Background The role of surgery for incidentally discovered diffuse low-grade gliomas (iLGGs) is debatable and poorly documented in current literature. Objective The aim was to identify factors that influence survival for patients that underwent surgical resection of iLGGs in a large multicenter population. Methods Clinical, radiological, and surgical data were retrospectively analyzed in 267 patients operated for iLGG from 4 neurosurgical Centers. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and tumor recurrence (TR). Results The OS rate was 92.41%. The 5- and 10-year estimated OS rates were 98.09% and 93.2% respectively. OS was significantly longer for patients with a lower preoperative tumor volume (p=0.001) and higher extent of resection (EOR) (p=0.037), regardless the WHO defined molecular class (p=0.2). In the final model, OS was influenced only by the preoperative tumor volume (p=0.006), while TR by early surgery (p=0.028). A negative association was found between preoperative tumor volumes and EOR (rs = -0.44, p<0.001). The median preoperative tumor volume was 15 cm 3. The median EOR was 95%. Total or supratotal resection of FLAIR abnormality was achieved in 61.62% of cases. Second surgery was performed in 26.22%. The median time between surgeries was 5.5 years. Histological evolution to high grade glioma was detected in 22.85% of cases (16/70). Permanent mild deficits were observed in 3.08% of cases. Conclusions This multicenter study confirms the results of previous studies investigating surgical management of iLGGs and thereby strengthens the evidence in favour of early surgery for these lesions.
OBJECTIVE Patient outcomes of ventriculoperitoneal (VP) shunt surgery, the mainstay treatment for hydrocephalus in adults, are poor because of high shunt failure rates. The use of neuronavigation or laparoscopy can reduce the risks of proximal or distal shunt catheter failure, respectively, but has less independent effect on overall shunt failures. No adult studies to date have combined both approaches in the setting of a shunt infection prevention protocol to reduce shunt failure. The goal of this study was to determine whether combining neuronavigation and laparoscopy with a shunt infection prevention strategy would reduce the incidence of shunt failures in adult hydrocephalic patients. METHODS Adult patients (age ≥ 18 years) undergoing VP shunt surgery at a tertiary care institution prior to (pre–Shunt Outcomes [ShOut]) and after (post-ShOut) the start of a prospective continuous quality improvement (QI) study were compared. Pre-ShOut patients had their proximal and distal catheters placed under conventional freehand approaches. Post-ShOut patients had their shunts inserted with neuronavigational and laparoscopy assistance in placing the distal catheter in the perihepatic space (falciform technique). A shunt infection reduction protocol had been instituted 1.5 years prior to the start of the QI initiative. The primary outcome of interest was the incidence of shunt failure (including infection) confirmed by standardized criteria indicating shunt revision surgery. RESULTS There were 244 (115 pre-ShOut and 129 post-ShOut) patients observed over 7 years. With a background of shunt infection prophylaxis, combined neuronavigation and laparoscopy was associated with a reduction in overall shunt failure rates from 37% to 14%, 45% to 22%, and 51% to 29% at 1, 2, and 3 years, respectively (HR 0.44, p < 0.001). Shunt infection rates decreased from 8% in the pre-ShOut group to 0% in the post-ShOut group. There were no proximal catheter failures in the post-ShOut group. The 2-year rates of distal catheter failure were 42% versus 20% in the pre- and post-ShOut groups, respectively (p < 0.001). CONCLUSIONS Introducing a shunt infection prevention protocol, placing the proximal catheter under neuronavigation, and placing the peritoneal catheter in the perihepatic space by using the falciform technique led to decreased rates of infection, distal shunt failure, and overall shunt failure.
The C-linked phenolic adduct, C8-(2″-hydroxyphenyl)-2'-deoxyguanosine (o-PhOHdG), has been employed to study the impact of N7-metalation of 2'-deoxyguanosine (dG) within duplex DNA. The phenolic group of o-PhOHdG assists selective metal ion coordination by the N7-site of the attached dG moiety, which is the most important metal binding site in duplex DNA. The biaryl nucleobase probe o-PhOHdG is highly fluorescent in water (Φ(fl) = 0.44), and changes in its absorption and emission were used to determine apparent association constants (K(a)) for binding to Cu(II), Ni(II), and Zn(II). The nucleoside was found to bind Cu(II) (log K(a) = 4.59) and Ni(II) (log K(a) = 3.65) effectively, but it showed relatively poor affinity for Zn(II) (log K(a) = 2.55). The fluorescent nucleobase o-PhOHdG was incorporated into a pyrimidine-rich oligonucleotide substrate (ODN1) and a purine-rich (ODN2) substrate to monitor selective binding of Cu(II) through fluorescence quenching of the enol emission of o-PhOHdG within the DNA substrates. The pyrimidine-rich substrate ODN1 was found to possess greater affinity for Cu(II) than the free nucleobase, while the purine-rich substrate ODN2 exhibited diminished Cu(II) binding affinity. The impact of Cu(II) on duplex stability and structure was determined using UV melting temperature analysis and circular dichroism (CD) measurements. These studies highlight the syn preference for Cu(II)-bound o-PhOHdG within ODN1 duplexes and demonstrate competitive Cu(II) binding by other natural dG nucleobases within ODN2. The metal binding properties of o-PhOHdG are compared to the structurally similar 2-(2'-hydroxyphenyl)benzoxazole (HBO) derivatives and the nucleoside C8-(2-pyridyl)-dG (2PydG) that has also been used to control N7-metal coordination in DNA. Our results show certain advantages to the use of o-PhOHdG that stem from its highly fluorescent nature in aqueous media and provide additional tools for studying the effects of N7-metalation on the structure and stability of duplex DNA.
OBJECTIVE Endoscopic third ventriculostomy and choroid plexus cauterization (ETV+CPC) is a novel procedure for infant hydrocephalus that was developed in sub-Saharan Africa to mitigate the risks associated with permanent implanted shunt hardware. This study summarizes the hydrocephalus literature surrounding the ETV+CPC intraoperative abandonment rate, perioperative mortality rate, cerebrospinal fluid infection rate, and failure rate. METHODS This systematic review and meta-analysis followed a prespecified protocol and abides by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy using MEDLINE, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 2019. Studies included controlled trials, cohort studies, and case-control studies of patients with hydrocephalus younger than 18 years of age treated with ETV+CPC. Pooled estimates were calculated using DerSimonian and Laird random-effects modeling, and the significance of subgroup analyses was tested using meta-regression. The quality of the pooled outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS After screening and reviewing 12,321 citations, the authors found 16 articles that met the inclusion criteria. The pooled estimate for the ETV+CPC failure rate was 0.44 (95% CI 0.37–0.51). Subgroup analysis by geographic income level showed statistical significance (p < 0.01), with lower-middle-income countries having a lower failure rate (0.32, 95% CI 0.28–0.36) than high-income countries (0.53, 95% CI 0.47–0.60). No difference in failure rate was found between hydrocephalus etiology (p = 0.09) or definition of failure (p = 0.24). The pooled estimate for perioperative mortality rate (n = 7 studies) was 0.001 (95% CI 0.00–0.004), the intraoperative abandonment rate (n = 5 studies) was 0.04 (95% CI 0.01–0.08), and the postoperative CSF infection rate (n = 5 studies) was 0.0004 (95% CI 0.00–0.003). All pooled outcomes were found to be low-quality evidence. CONCLUSIONS This systematic review and meta-analysis provides the most comprehensive pooled estimate for the ETV+CPC failure rate to date and demonstrates, for the first time, a statistically significant difference in failure rate by geographic income level. It also provides the first reported pooled estimates for the risk of ETV+CPC perioperative mortality, intraoperative abandonment, and CSF infection. The low quality of this evidence highlights the need for further research to improve the understanding of these critical clinical outcomes and their relevant explanatory variables and thus to appreciate which patients may benefit most from an ETV+CPC. Systematic review registration no.: CRD42020160149 (https://www.crd.york.ac.uk/prospero/)
BACKGROUND In light of evidence from recent trials that endovascular thrombectomy (EVT) alone may potentially be noninferior to combined treatment, that is, with intravenous thrombolysis (IVT) with alteplase and EVT, we sought to understand physician and patient preferences around this issue. METHODS We conducted a 2‐stage mixed methods study that included a structured, international, web‐based cross‐sectional survey among stroke physicians, and a focus group involving stroke survivors and caregivers. Demographic information was collected from all participants. The survey offered multiple choice questions and options to respond via free text which was analyzed quantitatively. The focus group was conducted online and analyzed qualitatively using a grounded theory approach. RESULTS A total of 225 physicians (67% men) from 44 countries completed the survey. Most participants (70%) were between 31 and 50 years of age. Survey results showed that in current practice, 90% respondents would offer IVT to patients with large vessel occlusion stroke eligible for both IVT and EVT. When asked if their practice would change in light of recent trials, 63% responded no. When asked about the appropriate timing for IVT in the setting of large vessel occlusion stroke with EVT availability, 56% preferred to administer IVT immediately, 21% were willing to defer the decision for 30 minutes from groin puncture, and 8% were willing to defer for 60 minutes from groin puncture to assess if reperfusion was achieved with EVT. A total of 61% participants would choose to use tenecteplase over alteplase as the preferred drug for IVT if both drugs are backed by evidence. The focus group identified a need to better understand patient characteristics that may benefit from EVT‐only or combined strategies. The focus group also identified the need for more data to inform physician decision making. CONCLUSIONS Most physicians surveyed prefer IVT before EVT in patients with acute ischemic stroke attributable to large vessel occlusion, although there was some uncertainty around this issue. The need for further studies, including data on IVT with tenecteplase and among various patient subgroups to inform decision making, was apparent from both the survey and the patient focus group.
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