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A patient is presented with generalized morphea whose disease completely resolved after combination therapy with extracorporeal photopheresis and broad band UVA treatments.
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Fotoferese , Esclerodermia Localizada/tratamento farmacológico , Resistência a Medicamentos , Feminino , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Indução de RemissãoRESUMO
Local anesthetics which inhibit sodium channels are used for neural blockade during infiltration and locoregional anesthesia. Furthermore lidocaine given intravenously acts on other cellular systems and produces multiple properties, some of which are beneficial during the perioperative period. Indeed, intravenous lidocaine is analgesic, antihyperalgesic, antiinflammatory, and improves the recovery of bowel function after abdominal surgery. As a consequence, lidocaine has been added to postoperative analgesic strategies. This article reviews clinically relevant properties of intravenous lidocaine. Its future perspectives for the prevention of chronicisation of postoperative pain, facilitation of postoperative fast track programs, and prevention of tumoral recurrence are also discussed.
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Anestésicos Locais/uso terapêutico , Lidocaína/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Humanos , Infusões Intravenosas , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Assistência Perioperatória , Resultado do TratamentoRESUMO
An in-vitro model of human bone marrow mesenchymal stem cells (hBM-MSCs) myogenic commitment by synergic effect of a differentiation media coupled with human primary skeletal myoblasts (hSkMs) co-culture was developed adopting both conventional static co-seeding and perfused culture systems. Static co-seeding provided a notable outcome in terms of gene expression with a significant increase of Desmin (141-fold) and Myosin heavy chain II (MYH2, 32-fold) at day 21, clearly detected also by semi-quantitative immunofluorescence. Under perfusion conditions, myogenic induction ability of hSkMs on hBM-MSCs was exerted by paracrine effect with an excellent gene overexpression and immunofluorescence detection of MYH2 protein; furthermore, due to the dynamic cell culture in separate wells, western blot data were acquired confirming a successful cell commitment at day 14. A significant increase of anti-inflammatory cytokine gene expression, including IL-10 and IL-4 (15-fold and 11-fold, respectively) at day 14, with respect to the pro-inflammatory cytokines IL-12A (7-fold at day 21) and IL-1ß (1.4-fold at day 7) was also detected during dynamic culture, confirming the immunomodulatory activity of hBM-MSCs along with commitment events. The present study opens interesting perspectives on the use of dynamic culture based on perfusion as a versatile tool to study myogenic events and paracrine cross-talk compared to the simple co-seeding static culture.
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Células-Tronco Mesenquimais , Mioblastos , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Humanos , Mioblastos/metabolismoRESUMO
In summer 2008, leaf chlorosis, defoliation, exceptional fruit set, twig dieback, and wilt were observed on 4-year-old olive (Olea europea L.) trees cv. Tonda Iblea in a drip-irrigated orchard in eastern Sicily. Rot of fine roots was associated with these symptoms and on ~15% of symptomatic trees rot extended to the crown and basal stem. Trees declined slowly or collapsed suddenly with withered leaves still attached. Incidence of affected trees was ~10%. A fungus identified as Verticillium dahliae Kleb. was isolated from the xylem of main roots and basal stem. An oomycete identified as Phytophthora palmivora (Butler) Butler was isolated from roots and basal trunk bark. Both pathogens were recovered from symptomatic trees with mean frequency of positive isolations per tree of 80 and 30% for V. dahliae and P. palmivora, respectively. To isolate V. dahliae, wood chips were surface disinfested in 0.5% NaOCl for 1 min and plated onto potato dextrose agar (PDA). The fungus was identified on the basis of microsclerotia, verticillate arrangement of phialides on conidiophores, and hyaline single-celled conidia. Ten monoconidial isolates were characterized by PCR using primer pairs INTND2f/INTND2r and DB19/espdef01 (3). Only 824-bp amplicons, diagnostic of the virulent, nondefoliating V. dahliae pathotype, were obtained. P. palmivora was isolated on selective medium (2) and pure cultures were obtained by single-hypha transfers. Colonies grew on PDA between 10 and 35°C (optimum at 27°C). Chlamydospores and elliptical to ovoid, papillate, caducous (mean pedicel length = 5 µm) sporangia (length/breadth ratio of 1.8) were produced on V8 juice agar. All isolates were paired with reference isolates of P. nicotianae and produced gametangia only with isolates of the A2 mating type. PCR amplicons of a representative isolate generated using primers ITS 6 and ITS 4 (1) were sequenced and found to be identical to those of a reference isolate of P. palmivora (GenBank No. AY208126). Pathogenicity of V. dahliae (IMI 397476) and P. palmivora (IMI 397475) was tested on 6-month-old rooted cuttings of olive cv. Tonda Iblea. Ten cuttings were transplanted into pots with steam-sterilized soil and inoculum of P. palmivora (4% vol/vol) produced on wheat kernels. Ten olive cuttings were inoculated with V. dahliae by injecting the stem with 150 µl of a conidial suspension (107 conidia ml-1) and 10 cuttings were stem inoculated with V. dahliae and transplanted into soil infested with P. palmivora. Controls were 10 noninoculated cuttings transplanted into steam-sterilized soil. Pots were kept in a greenhouse (25 ± 3°C) for 4 months. No aerial symptoms were observed on cuttings transplanted into soil infested with P. palmivora. However, root dry weight was reduced by 40% in comparison with the controls. Cuttings inoculated solely with V. dahliae had a 15% reduction in height compared with the controls but only four cuttings wilted. All cuttings inoculated with P. palmivora and V. dahliae wilted, indicating a synergism between the two pathogens. Controls remained healthy. Each pathogen was reisolated solely from inoculated cuttings and both pathogens were reisolated from cuttings with double inoculations. A similar syndrome 'seca' (drying) was reported in Spain (4). References: (1) D. E. L. Cooke et al. Fungal Genet. Biol. 30:17, 2000. (2) H. Masago et al. Phytopathology 67:425, 1977. (3) J. Mercado-Blanco et al. Plant Dis. 87:1487, 2003. (4) M. E. Sánchez-Hernández et al. Eur. J. Plant Pathol. 104:34, 1998.
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Blastic plasmacytoid dendritic cell neoplasm (BPDCN), an extremely rare and aggressive tumor, derives from plasmacytoid dendritic cell precursors and is characterized by CD4 and CD56 positivity accompanied by the expression of isolated myeloid, B- or T-cell lineage markers. Despite the recent introduction of specific targeted therapies, prognosis is still poor with a median overall survival of one year, and allogeneic bone marrow transplantation remains the only curative treatment in eligible patients. In this series, we described two cases of adult BPDCN treated with high dose cytarabine and methotrexate and autologous hematopoietic stem cell transplantation, or fludarabine, cytarabine, and idarubicin achieving the first a complete lasting remission, while the second only a transient improvement in skin lesions.
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Farnesyltransferase inhibitors (FTIs) are a class of oral anti-cancer drugs currently tested in phase I-II clinical trials for treatment of hematological malignancies. The in vitro effects of various FTIs (alpha-hydroxyfarnesylphosphonic acid, manumycin-A and SCH66336) were tested on CD34+ KG1a cell line and in primary acute myeloid leukemia (AML) cells from 64 patients. By cell viability and clonogeneic methylcellulose assays, FTIs showed a significant inhibitory activity in CD34+ KG1a and primary bone marrow (BM) leukemic cells from 56% of AML patients. FTIs also induced activation of caspase-3 and Fas-independent apoptosis, confirmed by the finding that inhibition of caspase-8 was not associated with the rescue of FTI-treated cells. We concluded that other cellular events induced by FTIs may trigger activation of caspase-3 and subsequent apoptosis, but the expression of proapoptotic molecules, as Bcl-2 and Bcl-XL, and antiapoptotic, as Bcl-X(s), were not modified by FTIs. By contrast, expression of inducible nitric oxide synthase (iNOS) was increased in FTI-treated AML cells. Our results suggest a very complex mechanism of action of FTIs that require more studies for a better clinical use of the drugs alone or in combination in the treatment of hematological malignancies.
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T-large granular lymphocyte leukemia (T-LGLL) is a chronic clonal proliferation of effector memory cytotoxic CD3+CD57+CD56- T cells and the current guidelines suggest immunosuppressive therapy as first-line therapy, but the treatment of refractory/relapsed patients is still challenging due to the lack of prospective studies. We describe a series of two refractory/relapsed T-LGLL patients successfully treated with bendamustine, a chemotherapeutic agent largely used for B-cell neoplasms, but poorly investigated for the treatment of T-cell diseases. Complete remission (CR) was achieved in 3 and 6 months, respectively, and maintained for at least 20 months. One patient relapsed after a 20-month CR, but she was responsive to bendamustine therapy again, obtaining a further prolonged CR. Bendamustine as single agent or in combination could be a feasible therapeutic option in refractory/relapsed T-LGLL, especially for elderly patients because of its safety profile.
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Healthy allogeneic donors, who were treated with G-CSF and underwent peripheral blood haematopoietic precursor collection at our Institution, were enrolled in a short- and long-term haematological surveillance protocol for a 5--7--year period. To date, 94 donors have been assessed with a mean follow-up of 30 months (4--84); for 30 subjects, the follow-up is >or=48 months. During G-CSF administration, 23/94 donors showed a significant platelet count decrease from the baseline. Pre-apheresis platelet decrement correlated with the total G-CSF dose administered, baseline platelet level and donor age. Normal platelet counts returned within 4--8 months. PMN and/or lymphocyte lower values were observed in 55/94 donors 2 weeks after G-CSF administration, with mean drops from the baseline of 40 and 36% for PMN and lymphocytes, respectively. The PMN decrease correlated inversely with donor age, as younger donors were more affected than older ones, whereas the lymphocyte decrease correlated directly with the total blood volumes processed in the apheresis courses, in particular for donors subjected to large volume leukaphereses. Long-term observation showed moderate neutrophil reduction (25% count drop from the baseline) in four of the 30 donors observed for four years or more. 14 donors showed persistent, slight lymphocytopenia (mean drop of 13%) until the third year, with recovery in the fourth year of follow-up.
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Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Leucaférese , Vigilância da População , Doadores de Tecidos , Adulto , Fatores Etários , Contagem de Células Sanguíneas , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Contagem de Linfócitos , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Transplante de Células-Tronco de Sangue Periférico , Contagem de Plaquetas , Estudos Prospectivos , Fatores de Tempo , Transplante HomólogoRESUMO
Performing phacoemulsification during a triple corneal procedure has many advantages. Operating in a closed chamber makes surgery easier and safer. In some cases, however, a dense corneal opacity may prevent closed-chamber surgery, necessitating the use of an open-sky technique. In these cases, a temporary corneal graft using a corneal button not suitable for penetrating keratoplasty is proposed to allow phacoemulsification and foldable intraocular lens implantation through a corneal tunnel. The temporary corneal graft is replaced with a permanent graft after these steps are completed. This technique was effective in 3 patients with cataract and dense corneal opacity.
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Catarata/complicações , Opacidade da Córnea/complicações , Transplante de Córnea/métodos , Implante de Lente Intraocular/métodos , Facoemulsificação/métodos , Catarata/terapia , Opacidade da Córnea/cirurgia , HumanosRESUMO
BACKGROUND: Recent findings have indicated the association between APC-resistance and cerebrovascular disease. These reports prompted us to investigate whether resistance to APC could be found in patients suffering from stroke. METHODS: Therefore, we studied APC-resistance in 50 young adults (< or =45 yrs) with a history of ischemic stroke. Eleven out of fifty cerebrovascular subjects showed APC-resistance, while 2 had PC deficiency and 3 PS deficiency. No deficiencies in the anticoagulant protein AT III and in fibrinolytic proteins were found. The family history demonstrated a distribution of APC-resistance compatible with dominant autosomal inheritance. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hypercoagulable states, was also measured in patients and family members of resistant subjects (n = 38). RESULTS: DNA analysis showed factor V R506Q mutation (Leiden mutation) in 11 patients and their relatives with poor response to activated protein C detected by APTT tests. Of 11 investigated subjects with APC-resistance, 9 were heterozygotes and 2, with the lowest APC-ratio values, were homozygotes for factor V mutation. Among 38 relatives, 22 showed a poor response to APC and according to the APC-ratio values, 18 were heterozygotes and 4 homozygotes for FV Leiden mutation. The mutation, in heterozygous form, was also found in 2% of our normal population (n = 100). The plasma concentration of F1+2 was significantly higher both in 11 individuals carrying the FV:Q506 mutation and in 39 patients without APC-resistance compared to that found in the control group. However, the patients with FV:Q506 mutation showed the highest values in F1+2. In the studied family members F1+2 plasma levels were within normal values. CONCLUSIONS: Our findings indicate a possible involvement of APC-resistance in the pathogenesis of cerebral thrombosis in young adults and agree with the hypothesis that individuals with APC-resistance have an imbalance between pro-and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.
Assuntos
Arginina , Fator V/genética , Glutamina , Ataque Isquêmico Transitório/metabolismo , Fragmentos de Peptídeos/metabolismo , Mutação Puntual , Protrombina/metabolismo , Adulto , Resistência a Medicamentos , Feminino , Humanos , Ataque Isquêmico Transitório/genética , Masculino , Anamnese , Proteína C/farmacologia , Fatores de RiscoRESUMO
The aim of the present study was to evaluate the incidence of HIV infection and concomitant pathologies, paying special attention to those involving the respiratory tract, in the Province of Cosenza through a retrospective study of patients monitored by the Divisions of Infectious Diseases and Pneumology with the collaboration of the Virology Unit of the United Hospitals of Cosenza. The results obtained show that there is a lower incidence of AIDS and HIV-correlated respiratory pathologies in this area compared to the rest of Italy but, in spite of this, the authors highlight the need in Calabria for those centres and structures that have been planned but never completely realised (Law 135/90; DPR 7/4/94; etc.) which would enable infected subjects to be identified and the necessary measures for prevention, diagnosis and treatment to be implemented.
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Infecções por HIV/epidemiologia , Doenças Respiratórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Infecções por HIV/complicações , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Respiratórias/complicações , Estudos RetrospectivosRESUMO
The aim of this study was to underline the important role played by respiratory tract pathologies in HIV-infected subjects and to evaluate the incidence of respiratory pathologies in HIV-positive subjects in the province of Cosenza. After examining recently reported data, the authors analyse the patients studied by the Infectious Disease and Pneumology Divisions of the United Hospitals of Cosenza with the collaboration of the Virology Unit over the two-year period 1992-1994. As well as the lower incidence of HIV infection in this area compared to the rest of Italy, the paper highlights the reduced percentage of concomitant respiratory pathologies. The authors attempt to interpret the significance of these results.
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Síndrome da Imunodeficiência Adquirida/epidemiologia , Doenças Respiratórias/epidemiologia , Síndrome da Imunodeficiência Adquirida/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Respiratórias/complicações , Tuberculose/complicações , Tuberculose/epidemiologiaRESUMO
Microscopic procedures for therapy of obstructive azoospermia or of vasectomy reversals have resulted in accurate reapproximation of ductal structures. The success of vasovasostomy appears to be influenced by the length of time that has passed since the vasectomy was performed or the obstruction become. Failures of vasovasostomy may be attributed to anastomotic stenosis, sperm antibodies, epididymal dysfunction, or an unrecognized epididymal tubule blowout with subsequent obstruction. The latter condition should by suspected when, at the time of the initial vasovasostomy, there is lack of fluid containing spermatozoa in the cut end of the testicular portion of the vas. Chronic intratubular pressure may cause an epididymal blowout, with subsequent spermatic granuloma and obstruction in the epididymal tubule, that may also be related to a congenital disorder or a postinflammatory condition. Spermatozoa gain maturation and the capacity for motility as they move from the caput to the cauda of the epididymis as possible. Microsurgery allows direct microtubular anastomosis between the epididymal tubule and the cut end of the vas. Some conditions are not amenable to conventional surgical techniques, such obstructed azoospermia due to congenital bilateral absence of the vas deferens or to severe damage to the reproductive ducts. To treat these patients surgeons have devised reservoirs (artificial spermatoceles) to collect spermatozoa to be used for artificial insemination. An alternative treatment method for obstructed azoospermia is to obtain sperm from the epididymis with the use of an operating microscope. Although sperm have been obtained the poor sperm motility requires either in vitro fertilization or GIFT. The technique looks promising, although improved techniques to enhance the motility of the collected sperm will ultimately yield better results.
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Epididimo/cirurgia , Infertilidade Masculina/cirurgia , Microcirurgia , Oligospermia/etiologia , Oligospermia/cirurgia , Ducto Deferente/cirurgia , Vasovasostomia , Feminino , Fertilização in vitro , Transferência Intrafalopiana de Gameta , Humanos , Infertilidade Masculina/etiologia , Masculino , Motilidade dos EspermatozoidesRESUMO
The authors analyze problems inherent to the treatment of spine tumors (in particular surgical indications) especially with regard to metastases. The purpose of treatment must be that of improving the quality of life and, perhaps, prognosis. In this sense it is hoped that when indications exist surgical treatment will be as timely and radical as possible.
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Condrossarcoma/cirurgia , Linfoma não Hodgkin/cirurgia , Mieloma Múltiplo/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cordoma/cirurgia , Feminino , Hemangioma/cirurgia , Doença de Hodgkin/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoma Osteoide/cirurgia , Prognóstico , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/secundário , Tomografia Computadorizada por Raios XRESUMO
Hypocellular or hypoplastic myelodysplastic syndromes (HMDS) are a distinct subgroup accounting for 10-15% of all MDS patients, that are characterized by the presence of bone marrow (BM) hypocellularity, various degree of dysmyelopoiesis and sometimes abnormal karyotype. Laboratory and clinical evidence suggest that HMDS share several immune-mediated pathogenic mechanisms with acquired idiopathic aplastic anemia (AA). Different immune-mediated mechanisms have been documented in the damage of marrow hematopoietic progenitors occurring in HMDS; they include oligoclonal expansion of cytotoxic T lymphocytes (CTLs), polyclonal expansion of various subtypes of T helper lymphocytes, overexpression of FAS-L and of the TNF-related apoptosis-inducing ligand (TRAIL), underexpression of Flice-like inhibitory protein long isoform (FLIPL) in marrow cells as well as higher release of Th1 cytokines, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). It has also been documented that some HMDS patients have higher frequency of polymorphisms linked both to high production of proinflammatory cytokines such as TNF-α and transforming growth factor-ß and to the inhibition of T-cell mediated immune responses such as interleukin-10, further suggesting that immune-mediated mechanisms similar to those seen in AA patients may also operate in HMDS. Clinically, the strongest evidence for immune-mediated hematopoietic suppression in some HMDS is the response to immunosuppression including mainly cyclosporine, anti-thymocyte globulin and/or cyclosporine, or alemtuzumab. Here we review all these immune mechanisms as well as the influence of this deranged cellular and humoral immunologic mileau on the initiation and possible progression of MDS. All these observations are pivotal not only for a better understanding of MDS pathophysiology, but also for their immediate clinical implications, eventually leading to the identification of MDS patients who may benefit from immunosuppression.
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An adult male underwent a bowel transplant for tufting enteropathy, receiving alemtuzumab, tacrolimus, and steroids as immunosuppressants. Five years later, he developed an autoimmune hemolytic anemia (AIHA), anti-IgG positive, with reduced reticulocyte count, leukopenia, and thrombocytopenia with antiplatelet antibodies. After an unsuccessful initial treatment with high dose steroids, reduction in tacrolimus dose, and intravenous immunoglobulin (IVIG), a bone marrow biopsy revealed absence of erythroid maturation with precursor hyperplasia. The patient was switched to sirolimus and received four doses of rituximab plus two courses of plasmapheresis, which decreased his transfusion requirements. After a febrile episode one month later, the AIHA relapsed with corresponding decreases in platelet and leukocyte count: cyclosporine A (CsA) was started with a second course of rituximab and IVIG without response, even though repeat bone marrow biopsy did not reveal morphology correlated to an acquired pure red cell aplasia (APRCA). Considering the similarity in his clinical and laboratory findings to APRCA, alemtuzumab was added (three doses over a week) with CsA followed by steroids. The patient was eventually discharged transfusion-independent, with increasing hemoglobin (Hb) levels and normal platelet and leukocyte count. One year later he is still disease-free with functioning graft.
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Overwhelming post-splenectomy infection (OPSI) is a rare medical emergency, mainly caused by encapsulated bacteria, shortly progressing from a mild flu-like syndrome to a fulminant, potentially fatal, sepsis. The risk of OPSI is higher in children and in patients with underlying benign or malignant hematological disorders. We retrospectively assessed OPSI magnitude in a high risk cohort of 162 adult splenectomized patients with malignant (19%) and non malignant (81%) hematological diseases, over a 25-year period: 59 of them splenectomized after immunization against encapsulated bacteria, and 103, splenectomized in the previous 12-year study, receiving only life-long oral penicillin prophylaxis. The influence of splenectomy on the immune system, as well as the incidence, diagnosis, risk factors, preventive measures and management of OPSI are also outlined. OPSI occurred in 7 patients (4%) with a median age of 37 years at time interval from splenectomy ranging from 10 days to 12 years. All OPSIs occurred in non immunized patients, except one fatal Staphylococcus aureus -mediated OPSI in a patient adequately immunized before splenectomy. Our analysis further provides evidence that OPSI is a lifelong risk and that current immune prophylaxis significantly decreases OPSI development. Improvement in patients' education about long-term risk of OPSI and increased physician awareness to face a potentially lethal medical emergency, according to the current surviving sepsis guidelines, represent mandatory strategies for preventing and managing OPSI appropriately.
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Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) long-term survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and micro-architectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to auto-HSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after auto-HSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soon as abnormalities are detected.
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The efficacy and safety of low dose oral valgancyclovir (VGCV) as cytomegalovirus (CMV) reactivation prophylaxis was retrospectively evaluated in 32 consecutive patients which underwent allogeneic HLA-matched related and unrelated hematopoietic stem cell transplantation (HSCT). Thirty HSCT recipients showed pretransplant CMV seropositivity. Fifteen received a myeloablative conditioning regimen, while seventeen patients received a reduced-intensity conditioning regimen. Twenty-one patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporin A (CsA) and methotrexate (MTX), and the others CsA with MTX and anti-thymocyte globulin. CMV infection was monitored weekly using polymerase chain reaction (PCR). VGCV was administered orally at a dose of 450 mg daily for six months. Six patients developed a positive CMV-PCR on average 56 days after HSCT successfully treated with VGCV at 1800 mg/day, except one who developed fatal gastrointestinal CMV disease. At the time of CMV reactivation, four patients had been affected by grade II-IV acute GVHD and two by an extensive chronic GVHD. No significant specific VGCV-related toxicity was encountered. Seven patients presented hematological toxicity which did not require drug discontinuation. Our data suggest that low dose VGCV is safe and effective as CMV reactivation prophylaxis in allogeneic HSCT recipients. These results require further validation in prospective randomized studies.
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Antivirais/administração & dosagem , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/fisiologia , Ganciclovir/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ativação Viral/efeitos dos fármacos , Adolescente , Adulto , Antivirais/farmacologia , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valganciclovir , Adulto JovemRESUMO
Mucormycosis is an increasingly recognized invasive fungal infection (IFI) in patients with acute myeloid leukemia (AML) and after allogeneic (allo) stem cell transplantation (HSCT); it is mainly due to the severe and prolonged neutropenia related to high-dose chemotherapy. In such patients, the lung is the most frequently involved site in mucormycosis. Since rapidly progressive dissemination may occur after pulmonary mucormycosis in hematologic malignancies, early diagnosis and prompt initiation of an effective antifungal therapy is mandatory for a successful outcome. We report the case of a young AML patient who developed, early after the onset of neutropenia in the first induction phase of chemotherapy, a rapidly progressive pulmonary IFI, successfully treated with liposomal Amphotericin-B (LAmB) and then with a limited open toracothomy biopsy, clearly establishing diagnosis of mucormycosis and removing lung infiltrate. Secondary prophylaxis with LamB, applied during both consolidation therapy and myeloablative sibling allogeneic HSCT, was effective to prevent IFI recurrence despite the development of grade I acute graft-versus-host disease (GVHD) and limited chronic GVHD requiring immunosuppressive treatment. Our case report further provide evidence that the combined surgical and LAmB therapy is an effective and safe choice for the management of pulmonary mucormycosis in hematological immunocompromised patients.