Implementation of a Survey Spine Magnetic Resonance Imaging Protocol for Cord Compression in the Emergency Department: Experience at a Level-1 Trauma Center.

BACKGROUND AND PURPOSE: Imaging stewardship in the emergency department (ED) is vital in ensuring patients receive optimized care. While suspected cord compression (CC) is a frequent indication for total spine MRI in the ED, the incidence of CC is low. Recently, our level-I trauma center introduced a survey spine MRI protocol to evaluate for suspected CC while reducing exam time to avoid imaging overutilization. This study aims to evaluate the time savings, frequency of ordering patterns of the survey, and the symptoms and outcomes of patients undergoing the survey. MATERIALS AND METHODS: This retrospective study examined patients who received a survey spine MRI in the ED at our institution between 2018 and 2022. All exams were performed on a 1.5T GE scanner using our institutional CC survey protocol, which includes sagittal T2 and STIR sequences through the cervical, thoracic, and lumbar spine. Exams were read by a blinded, board-certified neuroradiologist. RESULTS: A total of 2,002 patients received a survey spine MRI protocol during the study period. Of these patients, 845 (42.2%, mean age 57 ± 19 years, 45% female) received survey spine MRI exams for the suspicion of CC, and 120 patients (14.2% positivity rate) had radiographic CC. The survey spine MRI averaged 5 minutes and 50 seconds (79% faster than routine MRI). On multivariate analysis, trauma, back pain, lower extremity weakness, urinary or bowel incontinence, numbness, ataxia, and hyperreflexia were each independently associated with CC. Of the 120 patients with CC, 71 underwent emergent surgery, 20 underwent non-emergent surgery, and 29 were managed medically. CONCLUSIONS: The survey spine protocol was positive for CC in 14% of patients in our cohort and acquired at a 79% faster rate compared to routine total spine. Understanding the positivity rate of CC, the clinical symptoms that are most associated with CC, and the subsequent care management for patients presenting with suspected cord compression who received the survey spine MRI may better inform the broad adoption and subsequent utilization of survey imaging protocols in emergency settings to increase throughput, improve allocation of resources, and provide efficient care for patients with suspected CC.ABBREVIATIONS: CC, cord compression; ED, emergency department; MRI, magnetic resonance imaging; T2; T2-weighted imaging sequence; STIR, short TI inversion recovery.

Subclinical, long-term psychological symptoms following sport-related concussion: are athletes more depressed than we think?

INTRODUCTION: In adolescent and collegiate athletes with sport-related concussion (SRC), we sought to evaluate the prevalence and predictors of long-term psychological symptoms. METHODS: A cohort study was conducted of athletes 12-24-year-old diagnosed with SRC between November 2017 and April 2022. Athletes/proxies were interviewed on psychological symptoms (i.e. anger, anxiety, depression, and stress). Participants who scored ≥75th percentile on one or more PROMIS (Patient-Reported Outcomes Measurement System) measures were operationalized to have subclinical, long-term psychological symptoms. Uni/multivariable regressions were used. RESULTS: Of 96 participants (60.4% male), the average age was 16.6 ± 2.6 years. The median time from concussion to interview was 286 days (IQR: 247-420). A total of 36.5% athletes demonstrated subclinical, long-term psychological symptoms. Univariate logistic regression revealed significant predictors of these symptoms: history of psychiatric disorder (OR = 7.42 95% CI 1.37,40.09), substance use (OR = 4.65 95% CI 1.15,18.81), new medical diagnosis since concussion (OR = 3.43 95% CI 1.27,9.26), amnesia (OR = 3.42 95% CI 1.02,11.41), other orthopedic injuries since concussion (OR = 3.11 95% CI 1.18,8.21), age (OR = 1.24 95% CI 1.03,1.48), days to return-to-play (OR = 1.02 95% CI 1.00,1.03), and psychiatric medication use (OR = 0.19 95% CI 0.05,0.74). Multivariable model revealed significant predictors: orthopedic injuries (OR = 5.17 95% CI 1.12,24.00) and return-to-play (OR = 1.02 95% CI 1.00,1.04). CONCLUSIONS: Approximately one in three athletes endorsed long-term psychological symptoms. Predictors of these symptoms included orthopedic injuries and delayed RTP.

Symptoms of Traumatic Encephalopathy Syndrome are Common in Community-Dwelling Adults.

BACKGROUND AND OBJECTIVES: The consensus criteria for traumatic encephalopathy syndrome (TES), the possible in vivo clinical syndrome associated with significant repetitive head impacts, have only been minimally studied to date. This study examined the prevalence of the proposed core clinical features of TES in a sample of healthy adults. METHODS: A cross-sectional survey study was conducted through ResearchMatch, a national health volunteer registry. Participants were assessed for symptoms of TES based on the 2021 consensus criteria, including prior repetitive head impacts and core clinical features. Additional health information (e.g., concussion history, psychological health, sleep, chronic pain) was also evaluated. The consensus proposed research criteria for TES (i.e., reporting at least one progressive core clinical feature of TES, as in progressive difficulties with episodic memory, executive functioning, or neurobehavioral dysregulation) were applied to the sample. RESULTS: Out of 1100 participants (average age = 53.6 ± 17.7 years, 55% women), 34.6% endorsed one or more progressive core clinical features of TES. Participants with a significant history of contact sports (i.e., ≥ 5 years total, with ≥ 2 years in high school or beyond) had similar rates of endorsing a progressive core clinical feature of TES compared to those without significant histories of repetitive head impacts (36.4% vs 32.8%, respectively, χ2 = 0.52, p = 0.47). A significant history of repetitive head impacts in sports was not associated with endorsing a core clinical feature of TES in univariable or multivariable models (p > 0.47), whereas current depression/anxiety (odds ratio [OR] = 6.94), a history of psychiatric disorders (OR = 2.57), current sleep problems (OR = 1.56), and younger age (OR = 0.99) were significant predictors of TES status in a multivariable model. In a subsample of 541 participants who denied a lifetime history of contact sports, other forms of repetitive head impacts, and concussions, approximately 31.0% endorsed one or more progressive core clinical features of TES. Additionally, 73.5% of neurotrauma-naïve participants with current anxiety or depression reported at least one core progressive feature of TES, compared with 20.2% of those without clinically significant depression/anxiety symptoms. CONCLUSIONS: A considerable proportion of adults without a significant history of repetitive head impacts from sports endorsed core TES features, particularly those experiencing mental health symptoms. Having a significant history of contact sports was not associated with endorsing a core progressive clinical feature of TES, whereas other health factors were. These findings underscore the need for validating and refining TES criteria in samples with and without substantial neurotrauma histories.

Trends in non-focal neurological chief complaints and CT angiography utilization among adults in the emergency department.

Prudent imaging use is essential for cost reduction and efficient patient triage. Recent efforts have focused on head and neck CTA in patients with emergent concerns for non-focal neurological complaints, but have failed to demonstrate whether increases in utilization have resulted in better care. The objective of this study was to examine trends in head and neck CTA ordering and determine whether a correlation exists between imaging utilization and positivity rates. This is a single-center retrospective observational study at a quaternary referral center. This study includes patients presenting with headache and/or dizziness to the emergency department between January 2017 and December 2021. Patients who received a head and neck CTA were compared to those who did not. The main outcomes included annual head and neck CTA utilization and positivity rates, defined as the percent of scans with attributable acute pathologies. Among 24,892 emergency department visits, 2264 (9.1%) underwent head and neck CTA imaging. The percentage of patients who received a scan over the study period increased from 7.89% (422/5351) in 2017 to 13.24% (662/5001) in 2021, representing a 67.4% increase from baseline (OR, 1.14; 95% CI 1.11-1.18; P < .001). The positivity rate, or the percentage of scans ordered that revealed attributable acute pathology, dropped from 16.8% (71/422) in 2017 to 10.4% (69/662) in 2021 (OR, 0.86; 95% CI 0.79-0.94; P = .001), a 38% reduction in positive examinations. Throughout the study period, there was a 67.4% increase in head and neck CTA ordering with a concomitant 38.1% decrease in positivity rate.

Do academic accommodations help students recover following sport-related concussion? A retrospective study of 96 youth athletes.

OBJECTIVE: Many schools utilize academic accommodations to help athletes return-to-learn after sport-related concussion, yet little is known about the impact of accommodations on recovery. In a cohort of adolescent athletes with sport-related concussion, the authors sought to 1) describe academic accommodations, 2) determine predictors of receiving accommodations, and 3) determine how accommodations influenced recovery, as defined by days to return-to-learn, symptom resolution, and return-to-play. METHODS: A retrospective survey study was undertaken that included all athletes between the ages of 12 and 24 years who were seen at a regional sport-related concussion center from April 1, 2020, to April 1, 2022. Demographic characteristics, past medical history, injury characteristics, school-related factors, and recovery were collected via a telephone-based survey and from medical charts. The independent variable was the use of academic accommodations by students. The outcome variables included days to return-to-learn, symptom resolution, and return-to-play. Univariable and multivariable logistic regression analyses were performed. RESULTS: Of 300 athletes contacted, 96 consented to participate in this study (mean age ± SD 16.6 ± 2.6 years, 60.4% male). The mean return-to-learn was 9.0 ± 13.2 days. In total, 63.5% of athletes received some kind of school accommodation. The most common accommodations included extra time on tests (46/96 [47.9%] athletes) and extra time for assignments (43/96 [44.8%]), whereas preferential seating in class (0/96 [0.0%]) and reduced workloads (4/96 [4.2%]) were the least commonly used accommodations. Multivariable logistic regression revealed that White race (OR 0.17, 95% CI 0.02-0.71, p = 0.03) and higher initial Post-Concussion Symptom Scale (PCSS) score (OR 1.04, 95% CI 1.01-1.07, p = 0.02) were predictive of receiving accommodations. Univariable models showed that receiving accommodations was not predictive of return-to-learn (ß = 4.67, 95% CI -0.92 to 10.25, p = 0.10), symptom resolution (ß = 24.71, 95% CI -17.41 to 66.83, p = 0.26), or return-to-play (ß = 13.35, 95% CI -14.56 to 41.27, p = 0.35). Regarding other predictors of each outcome, several factors emerged irrespective of accommodations. Multivariable analysis revealed that longer time to return-to-learn was associated with a history of psychiatric illness (ß = 8.00, 95% CI 1.71-14.29, p = 0.02) and initial PCSS score (ß = 0.14, 95% CI 0.06-0.23, p < 0.01). Finally, predictors of days to return-to-play included school personnel who were knowledgeable of concussion (ß = -5.07, 95% CI -9.93 to -0.21, p = 0.04) and higher initial PCSS score (ß = 0.67, 95% CI 0.04-1.29, p = 0.03). CONCLUSIONS: The most common accommodation was extra time on tests/assignments, whereas reduced workload was the least common. White race and greater initial PCSS score were associated with receiving accommodations. Receiving accommodations did not significantly impact days to return-to-learn, symptom resolution, or return-to-play.

Machine learning-based detection of sarcopenic obesity and association with adverse outcomes in patients undergoing surgical treatment for spinal metastases.

OBJECTIVE: The distributions and proportions of lean and fat tissues may help better assess the prognosis and outcomes of patients with spinal metastases. Specifically, in obese patients, sarcopenia may be easily overlooked as a poor prognostic indicator. The role of this body phenotype, sarcopenic obesity (SO), has not been adequately studied among patients undergoing surgical treatment for spinal metastases. To this end, here the authors investigated the role of SO as a potential prognostic factor in patients undergoing surgical treatment for spinal metastases. METHODS: The authors identified patients who underwent surgical treatment for spinal metastases between 2010 and 2020. A validated deep learning approach evaluated sarcopenia and adiposity on routine preoperative CT images. Based on composition analyses, patients were classified with SO or nonsarcopenic obesity. After nearest-neighbor propensity matching that accounted for confounders, the authors compared the rates and odds of postoperative complications, length of stay, 30-day readmission, and all-cause mortality at 90 days and 1 year between the SO and nonsarcopenic obesity groups. RESULTS: A total of 62 patients with obesity underwent surgical treatment for spinal metastases during the study period. Of these, 37 patients had nonsarcopenic obesity and 25 had SO. After propensity matching, 50 records were evaluated that were equally composed of patients with nonsarcopenic obesity and SO (25 patients each). Patients with SO were noted to have increased odds of nonhome discharge (OR 6.0, 95% CI 1.69-21.26), 30-day readmission (OR 3.27, 95% CI 1.01-10.62), and 90-day (OR 4.85, 95% CI 1.29-18.26) and 1-year (OR 3.78, 95% CI 1.17-12.19) mortality, as well as increased time to mortality after surgery (12.60 ± 19.84 months vs 37.16 ± 35.19 months, p = 0.002; standardized mean difference 0.86). No significant differences were noted in terms of length of stay or postoperative complications when comparing the two groups (p > 0.05). CONCLUSIONS: The SO phenotype was associated with increased odds of nonhome discharge, readmission, and postoperative mortality. This study suggests that SO may be an important prognostic factor to consider when developing care plans for patients with spinal metastases.

Implication of nutritional status for adverse outcomes after surgery for metastatic spine tumors.

OBJECTIVE: Surgery for metastatic spinal tumors can have a substantial impact on patients' quality of life by alleviating pain, improving function, and correcting spinal instability when indicated. The decision to operate is difficult because many patients with cancer are frail. Studies have highlighted the importance of preoperative nutritional status assessments; however, little is known about which aspects of nutrition accurately inform clinical outcomes. This study investigates the interaction and prognostic importance of various nutritional and frailty measures in patients with spinal metastases. METHODS: A retrospective analysis of consecutive patients who underwent surgery for spinal metastases between 2014 and 2020 at the Massachusetts General Hospital was performed. Patients were stratified according to the New England Spinal Metastasis Score (NESMS). Frailty was assessed using the metastatic spinal tumor frailty index. Nutrition was assessed using the prognostic nutritional index (PNI), preoperative body mass index, albumin, albumin-to-globulin ratio, and platelet-to-lymphocyte ratio. Outcomes included postoperative survival and complication rates, with focus on wound-related complications. RESULTS: This study included 154 individuals (39% female; mean [SD] age 63.23 [13.14] years). NESMS 0 and NESMS 3 demonstrated the highest proportions of severely frail patients (56.2%) and nonfrail patients (16.1%), respectively. Patients with normal nutritional status (albumin-to-globulin ratio and PNI) had a better prognosis than those with poor nutritional status when stratified by NESMS. Multivariable regression adjusted for NESMS and frailty showed that a PNI > 40.4 was significantly associated with decreased odds of 90-day complications (OR 0.93, 95% CI 0.85-0.98). After accounting for age, sex, primary tumor pathology, physical function, nutritional status, and frailty, a preoperative nutrition consultation was associated with a decrease in postoperative wound-related complications (average marginal effect -5.00%; 95% CI -1.50% to -8.9%). CONCLUSIONS: The PNI was most predictive of complications and may be a key biomarker for risk stratification in the 90 days following surgery. Nutrition consultation was associated with a reduced risk of wound-related complications, attesting to the importance of this preoperative intervention. These findings suggest that nutrition plays an important role in the postsurgical course and should be considered when developing a treatment plan for spinal metastases.

Parental Factors Associated With Recovery After Mild Traumatic Brain Injury: A Systematic Review.

While parental factors have been shown to potentially influence recovery after mild traumatic brain injury (mTBI) in children, both the strength and direction of the relationships remain unclear. We performed a systematic review regarding the association between parental factors and recovery after mTBI. PubMed, CINHL, Embase, PsychINFO, Web of Science, ProQuest, Cochrane Central, and Cochrane databases were queried for articles published between September 1, 1970, and September 10, 2022, reporting any parental factor and its association with recovery after mTBI in children younger than 18 years old. The review included both quantitative and qualitative studies published in English. Regarding the directionality of the association, only studies that assessed the effects of parental factors on recovery after mTBI were included. Study quality was assessed using a five-domain scale created by the Cochrane Handbook and the Agency for Healthcare Research and Quality. The study was prospectively registered with PROSPERO (CRD42022361609). Of 2050 studies queried, 40 met inclusion criteria, and 38 of 40 studies used quantitative outcome measures. Across 38 studies, 24 unique parental factors and 20 different measures of recovery were identified. The most common parental factors studied were socioeconomic status/income (SES; n = 16 studies), parental stress/distress (n = 11), parental level of education (n = 9), pre-injury family functioning (n = 8), and parental anxiety (n = 6). Among all associations between parental factors and recovery reported, having a family history of a neurologic disease (i.e., migraine, epilepsy, neurodegenerative disease; 5/6 significant associations reported, 83%), parental stress/distress (9/11, 82%), parental anxiety (4/6, 67%), parental level of education (5/9, 56%), and SES/income (11/19, 57.9%) were shown to have the strongest evidence reporting significant associations with recovery, while a family history of psychiatric disease (3/6, 50%) and pre-injury family functioning (4/9, 44%) showed mixed results. Evidence regarding other parental factors including parental sex, race/ethnicity, insurance status, parental history of concussion, family litigation status, family adjustment levels, and family psychosocial adversity were limited, as studies investigating such factors were few. The current review highlights literature describing several parental factors that significantly influence recovery from mTBI. It will likely be useful for future studies to incorporate parental SES, education, stress/distress, anxiety, quality of parent-child relationships, and parenting style when examining modifying factors in recovery after mTBI. Future studies should also consider how parental factors may serve as potential interventions or policy levers to optimize sport concussion-related policy and return-to-play guidelines.

Assessing the Relationship Between Race, Language, and Surgical Admissions in the Emergency Department.

INTRODUCTION: English proficiency and race are both independently known to affect surgical access and quality, but relatively little is known about the impact of race and limited English proficiency (LEP) on admission for emergency surgery from the emergency department (ED). Our objective was to examine the influence of race and English proficiency on admission for emergency surgery from the ED. METHODS: We conducted a retrospective observational cohort study from January 1-December 31, 2019 at a large, quaternary-care urban, academic medical center with a 66-bed ED Level I trauma and burn center. We included ED patients of all self-reported races reporting a preferred language other than English and requiring an interpreter or declaring English as their preferred language (control group). A multivariable logistic regression was fit to assess the association of LEP status, race, age, gender, method of arrival to the ED, insurance status, and the interaction between LEP status and race with admission for surgery from the ED. RESULTS: A total of 85,899 patients (48.1% female) were included in this analysis, of whom 3,179 (3.7%) were admitted for emergent surgery. Regardless of LEP status, patients identifying as Black (odds ratio [OR] 0.456, 95% CI 0.388-0.533; P<0.005), Asian [OR 0.759, 95% CI 0.612-0.929]; P=0.009), or female [OR 0.926, 95% CI 0.862-0.996]; P=0.04) had significantly lower odds for admission for surgery from the ED compared to White patients. Compared to individuals on Medicare, those with private insurance [OR 1.25, 95% CI 1.13-1.39; P <0.005) were significantly more likely to be admitted for emergent surgery, whereas those without insurance [OR 0.581, 95% CI 0.323-0.958; P=0.05) were significantly less likely to be admitted for emergent surgery. There was no significant difference in odds of admission for surgery between LEP vs non-LEP patients. CONCLUSION: Individuals without health insurance and those identifying as female, Black, or Asian had significantly lower odds of admission for surgery from the ED compared to those with health insurance, males, and those self-identifying as White, respectively. Future studies should assess the reasons underpinning this finding to elucidate impact on patient outcomes.

A prospective 18 F-fluorodeoxyglucose positron emission tomography/computed tomography study of the neurometabolic effects in cocaine use and HIV infection.

OBJECTIVES: HIV affects 36 million people globally with prevalence decreasing due to antiretroviral therapy (ART) and social awareness; transmission occurs during substance use. Cocaine usage independently affects brain activity and may result in reduced ART adherence. This study evaluates brain glucose metabolism measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in cocaine users with HIV infection. DESIGN: Sixty-three participants were categorized into groups: 36 HIV infected (HIV+) and 27 non-HIV infected (HIV-) individuals. Each group was further split into cocaine users (CO+) and non-cocaine users (CO-). Of the HIV+, half were cocaine users and half were not. Of the HIV-, 14 were cocaine users and 13 were not. 18 F-FDG-PET and low dose CT scans were performed on all participants. METHODS: Brain glucose metabolism was evaluated by 18 F-FDG uptake in the whole brain, cortex, basal ganglia, and cerebellum 120 min after injection. ROVER software was used for image analysis and regions of interest masks were applied via an adaptive threshold system. ANOVA tests and t -tests were performed to assess the respective differences between the four groups. RESULTS: Generally, the HIV+/CO+ group (group A) displayed the lowest levels of uptake whereas the HIV-/CO- group (group D) showed the highest; the HIV+/CO- and HIV-/CO+ groups (groups B and C) showed intermediate levels of activity across the whole brain, cortex, basal ganglia, and cerebellum. CONCLUSION: HIV infection and cocaine usage were independently associated with a decrease in brain glucose uptake as measured by 18 F-FDG PET/CT. When combined, positive HIV status and cocaine patients showed the most decreased 18 F-FDG uptake.

Lifetime Traumatic Brain Injury and Cognitive Domain Deficits in Late Life: The PROTECT-TBI Cohort Study.

Traumatic brain injury (TBI) causes cognitive impairment but it remains contested regarding which cognitive domains are most affected. Further, moderate-severe TBI is known to be deleterious, but studies of mild TBI (mTBI) show a greater mix of negative and positive findings. This study examines the longer-term cognitive effects of TBI severity and number of mTBIs in later life. We examined a subset (n = 15,764) of the PROTECT study, a cohort assessing risk factors for cognitive decline (ages between 50 and 90 years). Participants completed cognitive assessments annually for 4 years. Cognitive tests were grouped using a principal components analysis (PCA) into working memory, episodic memory, attention, processing speed, and executive function. Lifetime TBI severity and number were retrospectively recalled by participants using the Brain Injury Screening Questionnaire (BISQ). Linear mixed models (LMMs) examined the effect of severity of head injury (non-TBI head strike, mTBI, and moderate-severe TBI) and number of mTBI at baseline and over time. mTBI was considered as a continuous and categorical variable (groups: 0 mTBI, 1 mTBI, 2 mTBIs, 3 mTBIs, and 4+ mTBIs). Of the participants 5725 (36.3%) reported at least one mTBI and 510 (3.2%) at least one moderate-severe TBI, whereas 3711 (23.5%) had suffered at worst a non-TBI head strike and 5818 (32.9%) reported no head injuries. The participants had suffered their last reported head injury an average (standard deviation, SD) of 29.6 (20.0) years prior to the study. Regarding outcomes, there was no worsening in longitudinal cognitive trajectories over the study duration but at baseline there were significant cognitive deficits associated with TBI. At baseline, compared with those without head injury, individuals reporting at least one moderate-severe TBI had significantly poorer attention (B = -0.163, p < 0.001), executive scores (B = -0.151, p = 0.004), and processing speed (B = -0.075, p = 0.033). Those who had suffered at least a single mTBI also demonstrated significantly poorer attention scores at baseline compared with the no head injury group (B = -0.052, p = 0.001). Compared with those with no mTBI, those in the 3 mTBI group manifested poorer baseline executive function (B = -0.149, p = 0.025) and attention scores (B = -0.085, p = 0.015). At baseline, those who had suffered four or more mTBIs demonstrated poorer attention (B = -0.135, p < 0.001), processing speed (B = -0.072, p = 0.009), and working memory (B = -0.052, p = 0.036), compared with those reporting no mTBI. TBI is associated with fixed, dose, and severity-dependent cognitive deficits. The most sensitive cognitive domains are attention and executive function, with approximately double the effect compared with processing speed and working memory. Post-TBI cognitive rehabilitation should be targeted appropriately to domain-specific effects. Significant long-term cognitive deficits were associated with three or more lifetime mTBIs, a critical consideration when counseling individuals post-TBI about continuing high-risk activities.

Institutional Surgical Response and Associated Volume Trends Throughout the COVID-19 Pandemic and Postvaccination Recovery Period.

Importance: The COVID-19 pandemic is associated with decreased surgical procedure volumes, but existing studies have not investigated this association beyond the end of 2020, analyzed changes during the post-vaccine release period, or quantified these changes by patient acuity. Objective: To quantify changes in the volume of surgical procedures at a 1017-bed academic quaternary care center from January 6, 2019, to December 31, 2021. Design, Setting, and Participants: In this cohort study, 129 596 surgical procedure volumes were retrospectively analyzed during 4 periods: pre-COVID-19 (January 6, 2019, to January 4, 2020), COVID-19 peak (March 15, 2020, to May 2, 2020), post-COVID-19 peak (May 3, 2020, to January 2, 2021), and post-vaccine release (January 3, 2021, to December 31, 2021). Surgery volumes were analyzed by subspecialty and case class (elective, emergent, nonurgent, urgent). Statistical analysis was by autoregressive integrated moving average modeling. Main Outcomes and Measures: The primary outcome of this study was the change in weekly surgical procedure volume across the 4 COVID-19 periods. Results: A total of 129 596 records of surgical procedures were reviewed. During the COVID-19 peak, overall weekly surgical procedure volumes (mean [SD] procedures per week, 406.00 [171.45]; 95% CI, 234.56-577.46) declined 44.6% from pre-COVID-19 levels (mean [SD] procedures per week, 732.37 [12.70]; 95% CI, 719.67-745.08; P < .001). This weekly volume decrease occurred across all surgical subspecialties. During the post-COVID peak period, overall weekly surgical volumes (mean [SD] procedures per week, 624.31 [142.45]; 95% CI, 481.85-766.76) recovered to only 85.8% of pre-COVID peak volumes (P < .001). This insufficient recovery was inconsistent across subspecialties and case classes. During the post-vaccine release period, although some subspecialties experienced recovery to pre-COVID-19 volumes, others continued to experience declines. Conclusions and Relevance: This quaternary care institution effectively responded to the pressures of the COVID-19 pandemic by substantially decreasing surgical procedure volumes during the peak of the pandemic. However, overall surgical procedure volumes did not fully recover to pre-COVID-19 levels well into 2021, with inconsistent recovery rates across subspecialties and case classes. These declines suggest that delays in surgical procedures may result in potentially higher morbidity rates in the future. The differential recovery rates across subspecialties may inform institutional focus for future operational recovery.

The Association of Traumatic Brain Injury with Neurologic and Psychiatric Illnesses among Individuals Experiencing Homelessness: A Systematic Review and Meta-analysis.

Homeless individuals are more likely than others to experience a traumatic brain injury (TBI), but it is uncertain if such individuals are more likely to experience neuropsychiatric illnesses. METHODS: A systematic review was performed with searches in Medline, Embase, and PsychINFO for studies reporting on homeless persons with TBI and neuropsychiatric illnesses. A random-effects model was used to calculate odds ratios for having any neuropsychiatric diagnosis. RESULTS: Of 420 articles indexed, 19 were included for systematic review and 17 for meta-analysis reporting on 11,474 and 8,757 individuals, respectively. The pooled odds of a homeless individual with a TBI having any neurologic illness were 2.57 (95% CI [1.97, 3.44]; I2 = 68.0%) and 2.01 (95% CI [1.81, 2.25]; I2 = 79.2%) for any psychiatric illness. CONCLUSIONS: The odds of having a neuropsychiatric illness among homeless individuals with TBI are substantially higher than in the domiciled population with TBI.

Tau-PET imaging as a molecular modality for Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative condition. The definitive diagnosis of AD remains a post-mortem neuropathological study of the brain. Unfortunately, there are no established diagnostic criteria to achieve an accurate diagnosis of AD in a similarly objective fashion among living patients. Molecular imaging provides one way of enhancing clinical criteria where objective measures of AD correlate to the presence and progression of disease. In this article, the amyloid and tau hypotheses are considered with respect to pathological, imaging, and therapeutic studies. The value of beta-amyloid (Aß) PET and tau PET are ascertained. Subsequently, the binding characteristics and quality of Aß and tau tracers are explored. Finally, the value of Aß and tau imaging in AD can be determined relevant from in-vivo studies of AD patients. Considering the evolving literature in AD and PET imaging, it has become clear that PET can play a role in the diagnosis and prognosis of AD. The use of Aß imaging has been extensively studied with mixed results suggesting a limited clinical utility. Conversely, tau-PET has shown early success in similar applications as Aß imaging. Specifically, we find that there is value in FDG-PET and prospective utility in tau-PET. Ultimately, the community must acknowledge that the role of Aß imaging for diagnosing and managing AD is very limited and that FDG-PET will remain the study of choice at this time. Moreover, research efforts must continue to determine the prospective value of tau imaging to the assessment of this disease.

Genetic Therapies for Alzheimer's Disease: A Scoping Review.

Effective, disease modifying therapies for Alzheimer's disease (AD) remain a quandary, following a panoply of expensive failures in human clinical trials. Given the stagnation in therapeutics, alternative approaches are needed. Recent successes of genetic therapies in other neurodegenerative diseases may highlight the way forward. This scoping review explores suggested targets of genetic therapy in AD, with a focus on vector-based approaches in pre-clinical and clinical trials. Putative targets of genetic therapies tested in pre-clinical trials include amyloid pathway intermediates and enzymes modulation, tau protein downregulation, APOE4 downregulation and APOE2 upregulation, neurotrophin expression (nerve growth factor (NGF) and brain-derived neurotrophic factor), and inflammatory cytokine alteration, among several other approaches. There have been three completed human clinical trials for genetic therapy in AD patients, all of which upregulated NGF in AD patients, showing some mixed evidence of benefit. Several impediments remain to be surpassed before genetic therapies can be successfully applied to AD, including the challenge of delivering monogenic genetic therapies for complex polygenic disorders, risks in the dominant delivery method (intracranial injection), stability of genetic therapies in vivo, poor translatability of pre-clinical AD models, and the expense of genetic therapy production. Genetic therapies represent an exciting opportunity within the world of AD therapeutics, but clinical applications likely remain a long term, rather than short term, possibility.

The use of computational models in the management and prognosis of refractory epilepsy: A critical evaluation.

PURPOSE: Drug resistant epilepsy (DRE) affects approximately 30 percent of individuals with epilepsy worldwide. Surgery remains the most effective treatment for individuals with DRE, but referral to surgery is low and only about 60 percent of individuals who undergo surgery experience seizure control postoperatively. The present paper evaluates the evidence for using computational models in the prediction of surgical resection sites and surgical outcomes for patients with DRE. METHODS: We conducted a search in the Medline data base using the terms "refractory epilepsy", "drug-resistant epilepsy", "surgery", "computational model", and "artificial intelligence". Inclusion: original articles in English and case reports from 2000 to 2020. Reviews were excluded. RESULTS: Clinical applications of computational models may lead to increased utilisation of surgical services through improving our ability to predict outcomes and by improving surgical outcomes outright. The identification and optimisation of nodes that are crucial for the genesis and propagation of epileptiform activity offers the most promising clinical applications of computational models discussed herein. CONCLUSION: Advances in computational models may in the future significantly increase the application and efficacy of surgery for patients with DRE by optimising the site and amount of cortex to resect, but more research is needed before it achieves therapeutic utility.

An Update on the State of Tau Radiotracer Development: a Brief Review.

Evolving scientific evidence has begun to point towards hyperphosphorylated tau as a major neurotoxic component in the pathophysiological development of many major neurodegenerative conditions. In response to a need for accurate and reliable diagnosis and disease monitoring in clinical and trial settings, there has been great effort put into the development of tau radiotracers. While first-generation and second-generation radiotracers have provided a basis for assessing tau, concerns of inadequate specificity and selectivity have continued to motivate further study of these radiotracers and the development of novel radiopharmaceuticals. Given the prospective scientific and clinical value of a valid tau radiotracer, the molecular neuroimaging community must be aware of the most recent developments in the realm of tau radiotracer development. This brief review article will critically overview the most established tau radiotracers and, most importantly, concentrate on the progress of more recently developed tau radiotracers.

Impaired Lymphatic Drainage and Interstitial Inflammatory Stasis in Chronic Musculoskeletal and Idiopathic Pain Syndromes: Exploring a Novel Mechanism.

A normal functioning lymphatic pump mechanism and unimpaired venous drainage are required for the body to remove inflammatory mediators from the extracellular compartment. Impaired vascular perfusion and/or lymphatic drainage may result in the accumulation of inflammatory substances in the interstitium, creating continuous nociceptor activation and related pathophysiological states including central sensitization and neuroinflammation. We hypothesize that following trauma and/or immune responses, inflammatory mediators may become entrapped in the recently discovered interstitial, pre-lymphatic pathways and/or initial lymphatic vessels. The ensuing interstitial inflammatory stasis is a pathophysiological state, created by specific pro-inflammatory cytokine secretion including tumor necrosis factor alpha, interleukin 6, and interleukin 1b. These cytokines can disable the local lymphatic pump mechanism, impair vascular perfusion via sympathetic activation and, following transforming growth factor beta 1 expression, may lead to additional stasis through direct fascial compression of pre-lymphatic pathways. These mechanisms, when combined with other known pathophysiological processes, enable us to describe a persistent feed-forward loop capable of creating and maintaining chronic pain syndromes. The potential for concomitant visceral and/or vascular dysfunction, initiated and maintained by the same feed-forward inflammatory mechanism, is also described.

Gamma knife radiosurgery for uveal melanomas and metastases: a systematic review and meta-analysis.

BACKGROUND: Gamma knife radiosurgery is regarded as the gold-standard stereotactic radiosurgery modality for the treatment of intracranial tumours, and its use has been expanded for the treatment of intraocular malignancies. The aim of this study was to systematically evaluate the efficacy, outcomes, and complications of gamma knife radiosurgery for uveal melanomas and metastases. METHODS: We did a systematic review and meta-analysis to aggregate the clinical outcomes of patients with uveal melanomas or intraocular metastases treated primarily with gamma knife radiosurgery. We searched MEDLINE and Embase for studies published between Sept 1, 1960, and Feb 1, 2020, reporting the use of gamma knife radiosurgery as primary treatment for uveal melanoma or uveal metastases. The search was restricted to clinical studies and relevant grey literature published in English. Studies reporting treatment of benign tumours, extraocular tumours, or other forms of stereotactic radiosurgery were excluded to reduce heterogeneity. No restrictions were placed on participant criteria. Local tumour control and tumour regression were extracted as the primary outcomes and analysed via a random-effects meta-analysis of proportions using the DerSimonian and Laird method with a Freeman-Tukey double arcsine transformation. This study is registered with PROSPERO, CRD42019148165. FINDINGS: Our search returned 454 studies, of which 109 were assessed for full-text eligibility. 52 studies, reporting on 1010 patients with uveal melanoma and 34 intraocular metastases, were eligible for systematic review. 28 studies were included in the meta-analysis. 840 of 898 patients (0·96, 95% CI 0·94-0·97; I2=16%) from 19 studies had local control, and 378 of 478 patients (0·81, 0·70-0·90; I2=83%) from 16 studies experienced tumour regression. INTERPRETATION: Gamma knife radiosurgery is an efficacious primary method of treating uveal melanomas and intraocular metastases, with reliable tumour control rates. Randomised controlled trials should further evaluate the safety and efficacy of gamma knife radiosurgery in this setting. FUNDING: The Rhodes Trust and the Howard Brain Sciences Foundation.

Granzyme B PET imaging of immune-mediated tumor killing as a tool for understanding immunotherapy response.

BACKGROUND: Cancer immunotherapy research is expanding to include a more robust understanding of the mechanisms of treatment response and resistance. Identification of drivers of pro-tumor and anti-tumor immunity during treatment offers new strategies for effective alternative or combination immunotherapies. Currently, tissue or blood samples are collected and analyzed, then dichotomized based on clinical end points that may occur months or years after tissue is collected. While overall survival is ultimately the desired clinical outcome, this dichotomization fails to incorporate the nuances that may occur during an anti-tumor response. By failing to directly measure immune activation at the time of sampling, tumors may be misclassified and potentially obscure important biological information. Non-invasive techniques, such as positron emission tomography (PET), allow for global and quantitative measurements of cancer specific processes and are widely used clinically to help manage disease. METHODS: We have previously developed a novel PET agent that can non-invasively quantify granzyme B release in tumors and have demonstrated its ability to predict response to checkpoint inhibitor therapy in multiple murine models of cancer. Here, we used the quantitative measurement of granzyme B release as a direct and time-matched marker of immune cell activation in order to determine immune cell types and cytokines that correlate with effective checkpoint inhibitor therapy in both tumors and tumor-draining lymph nodes. RESULTS: Through PET imaging, we were able to successfully distinguish distinct microenvironments, based on tumor type, which influenced immune cell subpopulations and cytokine release. Although each tumor was marked by functionally distinct pathways of immune cell activation and inflammation, they also shared commonalities that ultimately resulted in granzyme B release and tumor killing. CONCLUSIONS: These results suggest that discrete tumor immune microenvironments can be identified in both responsive and non-responsive tumors and offers strategic targets for intervention to overcome checkpoint inhibitor resistance.