OBJECTIVE The authors previously described a graded approach to skull base repair following endonasal microscopic or endoscope-assisted tumor surgery. In this paper they review their experience with skull base reconstruction in the endoscopic era. METHODS A retrospective review of a single-institution endonasal endoscopic patient database (April 2010-April 2017) was undertaken. Intraoperative CSF leaks were graded based on size (grade 0 [no leak], 1, 2, or 3), and repair technique was documented across grades. The series was divided into 2 epochs based on implementation of a strict perioperative antibiotic protocol and more liberal use of permanent and/or temporary buttresses; repair failure rates and postoperative meningitis rates were assessed for the 2 epochs and compared. RESULTS In total, 551 operations were performed in 509 patients for parasellar pathology, including pituitary adenoma (66%), Rathke's cleft cyst (7%), meningioma (6%), craniopharyngioma (4%), and other (17%). Extended approaches were used in 41% of cases. There were 9 postoperative CSF leaks (1.6%) and 6 cases of meningitis (1.1%). Postoperative leak rates for all 551 operations by grade 0, 1, 2, and 3 were 0%, 1.9%, 3.1%, and 4.8%, respectively. Fat grafts were used in 33%, 84%, 97%, and 100% of grade 0, 1, 2, and 3 leaks, respectively. Pedicled mucosal flaps (78 total) were used in 2.6% of grade 0-2 leaks (combined) and 79.5% of grade 3 leaks (60 nasoseptal and 6 middle turbinate flaps). Nasoseptal flap usage was highest for craniopharyngioma operations (80%) and lowest for pituitary adenoma operations (2%). Two (3%) nasoseptal flaps failed. Contributing factors for the 9 repair failures were BMI ≥ 30 (7/9), lack of buttress (4/9), grade 3 leak (4/9), and postoperative vomiting (4/9). Comparison of the epochs showed that grade 1-3 repair failures decreased from 6/143 (4.1%) to 3/141 (2.1%) and grade 1-3 meningitis rates decreased from 5 (3.5%) to 1 (0.7%) (p = 0.08). Prophylactic lumbar CSF drainage was used in only 4 cases (< 1%), was associated with a higher meningitis rate in grades 1-3 (25% vs 2%), and was discontinued in 2012. Comparison of the 2 epochs showed increase buttress use in the second, with use of a permanent buttress in grade 1 and 3 leaks increasing from 13% to 55% and 32% to 76%, respectively (p < 0.001), and use of autologous septal/keel bone as a permanent buttress in grade 1, 2, and 3 leaks increasing from 15% to 51% (p < 0.001). CONCLUSIONS A graded approach to skull base repair after endonasal surgery remains valid in the endoscopic era. However, the technique has evolved significantly, with further reduction of postoperative CSF leak rates. These data suggest that buttresses are beneficial for repair of most grade 1 and 2 leaks and all grade 3 leaks. Similarly, pedicled flaps appear advantageous for grade 3 leaks, while CSF diversion may be unnecessary and a risk factor for meningitis. High BMI should prompt an aggressive multilayered repair strategy. Achieving repair failure and meningitis rates lower than 1% is a...

Background and Purpose Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iron-induced brain injury in vivo. Methods This study was divided into four parts. (1) Rats with different sizes of ICH were euthanized 3 days later for serum total iron and brain edema determination. (2) Rats had an ICH treated with minocycline or vehicle. Serum iron, brain iron, and brain iron handling proteins were measured. (3) Rats had an intracaudate injection of either saline, iron, iron+minocycline or iron+macrophage/microglia inhibitory factor and were used for brain edema and neuronal death measurements. (4) Rats had an intracaudate injection of iron and were treated with minocycline. The brains were used for edema measurement. Results After ICH, serum total iron and brain non-heme iron increased and these changes were reduced by minocycline treatment. Minocycline also reduced ICH-induced upregulation of brain iron handling proteins and neuronal death. Intracaudate injection of iron caused brain edema, blood-brain barrier leakage and brain cell death, all of which were significantly reduced by co-injection with minocycline. Conclusions The current study found that minocycline reduces iron overload after ICH and iron-induced brain injury. It is also well known minocycline is an inhibitor of microglial activation. Minocycline may be very useful for ICH patients because both iron accumulation and microglia activation contribute to brain damage following ICH.

This study aimed to investigate the correlation of long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) with clinicopathological feature and prognosis, and to explore its effect on cell proliferation and apoptosis as well as the relevant target genes in adult acute myeloid leukemia (AML). LncRNA TUG1 expression was detected in bone marrow samples from 186 AML patients and 62 controls. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor lentivirus vectors were transfected in KG-1 cells. Rescue experiment was performed by transfection of lncRNA TUG1 inhibitor and aurora kinase A (AURKA) mimic lentivirus vectors. Cell proliferation, apoptosis, RNA, and protein expressions were determined by CKK-8, annexin V-FITC-propidium iodide, quantitative polymerase chain reaction, and western blot assays. LncRNA TUG1 expression was higher in AML patients compared to controls and correlated with higher white blood cell counts, monosomal karyotype, FLT3-ITD mutation, poor-risk stratification, and poor prognosis, which independently predicted worse event-free survival and overall survival. In vitro, lncRNA TUG1 expression was higher in AML cell lines (KG-1, MOLM-14, HL-60, NB-4, and THP-1 cells) compared to controls. LncRNA TUG1 mimic promoted cell proliferation and decreased cell apoptosis rate, while lncRNA TUG1 inhibitor repressed cell proliferation and increased cell apoptosis rate. Rescue experiment showed that AURKA attenuated the influence of lncRNA TUG1 on AML cell proliferation and apoptosis. In conclusion, lncRNA TUG1 associates with advanced disease and worse prognosis in adult AML patients, and it induces AML cell proliferation and represses cell apoptosis via targeting AURKA.

BackgroundPrevious association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer’s disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations.MethodsTo confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies.ResultsSeventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ2 = 119.46, OR = 2.79, 95% CI = 2.31–3.36, P<0.01).ConclusionsThe APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.

Esophageal myotomy for achalasia can reduce the resting pressures of the esophageal body and LES and improve esophageal transit and dysphagia. Myotomy in combination with antireflux procedure can prevent gastroesophageal reflux to a certain extent, but further randomized studies should be carried out to demonstrate its efficacy.

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OBJECTIVE Intracerebral hemorrhage (ICH) is a fatal disease with high morbidity and mortality, which may be followed by white matter injury (WMI) due to the local oxidizing reaction induced by iron (Fe). In this study, the authors examined the effect of the tetracycline antibiotic minocycline on Fe-induced WMI and c-Jun N-terminal kinase (JNK) activation in rats. METHODS Thirty-six male Sprague-Dawley rats underwent an intracaudate injection of saline, Fe, or Fe + minocycline. Another 36 rats had an intracaudate injection of autologous blood and were treated with minocycline or vehicle (saline). Biomarkers of both WMI and JNK activation were examined. RESULTS In the Fe-injection group, minocycline suppressed WMI labeled by β-amyloid precursor protein (β-APP) and degraded myelin basic protein (dMBP)/MBP ratio. Protein levels of phosphorylated-JNK were increased after Fe injection, and could be suppressed by minocycline treatment. In the autologous blood-injection group, β-APP and dMBP/MBP levels increased in the ipsilateral site compared with the contralateral site, which could be suppressed by 7 days of minocycline intervention. CONCLUSIONS Iron plays a critical role in WMI after ICH, which can be suppressed by minocycline through reducing the damage induced by Fe.

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