Sex-dependent effects of chronic intermittent hypoxia: implication for obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) affects 10-26% of adults in the United States with known sex differences in prevalence and severity. OSA is characterized by elevated inflammation, oxidative stress (OS), and cognitive dysfunction. However, there is a paucity of data regarding the role of sex in the OSA phenotype. Prior findings suggest women exhibit different OSA phenotypes than men, which could result in under-reported OSA prevalence in women. To examine the relationship between OSA and sex, we used chronic intermittent hypoxia (CIH) to model OSA in rats. We hypothesized that CIH would produce sex-dependent phenotypes of inflammation, OS, and cognitive dysfunction, and these sex differences would be dependent on mitochondrial oxidative stress (mtOS). METHODS: Adult male and female Sprague Dawley rats were exposed to CIH or normoxia for 14 days to examine the impact of sex on CIH-associated circulating inflammation (IL-1ß, IL-6, IL-10, TNF-α), circulating steroid hormones, circulating OS, and behavior (recollective and spatial memory; gross and fine motor function; anxiety-like behaviors; and compulsive behaviors). Rats were implanted with osmotic minipumps containing either a mitochondria-targeting antioxidant (MitoTEMPOL) or saline vehicle 1 week prior to CIH initiation to examine how inhibiting mtOS would affect the CIH phenotype. RESULTS: Sex-specific differences in CIH-induced inflammation, OS, motor function, and compulsive behavior were observed. In female rats, CIH increased inflammation (plasma IL-6 and IL-6/IL-10 ratio) and impaired fine motor function. Conversely, CIH elevated circulating OS and compulsivity in males. These sex-dependent effects of CIH were blocked by inhibiting mtOS. Interestingly, CIH impaired recollective memory in both sexes but these effects were not mediated by mtOS. No effects of CIH were observed on spatial memory, gross motor function, or anxiety-like behavior, regardless of sex. CONCLUSIONS: Our results indicate that the impact of CIH is dependent on sex, such as an inflammatory response and OS response in females and males, respectively, that are mediated by mtOS. Interestingly, there was no effect of sex or mtOS in CIH-induced impairment of recollective memory. These results indicate that mtOS is involved in the sex differences observed in CIH, but a different mechanism underlies CIH-induced memory impairments.

Sleep apnea is a common sleeping condition in adults with a wide range of symptoms that include inflammation, oxidative stress, memory problems, anxiety, and compulsivity. Men are diagnosed with sleep apnea more often than women. Although there is limited information on how sleep apnea affects men and women differently, previous studies suggest that women may exhibit different sleep apnea symptoms than men. To examine the impact of male and female sex on common sleep apnea symptoms, we exposed adult male and female rats to a model of sleep apnea called chronic intermittent hypoxia (CIH). We found that many effects of CIH were different in males and females. CIH females had increased inflammation and motor problems, whereas CIH males had increased oxidative stress and compulsivity. To investigate the reason for these CIH sex differences, we blocked mitochondrial oxidative stress. Blocking mitochondrial oxidative stress decreased CIH associated sex differences. However, blocking mitochondrial oxidative stress had no impact on CIH-induced memory impairment that was observed in male and female rats. Our findings support previous reports that suggest that women exhibit different sleep apnea symptoms than men. Further, we extend these findings by showing that mitochondrial oxidative stress is involved in these sex differences. Clinically, patients diagnosed with sleep apnea are typically treated with continuous positive airway pressure (CPAP) machines, which have high rates of non-compliance (15­40%). Therefore, understanding why sleep apnea is causing these symptoms will be important in developing therapeutics.

Region partitioning of articular cartilage with streaming-potential-based parameters and indentation maps.

Articular cartilage exhibits site-specific tissue inhomogeneity, for which the tissue properties may continuously vary across the articular surface. To facilitate practical applications such as studying site-specific cartilage degeneration, the inhomogeneity may be approximated with several distinct region-wise variations, with one set of tissue properties for one region. A clustering method was previously developed to partition such regions using cartilage indentation-relaxation and thickness mapping instead of simply using surface geometry. In the present study, a quantitative parameter based on streaming potential measurement was introduced as an additional feature to assess the applicability of the methodology with independent datasets. Experimental data were collected from 24 sets of femoral condyles, extracted from fresh porcine stifle joints, through streaming potential mapping, automated indentation, and needle penetration tests. K-means clustering and Elbow method were used to find optimal region partitions. Consistent with previous findings, three regions were suggested for either lateral or medial condyle regardless of left or right joint. The region shapes were approximately triangular or trapezoidal, which was similar to what was found previously. Streaming potentials were confirmed to be region-dependent, but not significantly different among joints. The cartilage was significantly thicker in the medial than lateral condyles. The region areas were consistent among joints, and comparable to that found in a previous study. The present study demonstrated the capability of region partitioning methods with different variables, which may facilitate new applications whenever site-specific tissue properties must be considered.

Racial and Socioeconomic Disparities in Laminoplasty Versus Laminectomy With Fusion in Patients With Cervical Spondylosis.

STUDY DESIGN: A retrospective cohort study using prospectively collected data. OBJECTIVE: The aim of this study was to investigate preoperative differences in racial and socioeconomic factors in patients undergoing laminoplasty (LP) versus laminectomy and fusion (LF) for degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: DCM is prevalent in the United States, requiring surgical intervention to prevent neurological degeneration. While LF is utilized more frequently, LP is an emerging alternative. Previous studies have demonstrated similar neurological outcomes for both procedures. However, treatment selection is primarily at the discretion of the surgeon and may be influenced by social determinants of health that impact surgical outcomes. MATERIALS AND METHODS: The Quality Outcome Database (QOD), a national spine registry, was queried for adult patients who underwent either LP or LF for the management of DCM. Covariates associated with socioeconomic status, pain and disability, and demographic and medical history were collected. Multivariate logistic regression was performed to assess patient factors associated with undergoing LP versus LF. RESULTS: Of 1673 DCM patients, 157 (9.4%) underwent LP and 1516 (90.6%) underwent LF. A significantly greater proportion of LP patients had private insurance (P<0.001), a greater than high school level education (P<0.001), were employed (P<0.001), and underwent primary surgery (P<0.001). LP patients reported significantly lower baseline neck/arm pain and Neck Disability Index (P<0.001). In the multivariate regression model, lower baseline neck pain [odds ratio (OR)=0.915, P=0.001], identifying as non-Caucasian (OR=2.082, P<0.032), being employed (OR=1.592, P=0.023), and having a greater than high school level education (OR=1.845, P<0.001) were associated with undergoing LP rather than LF. CONCLUSIONS: In DCM patients undergoing surgery, factors associated with patients undergoing LP versus LF included lower baseline neck pain, non-Caucasian race, higher education, and employment. While symptomatology may influence the decision to choose LP over LF, there may also be socioeconomic factors at play. The trend of more educated and employed patients undergoing LP warrants further investigation.

Adult versus adolescent idiopathic scoliosis surgery: a meta-analysis of clinical and radiographic outcomes.

INTRODUCTION: While the natural history of adolescent idiopathic scoliosis (AIS) and adult idiopathic scoliosis (AdIS) is well documented in the literature, the impact of age on postoperative outcomes remains an active area of research. We performed a systematic review and meta-analysis to compare patients undergoing surgery for AIS and AdIS with respect to: (1) postoperative Cobb correction, (2) perioperative variables, and (3) postoperative complications. METHODS: A systematic literature search was performed in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. INCLUSION CRITERIA: studies published between 2002 and 2022, retrospective, and comparing AIS vs. AdIS patients undergoing deformity surgery. The primary outcome was postoperative Cobb correction. Secondary outcomes included estimated blood loss (EBL), operative time, total instrumented levels, length of stay (LOS), and postoperative complications. Random-effects models were performed according to the method of DerSimonian and Laird. RESULTS: Of 190 identified articles, 14 fit the inclusion criteria. A total of 1788 patients were included, 1275(71.3%) with AIS, and 513(28.7%) with AdIS. There was a significant age difference between AIS and AdIS (15.3 vs. 36.7 years, mean difference (MD) = 21.3 years, 95%CI = 14.3-28.4,p < 0.001). Mean postoperative Cobb percentage correction was reported in 5 articles and was significantly higher in AIS (68.4%) vs. AdIS (61.4%) (MD = -7.2, 95%CI = -11.6,-2.7,p = 0.001). EBL was not significantly different between AIS and AdIS (695.6 mL vs 817.7 mL,p = 0.204). Furthermore, no difference was found in operative time (MD = 37.9 min,95%CI = -10.7;86.6,p = 0.127), total instrumented level (MD = 0.88,95%CI = -0.7,2.4,p = 0.273), and LOS (MD = 0.5, 95%CI = -0.2;1.2, p = 0.188). Four articles reported postoperative complications in AIS vs AdIS, with no difference in neurological deficit, instrumentation-related complications, and medical complications. CONCLUSION: AIS patients had better radiographic correction compared to AdIS. Though no difference was found in perioperative outcomes and complications, these findings emphasize the importance of counseling patients regarding the optimal timing of surgical correction.

Impact of occupational characteristics on return to work for employed patients after elective cervical spine surgery.

OBJECTIVE: In a cohort of employed patients undergoing elective cervical spine surgery with an uncomplicated postoperative course, the authors sought to determine the demographic, functional, and occupational characteristics associated with return to work (RTW) following surgery. METHODS: A retrospective cohort study of prospectively collected data was undertaken of patients undergoing elective cervical spine surgery for degenerative disease in the Quality Outcomes Database. Study inclusion criteria were: 1) employed prior to surgery and planned to RTW, 2) no unplanned readmissions, 3) achieved 30% improvement on the Neck Disability Index (NDI), and 4) were satisfied with the surgical outcome at 3 or 12 months postoperatively. A multivariable Cox regression model was built using demographic, functional, operative, and occupational characteristic to predict time to RTW. RESULTS: Of 5110 included patients, 4788 (93.7%) returned to work within 12 months, with a median time of 35 (IQR 19-60) days. Patients who did RTW were significantly younger (51.3 ± 9.4 vs 55.8 ± 9.6 years, p < 0.001), more often underwent an anterior approach (85.8% vs 80.7%, p = 0.009), were significantly more privately insured (82.1% vs 64.0%, p < 0.001), and were less likely to have workers' disability insurance (6.7% vs 14.6%, p < 0.001) compared with patients who did not RTW. On multivariable Cox regression, demographic factors associated with a longer RTW were older age (hazard ratio [HR] 0.99, 95% CI 0.99-1.00, p < 0.001) and Black race (HR 0.71, 95% CI 0.62-0.81, p < 0.001). Male sex was associated with a shorter RTW time (HR 1.19, 95% CI 1.11-1.26, p < 0.001). Regarding baseline functional status, worse preoperative NDI (HR 0.99, 95% CI 0.99-0.99, p < 0.001) was associated with a longer RTW, whereas the absence of myelopathy was associated with a shorter RTW (HR 1.17, 95% CI 1.09-1.25, p < 0.001). Having a sedentary (HR 1.81, 95% CI 1.65-1.99, p < 0.001), light-intensity (HR 1.60, 95% CI 1.45-1.76, p < 0.001), and medium-intensity (HR 1.11, 95% CI 1.01-1.22, p = 0.037) occupation was associated with a shorter RTW time compared with a heavy-intensity occupation at any time point. Heavy-intensity occupations were independently the strongest predictor of longer RTW. Similar predictors of shorter RTW were found in a subanalysis of occupation intensity and among operative approaches used. CONCLUSIONS: Among patients undergoing elective degenerative cervical spine surgery who had favorable surgical outcomes and planned to RTW before surgery, 94% had a successful RTW. Age was the strongest predictor of lower odds of RTW. Regarding time to RTW, having a sedentary, light-intensity, or medium-intensity occupation was associated with a shorter RTW time compared with a heavy-intensity occupation. These findings highlight the importance of considering the demographic and occupational characteristics when predicting postoperative RTW in patients with satisfactory surgical outcomes.

Correction: Accelerated Care of Patients with Hip Fractures is Associated with Lower Risk of Delirium and Infection, and a Shorter Length of Hospital Stay: Systematic Review and Meta-analysis of Level One Evidence.

[This corrects the article DOI: 10.1007/s43465-023-01026-x.].

Pregnancy-associated oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function.

Pregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress. Yet, the impact of systemic inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy are unclear. We hypothesized that the maternal hippocampal CA1, a brain region associated with cognition, would be protected from pregnancy-associated systemic elevations in inflammation and oxidative stress, mediating stable peripartum cognitive performance. Cognitive performance was tested using novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [non-pregnant (nulliparous), pregnant (near term), and two months post-pregnancy (primiparous); n = 7-8/group]. Plasma and CA1 proinflammatory cytokines were measured using a MILLIPLEX® magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via western blotting. Our results demonstrate CA1 oxidative stress-associated markers were elevated in pregnant compared to nulliparous rats ( p ≤ 0.017) but were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired ( p ≤ 0.007) while anxiety-like behavior ( p ≤ 0.034) was reduced in primiparous rats. Overall, our data suggest maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Thus, peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.

Nanolithium, a New Treatment Approach to Alzheimer's Disease: A Review of Existing Evidence and Clinical Perspectives.

Lithium has been approved and used for several decades in the treatment of psychiatric disorders, and its potential effect in neurodegenerative diseases has been subject to increasing research interest in recent years. Nanolithium is a new experimental product using a novel drug-delivery technology (Aonys®), which optimizes its bioavailability while reducing its toxicity profile. Therapeutic doses of lithium used in Nanolithium are more than 50 times lower than the minimal dose of classical lithium salts. In this review we report data from non-clinical pharmacology studies supporting Nanolithium efficacy and the mechanism of action in Alzheimer's disease. GSK-3ß inhibition is thought to be central to Nanolithium's mechanism of action, triggering a reduction of the production of toxic amyloid plaques and decrease in tau hyperphosphorylation, which could potentially benefit both neuropsychiatric symptoms and cognitive decline. We then summarize outcomes from non-clinical proof-of-concept studies. These data supported the initiation of a currently ongoing phase II proof-of-concept study to evaluate the safety and efficacy of Nanolithium in patients with mild-to-severe Alzheimer's disease. We highlight key aspects of the study design. We finish this review with a discussion on the potential place of Nanolithium in the current and future Alzheimer's disease treatment landscape.

SIFT IT: A feasibility and preliminary efficacy randomized controlled trial of a social cognition group treatment programme for people with acquired brain injury.

Making sense of social situations requires social cognitive skills, which can be impaired after acquired brain injury (ABI), yet few evidence-based treatment options are available. This study aimed to evaluate the feasibility of a multi-faceted social cognition group treatment programme, SIFT IT, for people after ABI using an RCT design. Twenty-eight participants were recruited, and 23 were randomized into either Treatment or Waitlist. SIFT IT consisted of 14 weekly 90-minute small group sessions facilitated by a Clinical Psychologist. Topics included: emotion self-awareness, emotion perception, perspective taking, and choosing adaptive social responses. Preliminary efficacy outcomes were assessed at baseline, post-treatment, and three-month follow-up. Demand for treatment was evident with 61% recruitment and 91% post-treatment retention rates, with 63% attending at least 13/14 sessions. Large between-group treatment effects (with non-zero 95% confidence intervals) were observed for emotion perception, detecting hints, and informant ratings of social cognitive deficits. Implementation challenges recruiting to groups and maintaining group allocation fidelity, with a small sample size does, however, raise questions about the appropriateness of an RCT design in a future efficacy trial. Overall, this study showed there is demand for social cognitive interventions after ABI and the SIFT IT programme was practicable and acceptable to participants.Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12617000405314.

Impact of Unplanned Readmission on Patient-Reported Outcomes After Cervical Spine Surgery: A National Study of 13 355 Patients.

BACKGROUND AND OBJECTIVES: Although risk factors for unplanned readmission after cervical spine surgery have been widely reported, less is known about how readmission itself affects patient-reported outcome measures (PROMs). Using the Quality Outcomes Database registry of patients undergoing elective cervical spine surgery, we sought to (1) determine the impact of unplanned readmission on PROMs and (2) compare the effect of specific readmission reasons on PROMs. METHODS: An observational study was performed using a multi-institution, retrospective registry for patients undergoing cervical spine surgery. The occurrence of 90-day unplanned readmission classified into medical, surgical, pain only, and no readmissions was the exposure variable. Outcome variables included 12-month PROMs of Neck Disability Index (NDI), Numeric Rating Scale (NRS)-neck/arm pain, EuroQol-5D (EQ-5D), and patient dissatisfaction. Multivariable models predicting each PROM were built using readmission reasons controlling for demographics, clinical characteristics, and preoperative PROMs. RESULTS: Data from 13 355 patients undergoing elective cervical spine surgery (82% anterior approach and 18% posterior approach) were analyzed. Unplanned readmission within 90 days of surgery occurred in 3.8% patients, including medical (1.6%), surgical (1.8%), and pain (0.3%). Besides medical reasons, wound infection/dehiscence was the most common reason for unplanned readmission for the total cohort (0.5%), dysphagia in the anterior approach (0.6%), and wound infection/dehiscence in the posterior approach (1.5%). Based on multivariable regression, surgical readmission was significantly associated with worse 12-month NDI, NRS-neck pain, NRS-arm pain, EQ-5D, and higher odds of dissatisfaction. Pain readmissions were associated with worse 12-month NDI and NRS-neck pain scores, and worse dissatisfaction. For specific readmission reasons, pain, surgical site infection/wound dehiscence, hematoma/seroma, revision surgery, deep vein thrombosis, and pulmonary embolism were significantly associated with worsened 12-month PROMs. CONCLUSION: In patients undergoing elective cervical spine surgery, 90-day unplanned surgical and pain readmissions were associated with worse 12-month PROMs compared with patients with medical readmissions and no readmissions.

Sex-dependent effects of chronic intermittent hypoxia: Implication for obstructive sleep apnea.

Background Obstructive sleep apnea (OSA) affects 10-26% of adults in the United States with known sex differences in prevalence and severity. OSA is characterized by elevated inflammation, oxidative stress (OS), and cognitive dysfunction. However, there is a paucity of data regarding the role of sex in the OSA phenotype. Prior findings suggest women exhibit different OSA phenotypes than men, which could result in under-reported OSA prevalence in women. To examine the relationship between OSA and sex, we used chronic intermittent hypoxia (CIH) to model OSA in rats. We hypothesized that CIH would produce sex-dependent phenotypes of inflammation, OS, and cognitive dysfunction, and these sex differences would be dependent on mitochondrial oxidative stress (mtOS). Methods Adult male and female Sprague Dawley rats were exposed to CIH or normoxia for 14 days to examine the impact of sex on CIH-associated circulating inflammation (IL-1ß, IL-4, IL-6, IL-10, TNF-α), circulating OS, and behavior (recollective and spatial memory; gross and fine motor function; anxiety-like behaviors; and compulsive behaviors). A subset of rats was implanted with osmotic minipumps containing either a mitochondria-targeting antioxidant (MitoTEMPOL) or saline vehicle 1 week prior to CIH initiation to examine how inhibiting mtOS would affect the CIH phenotype. Results Sex-specific differences in CIH-induced inflammation, OS, motor function, and compulsive behavior were observed. In female rats, CIH increased inflammation (plasma IL-6 and IL-6/IL-10 ratio) and impaired fine motor function. Conversely, CIH elevated circulating OS and compulsivity in males. These sex-dependent effects of CIH were blocked by inhibiting mtOS. Interestingly, CIH impaired recollective memory in both sexes but these effects were not mediated by mtOS. No effects of CIH were observed on spatial memory, gross motor function, or anxiety-like behavior, regardless of sex. Conclusions Our results indicate that the impact of CIH is dependent on sex, such as an inflammatory response and OS response in females and males, respectively, that are mediated by mtOS. Interestingly, there was no effect of sex or mtOS in CIH-induced impairment of recollective memory. These results indicate that mtOS is involved in the sex differences observed in CIH, but a different mechanism underlies CIH-induced memory impairments.

Accelerated Care of Patients with Hip Fractures is Associated with Lower Risk of Delirium and Infection, and a Shorter Length of Hospital Stay: Systematic Review and Meta-analysis of Level One Evidence.

Objectives: The aim of this systematic review was to assess the impact of time to surgery on patient mortality, peri-operative complication rates and length of stay following a hip fracture using level one data. Data Sources: Multiple databases (PubMed, Embase, Medline (Ovid), and Cochrane Library) were searched using terms for "hip fracture" and the intervention "early surgery". Results were filtered to only included randomised controlled trials in the English language published from the year 2000. Study Selection: All results were imported into Covidence and screened by two separate reviewers with conflicts resolved by a third reviewer. Studies were included if they reported data on the relationship between time to theatre and at least one of the outcome measures (mortality, peri-operative complications, and length of stay in hospital). Three papers were finalised to include in this review. Data Extraction: Once selected, each paper had a bias assessment completed by two separate reviewers using the Cochrane RoB2 tool. Any conflicts were resolved by a third reviewer. Data Synthesis: Data from each paper were inputted into RevMan5 for analysis. Approximated sample mean and standard deviation were collected from each paper and included for analysis. RevMan5 was then used to generate forest plots and report data on relative risk and mean difference. Conclusions: This review has shown that accelerated care of patients with hip fractures was associated with lower risks of delirium and infection, and a shorter length of hospital stay. However, the effect of time to surgery on patient mortality is not clear, as the standard care group had a lower mortality than expected for the population at risk and had surgery on average within 24-h of presentation.

Comparing Patient-Reported Outcomes, Complications, Readmissions, and Revisions in Posterior Lumbar Fusion With, Versus Without, an Interbody Device.

STUDY DESIGN: Retrospective analysis on prospectively collected data. OBJECTIVES: To compare posterior lumbar fusions with versus without an interbody in: (1) Patient-reported outcomes (PROs) at 1 year and (2) postoperative complications, readmission, and reoperations. SUMMARY OF BACKGROUND DATA: Elective lumbar fusion is commonly used to treat various lumbar pathologies. Two common approaches for open posterior lumbar fusion include posterolateral fusion (PLF) alone without an interbody and with an interbody through techniques, like transforaminal lumbar interbody fusion. Whether fusion with or without an interbody leads to better outcomes remains an area of active research. PATIENTS AND METHODS: The Lumbar Module of the Quality Outcomes Database was queried for adults undergoing elective primary posterior lumbar fusion with or without an interbody. Covariates included demographic variables, comorbidities, primary spine diagnosis, operative variables, and baseline PROs, including Oswestry Disability Index, North American Spine Society satisfaction index, numeric rating scale-back/leg pain, and Euroqol 5-dimension. Outcomes included complications, reoperations, readmissions, return to work/activities, and PROs. Propensity score matching and linear regression modeling were used to estimate the average treatment effect on the treated to assess the impact of interbody use on patient outcomes. RESULTS: After propensity matching, there were 1044 patients with interbody and 215 patients undergoing PLF. The average treatment effect on the treated analysis showed that having an interbody or not had no significant impact on any outcome of interest, including 30-day complications and reoperations, 3-month readmissions, 12-month return to work, and 12-month PROs. CONCLUSION: There were no discernible differences in outcomes between patients undergoing PLF alone versus with an interbody in elective posterior lumbar fusion. These results add to the growing body of evidence that posterior lumbar fusions with and without an interbody seem to have similar outcomes up to 1 year postoperatively when treating degenerative lumbar spine conditions.

Determining the Effect of Intraoperative TXA on Postoperative Blood Loss in ACDF.

STUDY DESIGN: Retrospective cohort study using prospectively collected data. OBJECTIVE: To determine the effectiveness of intraoperative tranexamic acid (TXA) in anterior cervical discectomy and fusion (ACDF) on postoperative blood loss. SUMMARY OF BACKGROUND DATA: TXA has been proven to be a safe and effective agent in reducing blood loss after cervical surgery; however, its efficacy when used intraoperatively for ACDF surgeries had yet to be researched. Currently, there are few studies examining the effects of intraoperative TXA in cervical spinal fusion, and none specifically examining TXA use in ACDF. METHODS: A tertiary medical center's prospectively collected spine registry was queried between 1/1/18 and 12/1/21 for all patients who underwent elective ACDF surgery and received a drain postoperatively. Patients were separated into 2 groups; those who had received intraoperative TXA and those who did not. Baseline demographic and operative variables were collected from the registry. The primary outcome was postoperative blood loss over a 24-hour period. Secondary outcomes included total drain output, intraoperative estimated blood loss, operative duration, drain duration, changes in preoperative to postoperative hemoglobin and hematocrit levels, and rate of transfusions, complications, revisions, and reoperations. Univariate and multivariate regression analyses were performed. RESULTS: Two hundred eighty-six patients were included. One hundred ninety patients underwent ACDF and did not receive intraoperative TXA, whereas 96 patients underwent ACDF and did receive TXA. There were no differences in any demographic or baseline variables. Multivariate analysis showed intraoperative TXA was associated with shorter drain duration (ß=-5.74, 95% CI: -10.9 to -0.53, P =0.031) and reduction in 24-hour drain output (ß=-12.2, 95% CI: -19.4 to -4.89, P =0.001) and total drain output (ß=-14.0, 95% CI: -22.9 to -5.05, P =0.002). CONCLUSIONS: TXA use during ACDF procedures leads to a decrease in perioperative blood loss and faster drain removal. TXA is an effective and safe agent for reducing perioperative blood loss in ACDF surgery. LEVEL OF EVIDENCE: III.

Validation of the brain injury associated visual impairment - impact questionnaire (BIVI-IQ).

PURPOSE: The Brain Injury associated Visual Impairment - Impact Questionnaire (BIVI-IQ) was developed to assess the impact of post-stroke visual impairment. The development of the questionnaire used robust methods involving stroke survivors and clinicians. The aim of this study was to assess the validity of the BIVI-IQ in a stroke population. METHODS: Stroke survivors with visual impairment were recruited from stroke units, outpatient clinics and non-healthcare settings. Participants were asked to complete questionnaire sets on three separate occasions; the BIVI-IQ at each visit with additional questionnaires at baseline and visit 2. Vision assessment and anchor questions from participants and clinicians were collected. The analysis included assessment of missing data, acceptability, Rasch model analysis, test-retest reliability, construct validity (NEI VFQ-25, EQ-5D-5L) and responsiveness to change. RESULTS: 316 stroke survivors completed at least one questionnaire of the 326 recruited. Mean age was 67 years and 64% were male. Adequate fit statistics to the Rasch model were reached (χ2 = 73.12, p = 0.02) with two items removed and thresholds of two adjusted, indicating validity and unidimensionality. Excellent test-retest reliability was demonstrated (ICC = 0.905) with a 3-month interval. Construct validity was demonstrated with a strong significant correlation to the NEI VFQ-25 (r = 0.837, p < 0.01). The BIVI-IQ also demonstrated responsiveness to change with significant differences identified between groups based on participant and clinician anchor questions (X2 = 23.29, p < 0.001; X2 = 24.56, p < 0.001). CONCLUSION: The BIVI-IQ has been shown to be valid and practical for 'everyday' use by clinicians and researchers to monitor vision-related quality of life in stroke survivors with visual impairment.

Sex and age differences in social and cognitive function in offspring exposed to late gestational hypoxia.

BACKGROUND: Gestational sleep apnea is a hypoxic sleep disorder that affects 8-26% of pregnancies and increases the risk for central nervous system dysfunction in offspring. Specifically, there are sex differences in the sensitivity of the fetal hippocampus to hypoxic insults, and hippocampal impairments are associated with social dysfunction, repetitive behaviors, anxiety, and cognitive impairment. Yet, it is unclear whether gestational sleep apnea impacts these hippocampal-associated functions and if sex and age modify these effects. To examine the relationship between gestational sleep apnea and hippocampal-associated behaviors, we used chronic intermittent hypoxia (CIH) to model late gestational sleep apnea in pregnant rats. We hypothesized that late gestational CIH would produce sex- and age-specific social, anxiety-like, repetitive, and cognitive impairments in offspring. METHODS: Timed pregnant Long-Evans rats were exposed to CIH or room air normoxia from GD 15-19. Behavioral testing of offspring occurred during either puberty or young adulthood. To examine gestational hypoxia-induced behavioral phenotypes, we quantified hippocampal-associated behaviors (social function, repetitive behaviors, anxiety-like behaviors, and spatial memory and learning), hippocampal neuronal activity (glutamatergic NMDA receptors, dopamine transporter, monoamine oxidase-A, early growth response protein 1, and doublecortin), and circulating hormones in offspring. RESULTS: Late gestational CIH induced sex- and age-specific differences in social, repetitive, and memory functions in offspring. In female pubertal offspring, CIH impaired social function, increased repetitive behaviors, and elevated circulating corticosterone levels but did not impact memory. In contrast, CIH transiently induced spatial memory dysfunction in pubertal male offspring but did not impact social or repetitive functions. Long-term effects of gestational CIH on social behaviors were only observed in female offspring, wherein CIH induced social disengagement and suppression of circulating corticosterone levels in young adulthood. No effects of gestational CIH were observed in anxiety-like behaviors, hippocampal neuronal activity, or circulating testosterone and estradiol levels, regardless of sex or age of offspring. CONCLUSIONS: Our results indicate that hypoxia-associated pregnancy complications during late gestation can increase the risk for behavioral and physiological outcomes in offspring, such as social dysfunction, repetitive behaviors, and cognitive impairment, that are dependent on sex and age.

Sleep apnea during late pregnancy is a common pregnancy complication that can impact the brain development of children born to mothers with sleep apnea. Children with impaired brain development may present with decreased social skills, memory issues, anxiety, and compulsivity. It is unclear if there is a cause and effect relationship between sleep apnea during late pregnancy and behavioral changes in offspring. Additionally, it is unknown whether male or female sex or age of the offspring affects these relationships. In this study, we exposed pregnant rats to a model of sleep apnea called chronic intermittent hypoxia (CIH) within late gestation and examined the behavior of the offspring and brain activity during puberty and young adulthood. We found that CIH during late pregnancy had long-term effects in the offspring that were different in males and females. Notably, female offspring displayed social impairments in response to late gestation CIH, whereas male offspring displayed cognitive dysfunction.

A Grid-based Method for Removing Overlaps of Dimensionality Reduction Scatterplot Layouts.

Dimensionality Reduction (DR) scatterplot layouts have become a ubiquitous visualization tool for analyzing multidimensional datasets. Despite their popularity, such scatterplots suffer from occlusion, especially when informative glyphs are used to represent data instances, potentially obfuscating critical information for the analysis under execution. Different strategies have been devised to address this issue, either producing overlap-free layouts that lack the powerful capabilities of contemporary DR techniques in uncovering interesting data patterns or eliminating overlaps as a post-processing strategy. Despite the good results of post-processing techniques, most of the best methods typically expand or distort the scatterplot area, thus reducing glyphs' size (sometimes) to unreadable dimensions, defeating the purpose of removing overlaps. This paper presents Distance Grid (DGrid), a novel post-processing strategy to remove overlaps from DR layouts that faithfully preserves the original layout's characteristics and bounds the minimum glyph sizes. We show that DGrid surpasses the state-of-the-art in overlap removal (through an extensive comparative evaluation considering multiple different metrics) while also being one of the fastest techniques, especially for large datasets. A user study with 51 participants also shows that DGrid is consistently ranked among the top techniques for preserving the original scatterplots' visual characteristics and the aesthetics of the final results.

Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes.

The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis in many pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Which Bone Mineral Density Measure Offers a More Reliable Prediction of Mechanical Complications in Adult Spinal Deformity Surgery: Hounsfield Units or DEXA Scan?

OBJECTIVE: In patients undergoing adult spinal deformity (ASD) surgery, we sought to: (1) determine the relationship between dual-energy x-ray absorptiometry (DEXA)-measured bone mineral density (BMD), T-scores, and Hounsfield units (HU), and (2) compare the ability of DEXA-measured BMD, T-scores, and HU to predict mechanical complications and reoperations. METHODS: A single-institution retrospective cohort study was undertaken for cases from 2013 to 2017. INCLUSION CRITERIA: ≥5-level-fusion, sagittal/coronal deformity, and 2-year follow-up. Multivariable regression controlled for age, body mass index, receiving anabolic medications, and postoperative sagittal vertical axis and pelvic-incidence lumbar-lordosis mismatch. A subanalysis was performed for osteopenic patients (-1 < T-score < -2). RESULTS: Of 145 patients undergoing ASD surgery, 72 (49.6%) had both preoperative DEXA and computed tomography scans. Mean DEXA-measured BMD was 0.91 ± 0.52 g/cm2, mean T-score was -1.61 ± 1.03, and mean HU was 153.5 ± 52.8. While no correlation was found between DEXA-measured BMD and HU (r = 0.17, P = 0.144), T-score and HU had a weakly positive correlation (r = 0.31, P = 0.007). Mechanical complications occurred in 48 (66.7%) patients, including 27 (37.5%) proximal junctional kyphosis (PJK), 1 (1.4%) distal junctional kyphosis, 5 (6.9%) implant failure, 30 (41.7%) rod fracture/pseudarthrosis, 42 (58.3%) reoperations, and 16 (22.2%) reoperations due to PJK. No association was found between DEXA-measured BMD or T-scores with mechanical complications or reoperations. While univariate regression showed a significant association between lower HU and PJK (OR 0.98, 95%CI 0.97-0.99, P = 0.011), the significance was lost after multivariable analysis. When considering osteopenic patients (n = 37), only DEXA-measured BMD was an independent risk factor for PJK (OR 0.01, 95%CI 0.00-0.09, P = 0.017), with a threshold of 0.82 g/cm2 (AUC 0.70, 95%CI 0.53-0.84, P = 0.019). CONCLUSIONS: Poor correlation was found between the 3 BMD modalities. DEXA-measured BMD may be superior to T-scores and HU in predicting PJK among patients with osteopenia with a threshold of BMD <0.82 g/cm2.

My assistive technology outcomes framework: rights-based outcome tools for consumers to 'measure what matters'.

AT outcomes research is the systematic investigation of changes produced by AT in the lives of AT users and their environments. In contrast to focal outcome measures, My Assistive Technology Outcomes Framework (MyATOF) envisions an alternative starting point, co-designing a holistic and evidence-based set of outcome dimensions enabling AT users to quantify their own outcomes. International classification systems, research evidence, regulatory and service delivery frameworks underpin six optional tools: supports, outcomes, costs, rights, service delivery pathway and customer experience. Designed to empower the consumer-as-researcher and self-advocate, MyATOF has the potential to fill an identified gap in policy-relevant, consumer-focussed and consumer-directed outcome measurement in Australia and internationally. This paper presents the need for consumer-focussed measurement and articulates the conceptual foundations of MyATOF. The iterative development and results of MyATOF use-cases collected to date are presented. The paper concludes with next steps in using the Framework internationally, as well as its future development.