Emergency reversal of vitamin-K antagonists related over-anticoagulation: case report and brief overview on the role of prothrombin complex concentrate.

Oral anticoagulation is a widely used treatment and atrial fibrillation (AF) is the most frequent indication. We review the therapeutic options on an important clinical challenge: rapid reversal anticoagulation in the setting of an urgent invasive procedure. We report a case of a 71-year-old man treated with warfarin who was over-anticoagulated when presented to the emergency department for syncope due to severe bradiarrhythmia and needed temporary pacing. Intravenous infusion of vitamin-k was not adequate for rapid reversal over anticoagulation whereas the administration of a Prothrombin Complex Concentrate (PCC) was able to quickly reverse anticoagulant activity and allowed the performance of an urgent invasive procedure without hemorrhagic complication. The aim of this paper is to draw attention to possible therapeutic strategies to reduce the risk of bleeding related to over-anticoagulation with vitamin-K antagonists (VKAs) in case of urgent invasive procedure, emphasizing the role of PCC in keeping with national and international guidelines.

The Impact of Workplace Violence on Headache and Sleep Problems in Nurses.

Workplace violence (WV) is a significant occupational hazard for nurses. Previous studies have shown that WV has a reciprocal relationship with occupational stress. Headaches and sleep problems are early neuropsychological signs of distress. This cross-sectional study aims to ascertain the frequency of physical or verbal assaults on nurses and to study the association of WV with headaches and sleep problems. During their regular medical examination in the workplace, 550 nurses and nursing assistants (105 males, 19.1%; mean age 48.02 ± 9.98 years) were asked to fill in a standardized questionnaire containing the Violent Incident Form (VIF) concerning the episodes of violence experienced, the Headache Impact Test (HIT-6) regarding headaches, and the Pittsburgh Sleep Quality Inventory (PSQI) on sleep quality. Occupational stress was measured using the Effort/Reward Imbalance questionnaire (ERI). Physical and non-physical violence experienced in the previous year was reported by 7.5% and 17.5% of workers, respectively. In the univariate logistic regression models, the workers who experienced violence had an increased risk of headaches and sleep problems. After adjusting for sex, age, job type, and ERI, the relationship between physical violence and headaches remained significant (adjusted odds ratio aOR = 2.25; confidence interval CI95% = 1.11; 4.57). All forms of WV were significantly associated with poor sleep in a multivariate logistic regression model adjusted for sex, age, job type, and ERI (aOR = 2.35 CI95% = 1.44; 3.85). WV was also associated with the impact of headaches and with sleep quality. WV prevention may reduce the frequency of lasting psychoneurological symptoms, such as headaches and poor sleep quality, that interfere with the ability to work.

Appropriateness of fresh-frozen plasma usage in hospital settings: a meta-analysis of the impact of organizational interventions.

BACKGROUND: Transfusions of fresh-frozen plasma (FFP) are a worldwide ever-growing practice. The most advanced health care organizations, to guarantee high-quality standards of interventions and safe procedures, should disseminate scientific evidence for promoting the appropriateness of transfusions and reducing avoidable risks. STUDY DESIGN AND METHODS: We carried out a systematic review of scientific literature searching for studies focused on the implementation of different strategy of organizational interventions aimed at improving clinicians' practice. RESULTS: Of 915 studies, 10 articles were included in our meta-analysis of risk of inappropriate transfusion after the implementation of an organizational intervention. The risk ratio of inappropriate transfusions before organizational interventions was 2.02 (95% confidence interval, 1.44-2.84) compared with after interventions. CONCLUSION: The organizational interventions showed a positive impact on the reduction of rates of inappropriate FFP transfusion episodes.

Autologous bone marrow mononuclear cell transplantation in patients undergoing coronary artery bypass grafting.

BACKGROUND: Recent studies have shown that autologous bone marrow mononuclear cell (aBM-MNC) transplantation can be effectively performed in human beings either by the coronary route or by endoventricular injections. However, scanty data are available for patients undergoing coronary artery bypass grafting (CABG). Accordingly, the aim of this study was to evaluate the feasibility and safety of aBM-MNC transplantation in patients with recent myocardial infarction undergoing CABG. METHODS AND RESULTS: The study population included 36 consecutive patients with recent myocardial infarction (< 6 months) undergoing CABG. Eighteen patients (17 men, mean age 64 years) underwent CABG plus aBM-MNC transplantation, whereas 18 subjects undergoing conventional CABG (17 men, mean age 67 years) served as control subjects. Cell transplantation was performed by direct injections in the border zone of the recently infarcted area. An average number of 292 +/- 232 x 10(6) aBM-MNCs was injected in each patient. When compared with control subjects, transplanted patients showed higher values of troponin I peak after CABG (median values of 1.65 ng/mL vs 0.64 ng/mL, P < .001). No major transplant-related adverse event could be detected. During follow-up, transplanted patients had an improvement in left ventricular ejection fraction (from 0.46 to 0.51, P < .05) and wall motion score index (from 1.71 to 1.42, P < .01). The incidence of arrhythmias immediately after CABG and during follow-up was similar in the 2 groups. CONCLUSIONS: Our data support the idea that direct injection of aBM-MNCs in the myocardium during CABG is feasible and safe. Larger studies are needed to assess the efficacy of such an approach in patients undergoing CABG.

Drug treatment in the development of mismatch repair defective acute leukemia and myelodysplastic syndrome.

DNA from therapy-related acute leukemia/myelodysplastic syndrome cases (tAL/MDS) from the GIMEMA [Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto] Archive was examined for the microsatellite instability (MSI(+)) phenotype that is diagnostic for defective DNA mismatch repair. More than 60% (16/25) of tAL/MDS cases were MSI(+) in contrast to <4% (0/28) of de novo cases. hMLH1 gene silencing was rare and evidence of promoter methylation was found in less than one-third of the MSI(+) cases. Among the GIMEMA patients who had been treated for breast cancer there was an apparent trend towards early onset primary breast disease. This suggests that there might be common predisposing factors for breast cancer and tAL/MDS. There were also three examples of mutations in the MRE11 gene among the 25 tAL/MDS cases suggesting that defective recombinational DNA repair may promote the development of secondary malignancy. MSI(+) tAL/MDS was significantly associated with previous chemotherapy and the frequency of MSI(+) among radiotherapy patients was considerably lower. In view of the established relationship between drug resistance and mismatch repair defects, we suggest that selection for therapeutic drug resistance may contribute to the incidence of MSI(+) tAL/MDS.

The treatment of acute lymphoblastic leukaemia in the elderly.

Acute lymphoblastic leukaemia (ALL) is rare in patients over 60 years of age, but because of the ageing of population in western countries, it could become an increasing problem in the coming years. Until now, only a few studies on the treatment of ALL in these patients have been published, with discouraging results. In fact, while in adult patients with ALL complete remission rates are about 90%, with a median overall survival time of 2 years, for elderly patients (> 60 years) the remission rate is below 70%, with a median overall survival of 7 months. Here we review the results of the literature, both in retrospective series and in prospective studies, concentrating on characteristics and treatment of elderly ALL patients, summarizing which factors have a prognostic relevance, and which are the therapeutic options in the treatment of this disease. Altogether, data on 514 patients with ALL > 55 years have been reported in the literature in 12 reports from 1990 to 2001.

Filamentous fungi infection in patients with myelodysplastic syndrome. A report of twelve cases.

In this report we analyse the risk factors, the clinical characteristics and outcome of patients with myelodysplastic syndrome (MDS) who developed an Invasive Fungi Infection (IFI). This was a multicentric study involving 14 Italian Haematological Divisions during a 10-year period whose object was to identify the characteristics of patients with this infection. The study recorded 391 consecutive documented IFI, 12 of which (3%) occurred in MDS patients, from 5 of the participating centres. The primary localization of infection was lung in 10 cases and skin and paranasal sinus in 1 case each. Ten patients died at the end of follow up. The death was mainly attributable to IFI progression in nine of them. The factors that appeared related to an unfavourable outcome were intensive chemotherapy within 30 days before IFI diagnosis, presence of multiple localization at chest X-ray in patients with isolated pulmonary IFI and multiple sites of infection.

Invasive fungal infection in patients with myelodysplastic syndrome: a report of twelve cases.

In this report we analyse the risk factors, clinical characteristics and outcome of patients with myelodysplastic syndrome (MDS) who developed a invasive fungal infection (IFI). This was a multicentric study involving 14 Italian Haematological Divisions during a 10-year-period whose object was to identify the characteristics of patients with this infection. The study recorded 391 consecutive documented IF, 12 of which (3%) occurred in MDS patients from five of the participating centres. The primary localisation of infection was the lung in 10 cases and skin and paranasal sinus in one case each. Ten patients died at the end of the follow up. The death was mainly attributable to IFI progression in nine of them. The factors which appeared related to an unfavourable outcome were intensive chemotherapy within 30 days before IFI diagnosis, presence of multiple localisation at chest X-ray in patients with isolated pulmonary IFI and multiple sites of infection.

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome after bupropion treatment for smoking cessation.

Bupropion hydrochloride is an effective drug for people who want stop smoking, and its use has recently increased in many countries. The main side effects of this drug are related to its dopaminergic activity and are dose dependent. To date, no cases of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) have been reported in literature. Here we describe a case of a woman who developed a sporadic form of TTP-HUS during a treatment with bupropion for smoking cessation, successfully treated with plasma ex-change therapy. The authors wish to make readers aware of bupropion as a possible cause of this potentially lethal disease.

Comparison of real-time PCR, conventional PCR, and galactomannan antigen detection by enzyme-linked immunosorbent assay using bronchoalveolar lavage fluid samples from hematology patients for diagnosis of invasive pulmonary aspergillosis.

An iCycler iQ real-time PCR assay targeting 18S rRNA Aspergillus-specific sequences was developed for the diagnosis of invasive pulmonary aspergillosis (IPA). Positive findings were obtained for 18 of 20 (90%) bronchoalveolar lavage (BAL) fluid specimens from patients with probable or confirmed IPA and were obtained for none of the 24 BAL samples from patients with no clinical evidence of aspergillosis. These results were concordant with those of a nested PCR assay, which detected 90% of the patients with IPA, while galactomannan ELISA revealed positivity for 100% of these patients, suggesting that combined use of methods might improve the diagnosis of IPA.

Chronic disseminated candidiasis in patients with hematologic malignancies. Clinical features and outcome of 29 episodes.

BACKGROUND AND OBJECTIVES: To evaluate the characteristics of patients affected by hematologic malignancies who developed a chronic disseminated candidiasis (CDC), and to ascertain the factors that influenced the outcome, in a retrospective study conducted between January 1990 and December 2000, in 4 Hematology Divisions. DESIGN AND METHODS: CDC was diagnosed by clinical features combined with radiological and/or histologic and/or microbiological data. RESULTS: Twenty-eight patients (male/female 14/14; average age 42 years, range 12-67) developed a CDC. Twenty had acute myeloid leukemia, 5 had acute lymphocytic leukemia and 3 had non-Hodgkin's lymphoma. All patients received chemotherapy, including cytarabine for 21 of them (75%). Before the infection, 22 patients (79%) were neutropenic (absolute neutrophil count < 0.5 x 10(9)/L) for an average of 20 days (8-36), but at CDC diagnosis only 3 patients (11%) were neutropenic. Twenty-two patients (75%) received antifungal prophylaxis for an average of 15 days (10-60). Before diagnosis of CDC, 9 patients (32%) had a candidemia. The sites compromised by CDC were: liver in 27 patients (96%) and/or spleen in 11 patients (38%). Ten patients had other organs involved: lung in 6 patients (21%), kidney in 4 patients (14%), other sites 2 patients (7%). Abdominal ultrasonography was positive in 96% of patients (27/28), and abdominal computed tomography-scan was positive in 100% of cases in which it was performed (21/21). Liver biopsy was positive in 10/15 patients (67%). The main signs and symptoms were: fever 86%, abdominal pain 54%, diarrhea 32%, tenderness 25%, vomiting 25%, jaundice 29%, dysphagia 7%. Among chemical analyses, the most sensitive test was alkaline phosphatase, with a 3-5-fold increase in 24 patients (86%); an increase of liver transaminases and g-glutamyl transferase was observed in less than 50% of patients. By 30 days after diagnosis 4 patients had died, 1 from infection, and 3 progression of the hematologic malignancy without signs of active CDC. Within 3 months from diagnosis 14 out of the remaining 24 patients (58%) received further chemotherapy: in particular, 2 patients underwent transplantation procedures. INTERPRETATION AND CONCLUSIONS: In our experience CDC is not a fatal complication of patients with hematologic malignancy, on the contrary to that observed for other fungal infections (i.e. aspergillosis, candidemia), characterized by a higher mortality rate. The major problem of this fungal complication is correlated to the delay in the following treatment for the hematologic malignancy with a high risk of progression of malignancy.

Negative prognostic value of glutathione S-transferase (GSTM1 and GSTT1) deletions in adult acute myeloid leukemia.

Glutathione S-transferases (GSTs) are enzymes involved in the detoxification of several environmental mutagens, carcinogens, and anticancer drugs. GST polymorphisms resulting in decreased enzymatic activity have been associated with several types of solid tumors. We determined the prognostic significance of the deletion of 2 GST subfamilies genes, M1 and T1, in patients with acute myeloid leukemia (AML). Using polymerase chain reactions, we analyzed the GSTM1 and GSTT1 genotype in 106 patients with AML (median age, 60.5 years; range, 19-76 years). The relevance of GSTM1 and GSTT1 homozygous deletions was studied with respect to patient characteristics, response to therapy, and survival. Homozygous deletions resulting in null genotypes at the GSTM1 and GSTT1 loci were detected in 45 (42%) and 30 (28%) patients, respectively. The double-null genotype was present in 19 patients (18%). GST deletions predicted poor response to chemotherapy (P =.04) and shorter survival (P =.04). The presence of at least one GST deletion proved to be an independent prognostic risk factor for response to induction treatment and overall survival in a multivariate analysis including age and karyotype (P =.02). GST genotyping was of particular prognostic value in the cytogenetically defined intermediate-risk group (P =.003). In conclusion, individuals with GSTM1 or GSTT1 deletions (or deletions of both) may have an enhanced resistance to chemotherapy and a shorter survival.

Pneumocystis carinii pneumonia in patients with malignant haematological diseases: 10 years' experience of infection in GIMEMA centres.

A retrospective survey was conducted over a 10-year period (1990-99) among 52 haematology divisions in order to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating haematological diseases. The study included 55 patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia, eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four with chronic lymphocytic leukaemia, four with multiple myeloma, three with myelodysplastic syndrome, two with myelofibrosis and one with thalassemia) who developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve patients (22%) developed PCP despite protective isolation in a laminar airflow room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non-productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia was present in 39 patients (71%). Chest radiography or computerized tomography showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12 patients (22%), and alveolar-interstitial infiltrates in nine patients (16%). Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18 patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients at autopsy. All patients except one started a specific treatment (52 patients trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed that prolonged steroid treatment (P < 0.006) and a radiological picture of diffuse lung involvement (P < 0.003) were negative diagnostic factors.

Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: the GIMEMA experience.

We analyzed the clinicobiological features and treatment outcome of a series of acute promyelocytic leukemias (APLs) occurring as a second tumor (APL-st's, n = 51) and compared these with a large group of de novo APL cases (n = 641), both observed by the Italian cooperative group GIMEMA. In the APL-st group, 37 patients had received radiotherapy and/or chemotherapy for their primary malignancy (PM), while 14 had been treated by surgery alone. Compared with de novo APL patients, APL-st patients were characterized by a predominance of females (P <.003), higher median age (P <.05), and worse performance status (P <.005). The median time elapsed between PM and APL-st was 36 months, with a longer latency for patients treated with surgery alone. No significant differences were found with regard to karyotypic lesions or type of promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha) fusion in the 2 cohorts. A high prevalence of PMs of the reproductive system was observed among the female APL-st population (24 [71%] of 34 patients in this group had suffered from breast, uterine, or ovarian cancer). Thirty-one APL-st and 641 de novo APL patients received homogeneous APL therapy according to the all-trans retinoic acid (ATRA) and idarubicin regimen (the AIDA regimen). The complete remission (CR), 4-year event-free survival (EFS), and 4-year overall survival (OS) rates were 97% and 93%, 65% and 68%, and 85% and 78% in the APL-st and de novo APL groups, respectively. In spite of important clinical differences (older age and poorer performance status), the APL-st group responded as well as the de novo APL group to upfront ATRA plus chemotherapy, probably reflecting genetic similarity.