Desensitization with plasmapheresis and anti-Cd20 for ABO incompatible kidney transplantation from living donor: experience of a single center in Italy.

OBJECTIVE: Blood group incompatibility in kidney transplants from a living donor can be successfully overcome by using various desensitization protocols: intravenous immunoglobulin, plasmapheresis (PP), immunoadsorption, and double filtration PP. PATIENTS AND METHODS: From July 2010 to October 2013, we performed 10 ABO incompatible kidney transplantation (KT) procedures from a living donor. The desensitization protocol was based on rituximab and PP+cytomegalovirus immune globulin. All patients received induction with basiliximab, except 1 case treated with Thymoglobuline® (ATG) for the simultaneous presence of donor-specific antibody. Tacrolimus and mycophenolate mofetil were initiated at the time of desensitization and continued after the transplant. RESULTS: After a mean follow-up of 11.6±10.4 months, all patients are alive with a functioning graft. The mean serum creatinine concentration at 1 month, 3 months, 6 months, and 1 year was 1.48±0.29, 1.47±0.18, 1.47±0.27, and 1.5±0.27 mg/dl. Three episodes of acute cellular rejection occurred in 2 patients. There was only 1 case of BK virus infection, treated with reduction of immunosuppressive therapy. The protocol biopsy specimens at 1, 3, and 6 months were C4d positive in the absence of acute rejection. CONCLUSIONS: Desensitization with rituximab, PP, and anti-cytomegalovirus immune globulin allowed us to perform transplants from living donors to ABO incompatible recipients with excellent results and reduced costs.

[A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs]. / Piccola storia della terapia antireumatica - VI. I farmaci dell'artrite reumatoide.

The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and inflammation, but without any influence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs). This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and leflunomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive ("therapeutic pyramid") or of more aggressive treatment, through the simultaneous use of two or more DMARDs ("combination therapy").

Treatment of symptomatic HyperLp(a)lipoproteinemia with LDL-apheresis: a multicentre study.

LDL-apheresis (LDLa) efficacy in the treatment of symptomatic HyperLp(a)lipoproteinemia -HyperLp(a)- has been studied in a multicentre trial. After 3.1+/-2.7 years of weekly and biweekly treatment, the data from 19 patients (males:12; females:7; aged 53.8+/-9.3 years; mean body mass index: 24.6+/-2.3 Kg/m²) were evaluated. Data were collected using the same questionnaire shared by 5 participating centres. A total of 2331 procedures were performed. A mean of 3593.7+/-800.3 ml of plasma or 8115.3+/-2150.1 ml of blood, depending upon the technique used (H.E.L.P., D.A.LI., Dextransulphate, Lipocollect 200), was regularly treated on average every 10.1+/-2.6 days. Baseline mean Lp(a) levels were 172.3+/-153.8 mg/dL. The mean pre-/post-apheresis Lp(a) levels decreased from 124.5+/-107.2 mg/dL (p<0.001 vs baseline) to 34.2+/-40.6 mg/dL (p<0.001 vs pre-). Baseline mean LDL-cholesterol (LDLC) levels were 152.3+/-74.6 mg/dL. The mean pre-/post-apheresis LDLC levels decreased from 130.4+/-61.1 mg/dL (p<0.004 vs baseline) to 41.2+/-25.1 mg/dL (p<0.001 vs pre-). The hypolipidemic drugs given to the patients during LDLa were: ezetimibe+simvastatin, atorvastatin, rosuvastatin, pravastatin, acipimox, and omega-3 fatty acids. 58% of the patients had arterial hypertension. Cigarette smokers were 5.3%. Alcohol intake was present in 21%. 52.6% were physically active. Patients with coronary artery disease (CAD) submitted to coronary catheterization before LDLa were 95%. In 5.5% (#1) CAD recurred despite treatment with LDLa. 79% were submitted to coronary revascularization before LDLa. CAD was: monovasal in 8 patients (42.1%), bivasal in 5 (26.4%), trivasal in 4 (21%), plurivasal in 2 (10.5%). In 94.5% of the sample the lesions were stable (< 0% deviation) over 3.1+/-2.7 years. 37% had both CAD and extra-coronary artery disease. This multicentre study confirmed that long-term treatment with LDLa was at least able to stabilize CAD in the majority of the individuals with symptomatic HyperLp(a).

Extracorporeal photochemotherapy may improve outcome in children with acute GVHD.

Acute GVHD (aGVHD) is a major cause of morbidity and mortality after unrelated BMT (UBMT). Our purpose was to analyze the role of extracorporeal photochemotherapy (ECP) in controlling grade II-IV aGVHD in children given UBMT. Of 41 consecutive children, 31 developed grade II-IV aGVHD after UBMT: 16 had a good response to steroids (GR group), whereas 15 underwent ECP (ECP group) within 100 days of UBMT. Eligibility criteria for starting ECP were steroid resistance, dependence or viral reactivations. Criteria for judging response to aGVHD treatment were that the resolution of all signs were considered a complete response (CR), at least a 50% improvement was classified as a partial response (PR) and stable or progressive disease was judged as no response (NR). On completing ECP, the CR rate was 73%, whereas the GR group had a CR rate of 56% by day 100. The 2-year overall survival and progression-free survival rates were 57 and 67% in the GR group vs 85 and 87% in the ECP group. Our data seem to suggest that ECP may improve outcome in patients after UBMT. These findings need to be confirmed in a larger population.

The Italian SIdEM registry for apheresis: an overview of the 2005 statistics.

Data collection on apheresis activities in Italy throughout 2005 including techniques, types of blood cell separators, clinical indications and adverse effects was performed by means of a standardized questionnaire. These data provided by 83 Apheresis Units from 16 Italian regions, albeit rough, are sufficiently informative, mainly in comparison with previous surveys on these statistics (1997 and 2000). In 2005 a total number of 204,746 apheresis procedures were carried out, with a clear-cut prevalence of apheresis production (87.7%), performed by 66 out of 83 Apheresis Units (79.5). Lombardy, Veneto and Tuscany were the most active regions for therapeutic apheresis (51.1% of the total national procedures). An increasing number in extracorporeal photochemotherapy as compared to the 2000 national survey (3,386 vs. 704 procedures) is the most striking observation to emerge from the 2005 data collection on therapeutic apheresis in Italy. Adverse effects, predominantly mild ones (i.e., paresthesia due to citrate-induced hypocalcemia), occurred in 0.12% of apheresis production and 6.04 of therapeutic sessions, particularly in the course of peripheral blood stem cell collection (20.79%), as already reported in the 2000 national survey.

[Historical evolution of the concept of fibromyalgia: the main stages]. / Evoluzione storica del concetto di fibromialgia: le tappe principali.

The concept of fibromyalgia is fairly recent, by evolving from previous notions such as muscular rheumatism and fibrositis. In this concise report the main stages leading to the development of the concept of fibromyalgia are sketched out, beginning from the notions of fibrositis nodules, trigger points and myofascial pain, up to the most recent knowledge including this clinical condition in the cluster of central sensitivity syndromes.

[Filippo Civinini (1805-1844) and the discovery of plantar neuroma]. / Filippo Civinini (1805-1844) e la scoperta del neurinoma plantare.

Pathological abnormality (neuroma) related to the painful foot condition commonly called "Morton's metatarsalgia" was first observed in 1835 by Filippo Civinini (1805-1844) of Pistoia, in course of a cadaverous dissection, and clearly described in the anatomic letter entitled "Su un nervoso gangliare rigonfiamento alla pianta del piede" ("On the neural ganglion swelling of the foot sole"). In this study a brief review on the history of Morton's metatarsalgia is carried out, and the importance of Civinini in the discovery of the neuroma of the III intermetatarsal web is underlined.

[Some historical notes on popliteal cysts] / Qualche annotazione storica sopra le cisti poplitee.

Popliteal cysts, more appropriately those involving the gastrocnemio-semimembranous bursa, are traditionally known as "Baker's cysts", since in 1877 the English surgeon William Morrant Baker published a paper on this topic ("On the formation of synovial cysts in the leg in connection with disease of the knee-joint"). As a matter of facts, some authors described popliteal cysts before Baker. In particular, in 1856 a French physician, E.Foucher, performed a clinical and experimental study on 18 patients, focusing on some important aspects on the semeiology and pathophysiology of popliteal cysts. In 1861, Pietro Antivari, a physician from Friuli, a northeastern region of Italy, graduated at the University of Padova by producing an interesting paper on the popliteal cysts ("Dell'idrope delle borse mucose poplitee con tre osservazioni"). In the present historical note we report in full one out of three cases described by Pietro Antivari.

A single institution's experience (1982-1999) with plasma-exchange therapy in patients with fulminant hepatic failure.

Fulminant hepatic failure is a rare, but often fatal complication of acute viral hepatitis. This condition, in absence of orthotopic liver transplantation (OLTx) surgery, is associated with a high mortality rate, despite the improvement of general intensive care. Plasma-exchange (PEx) therapy has been long used to treat FHF, in particular by removing toxic substances and correcting the severe coagulopathy. In this study we describe our experience with PEx treatment of FHF, beginning in 1982. Seventy patients affected with FHF due to various causes (HBV = 40; cryptogenic/non-A, non-E = 15; Amanita phalloides = 8; other = 7) were treated with PEx (altogether 348 sessions). Overall survival rate, comprising patients undergoing OLTx, was 51%, a little higher than what we observed in patients (N = 49) treated solely by PEx, i.e., 41%. The best outcome predictor was FHF aetiology, owing to the good survival rate in patients with Amanita phalloides intoxication and the very poor prognosis of patients suffering from cryptogenic/non-A, non-E FHF. Moreover, the marked increase in prothrombin time and alpha-fetoprotein levels after 48 hours from admission was associated with a good prognosis, whereas the patient's age and coma grade were not clearly predictive of survival. Additionally, lymphocyte subpopulation, resulting in a CD4/CD8 ratio lower than 1.0 along with CD8 activation with HLA-DR strong expression, were associated with a high rate of mortality and morbidity. Our data indicate that PEx therapy can improve survival in patients with sufficient residual capacity of liver regeneration. Moreover, the identification of certain prognostic factors may be useful for the rational planning of therapeutic strategy in FHF.

[Peripheral blood stem cell collection in pediatric oncohematology. Experience with patients weighing less than 15 kg]. / Raccolta di cellule staminali periferiche in oncoematologia pediatrica. Esperienza su soggetti di peso inferiore a 15 kg.

BACKGROUND: Leukapheresis for peripheral blood stem cell collection is increasingly being carried out in pediatric cancer patients. Aim of this study was to report experience of the Padua Apheresis Unit on a series of children weighting < 15 kg who have undergone such an apheresis procedure. METHODS: This retrospective study includes 15 pediatric patients affected with various malignancies (neuroblastoma: 7; acute myelogenous leukemia: 3; rhabdomyosarcoma: 2; PNET: 1; retinoblastoma: 1; Burkitt's lymphoma: 1) collecting peripheral blood stem cells by a Cobe Spectra blood cell separator. Main procedure parameters, including vascular access, leukapheresis duration, blood flow rate, processed blood volumes, side effects, mononuclear and CD34+ cell yields, have been registered. RESULTS: Altogether 22 sessions have been carried out, by processing a mean of 2.8 blood volumes. No leukapheresis related complications have been recorded, such as hypotension, hypocalcemia and hypothermia. Noteworthy, in 4 procedures two or more peripheral venipunctures have been performed to ensure an adequate blood flow. CONCLUSIONS: Leukapheresis for peripheral blood stem cell collection can be safely and efficaciously carried out in pediatric patients, even weighing < 15 kg, on the condition that certain aspects of apheresis practice in children (vascular access, volume shifts, anticoagulation, side effects) are carefully considered.

Changes in HCV viremia following LDL apheresis in a HCV positive patient with familial hypercholesterolemia.

It has been suggested that hepatitis C virus (HCV) can be associated with beta-lipoprotein in human serum. According to this, the LDL receptor could promote endocytosis of such a virus. In the present study, we evaluated the changes in HCV viremia in a HCV positive patient with familial hypercholesterolemia, undergoing both selective (DALI System, Fresenius) and non-selective (plasma exchange) LDL apheresis. HCV-RNA levels did not decrease following selective LDL apheresis, on the contrary showed a random, odd variation pattern (from -35% to +72%). Conversely, plasma exchange steadily induced a drop in HCV viremia (-35/43%), to a lower extent than that of a totally intravascular plasmaprotein, i.e., alpha 2-macroglobulin (-53/54%). These data indicate that beta-lipoprotein may not function as a plasma carrier of HCV, at least in the present case. Moreover, a continuous, quantitatively unforeseeable circulation of HCV virions from the intravascular plasma compartment to other extravascular and intracellular sites, seems to occur during an apheresis session.

Collection of peripheral blood stem cells in pediatric patients: a concise review on technical aspects.

Peripheral blood stem cells (PBSC) are now routinely collected for use as hematopoietic support after high-dose chemotherapy for various malignancies. Nevertheless, few data are still available on PBSC collection in pediatric patients, owing to technical problems associated with the leukapheresis procedure in children. This paper briefly summarizes current knowledge about some technical aspects of pediatric leukapheresis for PBSC collection, according to the review of the literature and our personal experience on 60 procedures performed in 36 children affected with various malignancies. Technical issues include venous access, risk of volume shift due to exceeding extracorporeal circulation, and anticoagulation, that can induce severe side-effects. Moreover, criteria for optimizing the PBSC harvesting procedure in children, in particular the correct timing of leukapheresis, are discussed.

Peripheral blood stem cell collection and transplantation in paediatric malignancies: a monocentric experience.

Thirty-seven patients underwent peripheral blood stem cell (PBSC) collection from May 1994 to May 1997. Twenty-five were males and 12 were females, the median age at collection was 11.5 years (range 1-27.4) and the median weight was 38 kg (range 9-80). As mobilising chemotherapy, cyclophosphamide, etoposide, doxorubicin and cytosine arabinoside were the drugs most frequently used in association with G-CSF for a total of 47 courses. Sixty-one aphereses were performed with a median collection of CD34+ and CFU-GM cells/kg of 3.6 x 10(6) (range 0.6-31.8) and 24.4 x 10(4) (range 0.1-1260), respectively. Minimal residual disease (MRD) was found in five of the 30 investigated aphereses. Twenty-one of the 37 patients underwent high-dose chemotherapy with autologous stem cell rescue: in seven the stem cell source was peripheral blood and bone marrow. The median duration of hospitalization was 18 days for the PBSC group and 23 days for the PBSC/ABMT group. Overall survival was 78.7% at a median follow-up of 18 months (range 2-31) and the DFS was 52% without difference depending on stem cell source. Compared to a historical group of ABMT patients, the PBSC group showed a statistical advantage in terms of neutrophils and platelet engraftment, blood and platelet requirements, and length of hospitalization. PBSC collection is a feasible procedure also in the paediatric setting providing that vascular access is adequate. As already reported, PBSC transplant results in faster engraftment and shorter hospitalization that could allow a better utilization of health financial resources. The question whether the source of stem cells could influence transplant outcome would require a prospective randomised study.

Anti-Hepatitis C Virus Serology in Immune Thrombocytopenia: A Retrospective Analysis in 101 Patients.

Hepatitis C virus (HCV), an RNA virus, is known to be the major cause of post-transfusion non-A, non-B hepatitis. HCV can induce several expressions of autoimmunity, including both serological abnormalities and clinical disorders. The relationship between the HCV infection and anti-platelet autoimmunity has been occasionally described, but is still far from well-defined. We retrospectively analysed 101 serum specimens, collected between 1988 and 1994, from patients with immune thrombocytopenia (ITP) for the presence of anti-HCV antibodies. Eighty-seven patients were classified as having idiopathic, and 14 secondary ITP (4 systemic lupus erythematosus, 9 non-Hodgkin's lymphoma and 1 Evan's syndrome). Anti-HCV antibodies were determined by second generation tests (ELISA + RIBA). A specimen was considered positive for HCV antibodies in the presence of ELISA reactivity (sample optical density/cut-off > 1.00) accompanied by RIBA reactivity to at least one HCV specific antigen. 20 sera (20%) were positive, with a prevalence higher in secondary than in idiopathic ITP (43% vs. 16%, p < 0.05). No differences were found between anti-HCV positive and negative patients regarding gender, platelet count, platelet associated immunoglobulins, hepatitis B virus serology and liver enzyme profile. On the contrary, mean age was higher in the HCV positive vs HCV negative ones (58±18SD vs. 44±20yrs, p < 0.01), in keeping with the increasing prevalence of HCV infection with ageing. HCV positive patients, showed a poor response to treatment (platelet count lower than 50,000/µl after conventional medical therapy for immune thrombocytopenia) compared to anti-HCV negative ones, (50% versus 7.3%, p < 0.001). When we excluded patients who were exposed to risk factors for HCV infection after ITP diagnosis and before the serum collection, the prevalence of anti-HCV antibodies was not very different (17.6%) from that found in the series as a whole (19.8%). Our results seem to indicate that HCV infection may play a role in triggering several cases ITP, and moreover might constitute a negative prognostic factor for therapy response.

Atypical hypergammaglobulinaemia D syndrome with amyloidosis: an overlap with familial Mediterranean fever?

A case of hypergammaglobulinaemia D and periodic fever syndrome, developing an amyloidosis-related nephrotic syndrome, is reported. Since such a complication represents a typical feature of another disease characterized by recurrent febrile attacks, i.e., familial Mediterranean fever, an overlap syndrome between these two rare clinical disorders can be suggested.

HLA expression in type II mixed cryoglobulinemia and chronic hepatitis C virus.

OBJECTIVE: Hepatitis C virus infection is closely associated not only with hepatic damage, but also with mixed cryoglobulinemia (MC) and other autoimmune and lymphoproliferative disorders. Because HCV is both hepatotropic and lymphotropic, the aim of this study was to investigate whether the genetic background may influence the clinical pattern seen in different patients. METHOD: Two groups of patients with HCV infection were studied: 16 with type II MC and 18 with chronic active hepatitis (CAH). 120 bone marrow donors were considered as the control group. In all patients HLA-A-B-C antigens were evaluated using the microlymphocytoxicity technique, and HLA-DR by the PCR-SSP method. RESULTS: The frequency of the HLA antigens expressed was not precisely defined in the two groups. However, the HLA-B51 and B35 antigens, which are often correlated with autoimmune disorders, were highly expressed in the MC patients (31.2%) compared to the controls (6.9%) and to the CAH group (11%). Moreover, HLA-A9 with its split A24 were present in 50% of the MC patients. More interesting was the expression of the HLA-DR7 antigen, which was found only in the CAH group, suggesting that it may influence the specific liver involvement in HCV infections. CONCLUSION: These findings indicate that the HLA system may play an important role in the clinical manifestations of HCV infection.

AIDS education practices among Massachusetts physicians.

Physicians have a major role to play in the prevention of AIDS transmission. Promotion of health behaviors needs to be expanded beyond the traditional AIDS high risk populations; however, little information is available on the AIDS education practices of physicians. A survey of Massachusetts physicians in four specialty groups, Family Medicine Practitioners, Internists, Obstetricians/Gynecologists and Pediatricians, was conducted to determine the extent of their AIDS education practices. Three hundred and ninety one physicians returned the questionnaire for an overall response rate of 66%. Sixty three percent (63%) of the physicians surveyed educate patients they believe to be at least at moderate risk for AIDS transmission or exposure. However, neither physicians screening for patients' AIDS risk status nor the content of the AIDS education was uniform. Also, very few physicians have received specific training in AIDS education. A number of practice, patient, and physician characteristics were found to be related to educational practices. This study suggests that a more comprehensive screening of patients' participation in AIDS risk behaviors be conducted as part of medical history taking, and that more comprehensive education be provided to those patients determined to be at least at moderate risk for AIDS transmission or exposure.