Selective dorsal rhizotomy in non-ambulant children with cerebral palsy: a multi-center prospective study.

PURPOSE: Assess the effects of selective dorsal rhizotomy (SDR) on motor function and quality of life in children with a Gross Motor Function Classification System (GMFCS) level of IV or V (non-ambulatory). METHODS: This is a prospective, observational study in three tertiary neurosurgery units in England, UK, performing SDR on children aged 3-18 with spastic diplegic cerebral palsy, and a GMFCS level of IV or V, between 2012 and 2019. The primary outcome measure was the change in the 66-item Gross Motor Function Measure (GMFM-66) from baseline to 24 months after SDR, using a linear mixed effects model. Secondary outcomes included spasticity, bladder function, quality of life, and pain scores. RESULTS: Between 2012 and 2019, 144 children who satisfied these inclusion criteria underwent SDR. The mean age was 8.2 years. Fifty-two percent were female. Mean GMFM-66 score was available in 77 patients (53.5%) and in 39 patients (27.1%) at 24 months after SDR. The mean increase between baseline and 24 months post-SDR was 2.4 units (95% CI 1.7-3.1, p < 0.001, annual change 1.2 units). Of the 67 patients with a GMFM-66 measurement available, a documented increase in gross motor function was seen in 77.6% (n = 52). Of 101 patients with spasticity data available, mean Ashworth scale decreased after surgery (2.74 to 0.30). Of patients' pain scores, 60.7% (n = 34) improved, and 96.4% (n = 56) of patients' pain scores remained the same or improved. Bladder function improved in 30.9% of patients. CONCLUSIONS: SDR improved gross motor function and reduced pain in most patients at 24 months after surgery, although the improvement is less pronounced than in children with GMFCS levels II and III. SDR should be considered in non-ambulant patients.

Quality of life outcomes in incidental and operated meningiomas (QUALMS): a cross-sectional cohort study.

INTRODUCTION: Few studies have evaluated meningioma patients' longer-term health-related quality of life (HRQoL) following diagnosis and treatment, particularly in those with incidental, actively monitored tumours. METHODS: A single-center, cross-sectional study was completed. Adult patients with surgically managed or actively monitored meningioma with more than five years of follow-up were included. The patient-reported outcome measures RAND SF-36, EORTC QLQ-C30 and QLQ-BN20 were used to evaluate HRQoL. HRQoL scores were compared to normative population data. Outcome determinants were evaluated using multivariate linear regression analysis. RESULTS: 243 patient responses were analyzed, and the mean time from diagnosis was 9.8 years (range 5.0-40.3 years). Clinically relevant, statistically significant HRQoL impairments were identified across several SF-36 and QLQ-C30 domains. Increasing education level (ß = 2.9, 95% CI 0.9 to 4.9), P = .004), employment (ß = 7.7, 95% CI 2.2 to 13.1, P = .006) and absence of postoperative complications (ß=-6.7, 95% CI -13.2 to (-)0.3, P = .041) were associated with a better QLQ-C30 summary score. Other tumour and treatment variables were not. CONCLUSION: This study highlights the longer-term disease burden of patients with meningioma nearly one decade after diagnosis or surgery. Patients with actively monitored meningioma have similar HRQoL to operated meningioma patients. Healthcare professionals should be mindful of HRQoL impairments and direct patients to sources of support as needed.

Health-related quality of life following cranioplasty - a systematic review.

Cranioplasty is a neurosurgical procedure that repairs a defect in the skull Coupled with the underlying pathology cranioplasty associated morbidity can have a large impact on patient quality of life, which is often poorly explored. The objective of this systematic review was to identify patient-reported outcomes evaluating health-related quality of life following cranioplasty. The review protocol was registered on PROSPERO (CRD42021251543) and a systematic review was conducted in accordance with the PRISMA statement. PubMed, Embase, CINAHL Plus, and the Cochrane databases were searched from inception to 1 May 2022. All studies reporting HRQoL following cranioplasty were included. Reporting was assessed using the ISOQOL checklist and risk of bias was assessed using the Newcastle-Ottawa Scale or the Johanna-Briggs Institute Scale, as appropriate. A total of 25 studies were included of which 20 were cross-sectional and 2 longitudinal. Most studies utilized study specific questionnaires and Likert scales to assess HRQoL. The studies found a significant improvement in physical functioning, social functioning, cosmetic outcome, and overall HRQoL following cranioplasty. Further longitudinal studies utilising validated measurement tools are required to better understand the effect of cranioplasty at a patient level.

How should we treat long-standing overt ventriculomegaly in adults (LOVA)? A retrospective cohort study.

Long-standing overt ventriculomegaly in adults (LOVA) is a heterogenous group of conditions with differing presentations. Few studies have evaluated success rates of available surgical treatments, or ascertained the natural history. There is a need to assess the efficacy of both endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) as first-line treatments. We conducted a retrospective, single-centre study of adults with LOVA at a tertiary neurosurgery centre in England, UK, aiming to identify presentation, management strategy, and outcome following treatment. A total of 127 patients were included (mean age 48.1 years, 61/127 male). Most patients were symptomatic (73.2%, n = 93/127, median symptom duration 10 months). The most common symptoms were gait ataxia, headache, and cognitive decline (52.8%, 50.4%, and 33.9%, respectively). Fourteen patients had papilloedema. Ninety-one patients (71.7%) underwent surgery (84 ETV, 7 VPS). Over a median follow-up of 33.0 months (interquartile range [IQR] 19.0-65.7), 82.4% had a clinical improvement after surgery, and 81.3% had radiological improvement. Clinical improvement rates were similar between ETV and VP shunt groups (82.1% vs 85.7%, p = 0.812). Surgical complication rates were significantly lower in the ETV group than the VP shunt group (4.8% vs 42.9%, p < 0.001). Of the patients treated surgically, 20 (22.0%) underwent further surgery, with 14 patients improving. This study demonstrates the efficacy of ETV as a first-line treatment for LOVA.

Meningioma systematic reviews and meta-analyses: an assessment of reporting and methodological quality.

INTRODUCTION: Systematic reviews (SR) and systematic reviews with meta-analysis (SRMA) can constitute the highest level of research evidence. Such evidence syntheses are relied upon heavily to inform the clinical knowledge base and to guide clinical practice for meningioma. This review evaluates the reporting and methodological quality of published meningioma evidence syntheses to date. METHODS: Eight electronic databases/registries were searched to identify eligible meningioma SRs with and without meta-analysis published between January 1990 and December 2020. Articles concerning spinal meningioma were excluded. Reporting and methodological quality were assessed against the following tools: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2), and Risk Of Bias in Systematic reviews (ROBIS). RESULTS: 116 SRs were identified, of which 57 were SRMAs (49.1%). The mean PRISMA score for SRMA was 20.9 out of 27 (SD 3.9, 77.0% PRISMA adherence) and for SR without meta-analysis was 13.8 out of 22 (SD 3.4, 63% PRISMA adherence). Thirty-eight studies (32.8%) achieved greater than 80% adherence to PRISMA. Methodological quality assessment against AMSTAR 2 revealed that 110 (94.8%) studies were of critically low quality. Only 21 studies (18.1%) were judged to have a low risk of bias against ROBIS. CONCLUSION: The reporting and methodological quality of meningioma evidence syntheses was poor. Established guidelines and critical appraisal tools may be used as an adjunct to aid methodological conduct and reporting of such reviews, in order to improve the validity and transparency of research which may influence clinical practice.

The effect of GMFCS level, age, sex, and dystonia on multi-dimensional outcomes after selective dorsal rhizotomy: prospective observational study.

PURPOSE: Investigate the effect of age category (1-9 years vs 10-18 years), sex, Gross Motor Function Classification System (GMFCS) level, and presence of dystonia on changes in eight function test parameters 24 months after selective dorsal rhizotomy (SDR). METHODS: Prospective, single-center study of all children aged 3-18 years with bilateral cerebral palsy with spasticity who underwent SDR at a tertiary pediatric neurosurgery center between 2012 and 2019. A linear mixed effects model was used to assess longitudinal changes. RESULTS: From 2012 to 2019, 42 children had follow-up available at 24 months. Mean GMFM-66 scores increased after SDR (mean difference 5.1 units: 95% CI 3.05-7.13, p < 0.001). Statistically significant improvements were observed in CPQoL, PEDI Self-care and Mobility, 6MWT, Gillette, and MAS scores. There was no significant difference in the improvements seen for age category, sex, GMFCS level, and presence of dystonia for most of the parameters tested (5/8, 6/8, 5/8, and 6/8 respectively). CONCLUSION: SDR may improve gross and fine motor function, mobility and self-care, quality of life, and overall outcome based on extensive scoring parameter testing at 24 months. Atypical patient populations may benefit from SDR if appropriately selected. Multi-center, prospective registries investigating the effect of SDR are required.

The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in Individuals with Knee Osteoarthritis.

OBJECTIVE: Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the efficacy of a dietary intervention to reduce KOA. DESIGN: A randomized controlled pilot study to test the efficacy of two dietary interventions. SUBJECTS: Adults 65-75 years of age with KOA. METHODS: Participants were asked to follow one of two dietary interventions (low-carbohydrate [LCD], low-fat [LFD]) or continue to eat as usual (control [CTRL]) over 12 weeks. Functional pain, self-reported pain, quality of life, and depression were assessed every three weeks. Serum from before and after the diet intervention was analyzed for oxidative stress. RESULTS: Over a period of 12 weeks, the LCD reduced pain intensity and unpleasantness in some functional pain tasks, as well as self-reported pain, compared with the LFD and CTRL. The LCD also significantly reduced oxidative stress and the adipokine leptin compared with the LFD and CTRL. Reduction in oxidative stress was related to reduced functional pain. CONCLUSIONS: We present evidence suggesting that oxidative stress may be related to functional pain, and lowering it through our LCD intervention could provide relief from pain and be an opioid alternative.

Soluble antigens in plasma allow mismatched transfusion without hemolysis.

BACKGROUND: Universal plasma is a scarce resource when a massive transfusion protocol has been initiated. Previous studies have reported success using group A plasma in place of the universal plasma, group AB. It is unclear why there are not more reports of hemolytic reactions occurring from this practice. One possible explanation is the presence of water-soluble antigens in the patient plasma that bind to, and neutralize, the soluble antibodies present in the transfused plasma. STUDY DESIGN AND METHODS: Expired units of plasma were used to make dilutions that consisted of mixtures of group A and B plasma and saline. Serial dilutions of these samples were performed starting from undiluted up to 1024. The dilutions were titrated using a group B red blood cell preparation. The titrations were read after incubation. RESULTS: The titers that resulted from the mixed plasma dilutions were significantly lower or showed no agglutination when compared to the group A-specific saline dilutions. The differences between the saline dilutions and mixed group dilutions were significant (p < 0.001). CONCLUSION: Our study shows that secretor status would provide protection from isoantibodies. The dissolved B antigens in the group B plasma absorb and/or bind to the group B isoantibodies in the group A plasma. This mechanism gives a protective effect against hemolytic reactions in massive transfusion situations in the trauma setting when group A plasma is used instead of group AB plasma. This protective effect is revealed with the paucity of intravascular hemolysis observed in these out-of-group massive transfusions.

Bilateral Malar Reconstruction Using Patient-Specific Polyether Ether Ketone Implants in Treacher-Collins Syndrome Patients With Absent Zygomas.

The authors performed bilateral malar reconstruction using polyether ether ketone implants in 3 patients with Treacher-Collins syndrome with absent, as opposed to hypoplastic, zygomata. These patient-specific implants were fabricated using computed-aided design software reformatted from three-dimensional bony preoperative computed tomography images. The first time the authors performed this procedure the implant compressed the globe resulting in temporary anisocoria that was quickly recognized intraoperatively. The implant was immediately removed and the patient made a full-recovery with no ocular disturbance. The computer-aided design and manufacturing process was adjusted to include periorbital soft-tissue boundaries to aid in contouring the new implants. The same patient, and 2 further patients, subsequently underwent malar reconstruction using this soft tissue periorbital boundary fabrication process with an additional 2 mm relief removed from the implant's orbital surface. These subsequent procedures were performed without complication and with pleasing aesthetic results. The authors describe their experience and the salutary lessons learnt.

Postmortem Propofol Levels: A Case of Residual Detection Long After Administration.

Propofol has gained notoriety in recent years because of its involvement in high-profile deaths and has increasingly become a drug of misuse and abuse particularly by health care personnel with easy access to it. In addition, propofol has also been used for more nefarious purposes such as murder and suicide. These, coupled with the drug's routine use for both major and minor medical procedures, provide ample opportunities for it to be implicated as a cause of death or contributing factor. In such instances, forensic investigators may be faced with the task of not only detecting the presence of propofol on postmortem toxicology screening, but also determining if it was indeed responsible for the decedent's demise. While propofol has a high volume of distribution, it is thought to equilibrate and be eliminated rapidly and not show significant tissue accumulation. However, this article presents a case illustrating that propofol can accumulate in the tissues and may be found up to a week after administration. This capacity to accumulate implies that postmortem detection does not necessarily confirm administration near the time of death, and further investigation needs to be undertaken to determine the timeline of events in order to rule out other factors, such as recent medical interventions, before attributing the cause of death to the presence of the drug.

The Frequency of Truly Unknown/Undetermined Deaths: A Review of 452 Cases Over a 5-Year Period.

The forensic autopsy is often regarded as the final medical diagnosis and expert scientific opinion in matters of death investigation, usually in the legal setting, and sometimes in the clinical setting as well. There are however limitations to what the autopsy can answer, and sometimes the circumstances surrounding a death, despite our best efforts, are simply unable to be determined. Approximately 5% of cases reportedly remain unknown after a complete autopsy. With this in mind, we sought to examine the frequency of deaths in which both the cause and manner are unknown after complete forensic examination and autopsy. Data from 452 undetermined deaths over a 5-year period were analyzed; sudden unexpected infant deaths and decomposed or skeletonized remains were excluded, as well as those with a known cause but undetermined manner of death. After exclusion of these deaths, our analysis revealed that only 0.015% of cases during this period were truly undetermined in both cause and manner of death.

Using satellite data to assess spatial drivers of bird diversity.

Birds are useful indicators of overall biodiversity, which continues to decline globally, despite targets to reduce its loss. The aim of this paper is to understand the importance of different spatial drivers for modelling bird distributions. Specifically, it assesses the importance of satellite-derived measures of habitat productivity, heterogeneity and landscape structure for modelling bird diversity across Great Britain. Random forest (RF) regression is used to assess the extent to which a combination of satellite-derived covariates explain woodland and farmland bird diversity and richness. Feature contribution analysis is then applied to assess the relationships between the response variable and the covariates in the final RF models. We show that much of the variation in farmland and woodland bird distributions is explained (R 2 0.64-0.77) using monthly habitat-specific productivity values and landscape structure (FRAGSTATS) metrics. The analysis highlights important spatial drivers of bird species richness and diversity, including high productivity grassland during spring for farmland birds and woodland patch edge length for woodland birds. The feature contribution provides insight into the form of the relationship between the spatial drivers and bird richness and diversity, including when a particular spatial driver affects bird richness positively or negatively. For example, for woodland bird diversity, the May 80th percentile Normalized Difference Vegetation Index (NDVI) for broadleaved woodland has a strong positive effect on bird richness when NDVI is >0.7 and a strong negative effect below. If relationships such as these are stable over time, they offer a useful analytical tool for understanding and comparing the influence of different spatial drivers.

Incidence and epidemiology of cervical radiculopathy in the United States military: 2000 to 2009.

STUDY DESIGN: Epidemiological review of a prospectively collected military database. OBJECTIVE: This investigation sought to determine the incidence of cervical radiculopathy and risk factors for its development within the population of the United States military from 2000 to 2009. SUMMARY OF BACKGROUND DATA: Currently, the epidemiology of cervical radiculopathy remains poorly understood and risk factors for its development have not been reliably defined. METHODS: The military's Defense Medical Epidemiological Database was used to identify all servicemembers diagnosed with cervical radiculopathy (International Classification of Diseases code 723.4) between 2000 and 2009. Demographic data was obtained for all identified individuals including age group, sex, race, military rank, and branch of service. Like data was recorded for all servicemembers within the Armed Forces during the time period under study. The incidence of cervical radiculopathy was calculated and unadjusted incidence rate ratios were determined. Risk factors were analyzed by performing multivariate Poisson regression analysis, controlling for all other factors within the model. RESULTS: Between 2000 and 2009, about 24,742 individuals were diagnosed with cervical radiculopathy among a population-at-risk of 13,813,333, for an incidence of 1.79 per 1000 person-years. Statistically significant differences (P<0.001) in adjusted incidence rate ratios were identified for each successive age group with mutually exclusive 95% confidence intervals. Those age 40 years and above were found to have the greatest risk of cervical radiculopathy. Female sex (P<0.001), White race (P<0.001), senior positions within the rank structure (P<0.001), and service in the Army (P<0.001) or Air Force (P=0.01) were also identified as significant risk factors for cervical radiculopathy. CONCLUSIONS: This study is the first to attempt to define the incidence of cervical radiculopathy and characterize risk factors for its development within an American population. Findings presented here indicate that age is most likely the greatest risk factor for cervical radiculopathy, with female sex, White race, senior military positions, and Army or Air Force service also influencing risk to varying degrees.

Molecular Genetics and Targeted Therapies for Paediatric High-grade Glioma.

Brain tumours are the leading cause of paediatric cancer-associated death worldwide. High-grade glioma (HGG) represents a main cause of paediatric brain tumours and is associated with poor prognosis despite surgical and chemoradiotherapeutic advances. The molecular genetics of paediatric HGG (pHGG) are distinct from those in adults, and therefore, adult clinical trial data cannot be extrapolated to children. Compared to adult HGG, pHGG is characterised by more frequent mutations in PDGFRA, TP53 and recurrent K27M and G34R/V mutations on histone H3. Ongoing trials are investigating novel targeted therapies in pHGG. Promising results have been achieved with BRAF/MEK and PI3K/mTOR inhibitors. Combination of PI3K/mTOR, EGFR, CDK4/6, and HDAC inhibitors are potentially viable options. Inhibitors targeting the UPS proteosome, ADAM10/17, IDO, and XPO1 are more novel and are being investigated in early-phase trials. Despite preclinical and clinical trials holding promise for the discovery of effective pHGG treatments, several issues persist. Inadequate blood-brain barrier penetration, unfavourable pharmacokinetics, dose-limiting toxicities, long-term adverse effects in the developing child, and short-lived duration of response due to relapse and resistance highlight the need for further improvement. Future pHGG management will largely depend on selecting combination therapies which work synergistically based on a sound knowledge of the underlying molecular target pathways. A systematic investigation of multimodal therapy with chemoradiotherapy, surgery, target agents and immunotherapy is paramount. This review provides a comprehensive overview of pHGG focusing on molecular genetics and novel targeted therapies. The diagnostics, genetic discrepancies with adults and their clinical implications, as well as conventional treatment approaches are discussed.

Cytokine-based Cancer Immunotherapy: Challenges and Opportunities for IL-10.

Cancer immunotherapy is an evolving field of research. Cytokines have been conceptualized as an anticancer therapy for longer than most other cancer immunotherapy modalities. Yet, to date, only two cytokines are FDA-approved: IFN-α and IL-2. Despite the initial breakthrough, both agents have been superseded by other, more efficacious agents such as immune checkpoint inhibitors. Several issues persist with cytokine-based cancer therapies; these are broadly categorised into a) high toxicity and b) low efficacy. Despite the only moderate benefits with early cytokine-based cancer therapies, advances in molecular engineering, genomics, and molecular analysis hold promise to optimise and reinstate cytokine-based therapies in future clinical practice. This review considers five important concepts for the successful clinical application of cytokine-based cancer therapies including: (i) improving pharmacokinetics and pharmacodynamics, (ii) improving local administration strategies, (iii) understanding context-dependent interactions in the tumour-microenvironment, (iv) elucidating the role of genetic polymorphisms, and (v) optimising combination therapies. IL-10 has been the focus of attention in recent years and is discussed herein as an example.

Ultrahigh-birefringent squeezed lattice photonic crystal fiber with rotated elliptical air holes.

We report an experimental realization of a highly birefringent photonic crystal fiber as a result of compressing a regular hexagonal structure. The experimental measurements estimate a group birefringence of approximately 5.5x10(-3) at 1550 nm in good agreement with the numerical results. We study the influence of compressing the regular structure at different directions and magnifications, obtaining a method to realistically enhance the phase birefringence while moderating the group birefringence.

The effects of gap size on some microclimate variables during late summer and autumn in a temperate broadleaved deciduous forest.

The creation of gaps can strongly influence forest regeneration and habitat diversity within forest ecosystems. However, the precise characteristics of such effects depend, to a large extent, upon the way in which gaps modify microclimate and soil water content. Hence, the aim of this study was to understand the effects of gap creation and variations in gap size on forest microclimate and soil water content. The study site, in North West England, was a mixed temperate broadleaved deciduous forest dominated by mature sessile oak (Quercus petraea), beech (Fagus sylvatica) and ash (Fraxinus excelsior) with some representatives of sycamore (Acer pseudoplatanus). Solar radiation (I), air temperature (T(A)), soil temperature (T(S)), relative humidity (h), wind speed (v) and soil water content (Psi) were measured at four natural treefall gaps created after a severe storm in 2006 and adjacent sub-canopy sites. I, T(A), T(S), and Psi increased significantly with gap size; h was consistently lower in gaps than the sub-canopy but did not vary with gap size, while the variability of v could not be explained by the presence or size of gaps. There were systematic diurnal patterns in all microclimate variables in response to gaps, but no such patterns existed for Psi. These results further our understanding of the abiotic and consequent biotic responses to gaps in broadleaved deciduous forests created by natural treefalls, and provide a useful basis for evaluating the implications of forest management practices.

Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management.

We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.

Monitoring conservation effectiveness in a global biodiversity hotspot: the contribution of land cover change assessment.

Tropical forests, which play critical roles in global biogeochemical cycles, radiation budgets and biodiversity, have undergone rapid changes in land cover in the last few decades. This study examines the complex process of land cover change in the biodiversity hotspot of Western Ghats, India, specifically investigating the effects of conservation measures within the Indira Gandhi Wildlife Sanctuary. Current vegetation patterns were mapped using an IRS P6 LISS III image and this was used together with Landsat MSS data from 1973 to map land cover transitions. Two major and divergent trends were observed. A dominant degradational trend can be attributed to agricultural expansion and infrastructure development while a successional trend, resulting from protection of the area, showed the resilience of the system after prolonged disturbances. The sanctuary appears susceptible to continuing disturbances under the current management regime but at lower rates than in surrounding unprotected areas. The study demonstrates that remotely sensed land cover assessments can have important contributions to monitoring land management strategies, understanding processes underpinning land use changes and helping to inform future conservation strategies.