IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17–16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94–27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association

Effect of pathologic fractures on survival in multiple myeloma patients: a case control study

<p>Abstract</p> <p>Background</p> <p>Multiple Myeloma (MM) is a B cell neoplasm characterized by the clonal proliferation of plasma cells. Skeletal complications are found in up to 80% of myeloma patients at presentation and are major cause of morbidity.</p> <p>Methods</p> <p>49 patients were enrolled with MM admitted to Black Sea Technical University Hospital between 2002–2005. Pathologic fractures (PFs) were determined and the patients with or without PF were followed up minumum 3 years for survival analysis.</p> <p>Results</p> <p>PF was observed in 24 patients (49%) and not observed in 25 patients (51%). The risk of death was increased in the patients with PF compared with patients who had no fractures. While overall survival was 17.6 months in the patients with PFs, it was 57.3 months in the patients with no PFs.</p> <p>Conclusion</p> <p>These findings suggest that PFs may induce reduced survival and increased mortality in the MM patients, however, larger sample size is essential to draw clearer conclusions added to these data.</p

PROTOCOL: Effectiveness of interpersonal psychotherapy in comparison to other psychological and pharmacological interventions for reducing depressive symptoms in women diagnosed with postpartum depression in low and middle‐income countries: A systematic review

Postpartum Depression (PPD) is highly prevalent among women in low and middle income countries (LMICs). World Heath Organization has recognised interpersonal Psychotherapy (IPT) as the first line treatment for the postpartum depression. The primary aim of this review is to evaluate the effectiveness of IPT alone or in combination with pharmacotherapy or other psychosocial therapies for treating depressive symptoms in women with postpartum depression. The generated evidence from this review will help to inform policies in relation to the treatment of postpartum depression in LMICs

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features

Glenn Shunt as an Alternative Procedure for Rheumatoid Triple Valve Disease with Tricuspid Stenosis

A 41-year-old woman with rheumatoid triple valve disease was operated. Mitral and aortic valves were replaced with prosthetic valves. The tricuspid valve annulus was highly stenotic (valve area: 1.4 cm(2)), therefore a bidirectional Glenn Shunt procedure was performed to preserve the right ventricular function. In the long term, 4 years after the operation, the patient is still hemodynamically stable

Surgical treatment of Cushing's disease: Analysis of an experience of 12 years

This study reports our experience with respect to diagnosis and surgical treatment of 41 consecutive patients with Cushing's disease. The series consisted of 33 (79%) female, 8 (21%) male patents with a mean age of 35.4 years. Out of 41 patients, 18 underwent selective adenomectomy, 19 had partial hypophysectomy and 2 had subtotal hypophysectomy along with tumor removal. There were no serious complications attributable to the surgical interventions. The rate of initial remission was 92%. Six patients were treated for recurrences. After a mean follow up period of 38 months (range of 6 to 144 months), 35 of 41 patients remain in remission. In this study the results partial hypophysectomy was not found to be superior to selective adenonectomy. We conclude that radical transsphenoidal surgery is a safe and effective treatment method for Cushing's disease