Cytokine profile of autologous platelet-derived eye drops in patients with ocular chronic graft-versus-host disease.

Ocular chronic GVHD is efficaciously treated with autologous platelet-derived eye drops. We investigated the cytokine content of eye drops produced using a non-gelified lysate obtained from autologous platelet-rich plasma in six patients with ocular GVHD. In both the responding (n = 4) and the resistant (n = 2) patients, the eye drops were significantly enriched with various growth factors, in amounts proportional with the platelet counts. In contrast, chemokine ligand and interleukin levels were similar to those of plasma. The non-responding patients showed the highest levels of chemokine (C-X-C motif) ligand (CXCL)10. These findings provide possible explanations for beneficial or detrimental effects of eye drops.

Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party.

BACKGROUND: The best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy. PATIENTS AND METHODS: Twenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide. RESULTS: An overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3-4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long-term results were achieved in patients who received stem-cell transplantation after bortezomib induction. CONCLUSION: Bortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival.

Characterization of biofilm-forming cyanobacteria for biomass and lipid production.

AIMS: This work reports on one of the first attempts to use biofilm-forming cyanobacteria for biomass and lipid production. METHODS AND RESULTS: Three isolates of filamentous cyanobacteria were obtained from biofilms at different Italian sites and characterized by a polyphasic approach, involving microscopic observations, ecology and genetic diversity (studying the 16S rRNA gene). The isolates were grown in batch systems and in a semi-continuous flow incubator, specifically designed for biofilms development. Culture system affected biomass and lipid production, but did not influence the fatty acid profile. The composition of fatty acids was mainly palmitic acid (>50%) and less amounts of other saturated and monounsaturated fatty acids. Only two isolates contained two polyunsaturated fatty acids. CONCLUSIONS: Data obtained from the flow-lane incubator system would support a more economical and sustainable use of the benthic micro-organisms for biomass production. The produced lipids contained fatty acids suitable for a high-quality biodiesel production, showing high proportions of saturated and monounsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Data seem promising when taking into account the savings in cost and time derived from easy procedures for biomass harvesting, especially when being able to obtain the co-production of other valuable by-products.

High intraoperative blood product requirements in liver transplantation: risk factors and impact on the outcome.

OBJECTIVE: Liver transplantation (LT) is associated with a significant bleeding and the high transfusion requirements (HTR) negatively affect the outcome of LT patients. Our primary aim was to identify potential predictors of intraoperative transfusion requirements. Secondarily, we investigated, the effect of transfusion requirements on different clinical outcomes, including short-term morbidity and mortality. PATIENTS AND METHODS: Data collected in 219 adult LT from a deceased donor, grouped according to HTR (defined as the need of 5 or more red blood cell units), were compared. RESULTS: We found that previous portal vein thromboses (p=0.0156), hemoglobin (Hb) (p<0.0001), International Normalized Ratio (INR) (p=0.0010) at transplant and veno-venous by-pass (p=0.0048) independently predicted HTR. HTR was always associated with poorer outcomes, including higher simplified acute physiology II score at Intensive Care Unit admission (p=0.0005), higher rates of pulmonary infections (p=0.0015) and early rejection (p=0.0176), longer requirement of mechanical ventilation, (p<0.0001), more frequent need for hemodialysis after transplantation (p=0.0036), overall survival (p=0.0010) and rate of day-90 survival (p=0.0016). CONCLUSIONS: This study identified specific risk factors for HTR and confirmed the negative impact exerted by HTR on clinical outcomes, including recipient survival. Prospective investigations are worth to assess whether correcting pre-transplant Hb and INR levels may effectively reduce blood product need and improve prognosis.

Primary plasma cell leukemia: a retrospective multicenter study of 73 patients.

BACKGROUND: Epidemiological and clinical information on primary plasma cell leukemia (pPCL) are rarely reported. The aims are to evaluate the clinical features, prognostic factors, and efficacy of treatments in pPCL. PATIENTS AND METHODS: A multicenter retrospective cohort study was carried out from January 2000 to December 2008 in 26 Italian hematology divisions. A total of 128 cases of plasma cell leukemia were collected, and 73 of them (57%) were classified as primary (male/female 43/30). RESULTS: Sixty-four patients had at least 1 sign of end-organ damage and 10 had extramedullary localization. One patient died early; of the remaining patients, 36 (50%) received anthracycline-based regimens as first-line therapy, 17 (24%) single alkylating agents, and 30 (42%) bortezomib or thalidomide as additional (n = 11) or unique treatments (n = 19). Twenty-three patients (31%) underwent autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT). The median overall survival (OS) was 12.6 months; complete or partial response was achieved in 22 (30%) and 18 patients (25%), respectively; the median duration of response (DOR) was 16.4 months. HSCT patients had a longer OS and DOR (median 38.1 and 25.8 months, respectively) compared with nontransplanted patients (9.1 and 7.3 months, respectively, P < 0.001). OS was influenced by nonresponse to treatment, hypoalbuminemia, and HSCT. DOR was favorably influenced only by HSCT. CONCLUSIONS: pPCL is an aggressive disease with a poor prognosis and a low response rate to conventional therapy. HSCT is effective, increasing OS and DOR by 69% and 88%, respectively. The use of bortezomib and thalidomide may improve outcomes.

A very early and acute renal impairment due to polyomavirus allograft nephropathy.

Polyomavirus-associated nephropathy (PVAN) has become an important cause of graft loss in the last few years. The typical course of PVAN is characterized by an asymptomatic period of viruria followed, within weeks, by the development of viremia in the context of stable renal function. The persistence of viral replication characterized by high viremia, leads to parenchymal injuries and causes the development, within months, of PVAN that could lead to deterioration in graft function and graft loss. We reported, in a patient who received a renal transplant, an unusual presentation of PVAN characterized by the development of acute renal failurte earlier than would be expected after transplantation, where the histological presentation alone could be confused with an acute rejection. We underline the importance of the association of histological findings with the viral load in urine and blood and with ancillary techniques such as immunohistochemistry and polymerase chain reaction (PCR) in situ for virus detection. We also want to emphasize that decoy cells and PCR for BK virus DNA research could be considered among the diagnostic tools for possible acute renal failure in kidney transplant.

Efficacy of combined surgery and antifungal therapies for the management of invasive zygomycoses in patients with haematological malignancies.

We report two cases of invasive zygomycoses occurring in severely immunocompromised patients with haematological malignancies that were successfully treated with liposomal amphotericin B and surgical debridement, followed by oral administration of posaconazole. These cases demonstrated that an early instituted, aggressive and combined therapeutic approach results in a recovery from invasive fungal infection, without any relapse of infection, thanks to secondary prophylaxis using posaconazole.

Gemtuzumab ozogamicin, cytosine arabinoside, G-CSF combination (G-AraMy) in the treatment of elderly patients with poor-prognosis acute myeloid leukemia.

BACKGROUND: Gemtuzumab ozogamicin (GO) is effective as single agent in the treatment of acute myeloid leukemia (AML). We evaluated efficacy and safety of a chemotherapy including growth factors, cytarabine, and GO (G-AraMy) in the treatment of poor-prognosis AML in elderly patients. PATIENTS AND METHODS: In three Italian hematology departments from September 2003 to September 2006, 53 elderly patients [median age 69 years (range 65-77)] with untreated or primary refractory/relapsed AML were enrolled on the combination G-AraMy administered according to two consecutive schedules (G-AraMy1 and G-AraMy2), with intensified consolidation in the second. Twenty-three of 53 patients had a secondary acute myeloid leukemia (sAML). RESULTS: The overall response rate was 57%. The most common adverse event was myelosuppression. Seven patients died in induction (13%). No differences for response rate and toxicity profile were observed between untreated and primary resistant/relapsed patients, de novo AML and sAML, and in the two treatment trials. Median disease-free survival and overall survival were 8 months (range 2-23+) and 9 months (range 2-24+). CONCLUSIONS: G-AraMy therapy may be considered an useful treatment approach for poor-risk elderly AML patients, with a complete remission rate comparable to literature data with reduced side-effects, also in a poor-prognosis population.

Sporadic vascular dementia as clinical presentation of a new missense mutation within exon 7 of NOTCH3 gene.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disease characterized by ischemic stroke with early onset, migraine, seizures, and vascular dementia. CADASIL is associated with mutations within NOCT3 gene, mainly clustered in exons 3 and 4. We report a case of CADASIL presenting progressive subcortical dementia in the sixth decade. Neither family history, nor acute ischemic events were present. MRI findings were typical for CADASIL. NOTCH3 analysis disclosed a new missense mutation within exon 7, leading to the substitution of cysteine 366 with a tryptophan (Cys366Trp). Our finding suggests CADASIL diagnosis must be considered in patients with vascular dementia also in absence of stroke-like events and of family history.

Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne.

BACKGROUND: The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. METHODS: This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). RESULTS: Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). CONCLUSIONS: IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.

Noncontiguous finished genome sequence and description of Bacillus testis strain SIT10 sp. nov.

Bacillus testis strain SIT10 (= CSUR P1492 = DSMZ 101190) is the new type strain collected from stool from a 2-year-old boy from Senegal during a culturomics study. This Gram-positive bacterium is a facultative anaerobic rod and a member of the Bacillaceae family. We describe here the features of this bacterium, together with the complete genome sequence and annotation. The 3 987 349 bp long genome (one chromosome but no plasmid) with 42.8% GC content contains 4005 protein-coding and 171 sRNA genes, including 19 5S rRNA gene, 15 16S rRNA genes and ten 23S rRNA genes.

First detection of insertion sequence element ISPa1328 in the oprD porin gene of an imipenem-resistant Pseudomonas aeruginosa isolate from an idiopathic pulmonary fibrosis patient in Marseille, France.

We report here the first case of a carbapenem-resistant Pseudomonas aeruginosa clinical isolate harboring the insertion sequence (IS) element ISPa1328 in the oprD gene in an idiopathic pulmonary fibrosis patient in France previously treated with imipenem.

Longitudinal changes of brain amino acid content occurring before, during and after epileptic activity.

In cats affected with cortical epileptogenic foci induced by penicillin application to and cobalt implantation into the pericruciate area, the brain amino acids contents were determined in the focus as well as in extrafocal areas. In different groups of animals, brain removal for biochemical determinations was performed at different times before, during and after epilepsy and the values compared to controls. The only amino acid to show a significant change before appearance of spikes in both types of epilepsy was taurine, which decreased. Cobalt epilepsy was accompanied by changes in a larger number of amino acids than penicillin epilepsy: in the former the brain content of taurine, GABA, aspartate, glutamate, serine, threonine, glycine and alanine was altered. The changes were proportional to the severity of epilepsy and more prominent in the focus area. After disappearance of spikes the levels of most amino acids returned to normal except for some amino acids, previously unaffected by penicillin epilepsy, which were decreased. It is proposed that the decrease in brain taurine, occurring before the appearance of penicillin and cobalt epilepsy, could increase the excitability of a certain neuronal population and thus, by potentiating the effects on neurons of penicillin and cobalt, contribute to the initiation of epilepsy.

Occupational Mn parkinsonism: magnetic resonance imaging and clinical patterns following CaNa2-EDTA chelation.

We report a case of occupational parkinsonism due to manganese exposure in which professional exposure has been documented both by the high blood and urinary levels of the metal and by its presence in the materials used. A strong relation was evident among chelating treatment, cessation of exposure and clinical improvement. MRI confirmed the evolution of clinical pattern by means of reduction of heavy metal deposition in basal ganglia. These findings also agree with the few experimental and human studies published. This case study points to the need for an accurate occupational history collection and suggests the possibility of useful chelating therapy with CaNa2EDTA.

Report of a life-threatening arrhythmia after hospital discharge in a liver transplant recipient with previously unknown congenital long QT syndrome.

The long QT syndrome affects heart rhythm by prolonging ventricular repolarisation; it is potentially life-threatening since it can evolve into torsades de pointes (a polymorphic ventricular tachycardia) and/or ventricular fibrillation. The case is presented of a 55-year-old liver transplant recipient with a genetically determined long QT syndrome not detected by the standard preoperative cardiological evaluation. It was mild in the immediate post-operative period but developed into torsades de pointes after discharge, probably as a result of therapy. This case was particularly challenging because the first arrhythmic episodes were short and electocardiographically silent, and thus the related faints were thought to have a neurological basis. When the true cause emerged during a monitored episode of torsades de pointes, electric defibrillation was used to restore sinus rhythm and isoproterenol administered to increase heart rate and thus shorten the prolonged QT interval Long-term control was obtained by means of an implantable intracardiac defibrillator. In orthotopic liver transplant recipients with long QT syndrome, particular attention should be given to post-operative therapy as some routinely used drugs can trigger life-threatening ventricular arrhythmias.

Vla-3 distribution in normal and neoplastic non-lymphoid human tissues.

Using monoclonal antibody (mAb) M-Kid 2 to the alpha 3 beta 1 heterodimer, we have evaluated immunohistochemically the in vivo expression of the Vla-3 integrin in normal and transformed non-lymphoid human tissues. In normal tissues the alpha 3 beta 1 complex displays a polarized distribution at the baso-lateral aspect of most keratinizing and glandular epithelia. In addition the integrin is detected in perineurium, basal lamina of smooth muscular fibers, vascular media, podocytes and Bowman's capsule, myoepithelial cells of the parotid and breast, and in pulmonary alveoli. Neoplastic transformation is associated with qualitative and quantitative changes in expression of this integrin. The loss of polarized distribution often occurs in various malignancies. Furthermore, a significant decrease in expression occurs in 13% of the colon-rectum carcinomas, 75% of the ductal invasive, and 40% of the lobular invasive breast carcinomas. Among the lung malignancies tested, the small cell lung carcinomas (SCLC) were found to be consistently unreactive with mAb M-Kid 2. Analysis of Vla-3 expression in established tumor cell lines demonstrated that the integrin is almost invariably expressed by the plastic adherent cell subpopulations.

Giant aneurysm of the internal carotid bifurcation successfully clipped. Case report and description of postoperative CT scan and MRI modifications.

Surgery of giant internal carotid bifurcation aneurysms (GBICAA) is followed by high postoperative mortality and morbidity rate. One case of GBICAA successfully submitted to clipping at the neck is reported and the modifications of CT Scan and MRI pictures described.

High-performance liquid chromatographic determination of 2-furaldehyde and 5-hydroxymethyl-2-furaldehyde in fruit juices.

A method for the determination of 2-furaldehyde (F) and 5-hydroxymethyl-2-furaldehyde (HMF) in fruit juices by high-performance liquid chromatography (HPLC) is described. The method is based on the formation of the 2,4-dinitrophenylhydrazones of carbonyl compounds and subsequent separation of these derivatives. Derivatization is carried out by utilizing an acidic solution of 2,4-dinitrophenylhydrazine in acetonitrile. Precipitation of the derivatives of carbonyl compounds is thus avoided, and direct injection of the sample into the HPLC system is allowed. The procedure offers a high specificity and a detection limit of the order of 10(-8) mol/L. Recoveries of 95-98% are obtained from apple juice spiked at different levels with both analytes. The reproducibility (mean of six determinations) is +/- 2% for F and +/- 3% for HMF.

Treatment strategies for invasive aspergillosis in neutropenic patients: voriconazole or liposomal amphotericin-B?

The proportion of patients with cancers who develop invasive fungal infections has increased dramatically over the past few decades. Most of these infections are diagnosed in patients with hematological malignancies, mainly in patients with acute myeloid leukemia and those undergoing allogeneic hematopoietic stem cell transplantation. For years deoxycolate amphotericin B has been considered the drug of choice for the treatment of invasive aspergillosis, but it has been outclassed by its lipid formulations and new triazoles (i.e. voriconazole), that produced better response rates; nonetheless recovery from neutropenia remains the most important factor influencing outcome.

Caspofungin for the treatment of candidaemia in patients with haematological malignancies.

This study was prospectively conducted in 11 haematology divisions over a 2-year period to evaluate the efficacy of caspofungin in 24 neutropenic patients with haematological malignancies (HM) and candidaemia. These patients had received chemotherapy for HM and were neutropenic (PNN < 0.5 x 10(9)/L) for a median of 12 days (2-41) before candidaemia. The patients received caspofungin for a median duration of 12 days (range 6-26), obtaining a favourable overall response of 58%. At 30 days, 11 patients had died (46%); candidaemia was responsible for mortality in six patients (25%). These results suggest that treatment of candidaemia with caspofungin in neutropenic HM was efficacious, as it is in non-haematological subgroups.