The HBF is a versatile and reliable reconstructive technique for repairing defects of the anterior, middle, clival, and parasellar cranial base. Its use has resulted in a significant decrease in our incidence of CSF leaks after endonasal cranial base surgery. Attention to technical details is of paramount importance to achieve the best outcomes.

Endoscopic endonasal skull base surgery provides a viable median corridor based on anatomical landmarks and is customized according to the specific pathological process. This corridor should be considered as the sole access or may be combined with traditional approaches. With the incremental acquisition of skills and experience, endoscopic endonasal approaches have an acceptable safety profile in select patients presenting with various skull base pathologies.

Cranial base meningiomas can be successfully managed via a purely endoscopic endonasal approach with acceptable morbidity and mortality rates. The extent of resection is guided by patient factors and symptoms, not by approach. This series had a high cerebrospinal fluid leak rate. With the evolution of new reconstruction techniques, these rates have been substantially reduced.

Highlights d ER and nutrient stress increase mitochondrial oxidative phosphorylation d PERK increases formation of mitochondrial cristae and respiratory supercomplexes d PERK-ATF4 promotes assembly of respiratory supercomplexes through SCAF1 d PERK activation rescues bioenergetic failures in human complex I mutant cells

SUMMARY Melanoma is the deadliest form of commonly encountered skin cancers because of its rapid progression towards metastasis1,2. Although metabolic reprogramming is tightly associated with tumor progression, whether metabolic regulatory circuits affect metastatic processes is poorly understood. PGC1α is a transcriptional coactivator that promotes mitochondrial biogenesis, protects against oxidative stress3, and reprograms melanoma metabolism to influence drug sensitivity and survival4,5. Here, we provide data to indicate that PGC1α suppresses melanoma metastasis, acting through a pathway distinct from its bioenergetic functions. Elevated PGC1α expression inversely correlates with vertical growth in human melanomas. PGC1α silencing makes nonmetastatic melanoma cells highly invasive and conversely, PGC1α reconstitution suppresses metastasis. Within populations of melanoma cells, there is a marked heterogeneity in PGC1α levels, which predicts their inherent high or low metastatic capacity. Mechanistically, PGC1α directly increases transcription of ID2, which in turn binds to and inactivates the transcription factor TCF4. Inactive TCF4 causes downregulation of metastasis-related genes including integrins that are known to influence invasion and metastasis6–8. Inhibition of BRAFV600E using vemurafenib9, independently of its cytostatic effects, suppresses metastasis by acting on the PGC1α-ID2-TCF4-integrin axis. Taken together, our findings reveal that PGC1α maintains mitochondrial energetic metabolism and suppresses metastasis through direct regulation of parallel acting transcriptional programs. Consequently, components of these circuits define new therapeutic opportunities that may help curb melanoma metastasis.

In well-selected patients, the expanded endonasal approach represents a safe, effective, and minimally invasive technique for the treatment of skull base lesions in children. Incremental experience is needed for acquiring the skills with endoscopic techniques to progress to the more complex modular approaches.

Objective: To identify patterns of clinical presentation, imaging findings, and etiologies in a cohort of hospitalized patients with localized nontraumatic convexal subarachnoid hemorrhage.Methods: Twenty-nine consecutive patients with atraumatic convexal subarachnoid hemorrhage were identified using International Classification of Diseases-9 code from 460 patients with subarachnoid hemorrhage evaluated at our institution over a course of 5 years. Retrospective review of patient medical records, neuroimaging studies, and follow-up data was performed.Results: There were 16 women and 13 men between the ages of 29 and 87 years. Two common patterns of presentations were observed. The most frequent presenting symptom in patients Յ60 years (n ϭ 16) was a severe headache (n ϭ 12; 75%) of abrupt onset (n ϭ 9; 56%) with arterial narrowing on conventional angiograms in 4 patients; 10 (p ϭ 0.003) were presumptively diagnosed with a primary vasoconstriction syndrome. Patients Ͼ60 years (n ϭ 13) usually had temporary sensory or motor symptoms (n ϭ 7; 54%); brain MRI scans in these patients showed evidence of leukoaraiosis and/or hemispheric microbleeds and superficial siderosis (n ϭ 9; 69%), compatible with amyloid angiopathy (n ϭ 10; p Ͻ 0.0001). In a small group of patients, the presentation was more varied and included lethargy, fever, and confusion. Four patients older than 60 years had recurrent intracerebral hemorrhages in the follow-up period with 2 fatalities. Conclusion:Convexal subarachnoid hemorrhage is an important subtype of nonaneurysmal subarachnoid bleeding with diverse etiologies, though a reversible vasoconstriction syndrome appears to be a common cause in patients 60 years or younger whereas amyloid angiopathy is frequent in patients over 60. These observations require confirmation in future studies. Atraumatic localized convexal subarachnoid hemorrhage (cSAH) is an unusual presentation of subarachnoid bleeding, in which the bleeding is localized to the convexities of the brain without involvement of the adjacent parenchyma or extension into the interhemispheric fissures, basal cisterns, or ventricles. Since most saccular aneurysms arise from the circle of Willis, aneurysmal rupture is an unlikely source of cSAH. Diverse etiologies have been posited for its occurrence, including cortical vein occlusions, posterior reversible leukoencephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), coagulopathy, cocaine use, lupus vasculitis, cavernoma, brain abscesses, and cerebral amyloid angiopathy (CAA). 1-13Existing information about this condition is largely derived from case reports and small case series, which carry inherent referral and diagnostic biases. We undertook this study to systematically evaluate and review the potential causes and patterns of clinical and radiologic presentation of localized cSAH from the inpatient population at our institution.

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