Dendrimer nanotherapy targeting of glial dysfunction improves inflammation and neurobehavioral phenotype in adult female Mecp2-heterozygous mouse model of Rett syndrome.

Rett syndrome is an X-linked neurodevelopmental disorder caused by mutation of Mecp2 gene and primarily affects females. Glial cell dysfunction has been implicated in in Rett syndrome (RTT) both in patients and in mouse models of this disorder and can affect synaptogenesis, glial metabolism and inflammation. Here we assessed whether treatment of adult (5-6 months old) symptomatic Mecp2-heterozygous female mice with N-acetyl cysteine conjugated to dendrimer (D-NAC), which is known to target glia and modulate inflammation and oxidative injury, results in improved behavioral phenotype, sleep and glial inflammatory profile. We show that unbiased global metabolomic analysis of the hippocampus and striatum in adult Mecp2-heterozygous mice demonstrates significant differences in lipid metabolism associated with neuroinflammation, providing the rationale for targeting glial inflammation in this model. Our results demonstrate that treatment with D-NAC (10 mg/kg NAC) once weekly is more efficacious than equivalently dosed free NAC in improving the gross neurobehavioral phenotype in symptomatic Mecp2-heterozygous female mice. We also show that D-NAC therapy is significantly better than saline in ameliorating several aspects of the abnormal phenotype including paw clench, mobility, fear memory, REM sleep and epileptiform activity burden. Systemic D-NAC significantly improves microglial proinflammatory cytokine production and is associated with improvements in several aspects of the phenotype including paw clench, mobility, fear memory, and REM sleep, and epileptiform activity burden in comparison to saline-treated Mecp2-hetereozygous mice. Systemic glial-targeted delivery of D-NAC after symptom onset in an older clinically relevant Rett syndrome model shows promise in improving neurobehavioral impairments along with sleep pattern and epileptiform activity burden. These findings argue for the translational value of this approach for treatment of patients with Rett Syndrome.

Myocardial bridge in a child with cardiac arrest and ventricular fibrillation: a bridge over troubled water?

Resuscitated cardiac arrest in a child triggers a comprehensive workup to identify an aetiology and direct management. The presence of a myocardial bridge does not automatically imply causation. Careful determination of the haemodynamic significance of the myocardial bridge is critical to avoid an unnecessary sternotomy and to provide appropriate treatment.

Late Outcomes of Transcatheter Coarctation Intervention in Infants with Biventricular Anatomy.

Determine outcomes of catheter intervention for aortic coarctation in infants. Aortic coarctation in infants following surgical repair and in high surgical risk native cases remains a challenging problem. Catheter intervention is an alternative to surgical intervention. Single-center, chart review of infants with biventricular anatomy who underwent coarctation stent placement or balloon angioplasty between 04/2004 and 04/2020. Outcomes of interest included change in aortic lumen diameter, peak gradient, number of re-interventions, time to re-intervention, and adverse events. Thirty-four patients were included in analysis, of those 16 underwent stent placement. Patients' mean age was 4.0 ± 3.0 months and weight of 5.3 ± 1.9 kg. Follow-up interval was 5.4 ± 5.1 years (0.2-16.1 years). Twelve (35%) patients underwent procedure due to ventricular dysfunction; the rest were for high resting gradient. Coarctation diameter increased from 2.4 ± 1.0 to 4.5 ± 1.3 (p < 0.01) and gradient decreased from 32.0 ± 18.4 mmHg to 9.2 ± 8.8 mmHg (p < 0.01). Thirteen (81%) of the stented patients required at least one re-intervention, at an average of 1.7 ± 3.2 years from the index procedure. Five (28%) of those undergoing balloon angioplasty required repeat intervention. There was no mortality due to the procedure and one late mortality. One patient had a serious procedural adverse event. On follow-up, 12 (35%) were on anti-hypertensive medications. Catheter intervention, including stent placement, for aortic coarctation in infants is feasible with an acceptable adverse event profile. Repeat interventions are common.

Replace, amplify, transform: a qualitative study of how postgraduate trainees and supervisors experience and use telehealth for instruction in ambulatory patient care.

BACKGROUND: Little is known about using telehealth patient visits as an educational mode. Therefore, rapid implementation of telehealth during the COVID-19 pandemic had to be done without understanding how to optimize telehealth for education. With the likely sustained/post-pandemic use of telehealth in ambulatory patient care, filling gaps in our understanding of how telehealth can be used for instruction in this context is critical. This study sought to understand perceptions of pediatric postgraduate trainees and supervisors on the use of telehealth for instruction in ambulatory settings with the goal of identifying effective ways to enhance learning during telehealth visits. METHODS: In May-June of 2020, the authors purposefully sampled first- and third-year postgraduate trainees and supervising attendings from pediatric fellowship programs at one institution that implemented telehealth for instructional activities. They conducted semi-structured interviews; interviews lasted a median of 51 min (trainees) and 41 min (supervisors). They conducted interviews and data analysis iteratively until reaching saturation. Using thematic analysis, they created codes and constructed themes from coded data. They organized themes using the Replace-Amplify-Transform (RAT) model, which proposes that technology can replace in-person learning and/or amplify and transform learning. RESULTS: First-year trainees (n = 6), third-year trainees (n = 5) and supervisors (n = 6) initially used telehealth to replace in-person learning. However, skills that could be practiced in telehealth visits differed from in-person visits and instructional activities felt rushed or awkward. Trainees and supervisors adapted and used telehealth to amplify learning by enhancing observation and autonomy. They also transformed learning, using telehealth to develop novel skills. CONCLUSIONS: To harness telehealth for instructional activities, our findings indicated that trainees and supervisors should shift from using it as a direct replacement for in-person education to taking advantage of novel opportunities to amplify and transform education in PGME. The authors provide data-driven recommendations to help PGME trainees, supervisors and educators capitalize on the educational advantages of telehealth.

What is the association between student well-being and high-stakes examination scores?

INTRODUCTION: As educators seek to improve medical student well-being, it is essential to understand the interplay between distress and important outcomes. Performance on Step 1 of the United States Medical Licensing Examination has played a significant role in selection for postgraduate residency positions in the United States and consequently has been a source of great stress for medical students. The purpose of this study was to examine whether student well-being correlates with performance on a high stakes licensing examination. METHODS: Between 2014 and 2016, three sequential cohorts of medical students at the University of Michigan Medical School completed the Medical Student Well-Being Index (MSWBI) at the end of their 2nd-year curriculum, shortly before taking Step 1. Associations between well-being and Step 1 scores were investigated while adjusting for MCAT scores and cumulative second-year course scores. RESULTS: In total, 354 students were included in the analysis (68.1% of potential responders). On bivariate analysis, poor student well-being (0 = low distress [high well-being], 7 = high distress [poor well-being]) was associated with lower Step 1 examination scores (slope = -2.10, P < .01), and well-being accounted for 5% of overall Step 1 score variability (R2  = .05). However, after adjustment for MCAT scores and cumulative GPA (full model R2  = .51), the relationship between well-being and Step 1 score was no longer significant (slope = -0.70, P-value = .06). CONCLUSIONS: When controlling for metrics of academic performance, student well-being prior to taking Step 1 was not associated with how well students performed on Step 1 for the study sample.

Modified Microvascular Plug as a Flow Restrictor in Hypoplastic Left Heart Syndrome with Dysplastic Tricuspid and Pulmonary Valves.

While the Norwood operation is the most common palliative surgery for neonates with hypoplastic left heart syndrome (HLHS), initial hybrid strategy aiming to restrict pulmonary blood flow and maintain systemic output is necessary when Norwood is contraindicated or at high risk. The traditional mainstay of initial hybrid palliation is surgical pulmonary artery branch banding (PABB) plus interventional ductal stenting. We present a case of a transcatheter approach for pulmonary flow restriction (PFR) that was accomplished by modifying a Medtronic microvascular plug (MVP)™. The patient is a 2.4 kg neonate diagnosed with HLHS, dysplastic tricuspid and pulmonary valves with pulmonary stenosis, tricuspid stenosis, and regurgitation. He was not considered a candidate for surgical intervention. He started developing sequelae of unbalanced pulmonary and systemic blood flow; therefore, he underwent placement of transcatheter PFR as alternative to PABB. He underwent successful orthotopic heart transplant 104 days after index procedure. This case demonstrates the significant complexity that can occur in patients with HLHS and abnormal right sided valves. Additionally, it is another example that transcatheter branch pulmonary artery flow restriction can be a safe and feasible alternative to PABB as initial palliation strategy. It may benefit patients in whom primary Norwood procedure would have increased risks or who will undergo primary transplant.

What faculty write versus what students see? Perspectives on multiple-choice questions using Bloom's taxonomy.

BACKGROUND: Using revised Bloom's taxonomy, some medical educators assume they can write multiple choice questions (MCQs) that specifically assess higher (analyze, apply) versus lower-order (recall) learning. The purpose of this study was to determine whether three key stakeholder groups (students, faculty, and education assessment experts) assign MCQs the same higher- or lower-order level. METHODS: In Phase 1, stakeholders' groups assigned 90 MCQs to Bloom's levels. In Phase 2, faculty wrote 25 MCQs specifically intended as higher- or lower-order. Then, 10 students assigned these questions to Bloom's levels. RESULTS: In Phase 1, there was low interrater reliability within the student group (Krippendorf's alpha = 0.37), the faculty group (alpha = 0.37), and among three groups (alpha = 0.34) when assigning questions as higher- or lower-order. The assessment team alone had high interrater reliability (alpha = 0.90). In Phase 2, 63% of students agreed with the faculty as to whether the MCQs were higher- or lower-order. There was low agreement between paired faculty and student ratings (Cohen's Kappa range .098-.448, mean .256). DISCUSSION: For many questions, faculty and students did not agree whether the questions were lower- or higher-order. While faculty may try to target specific levels of knowledge or clinical reasoning, students may approach the questions differently than intended.

Factors Associated with Delayed Transition to Oral Feeding in Infants with Single Ventricle Physiology.

OBJECTIVES: To describe the duration of time to achieve exclusive oral feeding in infants with single ventricle physiology and to identify risk factors associated with prolonged gastrostomy tube dependence. STUDY DESIGN: Single center, retrospective study of infants with single ventricle physiology. The primary outcome was duration of time required to achieve oral feeding. Transition periods were defined as exclusive oral feeding by Glenn palliation (early), by 1 year of age (mid), or after 1 year of age (late). RESULTS: Seventy-eight infants were analyzed; 46 (59%) were discharged to home with a gastrostomy tube after the initial hospitalization. Overall, 39 infants (50%) achieved early transition, 14 (18%) mid, and 18 (23%) late. The group who achieved early transition had a higher percentage of preoperative oral feeding (P < .01), greater weight-for-age z score at initial discharge (P = .03), shorter initial intensive care unit duration (P < .01), shorter initial hospital length of stay (P < .01), and greater weight-for-age z score at Glenn admission (P = .02). No preoperative oral feeding (OR = 0.12, P = .02) and greater number of cardiac medications at initial discharge (OR = 3.8, P = .03) were associated with failure to achieve early transition. No preoperative oral feeding (OR = 0.09, P = .01) and longer initial intensive care unit duration (OR = 1.1, P = .03) were associated with failure to achieve mid transition. CONCLUSION: Preoperative oral feeding may potentially be a modifiable factor to help improve early transition to oral feeding.

Screening the apparently healthy athlete for risk: a paradigm in transition.

It has largely been accepted that pre-participation screening for student athletes is necessary, but there is still no consensus on the most effective and efficient ways to accomplish this. Most clinical strategies are based on retrospective case series. By applying the European Society of Cardiology and Seattle criteria, electrocardiography appears to afford the lowest false-positive rate for identifying potentially dangerous cardiac abnormalities in athletes. Prospective, randomised trials may help determine the most effective primary prevention. Normative data for age, gender, and ethnicity for screening tools need to be formulated to further reduce false-positive results. Targeted advanced screening aimed at the highest risk groups may be the most beneficial and cost-effective application of primary prevention.

Prevalence of Branch Pulmonary Artery Reintervention Following the Arterial Switch Operation.

BACKGROUND: The arterial switch operation (ASO) is the preferred surgical procedure used to correct dextro-transposition of the great arteries. A known complication of the ASO is branch pulmonary arteries (PAs) stenosis, which may require reintervention. Our goal is to determine the frequency of reintervention after the ASO and any factors associated with reintervention. METHODS: This was a single center, retrospective study of infants who underwent the ASO from June 6, 2011 to February 21, 2021. The primary outcome was the prevalence of reintervention on the PAs following the ASO. RESULTS: Sixty-eight infants were analyzed; 9 (13%) patients had 10 reinterventions. The mean age at time of the ASO was 6.52 ± 6.63 days; weight was 3.34 ± 0.57 kg. Those with a reintervention had a longer bypass time (P = .047). Mean age at reintervention was 0.80 ± 0.72 years; mean time from the ASO to reintervention was 0.799 ± 0.717 years. Six surgical procedures, two stent placements, and four balloon angioplasties were performed on a total of 13 branch PAs. There was no increased risk for reintervention on the right versus left PA. After reintervention, there was an improvement in the minimal PA diameter and echo gradient. There were no adverse events or mortality related to the reintervention. Mean follow-up was 6.17 ± 2.94 years. CONCLUSION: The prevalence of branch PA reintervention following the ASO in our cohort was 13%. There is an association between longer cardiopulmonary bypass time and reintervention. After reintervention, there was an increase in PA diameter and a decrease in echo gradient.

Left Main Coronary Artery Ostial Stenosis in a Pediatric Patient With Sudden Cardiac Arrest.

Pediatric resuscitated sudden cardiac arrest may result from diverse conditions and, therefore, warrants a comprehensive work-up. Although rare, coronary artery abnormalities must be ruled out in these patients. We describe a case with congenital left main coronary artery ostial stenosis diagnosed using advanced imaging techniques. (Level of Difficulty: Advanced.).

Novel utilization of deep brain stimulation in the pedunculopontine nucleus with globus pallidus internus for treatment of childhood-onset dystonia.

Introduction: Deep brain stimulation (DBS) is a well-documented therapy for dystonia utilized in many adult and pediatric movement disorders. Pedunculopontine nucleus (PPN) has been investigated as a DBS target primarily in adult patients with dystonia or dyskinesias from Parkinson's disease, showing improvement in postural instability and gait dysfunction. Due to the difficulty in targeting PPN using standard techniques, it is not commonly chosen as a target for adult or pediatric pathology. There is no current literature describing the targeting of PPN in DBS for childhood-onset dystonia. Methods: Two pediatric and one young adult patient with childhood-onset dystonia who underwent DBS implantation at our institution were identified. Patient 1 has Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN) syndrome. Patient 2 has Glutaric Aciduria Type 1 (GA1). Patient 3 has atypical pantothenate kinase-associated neurodegeneration (PKAN). PPN was identified as a potential target for these patients due to axial or orofacial dystonia. Pre- and post-operative videos taken as part of routine clinical assessments were evaluated and scored on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS). All patients had permanent electrodes placed bilaterally in PPN and globus pallidus internus (GPi). A Likert scale on quality of life was also obtained from the patient/parents as applicable. Results: Significant programming was necessary over the first 3-12 months to optimize patients' response to stimulation. All patients experienced at least a 34% improvement in the BFMDRS score. Patients 2 and 3 also experienced an over 30% improvement in BADS score. All patients/parents appreciated improvement in quality of life postoperatively. Discussion: Deep brain stimulation in PPN was safely and successfully used in two pediatric patients and one young adult patient with childhood-onset dystonia. These patients showed clinically significant improvements in BFMDRS scoring post operatively. This represents the first reported DBS targeting of PPN in pediatric patients, and suggests that PPN is a possible target for pediatric-onset dystonia with axial and orofacial symptoms that may be refractory to traditional pallidal stimulation alone.

Application of deep brain stimulation for the treatment of childhood-onset dystonia in patients with MEPAN syndrome.

Introduction: Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN) syndrome is a rare inherited metabolic condition caused by MECR gene mutations. This gene encodes a protein essential for fatty acid synthesis, and defects cause progressively worsening childhood-onset dystonia, optic atrophy, and basal ganglia abnormalities. Deep brain stimulation (DBS) has shown mixed improvement in other childhood-onset dystonia conditions. To the best of our knowledge, DBS has not been investigated as a treatment for dystonia in patients with MEPAN syndrome. Methods: Two children with MEPAN were identified as possible DBS candidates due to severe generalized dystonia unresponsive to pharmacotherapy. Temporary depth electrodes were placed in six locations bilaterally and tested during a 6-day hospitalization to determine the best locations for permanent electrode placement. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) were used for preoperative and postoperative testing to quantitatively assess dystonia severity changes. Patient 1 had permanent electrodes placed at the globus pallidus internus (GPi) and pedunculopontine nucleus (PPN). Patient 2 had permanent electrodes placed at the GPi and ventralis intermedius nucleus of the thalamus (VIM). Results: Both patients successfully underwent DBS placement with no perioperative complications and significant improvement in their BFMDRS score. Patient 2 also demonstrated improvement in the BADS. Discussion: We demonstrated a novel application of DBS in MEPAN syndrome patients with childhood-onset dystonia. These patients showed clinically significant improvements in dystonia following DBS, indicating that DBS can be considered for dystonia in patients with rare metabolic disorders that currently have no other proven treatment options.

A Trainee-Led Quality Improvement Project Using Change Management Theory to Improve Bedside Rounding.

OBJECTIVE: The coronavirus disease 2019 pandemic disrupted the practice of family-centered rounds. After the height of the pandemic, a trainee-led team identified a low percentage of bedside rounds on general pediatrics resident teams and combined a quality improvement framework and change management theory to increase bedside rounds. Initial efforts focused on a single general pediatrics team with the aim to increase bedside rounds from 18% to 50% within 6 months and sustain improvement for 12 months. A second aim was to increase bedside rounds from 7% to 50% for all general pediatrics resident teams within 6 months of spread. METHODS: The Model for Improvement informed the identification of 3 primary drivers of bedside rounds: knowledge, culture, and logistics. Twelve plan-do-study-act (PDSA) cycles were implemented. Measures included the percentage of bedside rounds (primary outcome), caregiver attendance (secondary outcome), and nurse attendance and rounding time (balancing measures). RESULTS: For the initial team, 13 522 patient days were analyzed for the primary outcome with the average percentage of weekly bedside rounds increasing from 18% to 89% with 12 months of sustained improvement. The spread of the intervention to all teams revealed an increase in bedside rounding from 7% to 54%. The most significant improvements occurred after PDSA cycle 2, a communication bundle, and PDSA cycle 5, when the project was spread to all teams. CONCLUSIONS: This trainee-led initiative reveals the strength of the incorporation of change management theory within a quality improvement framework, resulting in rapid and sustainable increase in bedside rounds.

Safety and Efficacy of High-Dose Tranexamic Acid in Spine Surgery: A Retrospective Single-Institution Series.

OBJECTIVE: Currently, tranexamic acid (TXA) is the most widely used antifibrinolytic agent in spine surgery and has been proven to reduce perioperative blood loss. However, the safety of high-dose regimens remains in established. METHODS: A retrospective chart review was performed to identify all adult patients who underwent spine surgery with high-dose TXA (50 mg/kg loading dose, mg/kg/h maintenance dose) between September 2019 and March 2020. RESULTS: Thirty-six patients were treated with intraoperative high-dose TXA during the study period. The mean age was 56.6 (range: 22-82). Average body mass index was 27.2 (5.1) kg/m2. Average preoperative Charlson Comorbidity Index was 3.0 (2.7). The mean number of spinal levels operated on was 6.9 (4.3). Seven cases (19.4%) were revision surgeries. The mean intraoperative blood loss was 587.1 (900.0) mL, and total blood loss was 623.8 (991.9) mL. Postoperatively, time to ambulation was on average 1.7 (1.7) days. The mean total length of stay was 9.8 days (7.9, range 2-41). The most common indication for surgery was tumor (n = 9, 25%), followed by fracture (n = 8, 22.2%), deformity (n = 7, 19.4%), pseudarthrosis (n = 6, 16.7%), and symptomatic lumbar disc herniation (n = 2, 5.6%). There were no thromboembolic or other significant complications among the 36 patients. CONCLUSIONS: This retrospective case series demonstrates that the use of high-dose TXA provides is potentially safe and efficacious in adult patients undergoing complex spine surgeries. However, further investigations are required before the true safety and optimal dosing can be determined for high-dose TXA.

Structure, optical properties, and magnetism of the full Zn(1-x)Cu(x)WO4 (0 ≤ x ≤ 1) composition range.

Microcrystalline and submicrometer powders of Zn(1-x)Cu(x)WO(4) (0 ≤ x ≤ 1) have been prepared by a solid-state synthesis from stoichiometric quantities of the constituent d-block metal oxide and tungsten oxide as well as from a Pechini sol-gel synthesis starting from the d-block metal nitrate and ammonium metatungstate. The stoichiometry of the product is confirmed by inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. X-ray diffraction shows that for the entire range of compositions, a single-phase product crystallizes in the wolframite structure, with a symmetry-lowering transition from P2/c to P1[overline] at x = 0.20, concomitant with the first-order Jahn-Teller distortion of Cu(2+). Far-IR spectroscopy corroborates that symmetry lowering is directly related to the tetragonal distortion within the CuO(6) octahedra, with the Zn-O A(u) symmetry mode at 320 cm(-1) (x = 0) splitting into two stretches at 295 and 338 cm(-1) (x = 0.3). UV-vis-NIR spectroscopy shows an optical absorption edge characteristic of an indirect band gap that linearly decreases in energy from 3.0 eV (x = 0) to 2.25 eV (x = 1). SQUID magnetometry shows that Zn(1-x)Cu(x)WO(4) (0.1 ≤ x ≤ 1) has an effective moment of 2.30 ± 0.19 µ(B) per mol copper, typical of Cu(2+) in extended solids. For high concentrations of copper (x ≥ 0.8), two transitions are observed: one at high-temperature, 82 K (x = 1.0) that decreases to 59 K (x = 0.8), and the Néel temperature, 23.5 K (x = 1.0) that decreases to 5.5 K (x = 0.8). For x < 0.8, no long-range order is observed. A physical 1:1 mixture of both CuWO(4):ZnWO(4) shows magnetic ordering identical to that of CuWO(4).

Successful use of stereotactic navigation in posterior spinal fusion T10-S2 with bilateral iliac screw fixation in a patient with prior spinal surgeries and osteoporosis: A case report.

INTRODUCTION AND IMPORTANCE: Degenerative lumbar scoliosis is a prominent cause of adult spinal deformity with an increasing prevalence as the population ages. This pathology is associated with debilitating symptoms, including radicular back pain and lower extremity claudication. Surgical realignment of the spine and restoration of sagittal imbalance can reduce low back pain. Chronic sacroiliac dysfunction commonly causes low back radicular pain. We present a complicated case where stereotactic navigation facilitated an extensive fusion and decompression procedure for adult spinal deformity in an obese patient with multiple prior surgeries for scoliosis and sacroiliac joint pathology. CASE PRESENTATION: A 69-year-old, obese female with scoliosis refractory to multiple interventions presented with severe, radicular lower back pain. On examination of the right lower extremity (RLE), she had mild weakness (3/5 strength) and reduced sensation to light touch over its anterolateral aspect (dermatome L4). She was unable to perform single leg stance or tandem walk. Imaging revealed moderate mid-lumbar levoscoliosis, severe degenerative disc disease and facet hypertrophy changes in the setting of prior multilevel lumbar fusion, and consecutive nerve root impingement between L1 and L5 (worst at L3-4). DEXA scan was consistent with osteoporosis. The patient underwent lumbar laminectomy with posterior fusion of T10-ilium, transforaminal lumbar interbody fusion, osteotomy, and decompression using stereotactic navigation. The presence of SI titanium dowels from her previous SI fusion procedure posed a challenge with respect to achieving pelvic fixation. CLINICAL DISCUSSION: Iliac screw placement is a critical adjunctive to lumbosacral fusion, notably for prevention of pseudoarthrosis; however, patients with prior SI fusion may present a biomechanical challenge to surgeons due to obstruction of the surgical site. The O-arm neuronavigation system was successfully used to bypass this obstruction and provide sacroiliac fixation in this procedure. CONCLUSION: Stereotactic navigation (The O-arm Surgical Imaging System) can effectively be used to circumvent prior SI fusion in osteoporotic bone.

The minimally conscious state: an analysis of current clinical trials registered in ClinicalTrials.gov.

The minimally conscious state (MCS) is a disorder of consciousness described in recent years for patients who have behavioral responses to stimuli that do not meet the classification of chronic vegetative state (CVS) or coma. This distinction is valuable in clinical practice, as minimally conscious patients may require different treatments and may have different long-term outcomes when compared to vegetative states or coma. In this report, we analyzed the ClinicalTrials.gov database to systematically assess all clinical trials regarding MCS. The database was queried using the term "minimally conscious state" in the "condition or disease" search parameter. Of the studies identified, those that had suspended, terminated, or otherwise unknown statuses were excluded. In total, 41 studies were analyzed. The included studies were initiated between 2008 and 2020, with the majority (63%) beginning in 2015 or later. Of the primary intervention modalities included, 15 (37%) evaluated stimulation modalities such as transcranial magnetic stimulation, transcranial direct current stimulation, implantable neurostimulation, vagus nerve stimulation, focused ultrasound and median nerve stimulation. Additionally, 5 (12%) used some form of behavioral therapy. A total of 4 (10%) studies involved pharmaceutical intervention, including dopamine agonists, analgesics and sedatives. Finally, 4 (10%) studies sought to determine the validity of current diagnostic methods and systems used to assess the status of patients in MCSs. Since the definition and criteria for CVS and MCS have been established, these two conditions remain closely associated despite evidence of different patient outcomes and treatment options. Many clinical trials are underway assessing interventions with stimulation. However, the trials are lacking with respect to diagnostic methods and pharmaceutical treatment.

Evaluating the incidence and predictors of anti-NMDAR encephalitis in a contemporary cohort of patients diagnosed with dermoid tumors: A national inpatient sample analysis.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a form of encephalitis previously associated with dermoid tumors. However, most studies in the literature evaluating the disease are case reports and small patient cohorts, limiting robust statistical analysis. Here, we demonstrate predictors of anti-NMDAR encephalitis in a large cohort of US patients. METHODS: We used the 2016 National Inpatient Sample (NIS) to identify a cohort of 24,270 admitted for an ovarian dermoid tumor. Of these patients, 50 (0.21%) were diagnosed with anti-NMDAR encephalitis. Patient demographics, hospital characteristics, length of stay (LOS), and complications were collected. Statistical analysis consisted of odds ratios with chi-square testing to compare categorical variables. RESULTS: The mean age of all patients with dermoid tumors was 45.5 ± 18.0 years, and the mean age of patients with diagnosed anti-NMDAR encephalitis was 27.4 ± 4.9 years. The mean LOS in the dermoid tumor cohort was 3.5 ± 4.9 days, while the mean LOS in the anti-NMDAR encephalitis cohort was 31.9 ± 25.9 days (p < 0.001). The mean cost in the dermoid tumor cohort was $44,813.18±$54,305.90, while the mean cost in the anti-NMDAR encephalitis cohort was $445,628.60±$665,423.40 (p < 0.001). Patients with age above 30 years with dermoid tumors had significantly lower odds of developing anti-NMDAR encephalitis compared to patients younger than 30 years (OR: 0.19; 95%CI: 0.045-0.67; p-value: 0.003). White patients had significantly lower odds of developing anti-NMDAR encephalitis (OR: 0.19; 95%CI: 0.026-0.77; p-value: 0.013), and Black patients had significantly higher odds of developing anti-NMDAR encephalitis (OR: 3.45; 95%CI: 1.00-12.46; p-value: 0.044). CONCLUSION: Patient predictors of developing anti-NMDAR encephalitis include age, race, ethnicity and patients who go on to develop anti-NMDAR encephalitis have a significantly increased hospital LOS and cost compared to those who do not. Future research, including multi-center clinical trials and longitudinal data, is necessary to fully cement the findings of this manuscript.

Cost analysis comparison between anterior and posterior cervical spine approaches.

Background: The costs of cervical spine surgery have steadily increased. We performed a 5-year propensity scoring-matched analysis of 276 patients undergoing anterior versus posterior cervical surgery at one institution. Methods: We performed propensity score matching on financial data from 276 patients undergoing 1-3 level anterior versus posterior cervical fusions for degenerative disease (2015-2019). Results: We found no significant difference between anterior versus posterior approaches for hospital costs ($42,529.63 vs. $45,110.52), net revenue ($40,877.25 vs. $34,036.01), or contribution margins ($14,230.19 vs. $6,312.54). Multivariate regression analysis showed variables significantly associated with the lower contribution margins included age (ß = -392.3) and length of stay (LOS; ß = -1151). Removing age/LOS from the analysis, contribution margins were significantly higher for the anterior versus posterior approach ($17,824.16 vs. $6,312.54, P = 0.01). Conclusion: Anterior cervical surgery produced higher contribution margins compared to posterior approaches, most likely because posterior surgery was typically performed in older patients requiring longer LOS.