Clinical significance of clonality assessment in JAK2V617F-negative essential thrombocythemia

JAK2V617F-negative essential thrombocythemia (ET) is a heterogeneous disease including clonal cases and others without evidence of clonality. However, it is unknown if the detection of myeloid clonality in JAK2V617F-negative ET patients confers a different clinical outcome than those in whom clonal hematopoiesis cannot be demonstrated. The objective of the present study was to evaluate the clinical significance of clonality assessment in patients with JAK2V617F-negative ET. Clonality investigation including mutational status of MPL, TET2, and ASXL1 genes and human androgen receptor (HUMARA) assay was performed in 73 JAK2V617F-negative cases out of 186 subjects consecutively diagnosed with ET in a single institution, at diagnosis or during follow-up. Mutations in MPL, TET2, and ASXL1 were observed in 7, 4, and 2 cases, respectively, whereas clonality by HUMARA assay was demonstrated in 21 out of 46 (46?%) female patients. With a median follow-up of 8?years, death, thrombosis, bleeding, and disease transformation were registered in 7, 10, 8, and 6 patients, respectively. No differences in thrombosis, bleeding or survival were observed according to clonality assessment. The probability of disease transformation at 10?years was higher in patients showing clonal hematopoiesis by presenting mutations in either MPL, TET2, or ASXL1 (64 versus 2?% in patients without mutations, p?相似文献   

Influence of HTLV-1 on the clinical, microbiologic and immunologic presentation of tuberculosis

ABSTRACT: BACKGROUND: HTLV-1 is associated with increased susceptibility to Mycobacterium tuberculosis infection and severity of tuberculosis. Although previous studies have shown that HTLV-1 infected individuals have a low frequency of positive tuberculin skin test (TST) and decreasing in lymphoproliferative responses compared to HTLV-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of M. tuberculosis infection. Therefore the reasons why HTLV-1 infection increases susceptibility to infection and severity of tuberculosis are not understood.The aim of this study was to evaluate how HTLV-1 may influence the clinical, bacteriologic and immunologic presentation of tuberculosis. METHODS: The study prospectively enrolled and followed 13 new cases of tuberculosis associated with HTLV-1 (cases) and 25 patients with tuberculosis without HTLV-1 infection (controls). Clinical findings, bacterial load in the sputum, x-rays, immunological response and death were compared in the two groups. RESULTS: There were no differences in the demographic, clinical and TST response between the two study groups. IFN-gamma and TNF-alpha production was higher in unstimulated cultures of mononuclear cells of case than in control patients (p < 0.01). While there was no difference in IFN-gamma production in PPD stimulated cultures, TNF-alpha levels were lower in cases than in controls (p = 0.01). There was no difference in the bacterial load among the groups but sputum smear microscopy results became negative faster in cases than in controls. Death only occurred in two co-infected patients. CONCLUSION: While the increased susceptibility for tuberculosis infection in HTLV-1 infected subjects may be related to impairment in TNF-alpha production, the severity of tuberculosis in co-infected patients may be due to the enhancement of the Th1 inflammatory response, rather than in their decreased ability to control bacterial growth.     

Developmental trajectories of social cognition from preschool to adolescence

This longitudinal study aims to define the developmental trajectories of social cognition (SC) in a community sample (N = 378) assessed from preschool (3 years old) to preadolescence (12 years old). Parents and teachers reported on a SC measure at ages 5, 10, and 12. We tested the existence of different trajectories and whether they discriminated outcomes in early adolescence. The data were collected from different sources, the children, the parents, and teachers, by means of different methods. Using Growth Mixture Modeling (GMM), we identified three distinct social cognition trajectories: persistently mild difficulties reported by parents and teachers (7.9% of the children), stable low problems reported by parents and increased difficulties reported by teachers (10.5% of the sample), and stable low problems reported by both informants for most of the participants (81.5%). Comparison of the psychological outcomes between classes using regression models showed that the two trajectories including children with any level of problems differ from the normative one as regards their association with psychological problems, daily functioning, and variables, such as aggressive behavior and callousness. The two non-normative trajectories also differ from each other in terms of the personal characteristics of the adolescents included in them. Adolescents in the increasing problematic class in the school have a tougher and more problematic style of social relating, while children with persistent and non-context-dependent difficulties are more anxious. These results might help to better detect and design specific interventions for children with deficits in SC that might respond to different personal characteristics leading to different outcomes.

     

Bilaminar Device of Poly(Lactic‐co‐Glycolic Acid)/Collagen Cultured With Adipose‐Derived Stem Cells for Dermal Regeneration

Several materials are commercially available as substitutes for skin. However, new strategies are needed to improve the treatment of skin wounds. In this study, we developed and characterized a new device consisting of poly(lactic‐co‐glycolic acid) (PLGA) and collagen associated with mesenchymal stem cells derived from human adipose tissue. To develop the bilaminar device, we initially obtained a membrane of PLGA by dissolving the copolymer in chloroform and then produced a collagen type I scaffold by freeze‐drying. The materials were characterized physically by gel permeation chromatography, scanning electron microscopy, and mass loss. Biological activity was assessed by cell proliferation assay. A preliminary study in vivo was performed with a pig model in which tissue regeneration was assessed macroscopically and histologically, the commercial device Integra being used as a control. The PLGA/collagen bilaminar material was porous, hydrolytically degradable, and compatible with skin growth. The polymer complex allowed cell adhesion and proliferation, making it a potentially useful cell carrier. In addition, the transparency of the material allowed monitoring of the lesion when the dressings were changed. Xenogeneic mesenchymal cells cultured on the device (PLGA/collagen/ASC) showed a reduced granulomatous reaction to bovine collagen, down‐regulation of α‐SMA, enhancement in the number of neoformed blood vessels, and collagen organization as compared with normal skin; the device was superior to other materials tested (PLGA/collagen and Integra) in its ability to stimulate the formation of new cutaneous tissue.     

Successful use of “Hour 1” transfer of sperm microinjected oocytes in natural cycles of poor responder women: a prospective randomized controlled pilot study

The aim of the study is to demonstrate the successful use of “Hour 1” transfer of sperm microinjected oocytes in natural cycles of poor responder women. Seventy women were selected from 92 consecutive poor responders undergoing intracytoplasmatic sperm injection (ICSI) in a natural cycle at our Sterility and Assisted Reproduction Unit from September 2009 to July 2013, and randomly distributed in two homogeneous groups: Group A or B. Women in Group A (35) underwent transfer within 1 h after ICSI; Group B (35, control group) underwent transfer 3 days after ICSI. In Group A, seven clinical pregnancy and one miscarriage occurred; in Group B, eight clinical pregnancies and two miscarriages were observed. Pregnancy, miscarriage, term pregnancy and overall live birth rates’ difference between the two groups was not statistically significant (p?>?0.05). Difference between the two groups in terms of timing, type of delivery and newborn birthweight was not observed. Neither ectopic pregnancy nor multiple pregnancies occurred. “Hour 1” uterine transfer of ICSI oocytes, still to be considered with caution because of the relatively low number of observations of the pilot study, deserves further attention on a larger scale, and might be evaluated for clinical and financial effectiveness in other clinical settings.     

Gain of multiple copies of the CBFB gene: a new genetic aberration in a case of granulocytic sarcoma

Granulocytic sarcomas (GS) are tumor masses of immature myeloid cells presenting at an extramedullary site, mainly the skin, bone, and lymph node. They are often associated with acute myeloid leukemia (AML) with monoblastic or myelomonocytic differentiation, including either AML M2 with t(8;21)(q22;q22) or AML M4Eo with inv(16)(p13q22). We present a case diagnosed with GS associated with AML M4 that presented a normal karyotype with conventional cytogenetic analysis. Although the myeloblasts did not show the inv(16)(p13q22) (CBFB/MYH11), a gain of multiple copies of the CBFB gene was detected with fluorescence in situ hybridization analysis. To our knowledge, no cases with this rare genetic anomaly have been previously described.