Spontaneous Subdural Hematoma in Patient with Polycythemia Vera.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative disorder usually characterized by an increase tendency toward thromboembolic events. Spontaneous hemorrhage/bleeding in PV patients is seldom reported in neurosurgical literature. CASE DESCRIPTION: We report the case of a 76-year-old male with PV who developed a spontaneous subdural hematoma requiring surgical evacuation. He improved significantly after the resolution of brain compression and mass effect caused by the hematoma. CONCLUSIONS: Sporadic reports of hemorrhage within the central nervous system in the setting of PV exist and are attributed to microvascular thrombotic events with hemorrhagic conversion. Though rare, spontaneous central nervous system hemorrhage in the absence of vascular malformation or an inciting event such as trauma can occur in the setting of myeloproliferative disorders like PV.

Tumour and host cell PD-L1 is required to mediate suppression of anti-tumour immunity in mice.

Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics. Using genetic deletion in preclinical mouse models, here we show that PD-L1 from disparate cellular sources, including tumour cells, myeloid or other immune cells can similarly modulate the degree of cytotoxic T-cell function and activity in the tumour microenvironment. PD-L1 expression in both the host and tumour compartment contribute to immune suppression in a non-redundant fashion, suggesting that both sources could be predictive of sensitivity to therapeutic agents targeting the PD-L1/PD-1 axis.

Positive regulation of IkappaB kinase signaling by protein serine/threonine phosphatase 2A.

Transcription factor NF-kappaB plays a key regulatory role in the cellular response to pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF). In the absence of TNF, NF-kappaB is sequestered in the cytoplasm by inhibitory IkappaB proteins. Phosphorylation of IkappaBby the beta-catalytic subunit of IKK, a multicomponent IkappaB kinase, targets the inhibitor for proteolytic destruction and facilitates nuclear translocation of NF-kappaB. This pathway is initiated by TNF-dependent phosphorylation of T loop serines in IKKbeta, which greatly stimulates IkappaB kinase activity. Prior in vitro mixing experiments indicate that protein serine/threonine phosphatase 2A (PP2A) can dephosphorylate these T loop serines and inactivate IKK, suggesting a negative regulatory role for PP2A in IKK signaling. Here we provided several in vivo lines of evidence indicating that PP2A plays a positive rather than a negative role in the regulation of IKK. First, TNF-induced degradation of IkappaB is attenuated in cells treated with okadaic acid or fostriecin, two potent inhibitors of PP2A. Second, PP2A forms stable complexes with IKK in untransfected mammalian cells. This interaction is critically dependent on amino acid residues 121-179 of the IKKgamma regulatory subunit. Third, deletion of the PP2A-binding site in IKKgamma attenuates T loop phosphorylation and catalytic activation of IKKbeta in cells treated with TNF. Taken together, these data provide strong evidence that the formation of IKK.PP2A complexes is required for the proper induction of IkappaB kinase activity in vivo.

Manejo de la patología tiroídea: utilidad y limitaciones de la biopsia percutánea con aguja fina y de la biopsia rápida / Management of thyroid pathology: usefulness and limitations of percutaneous biopsy with fine needle and quick biopsy

Fine needle aspiration biopsy of the thyroid (FNAB) has become an accepted procedure for evaluation of the thyroid nodule, with 899 performed at the Lahey Clinic from 1981 to 1990. We examined them by medical record, pathology and cytology review, with follow up by chart or personal communication. Three hundred forty five came to surgery, of which 188 (34 percent) were malignant; the specificity of the aspirate was 97 percent, sensitivity 92 percent, with false negative of 8 percnt and false positive rate of 5 percent. In combination with frozen section, the fine needle aspirate result improved the accuracy of the intraoperative estimate of malignancy (p=0.03). When the aspiration was benign but the lesion was clinically suspicious, a cancer was found at surgery in 13 percent of cases. Of the patients observed for a minimum of 5 years, 1,3 percent developed a carcinoma. Both cases had a non diagnostic FNAB. None of the patients with a clinical and cytological benign lesion developed cancer. The complication rate of FNAB was 1.3 percent. FNAB is a helpful and low risk diagnostic procedure but it needs to be done and read appropriately and its result used within the clinical context. Each medical team needs to monitor their results (continued quality control)