Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets.

The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive to neurotransmitter signaling. mTORC2, which is modulated by growth factor signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, thereby suggesting that the inhibition of mTOR may have therapeutic potential. Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through an allosteric mechanism that only suppresses mTORC1, albeit incompletely. ATP-catalytic binding site inhibitors are designed to inhibit both complexes. This review describes the regulation of mTOR and the targeting of its complexes in the treatment of cancers, such as glioblastoma, and their stem cells.

Patterns for Child Protective Service Referrals in a Pediatric Burn Cohort.

BACKGROUND: Pediatric non-accidental trauma often necessitates the involvement of protective services. However, the subjectivity and lack of standardization of referral infrastructure may result in some discrepancies between referral patterns and instances of child abuse. METHODS: An institutional retrospective chart review was conducted between 2015 and 2021, in which all cases of patients under the age of 14 who suffered a burn injury and received a child protective service (CPS) consult were reviewed. Baseline demographics and characteristics were defined. Multivariate analysis was utilized to identify predictors of CPS involvement, while the regression analysis was employed to parse associations between burn injuries and CPS involvement. RESULTS: Between July 2015 and December 2021, 340 patients (median age two years, IQR: 1-6 years) under the age of 14 who experienced a burn injury were evaluated. Forty-four (12.9%) of the patients' cases received a CPS referral, of which three (0.9%) resulted in a CPS intervention. The most common mechanism of burn within the cohort was scald (241 patients, 70.9%). The median total body surface area (TBSA) was 3.0% (IQR: 1.0%-6.0%), and 76 (22.4%) suffered a high TBSA (>75th percentile). Caucasian race (p < 0.001) and scald mechanisms (p = 0.014) were associated with higher TBSA. When considering how such injuries translated to CPS referrals, increasing age was found to be associated with a decreased likelihood of CPS involvement. Meanwhile, the Black race (p = 0.027) and increasing area deprivation index (ADI) (p = 0.038) were associated with CPS involvement. Those with CPS involvement experienced a greater length of hospital stay (p = 0.001). Black race and intensive care unit level of care were found to be positive predictors of CPS involvement. In total, three (6.82%) of the 44 cases with CPS involvement were found to be substantiated. The three children who required CPS intervention were discharged to foster care settings. CONCLUSION: Hospitalized pediatric burn injuries must be investigated due to concern of child abuse, yet external factors such as race and socioeconomic status may play a role in the involvement of CPS. Such referrals may not always be substantiated and could lead to further injurious sequelae for children and their families.

High-Volume Centers Provide Superior Value of Care in the Surgical Treatment of Malignant Brain Tumor.

BACKGROUND: Improved outcomes in surgical patients have been associated with increasing volume of cases. This has led to the development of centers that facilitate care for a specific patient population. This study aimed to evaluate associations of outcomes with hospital characteristics in patients undergoing resection of malignant brain tumors. METHODS: The 2016-2020 National Inpatient Sample was queried for patients undergoing resection of malignant brain tumors. Teaching hospitals with caseloads >2 standard deviations above the mean (140 cases) were categorized as high-volume centers (HVCs). Value of care was evaluated by adding one point for each of the following: short length of stay, low total charges, favorable discharge disposition, and lack of major comorbidity or complication. RESULTS: In 3009 hospitals, 118,390 patients underwent resection of malignant brain tumors. HVC criteria were met by 91 (3%) hospitals. HVCs were more likely to treat patients of younger age or higher socioeconomic status (P < 0.01 for all). The Mid-Atlantic and South Atlantic regions had the highest percentage of cases and number of HVCs. Value of care was higher at HVCs (P < 0.01). Care at HVCs was associated with decreased complications (P < 0.01 for all) and improved patient outcomes (P < 0.01 for all). CONCLUSIONS: Patients undergoing craniotomy for malignant brain neoplasms have superior outcomes in HVCs. Trends of centralization may reflect the benefits of multidisciplinary treatment, geographic preferences, publicity, and cultural impact. Improvement of access to care is an important consideration as this trend continues.

Distinctive Characteristics of Thoracolumbar Junction Region Stenosis.

STUDY DESIGN: Retrospective case series and systemic literature meta-analysis. BACKGROUND: Thoracolumbar junction region stenosis produces spinal cord compression just above the conus and may manifest with symptoms that are not typical of either thoracic myelopathy or neurogenic claudication from lumbar stenosis. OBJECTIVE: As few studies describe its specific pattern of presenting symptoms and neurological deficits, this investigation was designed to improve understanding of this pathology. METHODS: A retrospective review assessed surgically treated cases of T10-L1 degenerative stenosis. Clinical outcomes were evaluated with the thoracic Japanese Orthopedic Association score. In addition, a systematic review and meta-analysis was performed in accordance with guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Of 1069 patients undergoing laminectomy at 1477 levels, 31 patients (16M/15F) were treated at T10-L1 a mean age 64.4 (SD=11.8). Patients complained of lower extremity numbness in 29/31 (94%), urinary dysfunction 11/31 (35%), and back pain 11/31 (35%). All complained about gait difficulty and objective motor deficits were detected in 24 of 31 (77%). Weakness was most often seen in foot dorsiflexion 22/31 (71%). Deep tendon reflexes were increased in 10 (32%), decreased in 11 (35%), and normal 10 (32%); the Babinski sign was present 8/31 (26%). Mean thoracic Japanese Orthopedic Association scores improved from 6.4 (SD=1.8) to 8.4 (SD=1.8) ( P <0.00001). Gait subjectively improved in 27/31 (87%) numbness improved in 26/30 (87%); but urinary function improved in only 4/11 (45%). CONCLUSIONS: Thoracolumbar junction stenosis produces distinctive neurological findings characterized by lower extremity numbness, weakness particularly in foot dorsiflexion, urinary dysfunction, and inconsistent reflex changes, a neurological pattern stemming from epiconus level compression and the myelomeres for the L5 roots. Surgery results in significant clinical improvement, with numbness and gait improving more than urinary dysfunction. Many patients with thoracolumbar junction stenosis are initially misdiagnosed as being symptomatic from lumbar stenosis, thus delaying definitive surgery.

The story of dexamethasone and how it became one of the most widely used drugs in neurosurgery.

Dexamethasone, a long-acting potent glucocorticoid, is one of the most widely used medications in neurosurgery. In this paper, the authors recount the history of dexamethasone's rise in neurosurgery and discuss its use in brain tumors in the context of emerging neuro-oncological immunotherapies. In 1958, Glen E. Arth synthesized a 16-alpha-methylated analog of cortisone (dexamethasone) for treatment of rheumatoid arthritis. Joseph Galicich, a neurosurgery resident at the time, applied the rheumatological drug to neurosurgery. He gave doses to patients who had undergone craniotomy for tumor removal and saw their paresis improve, midline shift resolve, and mortality rates decrease. He advocated for clinical trials and the drug became a mainstay in neurosurgery. As neuro-oncological treatments evolve to include immunotherapy, the immunosuppressive effects of dexamethasone are becoming an unwanted effect. The question then becomes: how does one treat the patient's symptoms if the only drug that has been used throughout history may become a detriment to their oncological treatment? Since its discovery, dexamethasone has maintained an impressive staying power in the field, acting as a standard drug for cerebral edema for more than 60 years. However, with the advent of immunotherapy, research is warranted to evaluate ways of treating symptomatic edema in the context of modern neuro-oncological therapies.

Brain Metastases Are Regulated by Immuno-inflammatory Signaling Pathways Governed by STAT3, MAPK and Tumor Suppressor p53 Status: Possible Therapeutic Targets.

BACKGROUND/AIM: Brain metastasis (BM) is a complex multi-step process involving various immune checkpoint proteins. Mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), and signal transducer and activator of transcription 3 (STAT3) are implicated in tumorigenesis and are critical upstream regulators of Programmed Death Ligand 1 (PD-L1), an immunotherapy target. Tumor suppressor p53, dysregulated in cancers, regulates STAT3 and ERK1/2 signaling. This study examined the roles of STAT3, MAPK and p53 status in BM initiation and maintenance. MATERIALS AND METHODS: Twenty-six BM, with various primary malignancies, were used (IRB-approved) to determine mutant p53 (p53mt), pSTAT3Tyr705, pERK1/2Thr202/Tyr204, and PD-L1 expression using immunohistochemistry. cDNA microarray was used for gene expression analysis. Brain-metastatic breast cancer cells (MDA-MB-231) were treated with STAT3 (NSC74859) or MAPK/ERK1/2 (U0126) inhibitors in regular or astrocytic media. ERK1/2 pathway was assessed using western blotting, and cell proliferation and migration were determined using MTT and scratch-wound assays, respectively. RESULTS: pSTAT3Tyr705 and pERK1/2Thr202/Tyr204 were expressed at tumor margins, whereas p53mt and PD-L1 were uniformly expressed, with significant overlap between expression of these proteins. Gene expression analysis identified alterations in 18 p53- and 32 STAT3- or MAPK-associated genes contributing to dysregulated immune responses and cell cycle regulation. U0126 and NSC74859 reduced pERK1/2Thr202/Tyr204 expression. Cell proliferation decreased following each treatment (p≤0.01). Migration stagnated following U0126 treatment in astrocytic media (p≤0.01). CONCLUSION: Activation of STAT3 and ERK1/2 promotes BM and provides compelling evidence for use of STAT3, ERK1/2 and p53 status as potential immunotherapeutic targets in BM.

Independent predictors of systemic inflammatory response syndrome for intramedullary nailing of femoral shaft fractures: Analysis of national inpatient sample database.

Background: The systemic inflammatory response syndrome (SIRS) is a clinical reaction that can occur due to a variety of stimuli. Reamed intramedullary femoral nailing is a common orthopedic surgery that has been shown to induce SIRS. To date, no nationwide analyses have been performed to evaluate the incidence, risk factors, and economic burdens of SIRS following intramedullary femoral nailing for femoral shaft fractures. The objective of this study is to investigate the independent predictors, incidence, post-operative, and economic burden of SIRS among patients treated with intramedullary nailing for femoral shaft fractures. Methods: We utilized the 2016-2019 National Inpatient Sample (NIS) to identify patients who underwent intramedullary femoral nailing and were diagnosed with non-infectious SIRS (NI-SIRS) based on ICD-10-CM coding. Identified patients who underwent intramedullary femoral nailing were dichotomized into SIRS and Non-SIRS groups to assess independent predictors of SIRS development, and to compare post-operative complications and costs. Results: A total of 65,240 patients with femur shaft fractures underwent IMFN, of which 665 (1.0 %) developed NI-SIRS. Patients with NI-SIRS had a higher incidence of laparotomy (OR = 13.97, p < 0.001), initial treatment with external fixation (OR = 1.845, p < 0.001), and late application of external fixation (OR = 4.884, p = 0.005). Routine discharge (OR = 0.491, p < 0.001) was less likely in patients with NI-SIRS. Length of stay (12.38 days vs 7.16 days, p < 0.001) and total charges ($278, 590 vs $145,118, p < 0.001) were both increased in patients with NI-SIRS. Conclusion: NI-SIRS is associated with increasing injury severity and post-operative complications. Those that developed NI-SIRS experienced higher healthcare resource utilization. Risk factors associated with development of NI-SIRS warrant further investigation.

A double-hit: End-stage renal disease patients suffer worse outcomes in intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) carries significant morbidity and mortality. Previous single-center retrospective analysis suggests that end-stage renal disease (ESRD) is a risk factor for severe ICH and worse outcomes. This investigation aims to examine the impact of ESRD on ICH severity, complications, and outcomes using a multicenter national database. METHODS: The International Classification of Disease, Ninth and Tenth Revision Clinical Modification codes were used to query the National Inpatient Sample for patients with ICH and ESRD between 2010 and 2019. Primary endpoints were the functional outcome, length of stay (LOS), and in-hospital mortality. Multivariate variable regression models and a propensity-score matched analysis were established to analyze patient outcomes associated with baseline patient characteristics. RESULTS: We identified 211,266 patients with ICH, and among them, 7,864 (3.77%) patients had a concurrent diagnosis of ESRD. Patients with ESRD were younger (60.85 vs. 67.64, P < 0.01) and demonstrated increased ICH severity (0.78 vs. 0.77, P < 0.01). ESRD patients experienced higher rates of sepsis (15.9% vs. 6.15%, P < 0.01), acute myocardial infarction (8.05% vs. 3.65%, P < 0.01), and cardiac arrest (5.94% vs. 2.4%, P < 0.01). In addition, ESRD predicted poor discharge disposition (odds ratio [OR]: 2.385, 95% confidence interval [CI]: 2.227-2.555, P < 0.01), longer hospital LOS (OR: 1.629, 95% CI: 1.553-1.709, P < 0.01), and in-hospital mortality (OR: 2.786, 95% CI: 2.647-2.932, P < 0.01). CONCLUSIONS: This study utilizes a multicenter database to analyze the effect of ESRD on ICH outcomes. ESRD is a significant predictor of poor functional outcomes, in-hospital mortality, and prolonged stay in the ICH population.

Intramedullary Spinal Hemorrhage in Behcet's Syndrome: A Case Report and Systematic Review.

Acute neurological manifestations in patients with Behcet's syndrome are rare yet may lead to devastating outcomes. Distinguishing primary neurological deficits from spontaneous hemorrhagic insults is of particular importance for the prognosis of patients with Behcet's syndrome. Here, we investigate the clinical characteristics, management, and outcomes of nontraumatic hemorrhagic injury in patients with Bechet's syndrome. Following the case presentation, a systematic review of the literature identified cases of spontaneous hemorrhage among patients with Behcet's syndrome. Variables of interest were collected from each article to characterize patient demographics, clinical manifestations, management, and reported outcomes. Additionally, a rare case of nontraumatic intramedullary spinal bleeding in a young male with Behcet's syndrome is presented. Including our case, we analyzed 12 cases of spontaneous bleeding associated with Behcet's syndrome in 12 articles. Patient age ranged from 16 to 71 (median = 36), with a male predominance (n = 11, 91.7%). Involvement of cardiothoracic structures (n = 3, 25%), pulmonary (n = 4, 33.3%), and gastrointestinal or genitourinary vasculature (n = 3, 25%) was most common, followed by extracranial (n = 2, 16.7%) and central nervous system vasculature (n = 1, 8.3%). Clinical presentation varied depending on which specific systems or anatomical structures were involved. Anticoagulation or antiplatelet therapy was mentioned in three cases (27.3%). Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) were noted to be elevated in six cases (54.5%). Most cases were managed surgically (n = 8, 66.7%); four cases were managed conservatively (33.3%). In our case, the patient's intramedullary bleed was allowed to dissolve without further manipulation. Of the reported outcomes, major recovery was achieved in 10 patients (83.3%), and two patients died from aneurysm or pseudoaneurysm rupture (16.7%). New-onset neurological findings in patients with Behcet's syndrome should raise suspicion for possible spontaneous hemorrhage. Our case presents the first reported instance of an abrupt onset of neurological injury secondary to intramedullary spinal cord bleed in Behcet's syndrome. A systematic review of the literature demonstrates no difference in mortality for patients managed conservatively compared to those who undergo surgical treatment.

Thecal sac ligation in the setting of thoracic spondyloptosis with complete cord transection.

Background: Traumatic spondyloptosis (TS) with complete spinal cord transection and unrepairable durotomy is particularly rare and can lead to a difficult-to-manage cerebrospinal fluid (CSF) leak. Methods: We performed a systematic review of the literature on TS and discuss the management strategies and outcomes of TS with cord transection and significant dural tear. We also report a novel case of a 26-year-old female who presented with thoracic TS with complete spinal cord transection and unrepairable durotomy with high-flow CSF leak. Results: Of 93 articles that resulted in the search query, 13 described cases of TS with complete cord transection. The approach to dural repair was only described in 8 (n = 20) of the 13 articles. The dura was not repaired in two (20%) of the cases. Ligation of the proximal end of the dural defect was done in 15 (75%) of the cases, all at the same institution. One (5%) case report describes ligation of the distal end; one (5%) case describes the repair of the dura with duraplasty; and another (5%) case describes repair using muscle graft to partially reconstruct the defect. Conclusion: Suture ligation of the thecal sac in the setting of traumatic complete spinal cord transection with significant dural disruption has been described in the international literature and is a safe and successful technique to prevent complications associated with persisting high-flow CSF leakage. To the best of our knowledge, this is the first report of thecal sac ligation of the proximal end of the defect from the United States.

Dural Closure Techniques and Cerebrospinal Fluid Leak Incidence After Resection of Primary Intradural Spinal Tumors: A Systematic Review.

STUDY DESIGN: This is a systematic review of primary intradural spinal tumors (PIDSTs) and the frequency of postoperative cerebrospinal fluid (CSF) leaks. OBJECTIVE: This study aimed to compare CSF leak rates among techniques for dural watertight closure (WTC) after the resection of PIDSTs. SUMMARY OF BACKGROUND DATA: Resection of PIDSTs may result in persistent CSF leak. This complication is associated with infection, wound dehiscence, increased length of stay, and morbidity. Dural closure techniques have been developed to decrease the CSF leak rate. METHODS: A PubMed search was performed in 2022 with these inclusion criteria: written in English, describe PIDST patients, specify the method of dural closure, report rates of CSF leak, and be published between 2015 and 2020. Articles were excluded if they had <5 patients. We used standardized toolkits to assess the risk of bias. We assessed patient baseline characteristics, tumor pathology, CSF leak rate, and dural closure techniques; analysis of variance and a 1-way Fisher exact test were used. RESULTS: A total of 4 studies (201 patients) satisfied the inclusion criteria. One study utilized artificial dura (AD) and fibrin glue to perform WTC and CSF diversion, with lumbar drainage as needed. The rate of CSF leak was different among the 4 studies (P=0.017). The study using AD with dural closure adjunct (DCA) for WTC was associated with higher CSF leak rates than those using native dura (ND) with DCA. There was no difference in CSF leak rate between ND-WTC and AD-DCA, or with any of the ND-DCA studies. CONCLUSIONS: After resection of PIDSTs, the use of autologous fat grafts with ND resulted in lower rates of CSF leak, while use of fibrin glue and AD resulted in the highest rates. These characteristics suggest that a component of hydrophobic scaffolding may be required for WTC. A limitation included articles with low levels of evidence. Continued investigation to understand mechanisms for WTC is warranted. LEVEL OF EVIDENCE: Level 3.

Incidence, Characteristics, and Outcomes of Stroke in Pediatric Patients with Celiac Disease.

(1) Background: Celiac disease (CD) can cause long-term inflammation and endothelial dysfunction and has been cited as a risk factor for acute ischemic stroke (AIS) in pediatric patients. However, the rate and outcomes of AIS in pediatric patients with CD has not been explored in a large population. Our objective is to explore the rate, severity, and outcomes of CD amongst pediatric AIS patients on a nationwide level. (2) Methods: The National Inpatient Sample (NIS) database was queried from 2016 to 2020 for pediatric patients with a principal diagnosis of AIS. Patients with a concurrent diagnosis of CD (AIS-CD) were compared to those without (AIS). Baseline demographics and comorbidities, clinical variables of severity, hospital complications, and the rates of tissue plasminogen activator (tPA) and mechanical thrombectomy were compared between the two groups. The main outcomes studied were mortality, discharge disposition, length of stay (LOS), and total hospital charges. (3) Results: Of 12,755 pediatric patients with a principal diagnosis of AIS, 75 (0.6%) had concurrent CD. There were no differences in the severity, discharge disposition, or mortality between the AIS-CD and AIS patients. Patients with AIS-CD were more likely to receive tPA at an outside hospital within 24 h of admission (p < 0.01) and more likely to undergo mechanical thrombectomy (p < 0.01) compared to the AIS patients. (4) Conclusions: CD patients made up only 0.6% of all pediatric AIS patients. No differences in the severity, mortality, or discharge disposition suggests a minimal to absent role of CD in the etiology of stroke. The CD-AIS patients were more likely to receive a tPA or undergo a mechanical thrombectomy; studies are needed to confirm the safety and efficacy of these interventions in pediatric patients.

Superior discrimination of the Risk Analysis Index compared with the 5-item modified frailty index in 30-day outcome prediction after anterior cervical discectomy and fusion.

OBJECTIVE: The objective of this paper was to compare the predictive ability of the recalibrated Risk Analysis Index (RAI-rev) with the 5-item modified frailty index-5 (mFI-5) for postoperative outcomes of anterior cervical discectomy and fusion (ACDF). METHODS: This study was performed using data of adult (age > 18 years) ACDF patients obtained from the National Surgical Quality Improvement Program database during the years 2015-2019. Multivariate modeling and receiver operating characteristic (ROC) curve analysis, including area under the curve/C-statistic calculation with the DeLong test, were performed to evaluate the comparative discriminative ability of the RAI-rev and mFI-5 for 5 postoperative outcomes. RESULTS: Both the RAI-rev and mFI-5 were independent predictors of increased postoperative mortality and morbidity in a cohort of 61,441 ACDF patients. In the ROC analysis for 30-day mortality prediction, C-statistics indicated a significantly better performance of the RAI-rev (C-statistic = 0.855, 95% CI 0.852-0.858) compared with the mFI-5 (C-statistic = 0.684, 95% CI 0.680-0.688) (p < 0.001, DeLong test). The results were similar for postoperative ACDF morbidity, Clavien-Dindo grade IV complications, nonhome discharge, and reoperation, demonstrating the superior discriminative ability of the RAI-rev compared with the mFI-5. CONCLUSIONS: The RAI-rev demonstrates superior discrimination to the mFI-5 in predicting postoperative ACDF mortality and morbidity. To the authors' knowledge, this is the first study to document frailty as an independent risk factor for postoperative mortality after ACDF. The RAI-rev has conceptual fidelity to the frailty phenotype and may be more useful than the mFI-5 in preoperative ACDF risk stratification. Prospective validation of these findings is necessary, but patients with high RAI-rev scores may benefit from knowing that they might have an increased surgical risk for ACDF morbidity and mortality.

High area deprivation index is associated with increased injury severity in pediatric burn patients.

BACKGROUND: Burn injuries play a significant role in pediatric injury-related mortality and morbidity. In this study, we aim to explore the relationship between patient demographics, socioeconomic factos and burn severity in pediatric patients. METHODS: Patients under age 14 hospitalized at Westchester Medical Center for burn injury between 2015 and 2021 were reviewed. Demographic variables including mechanism of burn, total body surface area (TBSA) involvement, surgical intervention, hospital length of stay (LOS), and LOS per TBSA burn were extracted. The Area Deprivation Index (ADI) was calculated to further assess socioeconomic factors. RESULTS: We included 399 patients under the age of 14 hospitalized for burn injuries at our institution between 2015 and 2021. The median age was 2 (IQR 1-6) years old, and 42.6% were female. High ADI (p = 0.018), Caucasian race (p = 0.001), and flame mechanism (p < 0.001) were independently associated with burn TBSA> 5%. LOS per TBSA was shorter in the Caucasian population (p = 0.022). CONCLUSION: In burn injury patients, further research is necessary to investigate modifiable risk factors in individuals of Caucasian race or lower socioeconomic status to target effective prevention campaigns.

Early tracheostomy in patients undergoing mechanical thrombectomy for acute ischemic stroke.

PURPOSE: Respiratory failure following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a known complication, and requirement of tracheostomy is associated with worse outcomes. Our objective is to evaluate characteristics associated with tracheostomy timing in AIS patients treated with MT. METHODS: The National Inpatient Sample was queried for adult patients treated with MT for AIS from 2016 to 2019. Baseline demographic characteristics, comorbidities, and inpatient outcomes were analyzed for associations in patients who received tracheostomy. Timing of early tracheostomy (ETR) was defined as placement before day 8 of hospital stay. RESULTS: Of 3505 AIS-MT patients who received tracheostomy, 915 (26.1%) underwent ETR. Patients who underwent ETR had shorter length of stay (LOS) (25.39 days vs 32.43 days, p < 0.001) and lower total hospital charges ($483,472.07 vs $612,362.86, p < 0.001). ETR did not confer a mortality benefit but was associated with less acute kidney injury (OR, 0.697; p = 0.013), pneumonia (OR, 0.449; p < 0.001), and sepsis (OR, 0.536; p = 0.002). CONCLUSION: An expected increase in complications and healthcare resource utilization is seen in AIS-MT patients receiving tracheostomy, likely reflecting the severity of patients' post-stroke neurologic injury. Among these high-risk patients, ETR was predictive of shorter LOS and fewer complications.

Disparities in anterior cervical discectomy and fusion provision and outcomes for cervical stenosis.

Background: Disparities in neurosurgical care have emerged as an area of interest when considering the impact of social determinants on access to health care. Decompression via anterior cervical discectomy and fusion (ACDF) for cervical stenosis (CS) may prevent progression towards debilitating complications that may severely compromise one's quality of life. This retrospective database analysis aims to elucidate demographic and socioeconomic trends in ACDF provision and outcomes of CS-related pathologies. Methods: The Healthcare Cost and Utilization Project National Inpatient Sample database was queried between 2016 and 2019 using International Classification of Diseases 10th edition codes for patients undergoing ACDF as a treatment for spinal cord and nerve root compression. Baseline demographics and inpatient stay measures were analyzed. Results: Patients of White race were significantly less likely to present with manifestations of CS such as myelopathy, plegia, and bowel-bladder dysfunction. Meanwhile, Black patients and Hispanic patients were significantly more likely to experience these impairments representative of the more severe stages of the degenerative spine disease process. White race conferred a lesser risk of complications such as tracheostomy, pneumonia, and acute kidney injury in comparison to non-white race. Insurance by Medicaid and Medicare conferred significant risks in terms of more advanced disease prior to intervention and negative inpatient. Patients in the highest quartile of median income consistently fared better than patients in the lowest quartile across almost every aspect ranging from degree of progression at initial presentation to incidence of complications to healthcare resource utilization. All outcomes for patients age > 65 were worse than patients who were younger at the time of the intervention. Conclusions: Significant disparities exist in the trajectory of CS and the risks associated with ACDF amongst various demographic cohorts. The differences between patient populations may be reflective of a larger additive burden for certain populations, especially when considering patients' intersectionality.

Upregulated Expression of the IL-9 Receptor on TRAF3-Deficient B Lymphocytes Confers Ig Isotype Switching Responsiveness to IL-9 in the Presence of Antigen Receptor Engagement and IL-4.

The pleiotropic cytokine IL-9 signals to target cells by binding to a heterodimeric receptor consisting of the unique subunit IL-9R and the common subunit γ-chain shared by multiple cytokines of the γ-chain family. In the current study, we found that the expression of IL-9R was strikingly upregulated in mouse naive follicular B cells genetically deficient in TNFR-associated factor 3 (TRAF3), a critical regulator of B cell survival and function. The highly upregulated IL-9R on Traf3-/- follicular B cells conferred responsiveness to IL-9, including IgM production and STAT3 phosphorylation. Interestingly, IL-9 significantly enhanced class switch recombination to IgG1 induced by BCR crosslinking plus IL-4 in Traf3-/- B cells, which was not observed in littermate control B cells. We further demonstrated that blocking the JAK-STAT3 signaling pathway abrogated the enhancing effect of IL-9 on class switch recombination to IgG1 induced by BCR crosslinking plus IL-4 in Traf3-/- B cells. Our study thus revealed, to our knowledge, a novel pathway that TRAF3 suppresses B cell activation and Ig isotype switching by inhibiting IL-9R-JAK-STAT3 signaling. Taken together, our findings provide (to our knowledge) new insights into the TRAF3-IL-9R axis in B cell function and have significant implications for the understanding and treatment of a variety of human diseases involving aberrant B cell activation such as autoimmune disorders.

Safety of vagus nerve stimulation and responsive neurostimulation used in combination for multifocal and generalized onset epilepsy in pediatric patients.

OBJECTIVE: The aim of this study was to assess the safety and efficacy of combined active responsive neurostimulation (RNS) and vagus nerve stimulation (VNS) therapies in pediatric patients with drug-resistant epilepsy. METHODS: A single-center retrospective chart review was conducted on pediatric patients implanted with the RNS System with a concomitant active VNS System (VNS+RNS) between 2015 and 2021. Patients with at least 1 month of overlapping concomitant VNS and RNS treatment were included. Patients who had an RNS device implanted after 21 years of age, those who had responsive neurostimulators implanted after their VNS was inactivated, or those in whom the VNS battery died and was not replaced before RNS System implantation were excluded. RESULTS: Seven pediatric VNS+RNS patients were identified, and their courses of treatment were evaluated. All patients tolerated concurrent VNS and RNS treatment well, no device-device interactions were identified, and no major treatment-related adverse effects were noted. The median follow-up after RNS System implantation was 1.2 years. By electroclinical criteria, all 7 patients achieved 75%-99% reductions in the frequency of disabling seizures after RNS System implantation. By patient and caregiver report, 2 patients (28.6%) had 75%-99% reductions in the frequency of their disabling seizures, 2 patients (28.6%) achieved 50%-74% reductions, 2 patients achieved 1%-24% reduction in frequency of disabling seizures, and 1 patient (14.3%) experienced a 1%-24% increase in seizure frequency. The available VNS magnet swipe data identified 2 patients with 75%-99% reductions in seizure frequency as measured by magnet swipes, one with 25%-49% reductions and the other with 1%-24% increases in seizure frequency as measured by magnet swipes. CONCLUSIONS: This study demonstrated that RNS and VNS therapies can safely be used simultaneously in pediatric patients. RNS may potentially augment the therapeutic effects of VNS treatment. Patients in whom a response to VNS has been suboptimal should still be considered for RNS therapy.

Risk factors for posttraumatic hydrocephalus after decompressive hemicraniectomy in pediatric patients with traumatic brain injury.

OBJECTIVE: Traumatic brain injuries (TBIs) play a significant role in pediatric mortality and morbidity. Decompressive hemicraniectomy (DHC) is a treatment option for severe pediatric TBI (pTBI) not amenable to medical management of intracranial pressure. Posttraumatic hydrocephalus (PTH) is a known sequela of DHC that may lead to further injury and decreased capacity for recovery if not identified and treated. The goal of this study was to characterize risk factors for PTH after DHC in patients with pTBI by using the Kids' Inpatient Database (KID). METHODS: The records collected in the KID from 2016 to 2019 were queried for patients with TBI using International Classification of Diseases, 10th Revision codes. Data defining demographics, complications, procedures, and outcomes were extracted. Multivariate regression was used to identify risk factors associated with PTH. The authors also investigated length of stay and hospital charges. RESULTS: Of 68,793 patients with pTBI, 848 (1.2%) patients underwent DHC. Prolonged mechanical ventilation (PMV) was required in 475 (56.0%) patients with pTBI undergoing DHC. Three hundred (35.4%) patients received an external ventricular drain (EVD) prior to DHC. PTH was seen in 105 (12.4%), and 50 (5.9%) received a ventriculoperitoneal shunt. DHC before hospital day 2 was negatively associated with PTH (OR 0.464, 95% CI 0.267-0.804; p = 0.006), whereas PMV (OR 2.204, 95% CI 1.344-3.615; p = 0.002) and EVD placement prior to DHC (OR 6.362, 95% CI 3.667-11.037; p < 0.001) were positively associated with PTH. PMV (OR 7.919, 95% CI 2.793-22.454; p < 0.001), TBI with subdural hematoma (OR 2.606, 95% CI 1.119-6.072; p = 0.026), and EVD placement prior to DHC (OR 4.575, 95% CI 2.253-9.291; p < 0.001) were independent predictors of ventriculoperitoneal shunt insertion. The mean length of stay and total hospital charges were significantly increased in patients with PMV and in those with PTH. CONCLUSIONS: PMV, presence of subdural hematoma, and EVD placement prior to DHC are risk factors for PTH in patients with pTBI who underwent DHC. Higher healthcare resource utilization was seen in patients with PTH. Identifying risk factors for PTH may improve early diagnosis and efficient resource utilization.

Frailty and outcomes in lacunar stroke.

BACKGROUND: Lacunar strokes (LS) are ischemic strokes of the small perforating arteries of deep gray and white matter of the brain. Frailty has been associated with greater mortality and attenuated response to treatment after stroke. However, the effect of frailty on patients with LS has not been previously described. OBJECTIVE: To analyze the association between frailty and outcomes in LS. METHODS: Patients with LS were selected from the National Inpatient Sample (NIS) 2016-2019 using the International Classification of Disease, 10th edition (ICD-10) diagnosis codes. The 11-point modified frailty scale (mFI-11) was used to group patients into severely frail and non-severely frail cohorts. Demographics, clinical characteristics, and complications were defined. Health care resource utilization (HRU) was evaluated by comparing total hospital charges and length of stay (LOS). Other outcomes studied were discharge disposition and inpatient death. RESULTS: Of 48,980 patients with LS, 10,830 (22.1%) were severely frail. Severely frail patients were more likely to be older, have comorbidities, and pertain to lower socioeconomic status categories. Severely frail patients with LS had worse clinical stroke severity and increased rates of complications such as urinary tract infection (UTI) and pneumonia (PNA). Additionally, severe frailty was associated with unfavorable outcomes and increased HRU. CONCLUSION: Severe frailty in LS patients is associated with higher rates of complications and increased HRU. Risk stratification based on frailty may allow for individualized treatments to help mitigate adverse outcomes in the setting of LS.