Characterization of purinergic signaling in tumor-infiltrating lymphocytes from lower- and high-grade gliomas.

Malignant gliomas are highly heterogeneous glia-derived tumors that present an aggressive and invasive nature, with a dismal prognosis. The multi-dimensional interactions between glioma cells and other tumor microenvironment (TME) non-tumoral components constitute a challenge to finding successful treatment strategies. Several molecules, such as extracellular purines, participate in signaling events and support the immunosuppressive TME of glioma patients. The purinergic signaling and the ectoenzymes network involved in the metabolism of these extracellular nucleotides are still unexplored in the glioma TME, especially in lower-grade gliomas (LGG). Also, differences between IDH-mutant (IDH-Mut) versus wild-type (IDH-WT) gliomas are still unknown in this context. For the first time, to our knowledge, this study characterizes the TME of LGG, high-grade gliomas (HGG) IDH-Mut, and HGG IDH-WT patients regarding purinergic ectoenzymes and P1 receptors, focusing on tumor-infiltrating lymphocytes. Here, we show that ectoenzymes from both canonical and non-canonical pathways are increased in the TME when compared to the peripheral blood. We hypothesize this enhancement supports extracellular adenosine generation, hence increasing TME immunosuppression.

Early Transcranial Doppler Evaluation of Cerebral Autoregulation Independently Predicts Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral autoregulation (CA) impairment after aneurysmal subarachnoid hemorrhage (SAH) has been associated with delayed cerebral ischemia and an unfavorable outcome. We investigated whether the early transient hyperemic response test (THRT), a transcranial Doppler (TCD)-based CA evaluation method, can predict functional outcome 6 months after aneurysmal SAH. METHODS: This is a prospective observational study of all aneurysmal SAH patients consecutively admitted to a single center between January 2016 and February 2017. CA was evaluated within 72 h of hemorrhage by THRT, which describes the changes in cerebral blood flow velocity after a brief compression of the ipsilateral common carotid artery. CA was considered to be preserved when an increase ≥ 9% of baseline systolic velocity was present. According to the modified Rankin Scale (mRS: 4-6), the primary outcome was unfavorable 6 months after hemorrhage. Secondary outcomes included cerebral infarction, vasospasm on TCD, and an unfavorable outcome at hospital discharge. RESULTS: Forty patients were included (mean age = 54 ± 12 years, 70% females). CA was impaired in 19 patients (47.5%) and preserved in 21 (52.5%). Impaired CA patients were older (59 ± 13 vs. 50 ± 9, p = 0.012), showed worse neurological conditions (Hunt&Hess 4 or 5-47.4% vs. 9.5%, p = 0.012), and clinical initial condition (APACHE II physiological score-12 [5.57-13] vs. 3.5 [3-5], p = 0.001). Fourteen patients in the impaired CA group and one patient in the preserved CA group progressed to an unfavorable outcome (73.7% vs. 4.7%, p = 0.0001). The impaired CA group more frequently developed cerebral infarction than the preserved CA group (36.8% vs. 0%, p = 0.003, respectively). After multivariate analysis, impaired CA (OR 5.15 95% CI 1.43-51.99, p = 0.033) and the APACHE II physiological score (OR 1.67, 95% CI 1.01-2.76, p = 0.046) were independently associated with an unfavorable outcome. CONCLUSIONS: Early CA impairment detected by TCD and admission APACHE II physiological score independently predicted an unfavorable outcome after SAH.

Perfuração intestinal e extrusão de catéter de derivação ventrículo-peritoneal via anal / Bowel Perforation and extrusion of a ventriculo-peritoneal shunt through the anus

Derivação Ventrículo-Peritoneal (DVP) é um dos procedimentos mais frequentemente realizados para o tratamento dehidrocefalia. Entretanto, mesmo sendo tecnicamente simples e bem conhecido, existem várias complicações graves que podemocorrer, sendo a perfuração intestinal uma delas. Esta complicação é rara, especialmente entre adultos e geralmente ocorredentro do primeiro ano após o procedimento cirúrgico. Esta pode ainda, ser agravada, tanto por infecção, do sistema nervosocentral ou sistêmica, quanto por aumento da pressão intracraniana devido ao mau funcionamento do sistema de drenagem. Oquadro clínico geralmente oligossintomático muitas vezes torna o diagnóstico difícil, sendo necessário o uso de múltiplos examescomplementares. Existem também inúmeras dúvidas quanto à fisiopatologia e fatores predisponentes para esta complicação.Ainda, devido à sua baixa incidência, sendo descrita, em sua maioria, através de relatos de caso ou pequenas séries, não existeconsenso para seu ideal manejo. O tratamento varia desde abordagens menos invasivas, preservando os componentes da DVP,até a retirada completa de todos os componentes e uso de antibióticos de amplo espectro. Relatamos um caso de perfuraçãointestinal e extrusão de cateter de DVP através do ânus em um paciente adulto, tardiamente, discutindo os dados da literaturasobre este assunto.