Frequency and predictors of implant-related complications after posterior cervical fusion.

STUDY DESIGN: Retrospective, observational study. PURPOSE: To determine the frequency and predictors of implant-related complications in adults after posterior cervical fusion. OVERVIEW OF LITERATURE: Published literature on lumbosacral fusion suggest that implant-related complications are not uncommon. Although posterior cervical fusion is a common operation, data on frequency and predictors of implant-related complications after posterior cervical fusion is still scarce. METHODS: 86 patients (with 740 screws) who underwent posterior cervical fusion were included. Implant-related complications were identified by the presence of: (1) halo sign, (2) screw pull-out/breakage (3) post-operative kyphosis and (4) implant-related complications requiring revision surgery. These were stratified into two groups: (a) minor - isolated halo sign or screw pull-out/breakage (b) major - post-operative kyphosis > 10 degrees, and revision surgery. Demographic, operative and radiological data was collected. Rates of implant-related complications were determined and associated risk factors identified. RESULTS: 33 (38.4%) patients had signs of implant-related complications. Of these, 29 (87.9%) had minor complications and 4 (12.1%) had major complications. Charlson Comorbidity Index (CCI) (p = 0.03179) and pre-op C2-C7 sagittal vertical alignment (SVA) (p = 0.02449) were the only significant risk factors for all-cause implant-related complications during multivariate logistic regression. Other intraoperative parameters (type of screw, length of fusion, levels decompressed, and extension of fusion beyond the levels decompressed) were not significantly associated with implant-related complications. CONCLUSIONS: Implant-related complications are not uncommon but rarely require revision surgery. Higher pre-operative SVA and CCI were significant risk factors; length of construct and extent of decompression were not. These findings may assist clinicians when deciding the extent of fusion and in selecting patients for closer follow-up.

We assessed the frequency and predictors of implant-related complications in adults after posterior cervical fusion. Implant-related complications (halo sign, screw pull-out/breakage, post-operative kyphosis) are not uncommon but rarely require revision surgery. Higher pre-operative SVA and CCI were significant risk factors; length of construct and extent of decompression were not.

Polypyrrole-Silicon Nanowire Arrays for Controlled Intracellular Cargo Delivery.

Intracellular cargo delivery is a critical and challenging step in controlling cell states. Silicon nanowire (NW) arrays have emerged as a powerful platform for accessing the intracellular space through a combination of their nanoscale dimensions and electrical properties. Here, we develop and characterize a conductive polypyrrole (PPy)-NW device for temporally controlled intracellular delivery. Fluorescent cargos, doped in electroresponsive PPy matrices at wire tips as well as entire NW arrays, are released with an applied reducing potential. Intracellular delivery into endothelial cells from PPy-Si substrates demonstrated comparable kinetics to solution-based delivery methods while requiring an order of magnitude less cargo loading. This hybrid polymer-semiconductor platform extends methods available for intracellular delivery and links electrical signaling from artificial systems with living molecular transduction.

Substrate-Mediator Duality of 1,4-Dicyanobenzene in Electrochemical C(sp2 )-C(sp3 ) Bond Formation with Alkyl Bromides.

Electrochemical approaches to form C(sp2 )-C(sp3 ) bonds have focused on coupling C(sp3 ) electrophiles that form stabilized carbon-centered radicals upon reduction or oxidation. Whereas alkyl bromides are desirable C(sp3 ) coupling partners owing to their availability and cost-effectiveness, their tendency to undergo radical-radical homocoupling makes them challenging substrates for electroreductive cross-coupling. Herein, we disclose a metal-free regioselective cross-coupling of 1,4-dicyanobenzene, a useful precursor to aromatic nitriles, and alkyl bromides. Alkyl bromide reduction is mediated directly by 1,4-dicyanobenzene radical anions, leading to negligible homocoupling and high cross-selectivity to form 1,4-alkyl cyanobenzenes. The cross-coupling scheme is compatible with oxidatively sensitive and acidic functional groups such as amines and alcohols, which have proven difficult to incorporate in alternative electrochemical approaches using carboxylic acids as C(sp3 ) precursors.

Endoscopic excision of an aqueduct of Sylvius cavernoma causing obstructive hydrocephalus: technical note.

BACKGROUND AND IMPORTANCE: Acquired lesions within the aqueduct of Sylvius are rare and their surgical management is challenging. Open transcranial approaches require dissection and manipulation of surrounding eloquent structures. Use of an endoscope can avoid potential morbidity from traversing and handling eloquent structures during open approaches whilst providing better visualisation of an intraventricular lesion. CLINICAL PRESENTATION: A 62-year-old female presented with insidious onset short-term memory loss, unsteady gait, urinary incontinence and left-sided dysaesthesia. Magnetic resonance imaging (MRI) revealed hydrocephalus from an obstructive haemorrhagic lesion consistent with a cavernoma at the central midbrain within the aqueduct of Sylvius. An endoscopic approach was selected to provide optimal visualisation of the lesion. As only a single instrument could be accommodated, rotational movements were employed to tease out the lesion. Gross total resection was achieved. Her symptoms improved immediately postoperatively and she made a complete recovery by 2 months. Post-operative MRI showed resolution of hydrocephalus and no evidence of residual/recurrence of the lesion. Unfortunately, she developed hydrocephalus 3 months post-op and required placement of a ventriculoperitoneal shunt. CONCLUSIONS: Endoscopic resection is safe and feasible for selected periaqueductal lesions as it provides direct access while minimising disruption of the surrounding anatomical structures. The limitation of only having a single instrument can be overcome by employing rotational movements.

Bacterial Phosphate Granules Contain Cyclic Polyphosphates: Evidence from 31P Solid-State NMR.

Polyphosphates (polyPs) are ubiquitous polymers in living organisms from bacteria to mammals. They serve a wide variety of biological functions, ranging from energy storage to stress response. In the last two decades, polyPs have been primarily viewed as linear polymers with varying chain lengths. However, recent biochemical data show that small metaphosphates, cyclic oligomers of [PO3](-), can bind to the enzymes ribonuclease A and NAD kinase, raising the question of whether metaphosphates can occur naturally as products of biological activity. Before the 1980s, metaphosphates had been reported in polyPs extracted from various organisms, but these results are considered artifactual due to the extraction and purification protocols. Here, we employ nondestructive 31P solid-state NMR spectroscopy to investigate the chemical structure of polyphosphates in whole cells as well as insoluble fractions of the bacterium Xanthobacter autotrophicus. Isotropic and anisotropic 31P chemical shifts of hydrated whole cells indicate the coexistence of linear and cyclic phosphates. Under our cell growth conditions and the concentrated conditions of the solid-state NMR samples, we found substantial amounts of cyclic phosphates in X. autotrophicus, suggesting that in fresh cells metaphosphate concentrations can be significant. The cellular metaphosphates are identified by comparison with the 31P chemical shift anisotropy of synthetic metaphosphates of known structures. In X. autotrophicus, the metaphosphates have a chemical shift anisotropy that is consistent with an average size of 3-8 phosphate units. These metaphosphates are enriched in insoluble and electron-dense granules. Exogenous hexametaphosphate added to X. autotrophicus cell extracts is metabolized to trimetaphosphates, supporting the presence and biological role of metaphosphates in cells. The definitive evidence for the presence of metaphosphates, reported here in whole bacterial cells for the first time, opens the path for future investigations of the biological function of metaphosphates in many organisms.

Valorization of CO2 through lithoautotrophic production of sustainable chemicals in Cupriavidus necator.

Coupling recent advancements in genetic engineering of diverse microbes and gas-driven fermentation provides a path towards sustainable commodity chemical production. Cupriavidus necator H16 is a suitable species for this task because it effectively utilizes H2 and CO2 and is genetically tractable. Here, we demonstrate the versatility of C. necator for chemical production by engineering it to produce three products from CO2 under lithotrophic conditions: sucrose, polyhydroxyalkanoates (PHAs), and lipochitooligosaccharides (LCOs). We engineered sucrose production in a co-culture system with heterotrophic growth 30 times that of WT C. necator. We engineered PHA production (20-60% DCW) and selectively altered product composition by combining different thioesterases and phaCs to produce copolymers directly from CO2. And, we engineered C. necator to convert CO2 into the LCO, a plant growth enhancer, with titers of ~1.4 mg/L-equivalent to yields in its native source, Bradyrhizobium. We applied the LCOs to germinating seeds as well as corn plants and observed increases in a variety of growth parameters. Taken together, these results expand our understanding of how a gas-utilizing bacteria can promote sustainable production.

Use of fluorescein sodium to obtain histological diagnosis of primary Central nervous system lymphoma ghost tumour despite disappearance on intraoperative magnetic resonance imaging: technical note and review of the literature.

BACKGROUND AND IMPORTANCE: Corticosteroid pre-treatment in patients with primary central nervous system lymphoma (PCNSL) can lead to the phenomenon of ghost tumours (GhT). This affects the diagnostic yield of biopsies and potentially causes misdiagnosis of the condition. The usual strategy of neuronavigation using preoperative magnetic resonance imaging (MRI) or localisation using intraoperative MRI (iMRI) can be rendered ineffective in this situation. CLINICAL PRESENTATION: A middle-aged Chinese male with newly diagnosed human immunodeficiency virus infection was found to have an intracranial lesion suggestive of PCNSL. Preoperatively corticosteroid led to an attenuation of the contrast enhancing lesion on iMRI. However, intraoperative use of FS allowed the successful identification, biopsy and diagnosis of the condition. CONCLUSION: FS is useful in the biopsy of PCNSL GhT even when the lesion is not seen in subsequent MRI imaging.

Two-year experience of multi-disciplinary team (MDT) outcomes for brain metastases in a tertiary neuro-oncology centre.

Brain metastases (BMs) are the most common intracranial tumour in adults and form a significant proportion of the neuro-oncology workload. Their management has progressed significantly in the last few decades but a gold-standard evidence-based management strategy has not been defined to date and several guidelines based on available evidence exist to support clinical decision-making. This paper evaluates the decision-making process of the neuro-oncology multi-disciplinary team (MDT) in a tertiary neuro-oncology centre over a two-year period. A retrospective review of all patients with BM discussed in the MDT was conducted. Data on patient demographics, tumour characteristics and MDT decision were collected from the MDT database, clinical notes and imaging studies. Patients were stratified into the three recursive partitioning analysis (RPA) classes and according to the graded prognostic assessment (GPA) score. MDT decisions were analysed by RPA class and for GPA score as well as single versus multiple BM. There were 362 patients with BM, representing 22% of the total cases discussed at the MDT. Decision-making was largely consistent with available guidelines. A concrete treatment decision was reached in 77.5% of patients and 32.2% of these received neurosurgical input. More patients with solitary BM underwent surgery compared to multiple BM (p = 0.001), and more patients in RPA classes I and II had surgical resection compared to class III (p = 0.005 and 0.001, respectively). Surgical patients also had higher GPA scores compared to palliative patients (p = 0.005). A greater absolute number and proportion of patients in RPA class II vs. class I underwent neurosurgical intervention. These patients were stratified into class II because of their age but would otherwise have been placed into class I. Survival data were available for 195 patients (53.8%) at 1 year post MDT discussion. A pattern of declining survival was observed along RPA classes which was statistically significant (p = 0.0025). Median survival was 4.7 (0-41), 3.7 (0-23), and 2.5 (range 0-24) months for RPA class I, II and III respectively. A similar pattern that did not reach statistical significance was found between GPA scores (p = 0.101). Median survival was 3 (0-13), 4.6 (range 0-41), and 4.6 (0-35) months for GPA scores 0-1.0, 1.5-2.5 and 3-4.0, respectively. Patient selection was generally in accordance to RPA class and GPA scoring, with the exception of surgery offered to elderly patients: this can be explained by the increasing number of otherwise fit patients as population ages.

Targeted Disruption of the Interaction between WD-40 Repeat Protein 5 (WDR5) and Mixed Lineage Leukemia (MLL)/SET1 Family Proteins Specifically Inhibits MLL1 and SETd1A Methyltransferase Complexes.

MLL1 belongs to the SET1 family of histone H3 lysine 4 (H3K4) methyltransferases, composed of MLL1-4 and SETd1A/B. MLL1 translocations are present in acute leukemias, and mutations in several family members are associated with cancer and developmental disorders. MLL1 associates with a subcomplex containing WDR5, RbBP5, ASH2L, and DPY-30 (WRAD), forming the MLL1 core complex required for H3K4 mono- and dimethylation and transcriptional activation. Core complex assembly requires interaction of WDR5 with the MLL1 Win (WDR5 interaction) motif, which is conserved across the SET1 family. Agents that mimic the SET1 family Win motif inhibit the MLL1 core complex and have become an attractive approach for targeting MLL1 in cancers. Like MLL1, other SET1 family members interact with WRAD, but the roles of the Win motif in complex assembly and enzymatic activity remain unexplored. Here, we show that the Win motif is necessary for interaction of WDR5 with all members of the human SET1 family. Mutation of the Win motif-WDR5 interface severely disrupts assembly and activity of MLL1 and SETd1A complexes but only modestly disrupts MLL2/4 and SETd1B complexes without significantly altering enzymatic activity in vitro Notably, in the absence of WDR5, MLL3 interacts with RAD and shows enhanced activity. To further probe the role of the Win motif-WDR5 interaction, we designed a peptidomimetic that binds WDR5 (Kd ∼3 nm) and selectively inhibits activity of MLL1 and SETd1A core complexes within the SET1 family. Our results reveal that SET1 family complexes with the weakest Win motif-WDR5 interaction are more susceptible to Win motif-based inhibitors.

Characteristics and Postoperative Outcomes for High Cervical versus Subaxial Cervical Intradural Extramedullary Tumors: A Multicenter Study.

BACKGROUND: High cervical intradural extramedullary tumors are uncommon. Their relationship to surrounding neural structures and vertebral arteries makes surgical excision challenging. No previous studies have compared high cervical to subaxial cervical intradural extramedullary spinal tumors to elucidate their unique characteristics and surgical outcomes. METHODS: We performed a retrospective study in which patients who underwent excision of a cervical intradural extramedullary tumor were divided into a high cervical group and a subaxial cervical group. Variables included sex, age, Charlson Comorbidity Index, volume, laterality, preoperative weakness, use of neuromonitoring and drains, instrumented fusion, complications, length of stay, histology, discharge location, recurrence, and duration of follow-up. Variables were compared between the 2 groups. Limb power and Nurick classification were charted preoperatively, at discharge, and at 6 months to plot their recovery trajectory. RESULTS: Eighty-four patients with a total of 90 tumors were enrolled, including 40 patients in the high cervical group and 44 patients in the subaxial spine group. More patients with neurofibromas (P = 0.011) and bilateral tumors (P = 0.044) were in the high cervical group. A greater prevalence of neurofibromatosis type 1 was significant for bilateral high cervical tumors (P = 0.033). More patients in the subaxial group had instrumented fusion (P = 0.045). More patients in the high cervical group had improvement in limb power (P = 0.025) and Nurick classification (P = 0.0001) postoperatively before discharge. By 6 months, both groups had similar recovery. No mortality was attributable to surgery in either group. CONCLUSION: High cervical intradural extramedullary spine tumors have more bilateral tumors associated with neurofibromatosis type 1. Despite the challenging anatomy, surgical resection is safe with good outcomes in this group.

Cerebral Arteriovenous Malformation Recurrence After Complete Surgical Excision in an Adult: Case Report and Review of the Literature.

Angiographically confirmed complete surgical excision of brain arteriovenous malformations (bAVMs) is conventionally considered curative. Recurrence in adults is rarely encountered; only 18 cases have been reported in the English literature over the past 30 years. The potential for recurrence and consequent need for routine long-term follow-up are important considerations in the management of these lesions. We report a case of a 23-year-old female with a recurrent bAVM discovered incidentally on routine imaging three years after complete surgical excision. We review the existing literature and discuss the options for surveillance and management.

Microcatheter-Assisted Protection of the Posterior Inferior Cerebellar Artery During Parent Artery Sacrifice of a Vertebral Artery Dissecting Aneurysm.

Branch vessel occlusion is a major cause of stroke in parent artery sacrifice (PAS) for vertebral artery dissecting aneurysms (VADA). There is now an increasing trend towards preservation of branch vessels during PAS. Stents are commonly employed to achieve this but bring with it the attendant risks of future thrombosis and lifelong antiplatelet use. Although a microcatheter protection technique has been utilised in branch artery protection of wide-necked saccular aneurysms, it has rarely been described in PAS for VADAs. We describe the use of a dual microcatheter technique in the protection and remodelling of the posterior inferior cerebellar artery (PICA) during PAS of the vertebral artery, which also served as a temporary scaffold to support placement of the coils during the embolisation process.

Posterior Fossa Surgery for Stroke: Differences in Outcomes Between Cerebellar Hemorrhage and Infarcts.

BACKGROUND: Posterior fossa surgery is the established treatment for large cerebellar strokes with brainstem compression. Despite this, there is a paucity of data for long-term outcomes. METHODS: A retrospective analysis of patients who underwent posterior fossa surgery for cerebellar hemorrhages and infarcts was performed to compare their difference in 6-month outcomes and to identify factors that affect outcomes. Patients were dichotomized into groups with good outcomes (modified Rankin scale [mRS] score 0-3) or poor outcomes (mRS score 4-6). Sex, age, preoperative Glasgow Coma Scale score, Charleston comorbidity index, time to surgery, intraventricular hemorrhage, surgical complications, length of intensive care unit and hospital stay, shunt dependence, and tracheostomy rates were analyzed. RESULTS: In total, 126 patients were recruited: 76 in hemorrhage group and 50 in infarct group. There was a greater mortality in the hemorrhage group (P = 0.0730). At 6 months, more patients in the hemorrhage group had poor outcomes (P = 0.0074, odds ratio 3.04) and greater mortality (P = 0.0730, odds ratio 2.20). More patients in the hemorrhage group required a tracheostomy (P = 0.0245). Factors predictive of poor outcome include older age (P = 0.0108), Glasgow Coma Scale score ≤8 (P = 0.0011), and tracheostomy (P = 0.0269). A total of 69.2% of patients had improvements in mRS scores at 6 months. Shorter length of stay (P = 0.0003) and discharge to a rehabilitation hospital (P = 0.0001) were predictive of functional improvement. CONCLUSIONS: Patients who underwent posterior fossa surgery for cerebellar hemorrhage had worse outcomes compared with patients with cerebellar infarcts and were more likely to require a tracheostomy. Rehabilitation helped to improved outcomes.

When hoofbeats mean zebras not horses: Tumour mimics of subdural haematoma - Case series and literature review.

Chronic subdural haematomas are common neurosurgical conditions, especially in the elderly patients, with straightforward surgical treatments. However, infrequently, tumours are misdiagnosed as subdural haematoma on initial brain CT scans and are only discovered intraoperatively. In this case series, we presented 3 different patients who were initially thought to have subdural haematoma but later found to be tumour mimics of different histological origin. A literature review and discussion of recently published tumour mimics of subdural haematoma was also performed. It is recommended that in patients with suggestive oncological or haematological history, or unusual characteristics on the plain CT brain, a high level of suspicion of tumour mimics needs to be maintained. A full workup with contrast-enhanced magnetic resonance imaging is important to distinguish from subdural haematoma, as the treatment paradigms and prognoses are vastly different.