On the Difficulty Predicting Word Recognition Performance After Cochlear Implantation.

HYPOTHESIS: Preimplantation word scores cannot reliably predict postimplantation outcomes. BACKGROUND: To date, there is no model based on preoperative data that can reliably predict the postoperative outcomes of cochlear implantation in the postlingually deafened adult patient. METHODS: In a group of 228 patients who received a cochlear implant between 2002 and 2021, we tested the predictive power of nine variables (age, etiology, sex, laterality of implantation, preimplantation thresholds and word scores, as well as the design, insertion approach, and angular insertion depth of the electrode array) on postimplantation outcomes. Results of multivariable linear regression analyses were then interpreted in light of data obtained from histopathological analyses of human temporal bones. RESULTS: Age and etiology were the only significant predictors of postimplantation outcomes. In agreement with many investigations, preimplantation word scores failed to significantly predict postimplantation outcomes. Analysis of temporal bone histopathology suggests that neuronal survival must fall below 40% before word scores in quiet begin to drop. Scores fall steeply with further neurodegeneration, such that only 20% survival can support acoustically driven word scores of 50%. Because almost all cochlear implant implantees have at least 20% of their spiral ganglion neurons (SGNs) surviving, it is expected that most cochlear implant users on average should improve to at least 50% word recognition score, as we observed, even if their preimplantation score was near zero as a result of widespread hair cell damage and the fact that ~50% of their SGNs have likely lost their peripheral axons. These "disconnected" SGNs would not contribute to acoustic hearing but likely remain electrically excitable. CONCLUSION: The relationship between preimplantation word scores and data describing the survival of SGNs in humans can explain why preimplantation word scores obtained in unaided conditions fail to predict postimplantation outcomes.

The relationship between expressive suppression, therapeutic bond, and treatment outcomes of a positive affect intervention for adults with anxiety and/or depression.

Expressive suppression (ES; reducing emotional expression) is linked with reduced social connectedness in individuals with anxiety or depression. One implication is that people who use ES may have difficulty establishing a bond with their therapist which may impede clinical improvement. We examined this hypothesis in 33 adults with clinically elevated anxiety or depression receiving treatment focused on enhancing positive thoughts, emotions, and behaviors. At baseline, participants rated ES for positive and negative emotions during a standardized conversation task designed to generate connectedness. They also rated measures of early (session 3) perceived therapeutic bond and treatment outcomes (i.e. positive affect and social connectedness). ES of positive (r = -.39, p = .018), but not negative (r = .06, p = .747), emotions was negatively associated with therapeutic bond. Therapeutic bond mediated the relationship between greater ES of positive emotions during affiliation and lower post-treatment positive affect, 95% bias-corrected bootstrap confidence interval [-0.021, -0.000], adjusted for pre-treatment positive affect, as well as lower post-treatment social connectedness [-0.397, -0.015]; however, the indirect effect was not significant when accounting for pre-treatment social connectedness (p > .05). ES of positive emotions may be an important factor in the development of therapeutic bond and therefore treatment outcomes for individuals with anxiety or depression.

Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Positive and negative affect change following psychotherapeutic treatment for anxiety-related disorders: A systematic review and meta-analysis.

BACKGROUND: Anxiety-related disorders feature elevated negative affect (NA), and in some cases, diminished positive affect (PA). It remains unclear how well extant psychotherapies for anxiety-related disorders improve PA versus NA. METHODS: We systematically searched the Cochrane Central Register of Controlled Trials, PubMed, PsychInfo, and Web of Science databases. Records included studies involving (1) patients with a principal or co-principal diagnosis of at least one anxiety-related disorder (i.e., generalized anxiety, social anxiety, panic, agoraphobia, health anxiety, specific phobia, obsessive-compulsive disorder, or posttraumatic stress disorder), and (2) pre- and post-treatment PA and NA scores or a change index between pre- and post-treatment PA and NA scores. Effect sizes were calculated for meta-analyses. RESULTS: Fourteen studies with 1001 adults with an anxiety-related disorder were included. Psychotherapeutic interventions included cognitive behavioral, present-centered, and imagery-based approaches. Treatments reduced NA (g = -0.90; 95%CI [-1.19, -0.61]) to a greater extent than they improved PA (g = 0.27; 95%CI [0.05, 0.59]), Z = -5.26, p < .001. The limited number of studies available precluded analyses of the relationship between changes in affect and symptoms. LIMITATIONS: Results should be considered with caution given the small number and heterogeneity of included studies. CONCLUSIONS: Current psychotherapeutic interventions for anxiety-related disorders may not improve PA and NA to comparable levels.

Differential Time-To-Promotion Trajectories Among Female and Male Neurosurgeons Contribute to Gender Disparities in Academic Rank Achievement.

OBJECTIVE: Despite the increasing representation of females in neurosurgical training, the fraction of female to male neurosurgeons decreases dramatically as faculty rank (Assistant, Associate, or Full Professor) increases. To assess this discrepancy, we quantified self-reported time-to-promotion trajectories for female and male neurosurgeons holding academic appointments. METHODS: In this cross-sectional institutional review board (IRB)-approved study, 147 female and 84 male neurosurgeons currently holding faculty positions in the US were contacted via email and invited to complete an anonymous, standardized survey. Respondents provided the calendar year of postgraduate training completion, promotion to different faculty ranks, geographic region of current practice (Western, Midwest, Southern, Northeast), and practice subspecialty. RESULTS: The response rate was 44.2% for females and 59.5% for males, with 114 participants included (65 female, 49 male). On average, female neurosurgeons required 25% longer to become an Associate Professor (P = 0.017), 34% longer to become a Full Professor (P = 0.004), 37% longer for promotion from Assistant to Associate Professor (P < 0.001), and 32% longer from Assistant to Full Professor (P = 0.012). Promotion timelines did not vary by region or specialty among male and female cohorts. Linear regressions revealed that female neurosurgeons with more recent training completion experienced shorter time-to-promotion to Associate and Full Professor compared to females of earlier generations (P = 0.005 and 0.001, respectively), while male timelines remained stable. CONCLUSIONS: This study identifies a significant delay in time-to-promotion for female neurosurgeons compared to their male counterparts. Investigation and standardization of promotion timelines are necessary to ensure meaningful representation gains from the increased number of women entering neurosurgical training.

Utilization of PROMIS Neuropathic Pain Quality for Detection and Monitoring Neuropathic Pain in Heel Pain Patients.

Background: Diagnosis and management of neuropathic pain (NP) in foot and ankle patients remain challenging. We investigated the plausibility of using Patient-Reported Outcomes Measurement Information System (PROMIS) Neuropathic Pain Quality (PQ-Neuro) as an initial screening tool to detect NP and track the treatment effects. Methods: Patients with heel pain were prospectively recruited and grouped to no-NP, mild-NP, and severe-NP based on the initial PROMIS PQ-Neuro t scores. Pain Interference (PI), Physical Function (PF), and Self-Efficacy (SE) scores were evaluated at baseline, 30-day, and 90-day follow-up. Other factors such as age, smoking, body mass index (BMI), low back/neck pain, anxiety/depression, and medications were analyzed. Linear mixed modeling was used to assess the main effects of time and NP on PROMIS t scores, comparing minimal clinically important difference (MCID). Results: Forty-eight patients with mean age of 52.4 years were recruited. Using the PROMIS PQ-Neuro as the assessment tool, 33 patients (69%) were detected to have NP at baseline-23 (48%) mild and 10 (21%) severe. BMI was the only independent factor associated with NP (P = .011). Higher baseline PQ-Neuro t score was significantly associated with higher follow-up PQ-Neuro (P < .001), PI (P = .005), and lower SE (P = .04) across time points. Patients with NP showed lower PF at baseline with significantly less improvement in PF (3 vs 9.9, P = .035) and did not meet MCID. Conclusion: Baseline PROMIS PQ-Neuro ≥46 was significantly associated with worse PI and SE across all time points, with less clinically significant improvements in PF. Prevalence of NP in heel pain patients was high. The PROMIS PQ-Neuro may serve as a valuable tool for detection of NP and guiding clinical treatment decision pathways for heel pain patients. Level of Evidence: Level III, prospective cohort study.

Updates on Pathophysiology of Discogenic Back Pain.

Discogenic back pain, a subset of chronic back pain, is caused by intervertebral disc (IVD) degeneration, and imparts a notable socioeconomic health burden on the population. However, degeneration by itself does not necessarily imply discogenic pain. In this review, we highlight the existing literature on the pathophysiology of discogenic back pain, focusing on the biomechanical and biochemical steps that lead to pain in the setting of IVD degeneration. Though the pathophysiology is incompletely characterized, the current evidence favors a framework where degeneration leads to IVD inflammation, and subsequent immune milieu recruitment. Chronic inflammation serves as a basis of penetrating neovascularization and neoinnervation into the IVD. Hence, nociceptive sensitization emerges, which manifests as discogenic back pain. Recent studies also highlight the complimentary roles of low virulence infections and central nervous system (CNS) metabolic state alteration. Targeted therapies that seek to disrupt inflammation, angiogenesis, and neurogenic pathways are being investigated. Regenerative therapy in the form of gene therapy and cell-based therapy are also being explored.

High inductance magnetic-core coils have enhanced efficiency in inducing suprathreshold motor response in rats.

Objective. Transcranial magnetic stimulation (TMS) coil design involves a tradeoff among multiple parameters, including magnetic flux density (B), inductance (L), induced electric (E) field, focality, penetration depth, coil heating, etc. Magnetic materials with high permeability have been suggested to enhance coil efficiency. However, the introduction of magnetic core invariably increases coil inductance compared to its air-core counterpart, which in turn weakens theEfield. Our lab previously reported a rodent-specific TMS coil with silicon steel magnetic core, achieving 2 mm focality. This study aims to better understand the tradeoffs amongB,L,andEin the presence of magnetic core.Approach. The magnetic core initially operates within the linear range, transitioning to the nonlinear range when it begins to saturate at high current levels and reverts to the linear range as coil current approaches zero; both linear and nonlinear analyses were performed. Linear analysis assumes a weak current condition when magnetic core is not saturated; a monophasic TMS circuit was employed for this purpose. Nonlinear analysis assumes a strong current condition with varying degrees of core saturation.Main results. Results reveal that, the secondaryEfield generated by the silicon steel core substantially changed the dynamics during TMS pulse. Linear and nonlinear analyses revealed that higher inductance coils produced stronger peakEfields and longerEfield waveforms. On a macroscopic scale, the effects of these two factors on neuronal activation could be conceptually explained through a one-time-constant linear membrane model. Four coils with differentB,L,andEcharacteristics were designed and constructed. BothEfield mapping and experiments on awake rats confirmed that inductance could be much higher than previously anticipated, provided that magnetic material possesses a high saturation threshold.Significance. Our results highlight the novel potentials of magnetic core in TMS coil designs, especially for small animals.

Price Transparency for Cervical Spinal Fusion Among High-Performing Spine Centers in the United States.

BACKGROUND AND OBJECTIVES: As of January 1, 2021, all US hospitals are required by the Hospital Price Transparency Final Rule (HPTFR) to publish standard charges for all items and services, yet the state of price transparency for cervical spinal fusion is unknown. Here, we assess the nationwide price transparency landscape for cervical spinal fusion among high-performing spine centers in the United States. METHODS: In this cross-sectional economic evaluation, we queried publicly available price transparency websites of 332 "high-performing" spine centers, as defined by the US News and World Report. We extracted variables including gross charges for cervical spinal fusion, payor options, price reporting methodology, and prices relevant to consumers including listed cash prices and minimum and maximum negotiated charges. RESULTS: While nearly all 332 high-performing spine surgery centers (99.4%) had an online cost estimation tool, the HPTFR compliance rate was only 8.4%. Gross charges for cervical spinal fusion were accessible for 68.1% of hospitals, discounted cash prices for 46.4% of hospitals, and minimum and maximum charges for 10.8% of hospitals. There were large IQRs for gross charges ($48 491.98-$99 293.37), discounted cash prices ($26 952.25-$66 806.63), minimum charges ($10 766.11-$21 248.36), and maximum charges ($39 280.49-$89 035.35). There was geographic variability in the gross charges of cervical spinal fusion among high-performing spine centers within and between states. There was a significant association between "excellent" discharge to home status and lower mean gross charges. CONCLUSION: Although online cost reporting has drastically increased since implementation of the HPTFR, data reported for cervical spinal fusion remain inadequate and difficult to interpret by both providers and patients.

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine tumors (NETs) are rare cancers that most often arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP)-NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation, and fate determination stages. Tumor and lymphoid compartments sparsely expressed immunosuppressive targets commonly investigated in clinical trials, such as the programmed cell death protein-1/programmed death ligand-1 axis. However, infiltrating myeloid cell types within both primary and metastatic GEP-NETs were enriched for genes encoding other immune checkpoints, including VSIR (VISTA), HAVCR2 (TIM3), LGALS9 (Gal-9), and SIGLEC10. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

An Analysis of Patient-Reported Outcomes Measurement Information System (PROMIS) in Non-operative Posterolateral Elbow Dislocations.

INTRODUCTION: The purpose of our study is to analyze the outcomes of traumatic posterolateral elbow dislocations using patient-reported outcomes measurement information system (PROMIS). We hypothesized that physical function (PF) and upper extremity (UE) scores in PROMIS will significantly improve over six months of follow-up and correlate with a positive change in the patient-acceptable symptom state (PASS). METHODS: This is a seven-year retrospective study of 165 consecutive adult patients with traumatic posterolateral elbow dislocations. Demographic information, PROMIS PF, PROMIS UE, PROMIS pain interference (PI), PROMIS depression, and PASS were recorded over six months of follow-up. RESULTS: At the time of injury, mean PROMIS scores were PF 41.24 (SD 11.16), UE 34.27 (SD 11.87), PI 60.44 (SD 8.07), and depression 49.82 (SD 10.42). At six months, the mean PROMIS scores were PF 39.71 (SD 9.71), UE 33.95 (SD 9.09), PI 57.35 (SD 8.59), and depression 51.43 (SD 10.62). The overall six-month changes in PROMIS scores were PF -1.53, UE -0.32, PI -3.09, and depression +1.61. At the 6-month follow-up, 41.7% responded positively on the PASS, which correlated only with PROMIS PI. CONCLUSIONS: Among patients who improved from negative to positive response on PASS, the PROMIS PF, UE, and depression scores did not significantly improve. Only PROMIS PI correlated with PASS at the six-month follow-up; PROMIS PI significantly improved among simple posterolateral elbow dislocation patients at both short-term and long-term follow-up points. PROMIS PF, UE, and depression did not significantly differ between time of injury and short-term and long-term follow-up points.

Where Does Ultrasound Fit in the Diagnostic Algorithm for Cubital Tunnel Syndrome?

BACKGROUND: Ultrasound (US) has emerged as a promising supplement to electrodiagnostic studies (EDX) in the diagnosis of cubital tunnel syndrome (CuTS) and has potential to be performed by novice operators. Our objective is to understand the discrepancies in assessment between the two modalities and to assess the utility of US in CuTS diagnosis by a novice operator. METHODS: Patients who presented to a single tertiary academic medical center and clinically diagnosed with CuTS were prospectively enrolled. Electrodiagnostic studies were performed along with US measurements of the cross-sectional area (CSA) of the ulnar nerve by both a board-certified physiatrist and novice operator. Electrodiagnostic study and US outcomes were compared among four diagnostic impression groups: EDX-/US-, EDX+/US-, EDX-/US+, and EDX+/US+. RESULTS: Sixteen patients were classified as abnormal by both EDX and US, 14 were classified abnormal by US only, 3 were classified abnormal by EDX only, and 6 were classified normal by both EDX and US (P = .008, K = 0.14). The EDX+/US+ group had a significantly reduced sensory amplitude compared with the EDX-/US+ (P = .04) group. Diagnostic classifications between a board-certified physiatrist and novice operator were in moderate agreement (K = 0.58, P = .08). CONCLUSIONS: Ultrasound detected a greater proportion of patients as abnormal than EDX. A subset of patients with clinical diagnoses of CuTS had normal sensory amplitudes but increased maximum nerve CSAs. Competency in US may be easily acquired with minimal training, suggesting its potential to be extended for use by other members of the health care team.

Recent oncolytic virotherapy clinical trials outline a roadmap for the treatment of high-grade glioma.

Adult and pediatric high-grade gliomas (HGGs) are aggressive cancers of the central nervous system that confer dismal clinical prognoses. Standard radiation and chemotherapy have demonstrated only limited efficacy in HGGs, motivating the accelerated investigation of novel modalities such as oncolytic virus (OV) therapies. OV centered therapies work through a mixed mechanism centered on oncolysis and the stimulation of an antitumor immune response. Three recent clinical trials utilizing herpes simplex virus-1 and adenovirus-based oncolytic virotherapy demonstrated not only the safety and efficacy of OVs but also novel dosing strategies that augment OV response potential. Considering these recent trials, herein we present a roadmap for future clinical trials of oncolytic immunovirotherapy in both adult and pediatric HGG, as well as persistent roadblocks related to the assessment of OV efficacy within and between trials.

Endoscopic Versus Open Carpal Tunnel Surgery: Risk Factors and Rates of Revision Surgery.

PURPOSE: The purpose of our study was to compare the 1-year revision surgery rates and outcomes of open versus endoscopic carpal tunnel release. Our hypothesis was that, compared to open release, endoscopic carpal tunnel release was an independent risk factor for revision surgery within 1-year. METHODS: This was a retrospective cohort study of 4338 patients undergoing isolated endoscopic or open carpal tunnel release. Demographic data, medical comorbidities, surgical approach, need for revision surgery, hand dominance, history of prior injection, and Patient Reported Outcomes Measurement Information System upper extremity (UE), pain interference (PI) and physical function scores were analyzed. Multivariable analysis was used to identify the risk factors for revision surgery within one year of the index procedure. RESULTS: In total, 3280 patients (76%) underwent open and 1058 (24%) underwent endoscopic carpal tunnel release. Within one year of the index procedure, 45 patients required revision carpal tunnel release. The average time to revision was 143 days. The rate of revision carpal tunnel release in the open group was 0.71% compared to 2.08% in the endoscopic group. Multivariable analysis demonstrated that endoscopic surgery, male sex, cubital tunnel syndrome, tobacco use, and diabetes were associated independently with revision surgery. CONCLUSIONS: In this study, we found that endoscopic carpal tunnel release was associated independently with a 2.96 times greater likelihood of requiring revision carpal tunnel release within one year, compared to open carpal tunnel release. Male sex, concurrent cubital tunnel syndrome, tobacco use, and diabetes also were associated independently with greater risk of needing revision carpal tunnel release within one year. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Childhood Trauma Predicts Positive Expressive Suppression During Social Affiliation in Adults With Anxiety and/or Depression: Implications for Social Functioning.

Experiencing childhood trauma (CT) can create barriers for developing relationships and is a risk factor for anxiety and depression. Expressive suppression (ES; i.e., reducing expression associated with experiencing emotions) might explain the link between CT and relationship formation difficulties. We examined the association between (1) CT and ES during a dyadic paradigm intended to facilitate connectedness between unacquainted partners and (2) ES and desire for future interaction (DFI). Individuals with an anxiety or depressive disorder diagnosis (N = 77) interacted with a trained confederate; partners answered a series of increasingly intimate questions about themselves. Participant ES for positive and negative emotions, and participant and confederate DFI were collected during the task. Participants completed global anxiety, depression, and CT measures. CT correlated with positive (r = .35, p = .002), but not negative, ES (r = .13, p = .273). In a multiple linear regression model, CT predicted positive ES beyond symptom variables and gender, ß = .318, t = 2.59, p = .012. Positive ES correlated with participant (r = -.38, p = .001) and confederate DFI (r = -.40, p<.01); and predicted participant DFI beyond symptom variables and ethnicity, ß = -.358, t = -3.18, p = .002, and confederate DFI, ß = -.390, t = -3.51, p = .001, beyond symptom variables. Mediation analyses suggested positive ES accounted for the relationship between greater CT severity and less desire for future interaction from participants, 95%CI [-0.26, -0.02], and confederates, [-0.38, -0.01]. Positive ES may be an important factor in the reduced capacity to form new social relationships for individuals with a history of CT, anxiety, and depression.

Reduced time to imaging, length of stay, and hospital charges following implementation of a novel postoperative pathway for craniotomy.

OBJECTIVE: The authors created a postoperative postanesthesia care unit (PACU) pathway to bypass routine intensive care unit (ICU) admissions of patients undergoing routine craniotomies, to improve ICU resource utilization and reduce overall hospital costs and lengths of stay while maintaining quality of care and patient satisfaction. In the present study, the authors evaluated this novel PACU-to-floor clinical pathway for a subset of patients undergoing craniotomy with a case time under 5 hours and blood loss under 500 ml. METHODS: A single-institution retrospective cohort study was performed to compare 202 patients enrolled in the PACU-to-floor pathway and 193 historical controls who would have met pathway inclusion criteria. The pathway cohort consisted of all adult supratentorial brain tumor cases from the second half of January 2021 to the end of January 2022 that met the study inclusion criteria. Control cases were selected from the beginning of January 2020 to halfway through January 2021. The authors also discuss common themes of similar previously published pathways and the logistical and clinical barriers overcome for successful PACU pathway implementation. RESULTS: Pathway enrollees had a median age of 61 years (IQR 49-69 years) and 53% were female. Age, sex, pathology, and American Society of Anesthesiologists physical status distributions were similar between pathway and control patients (p > 0.05). Most of the pathway cases (96%) were performed on weekdays, and 31% had start times before noon. Nineteen percent of pathway patients had 30-day readmissions, most frequently for headache (16%) and syncope (10%), whereas 18% of control patients had 30-day readmissions (p = 0.897). The average time to MRI was 6 hours faster for pathway patients (p < 0.001) and the time to inpatient physical therapy and/or occupational therapy evaluation was 4.1 hours faster (p = 0.046). The average total length of stay was 0.7 days shorter for pathway patients (p = 0.02). A home discharge occurred in 86% of pathway cases compared to 81% of controls (p = 0.225). The average total hospitalization charges were $13,448 lower for pathway patients, representing a 7.4% decrease (p = 0.0012, adjusted model). Seven pathway cases were escalated to the ICU postoperatively because of attending physician preference (2 cases), agitation (1 case), and new postoperative neurological deficits (4 cases), resulting in a 96.5% rate of successful discharge from the pathway. In bypassing the ICU, critical care resource utilization was improved by releasing 0.95 ICU days per patient, or 185 ICU days across the cohort. CONCLUSIONS: The featured PACU-to-floor pathway reduces the stay of postoperative craniotomy patients and does not increase the risk of early hospital readmission.

Examining affective reactivity as a link between suicidality and social disconnection.

The link between suicidality and social disconnection is well-established. We explored possible mechanisms that may account for this link using a positive and negative valence systems framework in a clinical sample with and without suicidality (i.e., suicidal ideation and/or behaviors in the past month). Participants (N = 228) interacted with a trained confederate during a controlled conversation task designed to generate social affiliation. Participant-rated positive affect (PA) and negative affect (NA) were collected during the task (baseline, anticipation, post). Participant-rated desire for future interaction was collected after the task. We tested if (1) groups with (n = 82) and without (n = 146) suicidality differed in affect during the task and (2) whether affect accounted for the link between suicidality and desire for future interaction. Results revealed that groups differed in PA, but not NA, throughout the task. Participants with suicidality reported no significant changes in PA over the task (ps > .05); and, experienced less PA at post-task compared to those without (p = .003, d = 0.38) whereas participants without suicidality reported increased PA at post-task compared to baseline and anticipation of the task, ps < .001. Mediation analysis suggested blunted post-task PA accounted for the relationship between suicidality and less desire for future interaction, 95%CI [-2.59,-0.51]. Diminished PA reactivity during social affiliation opportunities may help explain the link between suicidality and social disconnection. Preliminary findings highlight PA as a potential mechanistic target for improving social connection for individuals at risk for suicide, though prospective and experimental research is needed.

Baseline executive functioning moderates treatment-related changes in quality of life in veterans with posttraumatic stress disorder and comorbid traumatic brain injury.

Posttraumatic stress disorder (PTSD) treatment has been associated with improvement in quality of life (QOL); however, little is known about factors that moderate treatment-related changes in QOL, particularly cognitive factors. Executive functioning (EF) is important for success across all aspects of everyday life and predicts better psychological and physical health. EF is important to QOL, but more work is needed to better understand the association between EF and QOL improvements following interventions. We hypothesized that poorer baseline EF would be associated with less improvement in overall life satisfaction and satisfaction with health following PTSD treatment. U.S. veterans who served after the September 11, 2001 terrorist attacks (post 9-11; N = 80) with PTSD and a history of mild-to-moderate traumatic brain injury were randomized to standard cognitive processing therapy (CPT) or CPT combined with cognitive rehabilitation (SMART-CPT). Multilevel modeling was used to examine whether baseline EF performance was associated with changes in QOL scores from pretreatment to follow-up across both groups. Results indicated that poorer baseline performance on EF tests of working memory and inhibition were associated with less treatment-related improvements in general life satisfaction and satisfaction with health, rs = .26-.36. Treatment condition did not moderate any results. Future research should examine whether implementing EF-focused techniques before and/or concurrently with CPT for individuals with poorer baseline working memory and inhibition enhances QOL treatment gains, particularly in terms of general life and health-related satisfaction.

Immunotherapy approaches for the treatment of diffuse midline gliomas.

Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy has emerged as a promising alternative treatment modality. This review summarizes the various immunotherapy-based treatments for DMG as well as their specific limitations. We explore the use of cell-based therapies, oncolytic virotherapy or immunovirotherapy, immune checkpoint inhibition, and immunomodulatory vaccination strategies, and highlight the recent clinical success of anti-GD2 CAR-T therapy in diffuse intrinsic pontine glioma (DIPG) patients. Finally, we address the challenges faced in translating preclinical and early phase clinical trial data into effective standardized treatment for DMG patients.