LRP1 is a master regulator of tau uptake and spread.

The spread of protein aggregates during disease progression is a common theme underlying many neurodegenerative diseases. The microtubule-associated protein tau has a central role in the pathogenesis of several forms of dementia known as tauopathies-including Alzheimer's disease, frontotemporal dementia and chronic traumatic encephalopathy1. Progression of these diseases is characterized by the sequential spread and deposition of protein aggregates in a predictable pattern that correlates with clinical severity2. This observation and complementary experimental studies3,4 have suggested that tau can spread in a prion-like manner, by passing to naive cells in which it templates misfolding and aggregation. However, although the propagation of tau has been extensively studied, the underlying cellular mechanisms remain poorly understood. Here we show that the low-density lipoprotein receptor-related protein 1 (LRP1) controls the endocytosis of tau and its subsequent spread. Knockdown of LRP1 significantly reduced tau uptake in H4 neuroglioma cells and in induced pluripotent stem cell-derived neurons. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule-binding repeat region of tau. Furthermore, downregulation of LRP1 in an in vivo mouse model of tau spread was found to effectively reduce the propagation of tau between neurons. Our results identify LRP1 as a key regulator of tau spread in the brain, and therefore a potential target for the treatment of diseases that involve tau spread and aggregation.

Estimating the prevalence of potential and actionable drug-gene interactions in Irish primary care: A cross-sectional study.

AIMS: Pharmacogenetics (PGx) is increasingly recognized as a strategy for medicines optimisation and prevention of adverse drug reactions. According to guidelines produced by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG), most medicines with drug-gene interactions (DGIs) are prescribed in primary care. This study aimed to estimate the prevalence of potential and actionable DGIs involving all medicines dispensed in Irish primary care. METHODS: Dispensings of 46 drugs to General Medical Services (GMS) patients in the Health Service Executive Primary Care Reimbursement Service Irish pharmacy claims database from 01 January 2021 to 31 December 2021 were analysed to estimate the national prevalence of total dispensings and incidence of first-time dispensings of drugs with potential DGIs according to the CPIC and/or DPWG guidelines. Phenotype frequency data from the UK Biobank and the CPIC were used to estimate the incidence of actionable DGIs. RESULTS: One in five dispensings (12 443 637 of 62 754 498, 19.8%) were medicines with potential DGIs, 1 878 255 of these dispensed for the first time. On application of phenotype frequencies and linked guideline based therapeutic recommendations, 2 349 055 potential DGIs (18.9%) required action, such as monitoring and guarding against maximum dose, drug or dose change. One in five (369 700, 19.7%) first-time dispensings required action, with 139 169 (7.4%) requiring a change in prescribing. Antidepressants, weak opioids and statins were most commonly identified as having actionable DGIs. CONCLUSIONS: This study estimated a high prevalence of DGIs in primary care in Ireland, identifying the need and opportunity to optimize drug therapy through PGx testing.

Evidencing general acceptability of open-label placebo use for tackling overtreatment in primary care: a mixed methods study.

BACKGROUND: Overtreatment poses a challenge to healthcare systems due to harmful consequences of avoidable side-effects and costs. This study presents the first account for examining the feasibility of placebo use for reducing overtreatment in primary care, including whether public attitudes support the use of different placebo types in place of inappropriate prescriptions of antibiotics, antidepressants, or analgesics. METHODS: We used a multi-study, mixed-methods design, including patient and public (PPI) consultations, focus groups (Study 1) and two pre-registered online experiments (Studies 2 and 3). RESULTS: Study 1 (N = 16) explored everyday conceptions and practicalities of potential placebo use in the context of respiratory infections. Findings highlighted the importance of trusting doctor-patient relationships and safety-netting. Study 2 employed a randomised experiment with a representative UK sample (N = 980), investigating attitudes towards 5 different treatment options for respiratory infections: (1) blinded + pure placebo, (2) open-label + pure placebo, (3) open-label + impure placebo, (4) antibiotic treatment, and (5) no treatment. Study 2 also examined how attitudes varied based on wording and individual differences. Findings indicated general support (ηp2 = .149, large effect size) for replacing inappropriate antibiotics with open-label + impure placebos, although personal placebo acceptability was lower. Also, older people, individuals suffering from chronic illness or those showing higher levels of health anxiety appeared less amenable to placebo use. Study 3 (N = 1177) compared attitudes towards treatment options across three clinical scenarios: respiratory infection, depression and pain. Findings suggested significant differences in the acceptability of placebo options based on the clinical context. In the infection scenario, options for open-label + pure placebos, open-label + impure placebos and no treatment were rated significantly more acceptable (ηp2 = .116, medium effect size) compared to the depression and pain scenarios. Again, general support for placebos was higher than placebo acceptability for personal use. CONCLUSIONS: Findings from PPI and three studies indicate general support for combatting overprescribing in primary care through clinical placebo use. This is an indicator for wider UK public support for a novel, behavioural strategy to target a long-standing healthcare challenge. General acceptability appears to be highest for the use of open-label + impure placebos in the context of antibiotic overprescribing.

Methylprednisolone, dexamethasone or hydrocortisone for acute severe pediatric asthma: does it matter?

OBJECTIVE: Various intravenous (IV) corticosteroids are available for acute severe asthma (ASA) treatment. The choice of IV corticosteroids varies broadly and depends on institution, country, or physician preferences. In this study, we compared the efficacy of IV methylprednisolone, hydrocortisone and dexamethasone in ASA treatment during pediatric intensive care unit (PICU) admission. METHODS: The study was a prospective randomized clinical trial. We enrolled patients of 1-21 years after they were admitted to the PICU requiring continuous beta-2 agonist treatment. Patients were randomized into three groups: Group A: IV Methylprednisolone, Group B: IV Hydrocortisone and Group C: IV Dexamethasone. The primary outcomes measured were durations of beta-2 agonist continuous nebulization treatment. Secondary outcomes, included PICU and hospital length of stay (LOS), pediatric asthma severity score (PASS), need for mechanical ventilation and maximum dose of beta-2 agonist treatment. RESULTS: 61 patients were included in the analysis. 22 patients recruited in Group A, 20 in group B and 19 group C. Median durations of beta-2-agonist treatment were 23 h (QR 16-38) for methylprednisolone, 27 h (QR 16-40) for hydrocortisone, and 32 h (QR 16-48) for dexamethasone (p = 0.90). There was no difference in PICU LOS, hospital LOS, PASS score, B2 agonist maximum dose, or need for ventilation support. CONCLUSIONS: The use of IV methylprednisolone, hydrocortisone, and dexamethasone have equivalent efficacy when used at the appropriate doses. Studies with larger cohorts are needed to compare the effectiveness of IV corticosteroids in the management of ASA in the PICU setting.

Natural History and Predictors of Parastomal Hernia after Robot-Assisted Radical Cystectomy and Ileal Conduit Urinary Diversion.

PURPOSE: We investigated the prevalence of and variables associated with parastomal hernia and its outcomes after robot-assisted radical cystectomy and ileal conduit creation for bladder cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent robot-assisted radical cystectomy at our institution. Parastomal hernia was defined as the protrusion of abdominal contents through the stomal defect in the abdominal wall on cross-sectional imaging. Parastomal hernia was further described in terms of patient and hernia characteristics, symptoms, management and outcomes. The Kaplan-Meier method was used to determine time to parastomal hernia and time to surgery. Multivariate stepwise logistic regression was done to evaluate variables associated with parastomal hernia. RESULTS: A total of 383 patients underwent robot-assisted radical cystectomy and ileal conduit creation. Of the patients 75 (20%) had parastomal hernia, which was symptomatic in 23 (31%), and 11 (15%) underwent treatment. Median time to parastomal hernia was 13 months (IQR 9-22). Parastomal hernia developed in 9%, 23% and 32% of cases at 1, 2 and 3 years, respectively. Patients with parastomal hernia had a significantly higher body mass index (30 vs 28 kg/m2, p = 0.02), longer overall operative time (357 vs 340 minutes, p = 0.01) and greater blood loss (325 vs 250 ml, p = 0.04). On multivariate analysis operative time (OR 1.25, 95% CI 1.21-3.90, p <0.001), a fascial defect 30 mm or greater (OR 5.23, 95% CI 2.32-11.8, p <0.001) and a lower postoperative estimated glomerular filtration rate (OR 2.17, 95% CI 1.21-3.90, p = 0.01) were significantly associated with parastomal hernia. CONCLUSIONS: Symptoms develop in approximately a third of patients with parastomal hernia and 15% will require surgery. The risk of parastomal hernia plateaued after postoperative year 3. Longer operative time, a larger fascial defect and lower postoperative kidney function were associated with parastomal hernia.

Outcomes of Intracorporeal Urinary Diversion after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: This study aimed to provide an update and compare perioperative outcomes and complications of intracorporeal and extracorporeal urinary diversion following robot-assisted radical cystectomy using data from the multi-institutional, prospectively maintained International Robotic Cystectomy Consortium database. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,125 patients from a total of 26 institutions. Intracorporeal urinary diversion was compared with extracorporeal urinary diversion. Multivariate logistic regression models using stepwise variable selection were fit to evaluate preoperative, operative and postoperative predictors of intracorporeal urinary diversion, operative time, high grade complications and 90-day hospital readmissions after robot-assisted radical cystectomy. RESULTS: In our cohort 1,094 patients (51%) underwent intracorporeal urinary diversion. These patients demonstrated shorter operative time (357 vs 400 minutes), less blood loss (300 vs 350 ml) and fewer blood transfusions (4% vs 19%, all p <0.001). They experienced more high grade complications (13% vs 10%, p = 0.02). Intracorporeal urinary diversion use increased from 9% of all urinary diversions in 2005 to 97% in 2015. Complications after this procedure decreased significantly with time (p <0.001). On multivariable analysis higher annual cystectomy volume (OR 1.02, 95% CI 1.01-1.03, p <0.002), year of robot-assisted radical cystectomy (2013-2016 OR 68, 95% CI 44-105, p <0.001) and American Society of Anesthesiologists® score less than 3 (OR 1.75, 95% CI 1.38-2.22, p <0.001) were associated with undergoing intracorporeal urinary diversion. The procedure was associated with a shorter operative time of 27 minutes (p = 0.001). CONCLUSIONS: The use of intracorporeal urinary diversion has increased in the last decade. A higher annual institutional volume of robot-assisted radical cystectomy was associated with intracorporeal urinary diversion as well as with shorter operative time. Although intracorporeal urinary diversion was associated with higher grade complications than extracorporeal urinary diversion, they decreased with time.

Variability and interpretation of communication taxonomy during robot-assisted surgery: do we all speak the same language?

OBJECTIVE: To investigate and analyse the different ways surgeons communicate with bedside assistants during robot-assisted surgery (RAS). METHODS: We retrospectively reviewed video and audio recordings of 26 RAS procedures (23 prostatectomies and three cystectomies). Three cameras and eight lapel microphones were used to record the operating theatre environment. We identified five common tasks and categorized them into 'specific', 'non-specific' and 'unclear' categories. We also determined the frequency, time to execute the task, inconveniences and acknowledgements associated with each category. The most efficient category was the one that took the shortest duration to accomplish and was associated with the fewest inconveniences. RESULTS: A total of 1 000 requests were made by three surgeons for six bedside assistants by three surgeons. The five identified tasks were: instrument change; clipping; suction; irrigation; and retraction. For instrument change, non-specific requests were the most frequent compared with the other categories (77% vs 18% vs 5%; P < 0.001). For suction, specific requests were the most frequently used of the three categories (73% vs 27% vs 0%; P < 0.001) and this task was associated with the fewest inconveniences (38% vs 62%; P = 0.01). For clipping, irrigation and retraction, both specific and non-specific requests were similar in terms of their frequency, action time and inconveniences. Comparing complete vs incomplete requests, incomplete requests had significantly shorter median action time (5 vs 8 s; P < 0.001) but did not significantly differ in terms of inconveniences and acknowledgement. CONCLUSION: To our knowledge, this is the first study to provide a detailed analysis of communication during RAS. It lays a foundation for standardized taxonomy to improve communication, surgical efficiency and patient safety.

Natural History, Predictors and Management of Ureteroenteric Strictures after Robot Assisted Radical Cystectomy.

PURPOSE: Ureteroenteric strictures represent the most common complication requiring reoperation after radical cystectomy. We investigated the prevalence, outcomes, predictors and management of ureteroenteric strictures. MATERIALS AND METHODS: We retrospectively reviewed our quality assurance, robot assisted radical cystectomy database to identify patients in whom ureteroenteric strictures developed. Data were reviewed for demographics, perioperative outcomes and ureteroenteric stricture characteristics. The Kaplan-Meier method was used to calculate time to ureteroenteric stricture and multivariable stepwise regression was done to evaluate predictors of ureteroenteric strictures. RESULTS: Ureteroenteric strictures developed in 12%, 16% and 19% of 51 patients (13%) at 1, 3 and 5 years after robot assisted radical cystectomy, respectively. All patients were initially treated endoscopically or percutaneously, including 57% treated only endoscopically or percutaneously and 43% who required surgery, which was open repair in 6 and robot assisted repair in 16. At a median followup of 23 months 33 patients (65%) were free of disease, including 13 after endoscopic or percutaneous treatment, 15 after robot assisted repair and 5 after open revision. Open and robot assisted revisions showed comparable perioperative outcomes. On multivariable analysis the predictors of ureteroenteric anastomotic strictures were body mass index (OR 1.07, 95% CI 1.01-1.13, p = 0.02), intracorporeal urinary diversion (OR 3.28, 95% CI 1.41-7.61, p = 0.006), length of the right resected ureter (OR 0.66, 95% CI 0.50-0.88, p = 0.004), estimated glomerular filtration rate 30 days after assisted radical cystectomy (OR 0.85, 95% CI 0.74-0.98, p = 0.03), urinary tract infection (OR 2.68, 95% CI 1.31-5.49, p = 0.007) and leakage (OR 3.85, 95% CI 1.05-14.1, p = 0.04). Male gender (OR 0.19, 95% CI 0.04-0.96, p = 0.04) and higher body mass index (OR 0.85, 95% CI 0.72-0.996, p = 0.05) were associated with lower odds of successful endoscopic management. CONCLUSIONS: Multiple modifiable factors were associated with ureteroenteric anastomotic strictures following robot assisted radical cystectomy. Surgical revision can provide a definitive management with comparable outcomes for open and robotic repairs.

A discrete choice experiment to assess people living with HIV's (PLWHIV's) preferences for GP or HIV clinic appointments.

OBJECTIVES: To understand which aspects of general practitioner (GP) and HIV clinic appointments people living with HIV (PLWHIV) most value when seeking advice for new health problems. METHODS: A discrete choice experiment using a convenience sample of people diagnosed with HIV. Participants were recruited from 14 general HIV clinics in the South East of England between December 2014 and April 2015. ORs were calculated using conditional logit (CLOGIT) and latent class models (LCMs). RESULTS: A total of 1106 questionnaires were returned. Most participants were male (85%), white (74%) and were men who have sex with men (69%). The CLOGIT analysis showed people particularly valued shorter appointment waiting times (ORs between 1.52 and 3.62, p<0.001 in all instances). The LCM analysis showed there were two distinct classes, with 59% and 41% of respondents likely to be in each. The first class generally preferred GP to HIV clinic appointments and particularly valued 'being seen quickly'. For example, they had strong preferences for shorter appointment waiting times and longer GP opening hours. People in the second class also valued shorter waiting times, but they had a strong general preference for HIV clinic rather than GP appointments. CONCLUSIONS: PLWHIV value many aspects of care for new health problems, particularly short appointment waiting times. However, they appear split in their general willingness to engage with GPs.

Robot-assisted approach to 'W'-configuration urinary diversion: a step-by-step technique.

OBJECTIVE: To describe a detailed step-by-step approach of our technique for robot-assisted intracorporeal 'W'-configuration orthotopic ileal neobladder. PATIENTS AND METHODS: Five patients underwent robot-assisted radical cystectomy (RARC), extended pelvic lymph node dissection and intracorporeal neobladder (ICNB). ICNB was divided into six key steps to facilitate and enable a detailed analysis and auditing of the technique. No conversion to open surgery was required. Timing for each step was noted. All patients had at least 3 months of follow-up. RESULTS: The mean age was 57 years. The mean overall console and diversion times were 357 and 193 min, respectively. None of the patients had any evidence of residual disease after RARC. Four of the five patients had complications; three developed fevers due to urinary tract infections (one required readmission), and one developed myocardial infarction and required coronary angiography and stenting. Looking at the timing for the individual steps, bowel detubularisation and construction of the posterior plate were consistently the longest among the key steps (average 46 min, 13% of the overall operative time), followed by uretero-ileal anastomosis (37 min, 10%), neobladder-urethral anastomosis (23 min, 6%), and identification and fixation of the bowel (26 min, 7%). CONCLUSION: We described our step-by-step technique and initial perioperative outcomes of our first five ICNBs with 'W' configuration.

Development of a patient and institutional-based model for estimation of operative times for robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVES: To design a methodology to predict operative times for robot-assisted radical cystectomy (RARC) based on variation in institutional, patient, and disease characteristics to help in operating room scheduling and quality control. PATIENTS AND METHODS: The model included preoperative variables and therefore can be used for prediction of surgical times: institutional volume, age, gender, body mass index, American Society of Anesthesiologists score, history of prior surgery and radiation, clinical stage, neoadjuvant chemotherapy, type, technique of diversion, and the extent of lymph node dissection. A conditional inference tree method was used to fit a binary decision tree predicting operative time. Permutation tests were performed to determine the variables having the strongest association with surgical time. The data were split at the value of this variable resulting in the largest difference in means for the surgical time across the split. This process was repeated recursively on the resultant data sets until the permutation tests showed no significant association with operative time. RESULTS: In all, 2 134 procedures were included. The variable most strongly associated with surgical time was type of diversion, with ileal conduits being 70 min shorter (P < 0.001). Amongst patients who received neobladders, the type of lymph node dissection was also strongly associated with surgical time. Amongst ileal conduit patients, institutional surgeon volume (>66 RARCs) was important, with those with a higher volume being 55 min shorter (P < 0.001). The regression tree output was in the form of box plots that show the median and ranges of surgical times according to the patient, disease, and institutional characteristics. CONCLUSION: We developed a method to estimate operative times for RARC based on patient, disease, and institutional metrics that can help operating room scheduling for RARC.

Serum IL-17 in patients with erythema multiforme or Stevens-Johnson syndrome/toxic epidermal necrolysis drug reaction, and correlation with disease severity.

BACKGROUND: There is strong evidence that drug-induced cutaneous eruptions have an immunological component. Interleukin (IL)-17, a proinflammatory cytokine that is predominantly produced by T helper 17 cells, has been linked to various autoimmune and inflammatory diseases. AIM: To measure serum IL-17 levels in patients with cutaneous drug reactions [erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)] in order to study the associations between IL-17 and disease severity. METHODS: In total, 32 patients (13 with EM and 19 with SJS/TEN) and 15 age- and sex-matched healthy controls (HCs) were enrolled. Patients with SJS/TEN were assessed clinically using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Serum IL-17 levels were determined by ELISA. RESULTS: Serum IL-17 levels were significantly higher compared with HCs (16.46 ± 5.21 pg/mL) in the EM (35.1 ± 23.89 pg/mL, P < 0.02) and SJS/TEN (68.19 ± 35.42 pg/mL, P = 0.001) groups. IL-17 levels were also significantly higher in the SJS/TEN group than in the EM group (P = 0.004). Mean affected body surface area percentage was 0.9 ± 0.21 in the EM group and 22.8 ± 10.67 in the SJS/TEN group. The SJS/TEN SCORTEN ranged from 1 to 5, with a mean of 2.5 ± 1. Serum IL-17 level correlated positively with both percentage surface area of detached skin and SCORTEN. CONCLUSIONS: Serum IL-17 levels may have prognostic and diagnostic value in patients with EM or SJS/TEN reactions, and can provide a valuable approach in managment.

Which aspects of health care are most valued by people living with HIV in high-income countries? A systematic review.

BACKGROUND: Increasing numbers of people with HIV are living into older age and experiencing comorbidities. The development of new models of care to meet the needs of this population is now a priority. It is important that the views and preferences of patients inform the development of services in order to maintain high levels of patient satisfaction and engagement. The aim of this systematic review was to determine which aspects of healthcare are particularly valued by people living with HIV. METHODS: We searched electronic databases and reference lists of relevant articles. The search strategy was developed to identify articles reporting on HIV positive patients' perceptions, evaluations or experiences of healthcare services and factors associated with satisfaction with care. Peer-reviewed papers and conference abstracts were included if the study reported on aspects of health care that were valued by people living with HIV, data were collected during the era of combination therapy (from 1996 onwards), and the paper was published in English. A thematic approach to data synthesis was used. RESULTS: Twenty-three studies met the inclusion criteria. Studies used both qualitative and quantitative methods. Six studies specifically reported on relative importance to patients of different aspects of care. The valued aspects of care identified were grouped into seven themes. These highlighted the importance to patients of: a good health care professional-patient relationship, HIV specialist knowledge, continuity of care, ease of access to services, access to high quality information and support, effective co-ordination between HIV specialists and other healthcare professionals, and involvement in decisions about treatment and care. We were unable to determine the relative importance to patients of different aspects of care because of methodological differences between the studies. CONCLUSIONS: This review identified several attributes of healthcare that are valued by people living with HIV, many of which would be relevant to any future reconfiguration of services to meet the needs of an ageing population. Further research is required to determine the relative importance to patients of different aspects of care.

The life cycle of Hexangium sigani Goto & Ozaki, 1929 (Digenea: Microscaphidiidae) from the Red Sea.

The microscaphidiid Hexangium sigani Goto & Ozaki, 1929 was found in the intestine of Siganus rivulatus, a siganid fish permanently resident in a lagoon within the mangrove swamps on the Egyptian coast of the Gulf of Aqaba. Intra-molluscan stages of this trematode (mother sporocysts, rediae and cercariae) were found in the gonads and digestive gland of Nassarius pullus (Gastropoda: Nassariidae), a common snail in the same lagoon. Consequently, the life cycle of H. sigani was elucidated under natural conditions: eggs are directly ingested by the snail; mother sporocysts and rediae reach maturity 5-7 and 16-17 weeks post-infection; rediae contain 18-26 developing cercariae; fully developed cercariae are monostome, without penetration glands, emerge from the snail during the night 18-19 weeks post-infection and rapidly encyst on aquatic vegetation (there is no second intermediate host); encysted metacercariae are not progenetic; 2-day-old metacercariae encysted on filamentous algae fed to S. rivulatus developed into fully mature worms 5-6 weeks post-infection. The cycle was completed in about 24 weeks. The intra-molluscan stages are very similar to those of Dictyangium chelydrae Stunkard, 1943, the only described intra-molluscan stages of any microscaphidiid. However, they are also similar to those of the family Mesometridae. The present study of H. sigani describes the first complete microscaphidiid life cycle, and implicitly supports the phylogenetic relationship of this family with the Mesometridae inferred from molecular phylogenetic studies.

Technical Aspects of Motor and Language Mapping in Glioma Patients.

Gliomas are infiltrative primary brain tumors that often invade functional cortical and subcortical regions, and they mandate individualized brain mapping strategies to avoid postoperative neurological deficits. It is well known that maximal safe resection significantly improves survival, while postoperative deficits minimize the benefits associated with aggressive resections and diminish patients' quality of life. Although non-invasive imaging tools serve as useful adjuncts, intraoperative stimulation mapping (ISM) is the gold standard for identifying functional cortical and subcortical regions and minimizing morbidity during these challenging resections. Current mapping methods rely on the use of low-frequency and high-frequency stimulation, delivered with monopolar or bipolar probes either directly to the cortical surface or to the subcortical white matter structures. Stimulation effects can be monitored through patient responses during awake mapping procedures and/or with motor-evoked and somatosensory-evoked potentials in patients who are asleep. Depending on the patient's preoperative status and tumor location and size, neurosurgeons may choose to employ these mapping methods during awake or asleep craniotomies, both of which have their own benefits and challenges. Regardless of which method is used, the goal of intraoperative stimulation is to identify areas of non-functional tissue that can be safely removed to facilitate an approach trajectory to the equator, or center, of the tumor. Recent technological advances have improved ISM's utility in identifying subcortical structures and minimized the seizure risk associated with cortical stimulation. In this review, we summarize the salient technical aspects of which neurosurgeons should be aware in order to implement intraoperative stimulation mapping effectively and safely during glioma surgery.

Recognizing the psychological impact of a glioma diagnosis on mental and behavioral health: a systematic review of what neurosurgeons need to know.

A cancer diagnosis is life altering and frequently associated with both acute and long-lasting psychosocial and behavioral distress for patients. The impact of a diffuse glioma diagnosis on mental health is an important aspect of the patient experience with their disease. This needs to be understood by neurosurgeons so these concerns can be appropriately addressed in a timely fashion and integrated into the multidisciplinary care of neuro-oncology patients. The relatively grave prognosis associated with diffuse gliomas, the morbidity associated with treatment, and the constant threat of developing a new neurological deficit all can negatively affect a patient's mental ability to cope and ultimately manifest in mental health disorders such as anxiety and depression. The objective of this systematic review was to describe the variety of behavioral health disorders patients may experience following a glioma diagnosis and discuss possible treatment options. The PubMed, Web of Science, Embase, and PsycINFO databases were searched through July 1, 2022, using broad search terms, which resulted in 5028 studies that were uploaded to Covidence systematic review software. Duplicates, non-English-language studies, and studies with irrelevant outcomes or incorrect design were removed (n = 3167). A total of 92 articles reporting behavioral health outcomes in brain tumor patients were categorized and extracted for associations with overall mental health, anxiety, depression, distress, stress, pharmacology, interventions, and mental health in caregivers. The authors identified numerous studies reporting the prevalence of mental health disorders and their negative influence in this population. However, there is a paucity of literature on therapeutic options for patients. Given the strong correlation between patient quality of life and mental well-being, there is a considerable need for early recognition and treatment of these behavioral health disorders to optimize everyday functioning for patients.

Advances in Intraoperative Glioma Tissue Sampling and Infiltration Assessment.

Gliomas are infiltrative brain tumors that often involve functional tissue. While maximal safe resection is critical for maximizing survival, this is challenged by the difficult intraoperative discrimination between tumor-infiltrated and normal structures. Surgical expertise is essential for identifying safe margins, and while the intraoperative pathological review of frozen tissue is possible, this is a time-consuming task. Advances in intraoperative stimulation mapping have aided surgeons in identifying functional structures and, as such, has become the gold standard for this purpose. However, intraoperative margin assessment lacks a similar consensus. Nonetheless, recent advances in intraoperative imaging techniques and tissue examination methods have demonstrated promise for the accurate and efficient assessment of tumor infiltration and margin delineation within the operating room, respectively. In this review, we describe these innovative technologies that neurosurgeons should be aware of.

Repurposing a PICU for Adult Care in a State Mandated COVID-19 Only Hospital: Outcome Comparison to the MICU Cohort to Determine Safety and Effectiveness.

Objective: The ongoing coronavirus 2019 (COVID-19) pandemic is disproportionally impacting the adult population. This study describes the experiences after repurposing a PICU and its staff for adult critical care within a state mandated COVID-19 hospital and compares the outcomes to adult patients admitted to the institution's MICU during the same period. Design: A retrospective chart review was performed to analyze outcomes for the adults admitted to the PICU and MICU during the 27-day period the PICU was incorporated into the institution's adult critical care surge plan. Setting: Tertiary care state University hospital. Patients: Critically ill adult patients with proven or suspected COVID-19. Interventions: To select the most ideal adult patients for PICU admission a tiered approach that incorporated older patients with more comorbidities at each stage was implemented. Measurements and Main Results: There were 140 patients admitted to the MICU and 9 patients admitted to the PICU during this period. The mean age of the adult patients admitted to the PICU was lower (49.1 vs. 63.2 p = 0.017). There was no statistically significant difference in the number of comorbidities, intubation rates, days of ventilation, dialysis or LOS. Patients selected for PICU care did not have coronary artery disease, CHF, cerebrovascular disease or COPD. Mean admission Sequential Organ Failure Assessment (SOFA) score was lower in patients admitted to the PICU (4 vs. 6.4, p = 0.017) with similar rates of survival to discharge (66.7 vs. 44.4%, p = 0.64). Conclusion: Outcomes for the adult patients who received care in the PICU did not appear to be worse than those who were admitted to the MICU during this time. While limited by a small sample size, this single center cohort study revealed that careful assessment of critical illness considering age and type of co-morbidities may be a safe and effective approach in determining which critically ill adult patients with known or suspected COVID-19 are the most appropriate for PICU admission in general hospitals with primary management by its physicians and nurses.