Risk Factors for Neural-Tube Defects Detected in Utero: A Prospective Community-Based Study from Addis Ababa.

BACKGROUND: A recent community-based study from Addis Ababa identifying Neural Tube Defect (NTD) cases by ultrasound examination of pregnant women showed a higher prevalence of 17 per 1000 fetuses. The risk factors behind the high prevalence remain unclear. METHODS: Altogether 891 of the 958 women participated in the ultrasound examination. Thirteen with unaffected twin pregnancies were excluded. Among 878 singleton pregnancies, 15 NTD cases were identified. Serum Folate, vitamin B12, and homocysteine levels were measured in case-mothers and a sub-set of 28 noncase mothers. Because of the modest sample size, exact logistic regression analysis was used to estimate associations between risk factors and NTDs. RESULTS: Serum vitamin status was generally poor for participants in the study. Still, relatively higher values of folate or vitamin B12 in serum, appeared to be protective for NTD (odds ratio [OR] = 0.61 per ng/ml, 95% Confidence interval [CI]: 0.42-0.85 and OR = 0.67 per 100 pg/ml, 95% CI: 0.41-1.02, respectively). High serum homocysteine was associated with higher risk of NTD (OR = 1.3 per µmol/l, 95% CI: 1.02-1.8). Women aged 30 years or more had an OR of 3.5 (95% CI: 1.1-12) for having a NTD child, and families with NTD children had lower household income. Women in the NTD group also had more spontaneous abortions or stillbirths in previous pregnancies. Self-reported intake of folate did not appear to protect against NTDs. CONCLUSIONS: Within this high-prevalence community, poor vitamin status was identified as a risk factor for NTDs detected at ultrasound examination. Improving food security and fortification of foods or food ingredients could be alternative measures.

Surgical treatment outcome of children with neural-tube defect: A prospective cohort study in a high volume center in Addis Ababa, Ethiopia.

Introduction: Prevalence of neural tube defects (NTD) is high thus many children are born with a neural tube defect in Addis Ababa, and surgical closure is a commonly performed procedure at the pediatric neurosurgical specialty center. Research question: The primary aim is to study the outcomes in children undergoing surgical closure of NTDs and to identify risk factors for readmission, complications and mortality. Material and methods: Single-center prospective study of all surgically treated NTDs from April 2019 to May 2020. Results: A total of 228 children, mean age 11 days (median 4) underwent surgery during the study period. There were no in-hospital deaths. Perioperatively 11 (4.8%) children developed wound complications, none of them needed surgery and there was no perioperative mortality. The one-year follow-up rate was 62.7% (143/228) and neurological status remained stable since discharge in all. The readmission and reoperation rates were 38 % and 8 % and risk factors for readmission were hydrocephalus (80%) and open defects (88%). Hydrocephalus (P = 0.05) and younger age (P = 0.02) were identified as risk factors for mortality. The wound-related complication rate was 55% at and was associated with large defects (P = 0.04) and delayed closure due to late hospital presentation (P = 0.01). Discussion and conclusion: The study reveals good perioperative surgical outcome and further need for systematic improvement in treatment and follow-up of NTD patients especially with hydrocephalus. We identified risk factors for wound-related complications, readmission and mortality.

Impact of extent of resection on outcome from glioblastoma using the RANO resect group classification system: a retrospective, population-based cohort study.

Background: Extent of resection (EOR) is associated with survival in glioblastoma. A standardized classification for EOR was lacking until a system was recently proposed by the response assessment in neuro-oncology (RANO) resect group. We aimed to assess EOR in an unselected glioblastoma cohort and use this classification system to evaluate the impact on survival in a real-world setting. Methods: We retrospectively identified all patients with histologically confirmed glioblastoma in Western Norway between 1.1.2007 and 31.12.2014. Volumetric analyses were performed using a semi-automated method. EOR was categorized according to the recent classification system. Kaplan-Meier method and Cox proportional hazard ratios were applied for survival analyses. Results: Among 235 included patients, biopsy (EOR class 4) was performed in 50 patients (21.3%), submaximal contrast enhancement (CE) resection (EOR class 3) in 66 patients (28.1%), and maximal CE resection (EOR class 2) in 119 patients (50.6%). Median survival was 6.2 months, 9.2 months, and 14.9 months, respectively. Within EOR class 2, 80 patients underwent complete CE resection (EOR class 2A) and had a median survival of 20.0 months, while 39 patients had a near-total CE resection, with ≤1 cm3 CE residual volume (EOR class 2B), and a median survival of 11.1 months, P < 0.001. The 2-year survival rate in EOR class 2A was 40.0%, compared to 7.7% in EOR class 2B. Conclusions: RANO resect group classification for the extent of resection reflected outcome from glioblastoma in a real-world setting. There was significantly superior survival after complete CE resection compared to near-total resection.

Quality indicators and early adverse in surgery for atypical meningiomas: A 16-year single centre study and systematic review of the literature.

Introduction: Atypical meningiomas represent approximately 20% of all intracranial meningiomas and are characterized by distinct histopathological criteria and an increased risk of postoperative recurrence. Recently, quality indicators have been introduced to monitor quality of the delivered care. Research question: Which quality indicators/outcome measures are being applied in patients being operated for atypical meningiomas? What are risk factors associated with poor outcome? How is the surgical outcome and which quality indicators are reported in the literature? Material and methods: The primary outcomes of interest were 30-days readmission-, 30-day reoperation-, 30-day mortality-, 30-day nosocomial infection- and the 30-day surgical site infection (SSI) rate, CSF-leakage, new neurological deficit, medical complications, and lengths of stay. The secondary aim was the identification of prognostic factors for the mentioned primary outcomes. A systematic review of the literature was performed screening studies for the mentioned outcomes. Results: We included 52 patients. 30-days outcomes in terms of unplanned reoperation were 0%, unplanned readmission 7.7%, mortality 0%, nosocomial infection 17.3%, and SSI 0%. Any adverse event occurred in 30.8%. Preoperative C-reactive protein over 5 â€‹mg/l was independent factor for the occurrence of any postoperative adverse event (OR: 17.2, p â€‹= â€‹0.003). A total of 22 studies were included into the review. Discussion and conclusion: The 30-days outcomes at our department were comparable with reported outcomes in the literature. Currently applied quality indicators are helpful in determining the postoperative outcome but mainly report the indirect outcome after surgery and are influenced of patient, tumor and treatment related factors. Risk adjustment is vital.

Prevalence of neural tube defects among pregnant women in Addis Ababa: a community-based study using prenatal ultrasound examination.

PURPOSE: The primary aim of this study was to estimate the prevalence of NTDs at ultrasound examination in communities of Addis Ababa and secondarily to provide a description of the dysmorphology of the NTD cases. METHODS: We enrolled 958 pregnant women from 20 randomly selected health centers in Addis Ababa during the period from October 1, 2018, to April 30, 2019. Of these 958 women, 891 had an ultrasound examination after enrollment, with a special focus on NTDs. We estimated the prevalence of NTDs and compared it with previously reported hospital-based birth prevalence estimates from Addis Ababa. RESULTS: Among 891 women, 13 had twin pregnancies. We identified 15 NTD cases among 904 fetuses, corresponding to an ultrasound-based prevalence of 166 per 10,000 (95% CI: 100-274). There were no NTD cases among the 26 twins. Eleven had spina bifida (122 per 10,000, 95% CI: 67-219). Among the 11 fetuses with spina bifida, three had a cervical and one had a thoracolumbar defect while the anatomical site for 7 was not registered. Seven of the 11 spina bifida defects had skin covering, while two of the cervical lesions were uncovered. CONCLUSION: We report a high prevalence of NTDs among pregnancies in communities of Addis Ababa based on screening by ultrasound. The prevalence was higher than in previous hospital-based studies in Addis, and the prevalence of spina bifida was particularly high.

Butterfly glioblastoma: Clinical characteristics, treatment strategies and outcomes in a population-based cohort.

Background: Butterfly glioblastoma is a rare subgroup of glioblastoma with a bihemispheric tumor crossing the corpus callosum, and is associated with a dismal prognosis. Prognostic factors are previously sparsely described and optimal treatment remains uncertain. We aimed to analyze clinical characteristics, treatment strategies, and outcomes from butterfly glioblastoma in a real-world setting. Methods: This retrospective population-based cohort study included patients diagnosed with butterfly glioblastoma in Western Norway between 01/01/2007 and 31/12/2014. We enrolled patients with histologically confirmed glioblastoma and patients with a diagnosis based on a typical MRI pattern. Clinical data were extracted from electronic medical records. Molecular and MRI volumetric analyses were retrospectively performed. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards regression models. Results: Among 381 patients diagnosed with glioblastoma, 33 patients (8.7%) met the butterfly glioblastoma criteria. Median overall survival was 5.5 months (95% CI 3.1-7.9) and 3-year survival was 9.1%. Hypofractionated radiation therapy with or without temozolomide was the most frequently used treatment strategy, given to 16 of the 27 (59.3%) patients receiving radiation therapy. Best supportive care was associated with poorer survival compared with multimodal treatment [adjusted hazard ratio 5.11 (95% CI 1.09-23.89)]. Conclusion: Outcome from butterfly glioblastoma was dismal, with a median overall survival of less than 6 months. However, long-term survival was comparable to that observed in non-butterfly glioblastoma, and multimodal treatment was associated with longer survival. This suggests that patients with butterfly glioblastoma may benefit from a more aggressive treatment approach despite the overall poor prognosis.

A Health Economic Evaluation of the World Health Organization Surgical Safety Checklist: A Single Center Assessment.

OBJECTIVES: To evaluate cost-effectiveness of the WHO Surgical Safety Checklist. BACKGROUND: The clinical effectiveness of surgical checklists is largely understood. Few studies to-date have evaluated the cost-effectiveness of checklist use. METHODS: An economic evaluation was carried out using data from the only available randomized controlled trial of the checklist. Analyses were based on 3702 procedures. Costs considered included checklist implementation costs and length and cost of hospital stay, costs of warming blanket use, blood transfusions and antibiotics used in the operating room, and the cost of clinical time in the operating room - all calculated for each procedure and its associated admission. Nonparametric bootstrapping was used to simulate an empirical distribution of the mean effect of the checklist on total admission costs and the probability of observing a complication-free admission and to quantify sampling uncertainty around mean cost estimates. RESULTS: The overall cost of checklist implementation was calculated to be $900 per 100 admissions. Implementation of the WHO checklist resulted in an additional 5.9 complication-free admissions per 100 admissions and an average of 110 bed-days saved per 100 admissions. Accounting for all costs included in the analysis, for every 100 admissions, use of the WHO checklist was estimated to save $55,899. CONCLUSIONS: Implementation of the WHO checklist was a cost-effective strategy for improving surgical safety.

Treatment approach and survival from glioblastoma: results from a population-based retrospective cohort study from Western Norway.

OBJECTIVES: To evaluate treatment and survival from glioblastoma in a real-world setting. DESIGN AND SETTINGS: A population-based retrospective cohort study from Western Norway. PARTICIPANTS: 363 patients aged 18 years or older diagnosed with glioblastoma between 1 January 2007 and 31 December 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Overall survival and survival rates determined by Kaplan-Meier method, groups compared by log-rank test. Associations between clinical characteristics and treatment approach assessed by logistic regression. Associations between treatment approach and outcome analysed by Cox regression. RESULTS: Median overall survival was 10.2 months (95% CI 9.1 to 11.3). Resection was performed in 221 patients (60.9%), and was inversely associated with age over 70 years, higher comorbidity burden, deep-seated tumour localisation and multifocality. Median survival was 13.7 months (95% CI 12.1 to 15.4) in patients undergoing tumour resection, 8.3 months (95% CI 6.6 to 9.9) in patients undergoing biopsy and 4.5 months (95% CI 4.0 to 5.1) in patients where no surgical intervention was performed. Chemoradiotherapy according to the Stupp protocol was given to 157 patients (43%). Age over 70 years, higher comorbidity burden and cognitive impairment were associated with less intensive chemoradiotherapy. Median survival was 16.3 months (95% CI 14.1 to 18.5), 7.9 months (95% CI 6.7 to 9.0) and 2.0 months (95% CI 0.9 to 3.2) in patients treated according to the Stupp protocol, with less intensive chemoradiotherapy and with best supportive care, respectively. Surgical resection (HR 0.61 (95% CI 0.47 to 0.79)) and chemoradiotherapy according to the Stupp protocol (HR 0.09 (95% CI 0.06 to 0.15)) were strongly associated with favourable overall survival, when adjusted for clinical variables. CONCLUSIONS: In a real-world setting, less than half of the patients received full-course chemoradiotherapy, with a median survival comparable to results from clinical trials. Survival was considerably worse in patients receiving less intensive treatment. Our results point out a substantial risk of undertreating glioblastoma, especially in elderly patients.

Validation of a Norwegian version of SURgical PAtient Safety System (SURPASS) in combination with the World Health Organizations' Surgical Safety Checklist (WHO SSC).

Introduction: Surgical safety checklists may contribute to reduction of complications and mortality. The WHO's Surgical Safety Checklist (WHO SSC) could prevent incidents in operating theatres, but errors also occur before and after surgery. The SURgical PAtient Safety System (SURPASS) is designed to intercept errors with use of checklists throughout the surgical pathway. Objective: We aimed to validate a Norwegian version of the SURPASS' preoperative and postoperative checklists for use in combination with the already established Sign In, Time Out and Sign Out parts of the WHO SSC. Methods and materials: The validation of the SURPASS checklists content followed WHOs recommended guidelines. The process consisted of six steps: forward translation; testing the content; focus groups; expert panels; back translation; and approval of the final version. Qualitative content analysis was used to identify codes and categories for adaption of the SURPASS checklist items throughout Norwegian surgical care. Content validity index (CVI) was used by expert panels to score the relevance of each checklist item. The study was carried out in a neurosurgical ward in a large tertiary teaching hospital in Norway. Results: Testing the preoperative and postoperative SURPASS checklists was performed in 29 neurosurgical procedures. This involved all professional groups in the entire surgical patient care pathway. Eight clinical focus groups revealed two main categories: 'Adapt the wording to fit clinical practice' and 'The checklist items challenge existing workflow'. Interprofessional scoring of the content validity of the checklists reached >80% for all the SURPASS checklists. Conclusions: The first version of the SURPASS checklists combined with the WHO SSC was validated for use in Norwegian surgical care with face validity confirmed and CVI >0.80%. Trial registration number: NCT01872195.

Patient- versus physician-reported facial disability in vestibular schwannoma: an international cross-sectional study.

OBJECTIVE Patient-reported outcomes are increasingly used in studies of vestibular schwannoma (VS); however, few studies have examined self-evaluated facial nerve function and its relation to physician-reported outcomes. The primary objective of this study was to compare patient self-evaluations of facial disability with physician-evaluated facial nerve status and with self-evaluations of a healthy control group. The second objective was to provide insight into the controversial subject of the optimal initial management of small- and medium-sized VSs; consequently, the authors compared patient-reported facial nerve disability following treatment via observation (OBS), Gamma Knife surgery (GKS), or microsurgery (MS). Lastly, the authors sought to identify risk factors for facial nerve dysfunction following treatment for small- and medium-sized VSs. METHODS All patients with a VS 3 cm or smaller that was singly treated with OBS, GKS, or MS at either of 2 independent treatment centers between 1998 and 2008 were retrospectively identified. Longitudinal facial nerve measures and clinical data, including facial nerve evaluation according to the House-Brackmann (HB) grading system, were extracted from existing VS databases. Supplementing the objective data were Facial Disability Index (FDI) scores, which were obtained via survey of patients a mean of 7.7 years after initial treatment. RESULTS The response rate among the 682 eligible patients was 79%; thus, data from a total of 539 patients were analyzed. One hundred forty-eight patients had been managed by OBS, 247 with GKS, and 144 with MS. Patients who underwent microsurgery had larger tumors and were younger than those who underwent OBS or GKS. Overall, facial nerve outcomes were satisfactory following treatment, with more than 90% of patients having HB Grade I function at the last clinical follow-up. Treatment was the major risk factor for facial nerve dysfunction. Almost one-fifth of the patients treated with MS had an objective decline in facial nerve function, whereas only 2% in the GKS group and 0% in the OBS cohort had a decline. The physical subscale of the FDI in the VS patients was highly associated with HB grade; however, the social/well-being subscale of the FDI was not. Thus, any social disability caused by facial palsy was not detectable by use of this questionnaire. CONCLUSIONS The majority of patients with small- and medium-sized VSs attain excellent long-term facial nerve function and low facial nerve disability regardless of treatment modality. Tumor size and microsurgical treatment are risk factors for facial nerve dysfunction and self-reported disability. The FDI questionnaire is sensitive to the physical but not the social impairment associated with facial dysfunction.

Tumor versus stromal cells in culture--survival of the fittest?

Two of the signature genetic events that occur in human gliomas, EGFR amplification and IDH mutation, are poorly represented in experimental models in vitro. EGFR amplification, for example, occurs in 40 to 50% of GBM, and yet, EGFR amplification is rarely preserved in cell cultures derived from human tumors. To analyze the fate of EGFR amplified and IDH mutated cells in culture, we followed the development over time of cultures derived from human xenografts in nude rats enriched for tumor cells with EGFR amplification and of cultures derived from patient samples with IDH mutations, in serum monolayer and spheroid suspension culture, under serum and serum free conditions. We observed under serum monolayer conditions, that nestin positive or nestin and SMA double positive rat stromal cells outgrew EGFR amplified tumor cells, while serum spheroid cultures preserved tumor cells with EGFR amplification. Serum free suspension culture exhibited a more variable cell composition in that the resultant cell populations were either predominantly nestin/SOX2 co-expressing rat stromal cells or human tumor cells, or a mixture of both. The selection for nestin/SMA positive stromal cells under serum monolayer conditions was also consistently observed in human oligodendrogliomas and oligoastrocytomas with IDH mutations. Our results highlight for the first time that serum monolayer conditions can select for stromal cells instead of tumor cells in certain brain tumor subtypes. This result has an important impact on the establishment of new tumor cell cultures from brain tumors and raises the question of the proper conditions for the growth of the tumor cell populations of interest.

A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.

Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP) positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H) and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.

Angiogenesis-independent tumor growth mediated by stem-like cancer cells.

In this work, highly infiltrative brain tumors with a stem-like phenotype were established by xenotransplantation of human brain tumors in immunodeficient nude rats. These tumors coopted the host vasculature and presented as an aggressive disease without signs of angiogenesis. The malignant cells expressed neural stem cell markers, showed a migratory behavior similar to normal human neural stem cells, and gave rise to tumors in vivo after regrafting. Serial passages in animals gradually transformed the tumors into an angiogenesis-dependent phenotype. This process was characterized by a reduction in stem cells markers. Gene expression profiling combined with high throughput immunoblotting analyses of the angiogenic and nonangiogenic tumors identified distinct signaling networks in the two phenotypes. Furthermore, proinvasive genes were up-regulated and angiogenesis signaling genes were down-regulated in the stem-like tumors. In contrast, proinvasive genes were down-regulated in the angiogenesis-dependent tumors derived from the stem-like tumors. The described angiogenesis-independent tumor growth and the uncoupling of invasion and angiogenesis, represented by the stem-like cancer cells and the cells derived from them, respectively, point at two completely independent mechanisms that drive tumor progression. This article underlines the need for developing therapies that specifically target the stem-like cell pools in tumors.

[Decompressive craniectomy in acute encephalitis]. / Dekomprimerende kraniektomi ved akutt encefalitt.

We report a patient with acute encephalitis of unknown causation who underwent hemicraniectomy because of threatening herniation. The patient recovered uneventfully and three weeks later, findings on neurological examination were normal. Hemicraniectomy should be considered in all patients with encephalitis and threatening herniation.

Expression of extracellular matrix components in a highly infiltrative in vivo glioma model.

This work demonstrates the expression of extracellular matrix (ECM) components in a highly infiltrative brain tumor model developed by simple inoculation of spheroids from five human glioma biopsy tissues directly into the brains of immunodeficient rats. Non-invasive tumors derived from one glioblastoma biopsy specimen and two glioma cell lines (D-54MG and U-251MG) were also included in this study. The extent of tumor cell infiltration was studied using a pan-human monoclonal anti-vimentin antibody. The cellular origin for several of these ECM components was identified using human-specific monoclonal antibodies and polyclonal antibodies detecting epitopes from both species. Immunostaining revealed a diffuse parenchymal staining of glioma-produced tenascin, whereas vitronectin was produced mainly by the invading glioma cells. ECM components such as laminin, fibronectin and collagen type IV were most probably produced by the host and were mainly associated with the blood vessels in the tumors. However, some parenchymal staining with regional variations was observed. The expression pattern of these components was different in cell lines tumors as compared to the biopsy specimen tumors. The alpha3 and beta1 integrin subunits were mainly observed in areas of tumor cell invasion in the invasive tumors. In conclusion, the observed staining patterns clarify the cellular origin and indicate the possible biological function of tenascin, vitronectin, laminin, fibronectin and collagen type IV in these highly invasive malignant tumors of glial origin.