In-House Intraoperative Monitoring in Neurosurgery in England - Benefits and Challenges.

BACKGROUND: Intraoperative neurophysiological monitoring (IOM) is a valuable adjunct for neurosurgical operative techniques, and has been shown to improve clinical outcomes in cranial and spinal surgery. It is not necessarily provided by NHS hospitals so may be outsourced to private companies, which are expensive and at cost to the NHS trusts. We discuss the benefits and challenges of developing an in-house service. METHODS: We surveyed NHS neurosurgical departments across England regarding their expenditure on IOM over the period January 2018 - December 2022 on cranial neurosurgery and spinal surgery. Out of 24 units, all responded to our Freedom of Information requests and 21 provided data. The standard NHS England salary of NHS staff who would normally be involved in IOM, including physiologists and doctors, was also compiled for comparison. RESULTS: The total spend on outsourced IOM, across the units who responded, was over £8 million in total for the four years. The annual total increased, between 2018 and 2022, from £1.1 to £3.5 million. The highest single unit yearly spend was £568,462. This is in addition to salaries for staff in neurophysiology departments. The mean NHS salaries for staff is also presented. CONCLUSION: IOM is valuable in surgical decision-making, planning, and technique, having been shown to lead to fewer patient complications and shorter length of stay. Current demand for IOM outstrips the internal NHS provision in many trusts across England, leading to outsourcing to private companies. This is at significant cost to the NHS. Although there is a learning curve, there are many benefits to in-house provision, such as stable working relationships, consistent methods, training of the future IOM workforce, and reduced long-term costs, which planned expansion of NHS services may provide.

Laser- and cryogenic probe-assisted NMR enables hypersensitive analysis of biomolecules at submicromolar concentration.

Solution-state NMR typically requires 100 µM to 1 mM samples. This limitation prevents applications to mass-limited and aggregation-prone target molecules. Photochemically induced dynamic nuclear polarization was adapted to data collection on low-concentration samples by radiofrequency gating, enabling rapid 1D NMR spectral acquisition on aromatic amino acids and proteins bearing aromatic residues at nanomolar concentration, i.e., a full order of magnitude below other hyperpolarization techniques in liquids. Both backbone H1-C13 and side-chain resonances were enhanced, enabling secondary and tertiary structure analysis of proteins with remarkable spectral editing, via the 13C PREPRINT pulse sequence. Laser-enhanced 2D NMR spectra of 5 µM proteins at 600 MHz display 30-fold better S/N than conventional 2D data collected at 900 MHz. Sensitivity enhancements achieved with this technology, denoted as low-concentration photo-CIDNP (LC-photo-CIDNP), depend only weakly on laser intensity, highlighting the opportunity of safer and more cost-effective hypersensitive NMR applications employing low-power laser sources.

Is Disruptive Behavior Inherent to the Surgeon or the Environment? Analysis of 314 Events at a Single Academic Medical Center.

OBJECTIVE: In 2009, the Joint Commission mandated a process to manage disruptive behavior, as evidence suggests it undermines a culture of safety. This process often reviews only the reporter's side of the story as the truth. In this study, we compared both reporter account (RA) and involved party (IP) responses to determine if disruptive behavior was inherent to the surgeon or the hospital environment and its relationship to patient safety. METHODS: From 1/1/2015 through 12/31/2017, we prospectively recorded the RA and the IP response. This resulted in 314 reports involving 204 IPs. Four reviewers scored issues, interactions, modifiable stressors, and patient safety. Logistic regression determined factors associated with patient harm. Significance defined as P < 0.05. RESULTS: Surgical, medical, and other specialties were IPs 43%, 35%, and 22%, respectively; 73% had only one event. High-intensity environments (OR, ICU, etc.) made up 56% of the total. Perceived unprofessional or lack of communication was present in 70% and 44% of events. A significant direct relationship existed between the stress of the clinical situation and the egregiousness of the behavior (P < 0.0001). Logistic regression revealed that unclear hospital policies, the IP being a surgeon, and urgent competing responsibilities were associated with potential patient harm (P < 0.05). CONCLUSIONS: Unclear policies and urgent competing responsibilities in the surgical environment create stress, leading to conflict. Single events for the majority suggest the environment as the primary contributor. Tactics to improve stressful environments and clearly communicated policies may be more effective and sustainable than individually targeted interventions in enhancing patient safety.

Palladium Acetate Revisited: Unusual Ring-Current Effects, One-Electron Reduction, and Metal-Metal Bonding.

Palladium(II) acetate (1) and two new complexes of the ligand α,α,α',α'-tetramethyl-1,3-benzenedipropionate (esp2-), C s-Pd3(esp)3 ( Cs-2) and C3 h-Pd3(esp)3 ( C3 h-2), are studied in the solid state and in solution. Variable-temperature NMR and DFT studies of C s-2 reveal an unusual shielding region above the Pd atoms. The compounds show a surprising quasi-reversible reduction between -880 and -1200 mV versus Fc/Fc+, and the Pd3(esp)3 complexes may be cleanly reduced electrochemically. EPR spectra of reduced samples show pseudo-axial signals with 105Pd hyperfine coupling, consistent with unprecedented, isostructural Pd35+ species with a valence-trapped PdII-PdII-PdI electronic structure.

Dynamics and Morphology of Nanoparticle-Linked Polymers Elucidated by Nuclear Magnetic Resonance.

Nanoparticles are frequently modified with polymer layers to control their physical and chemical properties, but little is understood about the morphology and dynamics of these polymer layers. We report here an NMR-based investigation of a model polymer-modified nanoparticle, using multiple NMR techniques including 1H NMR, diffusion-ordered spectroscopy (DOSY), total correlation spectroscopy (TOCSY), and T2 relaxometry to characterize the dynamics of the nanoparticle-polymer interface. Using 5 nm detonation nanodiamond covalently linked to poly(allylamine) hydrochloride as a model system, we demonstrate the use of NMR to distinguish between free and bound polymer and to characterize the degree to which the segments of the nanoparticle-wrapping polymer are mobile (loops and tails) versus immobile (trains). Our results show that the polymer-wrapped nanoparticle contains a large fraction of highly mobile polymer segments, implying that the polymer extends well into solution away from the nanoparticle surface. Flexible, distal polymer segments are likely to be more accessible to extended objects such as cell membranes, compared with polymer segments that are in close proximity to the nanoparticle surface. Thus, these flexible segments may be particularly important in controlling subsequent interactions of the nanoparticles. While reported here for a model system, the methodology used demonstrates how NMR methods can provide important insights into the structure and dynamics at nanoparticle-polymer interfaces, leading to new perspectives on the behavior and interactions of polymer-functionalized nanoparticles in aqueous systems.

Synthesis, Characterization, and Variable-Temperature NMR Studies of Silver(I) Complexes for Selective Nitrene Transfer.

An array of silver complexes supported by nitrogen-donor ligands catalyze the transformation of C═C and C-H bonds to valuable C-N bonds via nitrene transfer. The ability to achieve high chemoselectivity and site selectivity in an amination event requires an understanding of both the solid- and solution-state behavior of these catalysts. X-ray structural characterizations were helpful in determining ligand features that promote the formation of monomeric versus dimeric complexes. Variable-temperature 1H and DOSY NMR experiments were especially useful for understanding how the ligand identity influences the nuclearity, coordination number, and fluxional behavior of silver(I) complexes in solution. These insights are valuable for developing improved ligand designs.

Structurally Diverse Diazafluorene-Ligated Palladium(II) Complexes and Their Implications for Aerobic Oxidation Reactions.

4,5-Diazafluoren-9-one (DAF) has been identified as a highly effective ligand in a number of Pd-catalyzed oxidation reactions, but the mechanistic basis for its utility has not been elucidated. Here, we present the complex coordination chemistry of DAF and palladium(II) carboxylate salts. Multiple complexes among an equilibrating mixture of species have been characterized by (1)H and (15)N NMR spectroscopy and X-ray crystallography. These complexes include monomeric and dimeric Pd(II) species, with monodentate (κ(1)), bidentate (κ(2)), and bridging (µ:κ(1):κ(1)) DAF coordination modes. Titration studies of DAF and Pd(OAc)2 reveal the formation of two dimeric DAF/Pd(OAc)2 complexes at low [DAF] and four monomeric species at higher [DAF]. The dimeric complexes feature two bridging acetate ligands together with either a bridging or nonbridging (κ(1)) DAF ligand coordinated to each Pd(II) center. The monomeric structures consist of three isomeric Pd(κ(1)-DAF)2(OAc)2 complexes, together with Pd(κ(2)-DAF)(OAc)2 in which the DAF exhibits a traditional bidentate coordination mode. Replacing DAF with the structurally related, but more-electron-rich derivative 9,9-dimethyl-4,5-diazafluorene (Me2DAF) simplifies the equilibrium mixture to two complexes: a dimeric species in which the Me2DAF bridges the two Pd centers and a monomeric species with a traditional κ(2)-Me2DAF coordination mode. The use of DAF in combination with other carboxylate ligands (CF3CO2(-) or tBuCO2(-)) also results in a simplified collection of equilibrating Pd(II)-DAF complexes. Collectively, the results highlight the ability of DAF to equilibrate rapidly among multiple coordination modes, and provide valuable insights into the utility of DAF as a ligand in Pd-catalyzed oxidation reactions.

Kinetic and thermodynamic characterization of C-N bond rotation by N-methylacetohydroxamic acid in aqueous media.

Hydroxamic acids (HAs) perform tasks in medicine and industry that require bidentate metal binding. The two favored conformations of HAs are related by rotation around the C(=O)-N bond. The conformations are unequal in stability. Recently, we reported that the most stable conformation of a small secondary HA in water places the oxygen atoms anti to one another. The barrier to C-N bond rotation may therefore modulate metal binding by secondary HAs in aqueous media. We have now determined the activation barrier to C-N rotation from major to minor conformation of a small secondary HA in D2O to be 67.3 kJ/mol. The HA rotational barrier scales with solvent polarity, as is observed in amides, although the HA barrier is less than that of a comparable tertiary amide in aqueous solution. Successful design of new secondary HAs to perform specific tasks requires solid understanding of rules governing HA structural behavior. Results from this work provide a more complete foundation for HA design efforts.

Solwaric acids A and B, antibacterial aromatic acids from a marine Solwaraspora sp.

Two novel trialkyl-substituted aromatic acids, solwaric acids A and B, were isolated from a marine Solwaraspora sp. cultivated from the ascidian Trididemnum orbiculatum. Solwaric acids A and B were isotopically labeled with U-¹³C glucose, and analysis of a ¹³C-¹³C COSY allowed for unambiguous determination of the location of the phenyl methyl group. The two novel compounds demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA).

Brain tumours in children: importance of early identification.

A Brain tumours account for a quarter of all childhood cancers in the UK but are the leading cause of cancer-related deaths in children. Studies have previously shown that there is a delay in diagnosing brain tumours in children in the UK. The HeadSmart campaign was launched to increase awareness among health professionals working in different settings regarding brain tumour symptoms in children. Although headache is considered to be one of the most important symptoms, it is not often reported in paediatric practice, especially if the child is young. The HeadSmart symptom card is a useful resource and should be used when dealing with a child with symptoms suggestive of brain tumours. Nurses working in different settings play a vital role in early identification of brain tumours and also in supporting the child and his/her family through the child's journey following diagnosis of a brain tumour. The HeadSmart campaign has led to a reduction in the total diagnostic interval, to 7 weeks, and the ultimate aim is to reduce it further to 5 weeks which will be on a par with the time taken to diagnose brain tumours in children in other developed countries.

The role of the electroencephalogram (EEG) in determining the aetiology of catatonia: a systematic review and meta-analysis of diagnostic test accuracy.

Background: Catatonia is a psychomotor syndrome that has a wide range of aetiologies. Determining whether catatonia is due to a medical or psychiatric cause is important for directing treatment but is clinically challenging. We aimed to ascertain the performance of the electroencephalogram (EEG) in determining whether catatonia has a medical or psychiatric cause, conventionally defined. Methods: In this systematic review and meta-analysis of diagnostic test accuracy (PROSPERO CRD42021239027), Medline, EMBASE, PsycInfo, and AMED were searched from inception to May 11, 2022 for articles published in peer-reviewed journals that reported EEG findings in catatonia of a medical or psychiatric origin and were reported in English, French, or Italian. Eligible study types were clinical trials, cohort studies, case-control studies, cross-sectional studies, case series, and case reports. The reference standard was the final clinical diagnosis. Data extraction was conducted using individual patient-level data, where available, by two authors. We prespecified two types of studies to overcome the limitations anticipated in the data: larger studies (n ≥ 5), which were suitable for formal meta-analytic methods but generally lacked detailed information about participants, and smaller studies (n < 5), which were unsuitable for formal meta-analytic methods but had detailed individual patient level data, enabling additional sensitivity analyses. Risk of bias and applicability were assessed with the QUADAS-2 tool for larger studies, and with a published tool designed for case reports and series for smaller studies. The primary outcomes were sensitivity and specificity, which were derived using a bivariate mixed-effects regression model. Findings: 355 studies were included, spanning 707 patients. Of the 12 larger studies (5 cohort studies and 7 case series), 308 patients were included with a mean age of 48.2 (SD = 8.9) years. 85 (52.8%) were reported as male and 99 had catatonia due to a general medical condition. In the larger studies, we found that an abnormal EEG predicted a medical cause of catatonia with a sensitivity of 0.82 (95% CI 0.67-0.91) and a specificity of 0.66 (95% CI 0.45-0.82) with an I 2 of 74% (95% CI 42-100%). The area under the summary ROC curve offered excellent discrimination (AUC = 0.83). The positive likelihood ratio was 2.4 (95% CI 1.4-4.1) and the negative likelihood ratio was 0.28 (95% CI 0.15-0.51). Only 5 studies had low concerns in terms of risk of bias and applicability, but a sensitivity analysis limited to these studies was similar to the main analysis. Among the 343 smaller studies, 399 patients were included, resulting in a sensitivity of 0.76 (95% CI 0.71-0.81), specificity of 0.67 (0.57-0.76) and AUC = 0.71 (95% CI 0.67-0.76). In multiple sensitivity analyses, the results were robust to the exclusion of reports of studies and individuals considered at high risk of bias. Features of limbic encephalitis, epileptiform discharges, focal abnormality, or status epilepticus were highly specific to medical catatonia, but features of encephalopathy had only moderate specificity and occurred in 23% of the cases of psychiatric catatonia in smaller studies. Interpretation: In cases of diagnostic uncertainty, the EEG should be used alongside other investigations to ascertain whether the underlying cause of catatonia is medical. The main limitation of this review is the differing thresholds for considering an EEG abnormal between studies. Funding: Wellcome Trust, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust.

A comparative clinical, pathological, biochemical and genetic study of fused in sarcoma proteinopathies.

Neuronal intermediate filament inclusion disease and atypical frontotemporal lobar degeneration are rare diseases characterized by ubiquitin-positive inclusions lacking transactive response DNA-binding protein-43 and tau. Recently, mutations in the fused in sarcoma gene have been shown to cause familial amyotrophic lateral sclerosis and fused in sarcoma-positive neuronal inclusions have subsequently been demonstrated in neuronal intermediate filament inclusion disease and atypical frontotemporal lobar degeneration with ubiquitinated inclusions. Here we provide clinical, imaging, morphological findings, as well as genetic and biochemical data in 14 fused in sarcoma proteinopathy cases. In this cohort, the age of onset was variable but included cases of young-onset disease. Patients with atypical frontotemporal lobar degeneration with ubiquitinated inclusions all presented with behavioural variant frontotemporal dementia, while the clinical presentation in neuronal intermediate filament inclusion disease was more heterogeneous, including cases with motor neuron disease and extrapyramidal syndromes. Neuroimaging revealed atrophy of the frontal and anterior temporal lobes as well as the caudate in the cases with atypical frontotemporal lobar degeneration with ubiquitinated inclusions, but was more heterogeneous in the cases with neuronal intermediate filament inclusion disease, often being normal to visual inspection early on in the disease. The distribution and severity of fused in sarcoma-positive neuronal cytoplasmic inclusions, neuronal intranuclear inclusions and neurites were recorded and fused in sarcoma was biochemically analysed in both subgroups. Fused in sarcoma-positive neuronal cytoplasmic and intranuclear inclusions were found in the hippocampal granule cell layer in variable numbers. Cortical fused in sarcoma-positive neuronal cytoplasmic inclusions were often 'Pick body-like' in neuronal intermediate filament inclusion disease, and annular and crescent-shaped inclusions were seen in both conditions. Motor neurons contained variable numbers of compact, granular or skein-like cytoplasmic inclusions in all fused in sarcoma-positive cases in which brainstem and spinal cord motor neurons were available for study (five and four cases, respectively). No fused in sarcoma mutations were found in any cases. Biochemically, two major fused in sarcoma species were found and shown to be more insoluble in the atypical frontotemporal lobar degeneration with ubiquitinated inclusions subgroup compared with neuronal intermediate filament inclusion disease. There is considerable overlap and also significant differences in fused in sarcoma-positive pathology between the two subgroups, suggesting they may represent a spectrum of the same disease. The co-existence of fused in sarcoma-positive inclusions in both motor neurons and extramotor cerebral structures is a characteristic finding in sporadic fused in sarcoma proteinopathies, indicating a multisystem disorder.

Chemically reversible four-electron oxidation and reduction utilizing two inorganic functional groups.

Four-electron oxidation of the quadruply bonded W(2)(II,II) compound W(2)(2,2'-dipyridylamide)(4), 1, results in the formation of a novel, diamagnetic ditungsten terminal oxo compound [W(2)O(2,2'-dipyridylamide)(4)](2+), 2. In contrast to the chemical inertness of mononuclear tungsten oxo species, 2 undergoes a four-electron reduction including oxygen-atom transfer in reactions with excess tri-tert-butylphosphine in acetonitrile to recover 1. This unusual chemically reversible multielectron reactivity is ascribed to the cooperation of W-O and W-W multiple bonding.

Radical cation Diels-Alder cycloadditions by visible light photocatalysis.

Ruthenium(II) polypyridyl complexes promote the efficient radical cation Diels-Alder cycloaddition of electron-rich dienophiles upon irradiation with visible light. These reactions enable facile [4 + 2] cycloadditions that would be electronically mismatched under thermal conditions. Key to the success of this methodology is the availability of ligand-modified ruthenium complexes that enable rational tuning of the electrochemical properties of the catalyst without significantly perturbing the overall photophysical properties of the system.

Glyoxal in aqueous ammonium sulfate solutions: products, kinetics and hydration effects.

Reactions and interactions between glyoxal and salts in aqueous solution were studied. Glyoxal was found to react with ammonium to form imidazole, imidazole-2-carboxaldehyde, formic acid, N-glyoxal substituted imidazole, and minor products at very low concentrations. Overall reaction orders and rates for each major product were measured. Sulfate ions have a strong and specific interaction with glyoxal in aqueous solution, which shifts the hydration equilibria of glyoxal from the unhydrated carbonyl form to the hydrated form. This ion-specific effect contributes to the observed enhancement of the effective Henry's law coefficient for glyoxal in sulfate-containing solutions. The results of UV-vis absorption and NMR spectroscopy studies of solutions of glyoxal with ammonium, methylamine, and dimethylamine salts reveal that light absorbing compounds require the formation of nitrogen containing molecules. These findings have implications on the role of glyoxal in the atmosphere, both in models of the contribution of glyoxal to form secondary organic aerosol (SOA), the role of nitrogen containing species for aerosol optical properties and in predictions of the behavior of other carbonyls or dicarbonyls in the atmosphere.

Recurrent strokes in an occult case of recurrent Cutibacterium acnes prosthetic valve infective endocarditis: a case report.

BACKGROUND: Infective endocarditis (IE) is a known but uncommon cause of cardioembolic stroke and there are rare but recognized cases of IE without an inflammatory response. Cutibacterium acnes is an increasingly recognized source of invasive infections, including IE, but diagnosis is challenging due to its low virulence and fastidious nature. CASE SUMMARY: A 47-year-old man presented with a multi-focal stroke suggestive of a cardioembolic source. Outpatient transoesophageal echocardiography (TOE) was concerning for vegetation or thrombus associated with his previous mitral valve repair. He remained clinically well, with no evidence of an inflammatory response and sterile blood cultures. Computed tomography-positron emission tomography (CT-PET) corroborated the TOE findings, however, given the atypical presentation, he was treated for valvular thrombus. Following discharge, he quickly re-presented with further embolic phenomena and underwent emergency mitral valve replacement. Intraoperative findings were consistent with prosthetic valve IE (PVE) and a 6-week course of antibiotics commenced. C. acnes was identified on molecular testing. Eighteen months later, he re-presented with further neurological symptoms. Early TOE and CT-PET were consistent with IE. Blood cultures grew C. acnes after prolonged incubation. Given the absence of surgical indications, he was managed medically, and the vegetation resolved without valvular dysfunction. He continues to be followed up in an outpatient setting. DISCUSSION: In patients presenting with multi-territory stroke, IE should be considered despite sterile blood cultures and absent inflammatory response. C. acnes is an increasingly recognized cause of PVE in this context, often requiring surgical intervention. A high index of suspicion and collaboration with an Endocarditis Team is therefore essential to diagnose and treat.

A metastable RuIII azido complex with metallo-Staudinger reactivity.

The metastable purple [(Py5Me2)RuIII(N3)]2+ ion reacts with PPh3 at room temperature to form the phosphinimine complex [(Py5Me2)RuII(N(H)PPh3)]2+ and free [H2NPPh3]+ in a combined 23% conversion. Mechanistic studies suggest that this is the first metallo-Staudinger reaction of a late transition metal that bypasses the nitrido mechanism and instead utilizes a Ru-N[double bond, length as m-dash]N[double bond, length as m-dash]N-PPh3 phosphazide intermediate.

Influence of strand number on antiparallel beta-sheet stability in designed three- and four-stranded beta-sheets.

We describe experiments that probe whether antiparallel beta-sheet secondary structure becomes more stable as the number of strands increases. Several groups, including ours, have explored this issue with peptides designed to adopt three-stranded beta-sheet conformations, but the conclusions have not been consistent. In this study, we examine the effect on conformational stability of beta-sheet lengthening perpendicular to the strand direction via analysis of designed peptides that adopt three-stranded or four-stranded antiparallel beta-sheet conformations in aqueous solution. The findings reported here, along with the context provided by earlier studies, suggest that antiparallel beta-sheet does, in general, become more stable when the number of strands is increased from two to three. We show that this conclusion is not influenced by the rigidity of the loop segment used to link adjacent beta-strands (D-Pro-Gly versus Asn-Gly). We show that further extension, from three strands to four, leads to a further increase in antiparallel beta-sheet stability.

Abbreviated protocol for breast MRI: are multiple sequences needed for cancer detection?

OBJECTIVE: To evaluate the ability of an abbreviated breast magnetic resonance imaging (MRI) protocol, consisting of a precontrast T1 weighted (T1W) image and single early post-contrast T1W image, to detect breast carcinoma. MATERIALS AND METHODS: A HIPAA compliant Institutional Review Board approved review of 100 consecutive breast MRI examinations in patients with biopsy proven unicentric breast carcinoma. 79% were invasive carcinomas and 21% were ductal carcinoma in situ. Four experienced breast radiologists, blinded to carcinoma location, history and prior examinations, assessed the abbreviated protocol evaluating only the first post-contrast T1W image, post-processed subtracted first post-contrast and subtraction maximum intensity projection images. Detection and localization of tumor were compared to the standard full diagnostic examination consisting of 13 pre-contrast, post-contrast and post-processed sequences. RESULTS: All 100 cancers were visualized on initial reading of the abbreviated protocol by at least one reader. The mean sensitivity for each sequence was 96% for the first post-contrast sequence, 96% for the first post-contrast subtraction sequence and 93% for the subtraction MIP sequence. Within each sequence, there was no significant difference between the sensitivities among the 4 readers (p=0.471, p=0.656, p=0.139). Mean interpretation time was 44s (range 11-167s). The abbreviated imaging protocol could be performed in approximately 10-15 min, compared to 30-40 min for the standard protocol. CONCLUSION: An abbreviated breast MRI protocol allows detection of breast carcinoma. One pre and post-contrast T1W sequence may be adequate for detecting breast carcinoma. These results support the possibility of refining breast MRI screening protocols.