Splenectomy in Patients with Visceral Leishmaniasis Resistant to Conventional Therapy and Secondary Prophylaxis: A Retrospective Cohort.

Some patients with visceral leishmaniasis (VL), or kala-azar, suffer relapses and low quality of life despite adequate drug therapy, especially those co-infected with HIV. Occasionally, physicians indicate splenectomy, but the benefit of the procedure needs to be analyzed systematically. Therefore, a retrospective open cohort study was conducted in Teresina, Brazil. Inpatients from a reference hospital with relapsing VL who had a rescue splenectomy between 2012 and 2019 after the nationally recommended drug therapy failed were studied. The procedure's risks and benefits were assessed in a limited-resource setting. The primary outcomes were surgical complications, complete blood count, CD4+ cell count, hospitalizations, survival time, and medical complications preceding death. Thirteen adult patients received medical and surgical indications of splenectomy (12 men and one woman). Eleven had HIV infection. Two had early and two had late complications. Four died, all of whom were infected with HIV. An additional HIV-coinfected patient, apart from the cohort, died just before surgery. The death rate after surgery was 13.3 overall and 22.1 per 100 person-years among HIV-infected patients (31% overall and 36%, respectively). The impressive rise of complete blood counts and reduction of blood transfusions and hospitalizations were observed among all patients. Also, a meaningful increase in CD4+ cells in HIV-infected patients was noted. Splenectomy may benefit patients with relapsing VL. However, before performing splenectomy, available combined drug therapy for VL should be tried.

The mobilome of Drosophila incompta, a flower-breeding species: comparison of transposable element landscapes among generalist and specialist flies.

The Drosophila genus is one of the main model organisms in evolutionary studies, including those investigating the role of transposable elements (TE) in genomic evolution both at the nucleotide and chromosome levels. D. incompta is a species with restricted ecology, using Cestrum (Solanaceae) flowers as unique sources for oviposition, feeding and development. In the present study, we deeply characterise the D. incompta mobilome and generate a curated dataset. A total of 277 elements were identified, corresponding to approximately 14% of the genome, and 164 of these elements are new, of which 32.62% are putatively autonomous and 8.9% are transcriptionally active in adult flies. The restricted ecology does not seem to influence the dynamics of TE in this fly, since the proportion and diversity of TEs in its genome are similar to that of other Drosophila species. This result is reinforced by the absence of a clear pattern when comparing the TE landscape between generalist and specialist flies. Using 32 available Drosophila genomes-24 ecologically generalist species and 8 specialist species-no difference was found between their TE landscape patterns. However, differences were found between species of the Sophophora and Drosophila subgenus, indicating there are lineage-specific factors shaping TE landscapes.

High-resolution genomic mapping reveals consistent amplification of the fibroblast growth factor receptor substrate 2 gene in well-differentiated and dedifferentiated liposarcoma.

Well-differentiated liposarcoma (WDLS) is one of the most common malignant mesenchymal tumors and dedifferentiated liposarcoma (DDLS) is a malignant tumor consisting of both WDLS and a transformed nonlipogenic sarcomatous component. Cytogenetically, WDLS is characterized by the presence of ring or giant rod chromosomes containing several amplified genes, including MDM2, TSPAN31, CDK4, and others mainly derived from chromosome bands 12q13-15. However, the 12q13-15 amplicon is large and discontinuous. The focus of this study was to identify novel critical genes that are consistently amplified in primary (nonrecurrent) WDLS and with potential relevance for future targeted therapy. Using a high-resolution (5.0 kb) "single nucleotide polymorphism"/copy number variation microarray to screen the whole genome in a series of primary WDLS, two consistently amplified areas were found on chromosome 12: one region containing the MDM2 and CPM genes, and another region containing the FRS2 gene. Based on these findings, we further validated FRS2 amplification in both WDLS and DDLS. Fluorescence in situ hybridization confirmed FRS2 amplification in all WDLS and DDLS tested (n = 57). Real time PCR showed FRS2 mRNA transcriptional upregulation in WDLS (n = 19) and DDLS (n = 13) but not in lipoma (n = 5) and normal fat (n = 9). Immunoblotting revealed high expression levels of phospho-FRS2 at Y436 and slightly overexpression of total FRS2 protein in liposarcoma but not in normal fat or preadipocytes. Considering the critical role of FRS2 in mediating fibroblast growth factor receptor signaling, our findings indicate that FRS2 signaling should be further investigated as a potential therapeutic target for liposarcoma.

Reticular angiomatoid "malignant" fibrous histiocytoma--a case report with cytogenetics and molecular genetic analyses.

Angiomatoid "malignant" fibrous histiocytoma is a rare sarcoma of low malignant potential that occurs most commonly in the extremities of children and young adults. Herein, we present a case of angiomatoid malignant fibrous histiocytoma with unusual histologic features arising in the mediastinum of an 80-year-old man. The tumor exhibited a reticular growth pattern and myxoid stroma. The tumor cells expressed epithelial membrane antigen and desmin. Cytogenetic analysis revealed the translocation t(2;22)(q33;q12). Molecular genetic analysis confirmed the rearrangement of the EWSR1 locus and the presence of the EWSR1/CREB1 fusion. This report expands the clinicopathologic spectrum of angiomatoid malignant fibrous histiocytoma and underscores the value of integrating morphologic, immunophenotypic, and molecular findings in the identification of its unusual morphologic variants.