mandatory. The course of pregnancy is usually normal and the maternal and fetal outcomes are usually favorable. Although no fetal malformations have been reported, prolonged follow-up of these infants is required.

Cytotoxic T lymphocyte precursor frequency as a predictor of acute graft-versus-host disease in bone marrow transplantation from HLA-identical siblings.

The measurement of precursor frequencies of donor anti-recipient cytotoxic T lymphocytes (CTL-p) has been shown to predict the incidence and the severity of acute graft-versus-host disease (aGVHD) in unrelated donor bone marrow transplantation (BMT). In HLA-identical sibling BMT, where aGVHD is most likely caused by minor histocompatibility antigen mismatches, this assay did not appear to be sensitive enough to provide similar predictive information. In this study, the CTL-p frequencies and the incidence and severity of aGVHD in 51 onco-hematological patients transplanted from HLA-identical siblings were compared. Sibling donors were selected on the basis of HLA identity using serological typing for HLA-A, B, C antigens, whereas HLA-DRB was tested by molecular analysis. Sibling identity was also confirmed by DNA heteroduplex analyses. Fifteen out of 21 (71%) patients with high precursor frequency (>1:100 x 10(3)) and 12 out of 30 (40%) with low precursor frequency (<1:100 x 10(3)) experienced clinically significant (II-IV) aGVHD. A significant correlation (P = 0.04) between CTL-p frequency and severe aGVHD was demonstrated. Moreover there was a positive trend for a high frequency response according to an increasing grade of aGVHD, which was statistically significant (P = 0.04). In our experience the CTL-p assay is a helpful predictive test for aGVHD in HLA-identical sibling BMT, indicating high risk patients possibly requiring additional prophylaxis.

Insulin resistance in the aged: a quantitative evaluation of in vivo insulin sensitivity and in vitro glucose transport.

It has recently been made clear that reduced sensitivity to exogenous insulin can be demonstrated in the course of aging. This phenomenon has been further investigated with the aid of sophisticated techniques, such as the euglycemic clamp, which, when coupled with the measurement of hepatic glucose production, showed that "impaired tissue sensitivity to insulin is the primary factor responsible for the decrease of glucose tolerance in advancing age." Nevertheless, this study did not establish whether such impairment reflects reduced sensitivity (receptor deficiency) or reduced response (postreceptor or receptor plus postreceptor defect), as shown in other diseases. Evidence in favor of the view that receptor deficiency is responsible can be seen in our observation of an approximately 50% reduction in receptors in a study of insulin binding on isolated human fat cells. Two aspects of this question appeared to require further investigation: tissue sensitivity to receptor-saturating insulin concentration (euglycemic clamp at about 1000 microU/mL plasma insulin), and the glucose transport system coupled to the receptor. A decrease in receptors alone should shift the insulin sensitivity curve to the right, both in vivo (euglycemic clamp) and in vitro (glucose transport), with no reduction of the maximum effect. A solution to this question is proposed in the light of a study conducted on young volunteers and subjects over 65 years old.

Coeliac disease associated with Sjögren's syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism.

Although coeliac disease may occur in patients affected by another immune-mediated disorder, its coexistence with multiple autoimmune diseases is not frequently described. We report here the case of a 45-year-old woman referred to our centre because of diarrhoea and weight loss, who had already received a diagnosis of primary biliary cirrhosis, Sjögren's syndrome and renal tubular acidosis. Following the development of diarrhoea we established the diagnosis of coeliac disease, based on the presence of anti-endomysium antibodies and a compatible duodenal biopsy. Despite gluten withdrawal she went on to develop an autoimmune hyperthyroidism. The patient tested positive for HLA DRB1*03 and DQB1*02. The association is unlikely to be casual and may be explained by autoimmune mechanisms, genetic susceptibility and favouring environmental factors commonly shared by the diseases of our patient.

[Pregnancy after kidney transplantation. Review of the international literature and presentation of personal case reports]. / Gravidanza dopo trapianto di rene. Revisione della letteratura internazionale e presentazione della casistica personale.

BACKGROUND: Advances in surgical techniques and immunosuppression have improved the results in organ transplantation. The quality of life in these patients is good in the most of cases and pregnancy, which means for them to resume a normal life, isn't an exceptional event, specially for kidney transplant recipients. METHODS: Retrospective data regarding pregnancies observed at the Dept. of Nephrology and Dialysis of the S. Giovanni Battista Hospital in Turin, have been collected to value the pregnancy frequency and outcome (complications, miscarriage, therapeutic abortion), the mother follow-up as a function of transplant rejection risk, the newborn conditions, their hematological and immunological situation, and the children follow-up. RESULTS: This study includes 9 pregnancy (6 at term and 3 abortions), observed since 1987 in 6 kidney transplant recipients. Congenital malformations or immunological diseases have not been observed; according to the literature, there was a high frequency of preterm delivery and intrauterine grow retardation. Complications during pregnancy were observed in 5 cases (83.3%). CONCLUSIONS: The study confirms that kidney transplant recipients can carry a pregnancy through and give birth to healthy infants, but these pregnancies are to be regarded as being at high risk and require a multi-disciplinary approach.

["Heart transplantation program" in Piedmont. Results of a 3-year activity]. / "Programma trapianto di cuore" della Regione Piemonte. Risultati dopo tre anni di attività.

Since 1990 the "Heart Transplant Program" has been instituted in the Piemonte Region. Until now the program had regular development according to the number of transplantations and the high quality of clinical results. Sixty heart transplantations has been performed with a 36 month survival close to 80%. Our data demonstrate that after heart transplantation prognosis of end-stage cardiac disease is highly improved either for life expectancy and for quality of life. Our program includes several aspects of scientific research from physiology to clinic, from biochemistry to immunology, from infectivology to pathology, from intensive care to surgery. Several very positive multi disciplinary investigations have been activated.

[The Italian Registry of Bone Marrow Donors: genetic structure and recruitment strategy]. / Il Registro Italiano dei Donatori di Midollo Osseo: struttura genetica e strategie di reclutamento.

The genetic structure of the Italian bone marrow donor population was analysed by estimating the HLA-A, -B and -DR gene and haplotype frequencies for the total population and for the Italian administrative regions. The haplotype frequencies were used to predict the probability of finding HLA-compatible donors for Italian patients depending on the registry size, and the probability of recruiting in the different Italian regions a donor with a new phenotype. The analysis of these probabilities allows us to propose strategies for donors recruitment in order to increase the phenotypic variability of the registry, then its efficiency.

Role of non-HLA genetic polymorphisms in graft-versus-host disease after haematopoietic stem cell transplantation.

Graft-versus-host disease (GvHD) is the main complication after haematopoietic stem cells transplantation (HSCT) and acute forms (aGvHD) occur in 20-40% of cases even after donor (D) and recipient (R) HLA matching, apparently because of D/R minor histocompatibility antigen (mHA) mismatches and cytokine polymorphisms. The genotype of cytokines and mHA of 77 haematological R following HSCT from HLA identical siblings were determined to detect genetic polymorphisms correlated with GvHD. We analysed TNFA (-863 C/A, -857 C/T and G/A at positions -574, -376, -308, -244, -238), IL-10 (-1082 G/A, -819 C/A, -592 C/T), IL-1B (T/C +3953), IL-1RA (VNTR), HA-1 (H/R allele) and CD-31 (C/G at codon 125, A/G at codon 563). Allele frequencies were in Hardy-Weinberg equilibrium and similar to those of 77 healthy controls. We observed positive correlations between a lower risk of clinically significant aGvHD and both the presence of -1082G -819C -592C IL-10 haplotype when both R and D are considered together and the absence of R IL-1RA allele 2. Furthermore, we observed an association between the absence of TNF-A -238 A allele and the risk of extensive chronic GvHD. mHA and cytokines genotyping would thus seem a valid source of information for the prior identification of recipients with a higher risk of aGvHD.

Insulin resistance in human liver cirrhosis is not modified by porto-systemic surgical shunt.

Cirrhosis of the liver is characterized by glucose intolerance and hyperinsulinaemia. It is considered an insulin resistant state with both a receptor and a post-receptor defect of insulin activity. It would appear that reduced hepatic degradation rather than increased B-cell production is responsible for hyperinsulinaemia. The effect of surgical portosystemic shunt on insulin resistance was studied in 18 cirrhotics with impaired glucose tolerance (12 males, 6 females; mean age 46.9 +/- 0.7 years) by measuring: glucose production (3H-glucose infusion), glucose utilisation (euglycaemic clamp at approximately 100, approximately 1000 and approximately 10,000 microU/1), plasma insulin and C-peptide levels, and liver function indices (serum bilirubin, albumin, ALT, GGT) before and 2 months after surgery. Liver sorbitol clearance was also employed to measure variations in the functional liver plasma flow induced by the shunt. No significant changes were noted in: glucose production (1.94 +/- 0.17 SEM vs 1.96 +/- 0.17 mg/kg/min), glucose utilisation (metabolic clearance rate: 3.32 +/- 0.48 vs 3.42 +/- 0.43 at approximately microU/ml; 9.70 +/- 1.0 vs 9.16 +/- 0.9 at approximately 1000 microU/ml; 10.92 +/- 1.1 vs 11.07 +/- 0.8 ml/kg/min at approximately 10 000 microU/ml), fasting plasma insulin, C-peptide and C-peptide/insulin molar ratio (4.66 +/- 0.47 vs 5.50 +/- 0.54), and the liver function indices. By contrast, there was a significant decrease in functional liver plasma flow (813 +/- 34 vs 604 +/- 34 ml/min, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

HLA class II gene frequencies in Italy.

The frequency of HLA alleles at HLA-DR and DQ loci, and that of the related HLA-D specificities, were estimated in the Italian population. 109 healthy unrelated subjects, born in several Italian regions and living in the district of Torino, were studied. DNA typing was achieved by the restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta, DQ alpha and beta genes, hybridizing specific probes with TaqI digested DNAs. The present study allowed to define in more detail the HLA class II polymorphisms in the Italian population.