Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review.

INTRODUCTION: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes. METHODS: We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected. RESULTS: Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0-2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively. CONCLUSIONS: Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.

Radiographic alignment outcomes after the single-position prone transpsoas approach: a multi-institutional retrospective review of 363 cases.

OBJECTIVE: The aim of this paper was to evaluate the changes in radiographic spinopelvic parameters in a large cohort of patients undergoing the prone transpsoas approach to the lumbar spine. METHODS: A multicenter retrospective observational cohort study was performed for all patients who underwent lateral lumber interbody fusion via the single-position prone transpsoas (PTP) approach. Spinopelvic parameters from preoperative and first upright postoperative radiographs were collected, including lumbar lordosis (LL), pelvic incidence (PI), and pelvic tilt (PT). Functional indices (visual analog scale score), and patient-reported outcomes (Oswestry Disability Index) were also recorded from pre- and postoperative appointments. RESULTS: Of the 363 patients who successfully underwent the procedure, LL after fusion was 50.0° compared with 45.6° preoperatively (p < 0.001). The pelvic incidence-lumbar lordosis mismatch (PI-LL) was 10.5° preoperatively versus 2.9° postoperatively (p < 0.001). PT did not significantly change (0.2° ± 10.7°, p > 0.05). CONCLUSIONS: The PTP approach allows significant gain in lordotic augmentation, which was associated with good functional results at follow-up.

Macrocyclic Oxindole Peptide Epoxyketones-A Comparative Study of Macrocyclic Inhibitors of the 20S Proteasome.

Peptide macrocycles have recently gained attention as protease inhibitors due to their metabolic stability and specificity. However, the development of peptide macrocycles with improved binding potency has so far been challenging. Here we present macrocyclic peptides derived from the clinically applied proteasome inhibitor carfilzomib with an oxindole group that mimics the natural product TMC-95A. Fluorescence kinetic activity assays reveal a high potency of the oxindole group (IC50 = 0.19 µM) compared with agents lacking this motif. X-ray structures of the ligands with the ß5-subunit of the yeast 20S proteasome illustrate that the installed macrocycle forces strong hydrogen bonding of the oxindole group with ß5-Gly23NH. Thus, the binding of our designed oxindole epoxyketones is entropically and enthalpically favored in contrast to more flexible proteasome inhibitors such as carfilzomib.

Characterizing the frequency, morbidity, and types of traumatic brain injuries after the Mexico-San Diego border wall extension: a retrospective cohort review.

OBJECTIVE: The aim of this study was to investigate the impact of the US-Mexico border wall height extension on traumatic brain injuries (TBIs) and related costs. METHODS: In this retrospective cohort study, patients who presented to the UC San Diego Health Trauma Center for injuries from falling at the border wall between 2016 and 2021 were considered. Patients in the pre-height extension period (January 2016-May 2018) were compared with those in the post-height extension period (January 2020-December 2021). Demographic characteristics, clinical data, and hospital charges were analyzed. RESULTS: A total of 383 patients were identified: 51 (0 TBIs, 68.6% male) in the pre-height extension cohort and 332 (14 TBIs, 77.1% male) in the post-height extension cohort, with mean ages of 33.5 and 31.5 years, respectively. There was an increase in the average number of TBIs per month (0.0 to 0.34) and operative TBIs per month (0.0 to 0.12). TBIs were associated with increased Injury Severity Score (8.8 vs 24.2, p < 0.001), median (IQR) hospital length of stay (5.0 [2-11] vs 8.5 [4-45] days, p = 0.03), and median (IQR) hospital charges ($163,490 [$86,369-$277,918] vs $243,658 [$136,769-$1,127,920], p = 0.04). TBIs were normalized for changing migration rates on the basis of Customs and Border Protection apprehensions. CONCLUSIONS: This heightened risk of intracranial injury among vulnerable immigrant populations poses ethical and economic concerns to be addressed regarding border wall infrastructure.

Novel Association of Blunt Cerebrovascular Injuries with the San Diego-Mexico Border Wall Height Extension.

BACKGROUND: The San Diego-Mexico border wall height extension is associated with increased traumatic injuries and related costs after wall falls. We report previous trends and a neurological injury type not previously associated with border falls: blunt cerebrovascular injuries (BCVIs). METHODS: In this retrospective cohort study, patients who presented to the UC San Diego Health Trauma Center for injuries from border wall falls from 2016 to 2021 were considered. Patients were included if they were admitted before (January 2016 to May 2018) or after (January 2020 to December 2021) the height extension period. Patient demographics, clinical data, and hospital stay data were compared. RESULTS: We identified 383 patients, 51 (68.6% male; mean age, 33.5 years) in the pre-height extension cohort and 332 (77.1% male; mean age, 31.5 years) in the post-height extension cohort. There were 0 and 5 BCVIs in the pre- and post-height extension groups, respectively. BCVIs were associated with increased injury severity scores (9.16 vs. 31.33; P < 0.001), longer intensive care unit lengths of stay (median, 0 days; [interquartile range (IQR), 0-3 days]; vs. median, 5 days [IQR, 2-21 days]; P = 0.022), and increased total hospital charges (median, $163,490 [IQR, $86,578-$282,036]; vs. median, $835,260 [IQR, $171,049-$1,933,996]; P = 0.048). Poisson modeling found BCVI admissions were 0.21 (95% confidence interval, 0.07-0.41; P = 0.042) per month higher after the height extension. CONCLUSIONS: We review the injuries correlating with the border wall extension and reveal an association with rare, potentially devastating BCVIs that were not seen before the border wall modifications. These BCVIs and associated morbidity shed light on the trauma increasingly found at the southern U.S. border, which could be informative for future infrastructure policy decisions.

The impact of the Mexico-San Diego border wall extension on spine injuries: a retrospective cohort review.

BACKGROUND: The recent San Diego-Mexico border wall height extension has resulted in an increased injury risk for unauthorized immigrants falling from greater heights. However, the effects of the border wall extension on frequency and morbidity of spinal injuries and related economic costs have yet to be highlighted. METHODS: We retrospectively compared two cohorts who presented to the UC San Diego Health Trauma Center for border wall falls: pre-height extension (12 patients; January 2016-May 2018), and post-height extension (102 patients; January 2020-December 2021). Patients presented during border wall construction (June 2018-December 2019) were excluded. Demographics, clinical data and hospital costs were collected. Spinal injuries were normalized using Customs and Border Protection apprehensions. Costs were adjusted for inflation using the 2021 medical care price index. RESULTS: The increase in spine injuries per month (0.8-4.25) and operative spine injuries per month (0.3- 1.7) was statistically significant (P < 0.001). Increase in median length of stay from 6 [interquartile range (IQR) 2-7] to 9 days (IQR 6-13) was statistically significant (P = 0.006). Median total hospital charges increased from $174 660 to $294 421 and was also significant (P < 0.001). CONCLUSION: The data support that the recent San Diego-Mexico border wall extension is correlated with more frequent, severe and costly spinal injuries. This current infrastructure should be re-evaluated as border-related injuries represent a humanitarian and public health crisis.

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.

Bony fixation in the era of spinal robotics: A systematic review and meta-analysis.

BACKGROUND: Accurate spinal screw placement in spinal instrumentation is of utmost importance to avoid injury to surrounding neurovascular structures. This study was performed to investigate differences in accuracy, operating room time, length of stay, and operative blood loss across studies involving all types of spinal fixation. METHODS: PubMed, EMBASE, and Scopus were systematically queried to identify articles that fit the inclusion and exclusion criteria. Meta-analysis was performed using R software, and odds ratios and 95% CIs were calculated. RESULTS: Sixty-nine articles were included in qualitative synthesis, and 35 studies in the meta-analysis, for a total of 8,174 robotically placed screws in 1,492 patients compared to 9,791 conventionally placed screws in 1,638 patients. A total of 9 screw trajectories were studied in the literature, although only 4 had enough evidence to be included in the meta-analysis. Robotic screw placement was more accurate than conventional screw placement (OR 2.24; 95% CI, 1.71-2.94). Robotic placement was not associated with significantly different postoperative length of stay (SMD -0.32; 95% CI, -1.20, 0.51), operative blood loss (SMD -0.25; 95% CI, -0.79, 0.19), or operative duration (SMD 0.08; 95% CI -1.00, 1.39). A total of 8 robotic platforms were found in the literature with accuracy rates above 93%. CONCLUSION: Robotic spinal fixation is associated with increased screw placement accuracy and similar operative blood loss, length of stay, and operative duration. These findings support the safety and cost-effectiveness of robotic spinal surgery across the spectrum of robotic systems and screw types.