The effect of recreational cannabis legalization and commercialization on substance use, mental health, and injury: a systematic review.

OBJECTIVE: To determine the effect of recreational cannabis legalization (RCL) and/or recreational cannabis commercialization (RCC) on emergency department (ED) visits, hospitalizations, and deaths due to substance use, injury, and mental health among those aged 11 years and older. METHODS: A systematic review of six electronic databases up to February 1, 2023. Original, peer-reviewed articles with interrupted time series or before and after designs were included. Four independent reviewers screened articles and assessed risk of bias. Outcomes with 'critical' risk of bias were excluded. Protocol registered on PROSPERO (# CRD42021265183). RESULTS: After screening and risk of bias assessment, 29 studies were included which examined ED visits or hospitalizations for cannabis use or alcohol (N = 10), opioid mortality (N = 3), motor vehicle fatalities or injury (N = 11), and intentional injury/mental health (N = 5). Rates or number of cannabis-related hospitalizations increased after RCL in Canada and the USA. Immediate increases in rates of cannabis-related ED visits were found after both RCL and RCC in Canada. Rates of traffic fatalities increased after RCL and RCC in certain jurisdictions in the USA. CONCLUSIONS: RCL was associated with increased rates of cannabis-related hospitalizations. RCL and/or RCC was associated with increased rates of cannabis-related ED visits, consistently shown across sex and age groups. The effect on fatal motor vehicle incidents was mixed, with observed increases found after RCL and/or RCC. The effect of RCL or RCC on opioids, alcohol, intentional injury, and mental health is not clear. These results inform population health initiatives and international jurisdictions considering RCL implementation.

Correlation between Cranial Nerve Microstructural Characteristics and Vestibular Schwannoma Tumor Volume.

BACKGROUND AND PURPOSE: Vestibular schwannomas are common cerebellopontine angle tumors arising from the vestibulocochlear nerve and can result in cranial nerve dysfunction. Conventional MR imaging does not provide information that could correlate with cranial nerve compression symptoms of hearing loss or imbalance. We used multitensor tractography to evaluate the relationship between the WM microstructural properties of cranial nerves and tumor volume in a cohort of patients with vestibular schwannomas. MATERIALS AND METHODS: A retrospective study was performed in 258 patients with vestibular schwannomas treated at the Gamma Knife clinic at Toronto Western Hospital between 2014 and 2018. 3T MR images were analyzed in 160 surgically naïve patients with unilateral vestibular schwannomas. Multitensor tractography was used to extract DTI-derived metrics (fractional anisotropy and radial, axial, and mean diffusivities of the bilateral facial and vestibulocochlear nerves [cranial nerves VII/VIII]). ROIs were placed in the transition between cisternal and intracanalicular segments, and images were analyzed using the eXtended Streamline Tractography reconstruction method. Diffusion metrics were correlated with 3D tumor volume derived from the Gamma Knife clinic. RESULTS: DTI analyses revealed significantly higher fractional anisotropy values and a reduction in axial diffusivity, radial diffusivity, and mean diffusivity (all P < .001) within the affected cranial nerves VII and VIII compared with unaffected side. All specific diffusivities (axial, radial, and mean diffusivity) demonstrated an inverse correlation with tumor volume (axial, radial, and mean diffusivity, P < .01). CONCLUSIONS: Multitensor tractography allows the quantification of cranial nerve VII and VIII WM microstructural alterations in patients with vestibular schwannomas. Our findings support the hypothesis that tumor volume may cause microstructural alterations of the affected cranial nerves VII and VIII. This type of advanced imaging may represent a possible avenue to correlate diffusivities with cranial nerve function.

Patient engagement study to identify and improve surgical experience.

BACKGROUND: Patient engagement is the establishment of active partnerships between patients, families, and health professionals to improve healthcare delivery. The objective of this project was to conduct a series of patient engagement workshops to identify areas to improve the surgical experience and develop strategies to address areas identified as high priority. METHODS: Faculty surgeons and patients were invited to participate in three in-person meetings. Evaluation included identifying and developing strategies for three priority areas to improve the surgical experience and level of engagement achieved at each meeting. RESULTS: Sixteen faculty surgeons and 32 patients participated. Some 63 themes to improve the surgical experience were identified; the three highest-priority themes were physician communication, discharge process, and expectations at home after discharge. Individual improvement strategies for these three prioritized themes (12, 36 and 6 respectively) were used to develop a formal strategic plan, and included a physician communication survey, discharge process worksheet and video, and guideline regarding what to expect at home after discharge. Overall, the level of engagement achieved was considered high by over 85 per cent of the participants. CONCLUSION: A high level of patient engagement was achieved. Priorities were identified with patients and surgeons to improve surgical experience, and strategies were developed to address these areas.

Use of a flow-diverting stent for ruptured dissecting aneurysm treatment in a patient with sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) is a clinical phenotype that presents a unique challenge to the interventionalist, particularly when stent therapy is contemplated. Homozygous individuals are likely at increased risk for thromboembolic complications. There are no formal guidelines regarding antiplatelet therapy in the short or long term for intracranial stent use in SCD. The authors describe the novel use of a pipeline embolization device (PED) to treat a ruptured dissecting bilobed/fusiform vertebral artery V4 aneurysm in an SCD patient complicated by tortuous proximal anatomy and the anterior spinal artery arising from the diseased segment. Considerations regarding antiplatelet therapy in this scenario are discussed. CASE REPORT: A 50-year-old woman with homozygous recessive SCD was transported to the emergency department and presented with diffuse subarachnoid hemorrhage. CT angiography demonstrated a left-sided 3 × 5 mm fusiform bi-lobulated presumed dissecting vertebral artery aneurysm, immediately distal to the origin of the posterior inferior cerebellar artery (PICA). A PED was deployed within the V4 segment across the aneurysm. Post-treatment angiography showed patency of the parent artery, and patency of the "jailed" anterior spinal artery and of the PICA. DISCUSSION: Selecting a treatment method in SCD patients with a ruptured intracranial aneurysm is challenging and there are no clinical trials comparing treatment methods in this population. The authors demonstrate that flow diversion is feasible in SCD, which has not been described in the literature. Additionally, the case stresses the peri- and post-procedural management of SCD, as well as long-term considerations with a flow-diverting stent in place.

Invasive thymoma metastatic to the cavernous sinus.

BACKGROUND: Thymomas are typically benign tumors of thymic epithelium. Metastases to distal sites, particularly intracranial locations, are extremely rare. Herein, we present the third case of thymoma and the second invasive thymoma to metastasize to the cavernous sinus, adjacent to the pituitary. CASE DESCRIPTION: A 41-year-old female patient presented with headaches, stuffy nose, and drooping of the right face. A magnetic resonance imaging scan revealed a complex, multilobulated mass centered upon the right cavernous sinus. The mass was removed via transsphenoidal surgery, and histopathological investigation confirmed the diagnosis of metastatic thymoma. A positron emission tomography-computed tomography scan demonstrated a large anterior mediastinal mass. A biopsy confirmed the diagnosis of invasive thymoma morphologically identical to the World Health Organization type B2 sellar region metastasis. CONCLUSION: Although rare, thymomas can metastasize to the central nervous system. Our case is the second invasive thymoma to metastasize to the cavernous sinus, adjacent to the pituitary.

Body mass index as a risk factor for increased serum lactate during craniotomy.

BACKGROUND: An increase in serum lactate can occur in patients undergoing craniotomy. We hypothesized that prolonged craniotomy for brain tumor resection leads to inadequate tissue perfusion as demonstrated by increased level of lactate. This study attempts to determine the mechanism and identify any modifiable risk factors. METHODS. Prospective, observational study of 18 patients undergoing craniotomy for brain tumor resection. The primary outcome was that peak serum lactate would correlate with length of surgery. Secondary outcomes included lactate at 3, 6 and 9 hours, creatine kinase (CK) and myoglobinuria overtime. These values were correlated with expected risk factors for lactatemia including length of surgery, Body Mass Index (BMI), hypotension, hemoglobin and mannitol therapy. RESULTS. Serum lactate consistently increased in the first 3 hours in all patients (2.21±1.22 mmol/L) with a peak increase at 9 hours (3.73±1.62 mmol/L) (P<0.05 for both). The peak serum lactate did not correlate with length of surgery (P=0.799). However, the change in lactate over 3 hours (Δ3hrLactate) did correlate with BMI (P=0.010). Serum CK was increased at 12 hours (P<0.05) and reached a peak level greater than 1000 U/L in 8 of 18 patients. Six of these patients experienced myoglobinuria. No other parameters correlated with increased lactate. CONCLUSION: We observed a consistent and early increase in serum lactate in patients undergoing craniotomy, which correlated with BMI, but not length of surgery. Associated increases in CK and myoglobinuria support the hypothesis that elevated BMI contributed to muscle ischemia and tissue breakdown during craniotomy. Future studies are required to establish the overall clinical significance and mechanism of hyperlactatemia during neurosurgery.

Normal-pressure hydrocephalus: is there a genetic predisposition?

BACKGROUND: Normal-pressure hydrocephalus (NPH) is characterized by gait disturbance, cognitive impairment, with or without urinary incontinence, enlarged ventricles with or without cerebral atrophy and normal cerebrospinal fluid pressure. METHODS: We report two sisters with NPH who lived together their entire lives and whose natural history might provide insights into genetic and environmental mechanisms underlying this disorder. Both patients were in their early seventies, single, had similar daily habits and hypertension. No other family members had NPH. RESULTS: They both underwent shunt placement and showed improvement documented by history and neuropsychological assessment. Both showed a delayed deterioration due to vasculopathy. Both patients were homozygous for the apolipoprotein E (ApoE) e3 allele on chromosome 19. No environmental factors that might have influenced the development of NPH were identified. CONCLUSION: Our report of two sisters with NPH may indicate the presence of genetic predisposition and further studies involving genetics and environmental factors are necessary to elucidate their role in the pathogenesis of NPH.

Remodelling the injured CNS through the establishment of atypical ectopic perivascular neural stem cell niches.

Compelling evidence exists that somatic neural stem/precursor cell (NPC)-based therapies protect the central nervous system (CNS) from chronic inflammation-driven degeneration, such as that occurring in experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), cerebral ischemic/hemorrhagic stroke and spinal cord injury (SCI). However, while it was first assumed that NPC transplants may act through direct replacement of lost/damaged cells, it has now become clear that they are able to protect the damaged nervous system through a number of 'bystander' mechanisms other than the expected cell replacement. In immune-mediated experimental demyelination--both in rodents and non-human primates--others and we have shown that transplanted NPC possess a constitutive and inducible ability to mediate efficient 'bystander' myelin repair and axonal rescue. This novel mechanism(s), which may improve the success of transplantation procedures, is likely to be exerted by undifferentiated NPCs whose functional characteristics are regulated by both CNS-resident and blood-borne inflammatory cells releasing in situ major stem cell regulators. Here, we discuss some of these alternative 'bystander' mechanisms, while pointing at the formation of the atypical ectopic perivascular niches, as the most challenging example of reciprocal biologically sound cross talk between the inflamed microenvironment(s) and transplanted therapeutic NPCs.

Endoglin and CD-34 immunoreactivity in the assessment of microvessel density in normal pituitary and adenoma subtypes.

UNLABELLED: Vascularization is a prerequisite of tumor growth, invasion and metastasis. In the present work, microvessel density was assessed by quantitating using two different endothelial cell biomarkers, endoglin (CD-105) and CD-34. Fifty endocrinologically active and 36 clinically nonfunctioning pituitary adenomas, all surgically resected, as well as 10 autopsy-derived normal adenohypophyses were investigated by immunohistochemistry. The results showed that in every pituitary adenoma type endoglin, an assumed biomarker of proliferating endothelial cells, immunostained fewer vessels than CD-34 which revealed immunopositivity in all capillaries. Differences in endoglin versus CD-34 immunoexpression indicate varying degrees of vascularity in pituitary adenoma subtypes. The low levels of endoglin immunoexpression in pituitary tumors exposed to long-acting somatostatin analogs and dopamine agonists are consistent with the view that these agents inhibit angiogenesis. KEYWORDS: immunohistochemistry, endoglin, CD34, microvascular density, angiogenesis, pituitary.

FACT-MNG: tumor site specific web-based outcome instrument for meningioma patients.

To formulate Functional Assessment of Cancer Therapy-Meningioma (FACT-MNG), a web-based tumor site-specific outcome instrument for assessing intracranial meningioma patients following surgical resection or stereotactic radiosurgery. We surveyed the relevant literature available on intracranial meningioma surgery and subsequent outcomes (38 papers), making note of which, if any, QOL/outcome instruments were utilized. None of the surgveyed papers included QOL assessment specific to tumor site. We subsequently developed questions that were relevant to the signs and symptoms that characterize each of 11 intracranial meningioma sites, and incorporated them into a modified combination of the Functional Assessment of Cancer Therapy-Brain (FACT-BR) and SF36 outcome instruments, thereby creating a new tumor site-specific outcome instrument, FACT-MNG. With outcomes analysis of surgical and radiosurgical treatments becoming more important, measures of the adequacy and success of treatment are needed. FACT-MNG represents a first effort to formalize such an instrument for meningioma patients. Questions specific to tumor site will allow surgeons to better assess specific quality of life issues not addressed in the past by more general questionnaires.

Estrogen receptors alpha and beta immunohistochemical expression: clinicopathological correlations in pituitary adenomas.

AIM: We investigated the immunohistochemical expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) in pituitary adenoma subtypes combined with clinicopathological factors. MATERIALS AND METHODS: Pituitary adenomas (n=75) were immunostained for ERalpha and ERbeta using the streptavidin-biotin-peroxidase complex method with a monoclonal ERalpha antibody and polyclonal ERbeta antibody. RESULTS: Nuclear immunoreactivity for both receptors was highest among PRL, FSH/LH, null cell, and GH adenomas. ACTH, silent subtypes I and II corticotrophs, and subtype III adenomas were the least immunoreactive for both receptors. ACTH adenomas expressed significantly less ERalpha than FSH-LH, GH, and null cell adenomas. A significantly elevated ERalpha expression was observed in macroadenomas compared to microadenomas and non-invasive compared to invasive tumors. CONCLUSION: ERalpha and ERbeta are differentially expressed in the various pituitary adenoma subtypes suggesting a cell-specific function for these receptors. To elucidate the role of ERalpha in tumor size and invasiveness, additional studies are required.

Fatal hemorrhage following trans--sphenoidal resection of a pituitary adenoma: a case report and review of the literature.

A 58-year-old woman with acromegaly developed massive epistaxis 7 days following trans-sphenoidal resection of a growth hormone-secreting pituitary adenoma. At autopsy, it was determined that the source of the hemorrhage was a rupture of the intracavernous segment of the internal carotid artery secondary to a bacterial arteritis. We describe the gross dissection and histologic examination undertaken in this unusual case, discuss the possible etiology of the infection and review the potential complications of this surgical approach with a view to improving forensic examination of these patients.

School-age children's safety attitudes, cognitions, knowledge, and injury experiences: how do these relate to their safety practices?

BACKGROUND: A variety of factors affect the safety and risk practices of school-age children, but rarely have multiple factors been considered simultaneously. OBJECTIVE: To examine children's safety attitudes and cognitions more thoroughly and assess how these factors, along with children's safety knowledge and injury experiences, relate to children's safety practices. METHODS: Over several classroom sessions, boys and girls in two age groups (7-9, 10-12 years) completed a psychometrically sound questionnaire that indexes their behaviors, attitudes, cognitions, knowledge, and injury experiences. RESULTS: Fewer safety practices were reported by older than younger children and boys than girls. Children's attitudes, cognitions, knowledge, and injury experiences each correlated with safety practices, but only safety attitudes and injury experiences predicted practices in a multivariate model. CONCLUSION: Exploring the relative influence of numerous factors on safety practices highlights the important role that attitudes play in predicting children's safety practices. Implications of these results for injury prevention programming are discussed.

Effectiveness of multifaceted fall-prevention programs for the elderly in residential care.

BACKGROUND: Unintentional falls are particularly prevalent among older people and constitute a public health concern. Not much is known about the implications of multifaceted intervention programs implemented in residential care settings. OBJECTIVES: To evaluate the effectiveness of multifaceted intervention programs in reducing the number of falls, fallers, recurrent fallers, and injurious falls among older people living in residential care facilities. SEARCH STRATEGY: Comprehensive searches of Medline, PubMed, and EMBASE up to July 2007, the cited literature lists of each included study, and the internet engines Google Scholar, Yahoo, and Dogpile were performed to identify eligible studies. SELECTION CRITERIA: Eligible studies for this review were those that had randomized, controlled trials with adequate follow-up study components in their design. Studies that included elderly people in residential care who participated in multifaceted falls-prevention programs were included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the necessary data. Studies were assessed for quality by the criteria of Downs and Black. The results of the included studies have been reviewed narratively. MAIN RESULTS: From 21 articles potentially relevant to the topic, five studies met the inclusion criteria and all were reasonably well conducted. Three reported significant reductions in the number of recurrent fallers, two reported significant reductions in the number of falls, and one reported significant reductions in the number of fallers. One other reported a reduction in the number of injurious falls in those who received the multifaceted prevention program compared with the control group. However, the analyses of this specific study were not based on intent-to-treat, so the effect of intervention on the number of injurious falls remains inconclusive. No study reported on adverse events, costs, or sustainability of the interventions. CONCLUSIONS: Multifaceted programs that encompass a wide range of intervention strategies have shown some evidence of efficacy. However, more well-designed research is required that assesses effects on injurious falls, quality of life, cost-effectiveness, and sustainability.

Geomatics in injury prevention: the science, the potential and the limitations.

BACKGROUND: Geomatics describes the activities involved in acquiring and managing geographical data and producing geographical information for scientific, administrative and technical endeavors. As an emerging science, geomatics has a great potential to support public health. Geomatics provides a conceptual foundation for the development of geographic information systems (GIS), computerized tools that manage and display geographical data for analytical applications. As descriptive epidemiology typically involves the examination of person, place and time in the occurrence of disease or injury, geomatics and GIS can play an important role in understanding and preventing injury. AIM: This article provides a background to geomatics for those in the injury prevention field who are unfamiliar with spatial analysis. We hope to stimulate researchers and practitioners to begin to use geomatics to assist in the prevention of injury. METHODS: The authors illustrate the potential benefits and limitations of geomatics in injury prevention in a non-technical way through the use of maps and analysis. RESULTS: By analysing the location of patients treated for fall injuries in Central Toronto using GIS, some demographic and land use variables, such as household income, age, and the location of homeless shelters, were identified as explanatory factors for the spatial distribution. CONCLUSION: By supporting novel approaches to injury prevention, geomatics has a great potential for efforts to combat the burden of injury. Despite some limitations, those with an interest in injury prevention could benefit from this science.

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice.

In recent years, the use of dendritic cells (DC), the most powerful antigen presenting cells, has been proposed for the creation of vaccines against gliomas. This approach has been demonstrated to be safe and non-toxic in phase I or I-II trials (2, 3). Immunotherapy plays a central role in the search for new treatments for glioblastoma multiforme (GBM). In particular, several phase I studies have been performed using DC pulsed by GBM proteins as a vaccine for patients with relapsing GBM. The studies demonstrated that DC vaccination is safe and may produce a significant increase in overall survival. As the first step in the preparation of appropriate conditions for a clinical evaluation in Italy, we have performed pre-clinical experiments on immune-competent mice injected intra-cerebrally with syngeneic GL261GBM cells and treated subcutaneously and intra-tumorally with DC loaded with a GL261 homogenate. These results show that vaccination with DC pulsed with a tumor lysate increases considerably survival in mice bearing intracranial glioblastomas and supports the development of DC-based clinical trials for patients with glioblastomas that do not respond to standard therapies.

Pituitary corticotroph hyperplasia preceding adenoma in a patient with Nelson's syndrome.

We report the case of a 42-year-old woman with Cushing's disease and Nelson's syndrome. When she was 17 years old, transsphenoidal surgery was performed. A detailed morphologic study demonstrated nodular hyperplasia of corticotroph cells but no adenoma. Following a long-lasting remission (14 years), Cushing's disease recurred. After an unsuccessful second transsphenoidal surgery, Cushing's disease persisted and both adrenals were removed (at the age of 34). Subsequently the patient developed Nelson's syndrome. The pituitary tumor proved to be a corticotroph adenoma; it was removed by the transsphenoidal approach (at the age of 42). Although in most patients Cushing's disease is due to an ACTH-secreting pituitary corticotroph adenoma which precedes the manifestation of Nelson's syndrome, our case indicates not only that corticotroph hyperplasia may cause Cushing's disease but that it may exist before the development of Nelson's syndrome after the removal of both adrenals. Our study supports the view that protracted stimulation of corticotrophs resulting from the elimination of the negative inhibitory feedback effect by corticosteroids plays a role in adenoma initiation.

Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases.

The silent adenoma subtype 3 (SAS-3) of undetermined cellular derivation is a seemingly nonfunctioning aggressive pituitary tumor with a high recurrence rate. At the time of diagnosis SAS-3s are macro- or giant adenomas particularly aggressive in young individuals, especially women. They are usually associated with mild hyperprolactinemia and are unremarkable by histology. Immunohistochemistry, demonstrating scattered immunoreactivity mostly for GH, PRL, TSH, and alpha-subunit, is not diagnostic. Presently, only TEM permits conclusive diagnosis. Ultrastructurally, the large polar adenoma cells contain abundant RER, masses of SER, extensive multipolar Golgi apparatus, and unevenly clustered mitochondria, displaced by RER and SER, which may show close spatial relationship to RER. Cell membranes often form plexiform interdigitations. Nuclear pleomorphism and nuclear inclusions are common. The 100- to 200-nm secretory granules accumulate heavily in cell processes, which is a hallmark of glycoprotein hormone cell differentiation. The endothelial cells may contain tubuloreticular inclusions. Complete surgical removal of the large often invasive tumors is difficult necessitating postoperative treatment. SAS-3 is sensitive to conventional radiation. Some tumors express somatostatin receptors and respond well to somatostatin analogues, offering long-term control in patients with residual tumor. Possible derivation of SAS-3 from rostral thyrotrophs, a cell type presently known in rodents is contemplated.

Identification of SCP2165, a new SCP2-derived plasmid of Streptomyces coelicolor A3(2).

AIMS: Characterization of SCP2165, a plasmid identified in the Gram-positive bacterium Streptomyces coelicolor A3(2). METHODS AND RESULTS: Pulsed-field gel electrophoresis (PFGE) of mycelia of a S. coelicolor strain embedded in low melting agarose revealed the presence of a plasmid. Restriction enzyme mapping and sequence analysis of a 2.1 kb fragment revealed that this plasmid could be SCP2. SCP2 and its spontaneous derivative SCP2* are self-transmissible plasmids and have chromosome mobilizing ability (c.m.a.). SCP2* has a c. 1000-fold increased c.m.a. compared with SCP2. Interestingly the plasmid, named SCP2165, shows a c.m.a. from 5x10(-2) to 1x10(-1) which is 50-100-fold higher than that described for crosses involving SCP2*. CONCLUSIONS: SCP2165 is a SCP2 derivative plasmid with the highest c.m.a. so far described for SCP2 derivative plasmids. PFGE, under conditions we used, seems to be a fast way to identify large circular plasmids in Streptomyces strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Further knowledge of the SCP2 family may allow the construction of improved SCP2-derived cloning vectors. SCP2165 could be a potential tool for conjugational transfer of gene clusters between different Streptomyces species.

Prognostic indicators in an aggressive pituitary Crooke's cell adenoma.

OBJECTIVE: To investigate prognostic indicators in an aggressive Crooke's cell adenoma of the pituitary. METHODS: The surgically removed tumor was studied by histology, immunohistochemistry and transmission electron microscopy. RESULTS: An aggressive invasive sellar tumor removed by repeated surgeries from a 43-year-old woman with pituitary related Cushing's disease was classified as a Crooke's cell adenoma of the pituitary. The application of several cell proliferation markers confirmed the aggressive nature of the tumor. CONCLUSIONS: The investigation of the present case provides additional evidence that pituitary Crooke's cell adenomas may possess aggressive behavior.