Antibodies against double-stranded DNA and development of polymyositis during treatment with interferon

Alpha interferons have become effective palliative treatments for patients with neuroendocrine tumours such as carcinoids and endocrine pancreatic tumours. However, several reports indicate an increased incidence of both autoantibodies and autoimmune diseases in patients treated with interferon-alpha (IFN-alpha). We studied the development of antibodies against double-stranded DNA (dsDNA) and clinical signs of autoimmune disease in 214 patients with malignant carcinoids or endocrine pancreatic tumours consecutively admitted for treatment with IFN-alpha. Seventeen patients (8%) developed antibodies against dsDNA, predominantly females (12 females and 5 males). One patient had clinical and laboratory signs of polymyositis. Among the other 16 patients, three developed hypothyroidism and in six patients the anti- dsDNA autoantibodies normalized despite continuing therapy. Although a significant number of patients developed autoantibodies against dsDNA, overt autoimmune disease related to these antibodies is a rare event and many patients spontaneously normalize these titres despite continuing IFN-alpha treatment.      

Pityriasis versicolor

Pityriasis versicolor is a common superficial fungal infection of the skin. It is caused by Malassezia spp., which are normal human saprophytes. Under certain conditions, both exogenous and endogenous, the fungus can convert from a yeast to a pathogenic mycelial form. This alteration results in mild inflammation of the skin, and in characteristic clinical and histological changes. The taxonomy of Malassezia spp. has recently been modified to include six obligatorily lipophilic species, all of which can be found on human skin, plus one non-obligatorily lipophilic species, which only rarely colonizes human hosts. LEARNING OBJECTIVES: At the conclusion of this learning activity, participants should be aware of the role of Malassezia in the development of pityriasis versicolor, the clinical and histological changes arising from this dermatosis, and the diagnosis and treatment of this disorder.     

Expanding the spectrum of GLI1-altered mesenchymal tumors—A high-grade uterine sarcoma harboring a novel PAMR1::GLI1 fusion and literature review of GLI1-altered mesenchymal neoplasms of the gynecologic tract

GLI1-altered mesenchymal tumors comprise a group of seemingly unrelated entities, including pericytoma with t(7;12) translocation, plexiform fibromyxoma, gastroblastoma, malignant epithelioid neoplasm with GLI1 rearrangements, and GLI1-amplified mesenchymal neoplasms. Herein, we report a high-grade uterine sarcoma harboring a novel PAMR1::GLI1 fusion and present a literature review of GLI1-altered mesenchymal neoplasms of the gynecologic tract. A 57-year-old female presented with an abdomino-pelvic mass, felt since a decade prior. Magnetic resonance imaging showed a heterogenous myometrial mass extending beyond the serosa. The patient underwent oncologic surgical resection. Gross examination revealed a perforated multi-nodular uterine tumor (21 cm) with a firm white and soft fleshy cut surface, featuring hemorrhage and necrosis. The tumor was morphologically heterogenous, disclosing frankly sarcomatous areas composed of pleomorphic spindle and focally epithelioid cells, intermingled with a component of low-grade spindle cells arranged in fascicles. There was a rich vascular network and zones of necrosis with peripheral amianthoid-like collagen plaques. Lymphovascular invasion and metastasis to lymph nodes and omentum were present. The tumor was immunopositive for CD10 and cyclinD1, and negative for cytokeratins, myogenic, melanotic, and hormonal markers. ArcherTM Fusion Sarcoma Assay detected PAMR1(exon1)::GLI1(exon4) fusion, confirmed on RT-PCR and Sanger sequencing. The patient received chemo-radiotherapy, however, developed metastatic recurrence and demised 18 months post-surgery. Altogether, this is a rare and diagnostically challenging case of a uterine sarcoma harboring a novel GLI1 fusion. Emerging GLI/Hedgehog inhibitors provide clinical relevance to recognizing these tumors in modern pathology.     

The contribution of neurocognitive situation,physical capacity and daily life activities to quality of life in childhood acute lymphoblastic leukemia survivors

Background/aim There are no extensive studies on the QL in children who completed acute lymphoblastic leukemia (ALL) treatment and currently living without any disease in Turkey. Our study aimed to analyze both the QL and the effects of physical, neurocognitive capacities on QL in childhood ALL survivors aged 7–12 years at the time of recruitment.Materials and methodsPedsQL cancer module 3.0 child and proxy report, for ages 5–7 and 8–12 years, WeeFIM scale, BOTMP Short Form, RPM, reading, writing, and mathematics assessment tools, sociodemographic information form were carried out to the children and their family.Results There was no effect of the months since the completion of therapy on pain, anxiety, cognitive problems, perceived physical appearance, and the total QL scores of children and proxy reports (p > 0.05).Children’s physical capacities were significantly worse than healthy controls and have not reached the level of healthy children even after a long time since completion of ALL therapy. There was a significant association between physical capacity and daily independent living status (p < 0.001). Reading, writing, and mathematical skills were significantly associated with the mean time off-treatment (p < 0.001), and the total score of RPM and PedsQL of those with mathematical difficulties were significantly lower than those without any difficulty (p < 0.05).ConclusionThe months after the treatment (off-treatment time) have not affected total and subunit QL scores. As motor skills difficulties will lead to low academic achievement, early recognition direct the parents for immediate intervention. lead to low academic achievement, early recognition could direct the parents for immediate intervention. Planning psychosocial support programs for physical activity and age-appropriate development of patients from the initiation of treatment will increase the QL in childhood ALL with a survival rate of 80% or more.     

The inhibition of Src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits MAPK and STATs pathways

Background/aimThe purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings. Materials and methodsArthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund’s adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP –1, –3, and –13 levels in FLSs culture were determined by ELISA.ResultsThe tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP –1, –3, and –13 expressions from FLSs induced by IL-1β and TNF-α were increased, while dasatinib suppressed their productions from FLSs.ConclusionThe present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA.