Efficacy of deep brain stimulation for the treatment of anorexia nervosa: a systematic review and network meta-analysis of patient-level data.

OBJECTIVE: Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI). METHODS: A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews. RESULTS: Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD -1.51; 95% CI -2.39, -0.62). Similarly, at 9-12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD -1.18; 95% CI -2.21, -0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9-12 months (P-scores 0.9449 and 0.9771, respectively). CONCLUSIONS: Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.

Factors influencing geographic gender disparity in neurosurgery: a nationwide geospatial clustering analysis.

OBJECTIVE: Women neurosurgeons (WNs) continue to remain a minority in the specialty despite significant initiatives to increase their representation. One domain less explored is the regional distribution of WNs, facilitated by the hiring practices of neurosurgical departments across the US. In this analysis, the authors coupled the stated practice location of WNs with regional geospatial data to identify hot spots and cold spots of prevalence and examined regional predictors of increases and decreases in WNs over time. METHODS: The authors examined the National Provider Identifier (NPI) numbers of all neurosurgeons obtained via the National Plan and Provider Enumeration System (NPPES), identifying the percentage of WNs in each county for which data were appended with data from the US Census Bureau. Change in WN rates was identified by calculating a regression slope for all years included (2015-2022). Hot spots and cold spots of WNs were identified through Moran's clustering analysis. Population and surgeon features were compared for hot spots and cold spots. RESULTS: WNs constituted 10.73% of all currently active neurosurgical NPIs, which has increased from 2015 (8.81%). Three hot spots were found-including the Middle Atlantic and Pacific divisions-that contrasted with scattered cold spots throughout the East Central regions that included Memphis as a major city. Although relatively rapidly growing, hot spots had significant gender inequality, with a median WN percentage of 11.38% and a median of 0.61 WNs added to each respective county per year. CONCLUSIONS: The authors analyzed the prevalence of WNs by using aggregated data from the NPPES and US Census Bureau. The authors also show regional hot spots of WNs and that the establishment of WNs in a region is a predictor of additional WNs entering the region. These data suggest that female neurosurgical mentorship and representation may be a major driver of acceptance and further gender diversity in a given region.

Diagnostic predictive values for sport-related concussions: a systematic review and diagnostic meta-analysis.

OBJECTIVE: Sport-related concussions (SRCs) can cause significant neurological symptoms, and approximately 10%-15% of athletes with SRC experience a prolonged recovery. Given the lack of visible injury on brain imaging and their varied presentations, concussions can be difficult to diagnose. A variety of tests and examination methods have been used to elicit a concussion diagnosis; however, the sensitivity and specificity of these tests are variable. The authors performed a systematic review and meta-analysis to evaluate the sensitivity and specificity of standardized tests and visible signs like balance and vision changes in the diagnosis of SRC. METHODS: A PRISMA-adherent systematic review of concussion diagnostic examinations was performed using the PubMed, MEDLINE, Scopus, Cochrane, Web of Science, and Google Scholar databases on December 1, 2022. Search terms included "concussion," "traumatic brain injury," "diagnosis," "sensitivity," and "specificity." Each method of examination was categorized into larger group-based symptomatologic presentations or standardized tools. The primary outcome was the diagnosis of concussion. Pooled specificity and sensitivity for each method were calculated using a meta-analysis of proportion and were hierarchically ranked using P-scores calculated from a diagnostic frequentist network meta-analysis. RESULTS: Thirty full-length articles were identified for inclusion, 13 of which evaluated grouped symptomology examinations (balance and overall clinical presentation) and 17 of which evaluated established formalized tools (ImPACT, King-Devick [K-D] Test, Sport Concussion Assessment Tool [SCAT]). The pooled specificity of the examination methods differed minimally (0.8-0.85), whereas the sensitivity varied to a larger degree (0.5-0.88). In a random effects model, the SCAT had the greatest diagnostic yield (diagnostic OR 31.65, 95% CI 11.06-90.57). Additionally, P-score hierarchical ranking revealed SCAT as having the greatest diagnostic utility (p = 0.9733), followed sequentially by ImPACT, clinical presentation, K-D, and balance. CONCLUSIONS: In deciphering which concussion symptom-focused examinations and standardized tools are most accurate in making a concussion diagnosis, the authors found that the SCAT examination has the greatest diagnostic yield, followed by ImPACT, clinical presentation, and K-D, which have comparable value for diagnosis. Given the indirect nature of this analysis, however, further comparative studies are needed to validate the findings.

Traumatic Brain Injury Mortality and Correlates in Low- and Middle-Income Countries: A Meta-Epidemiological Study.

BACKGROUND: It is estimated that up to 69 million people per year experience traumatic brain injury (TBI) with the highest prevalence found in low- and middle-income countries (LMICs). A paucity of data suggests that the mortality rate after severe TBI is twice as high in LMICs than in high-income countries. OBJECTIVE: To analyze TBI mortality in LMICs and to evaluate what country-based socioeconomic and demographic parameters influence TBI outcomes. METHODS: Four databases were searched for the period January 1, 2002, to January 1, 2022, for studies describing TBI outcomes in LMICs. Multivariable analysis was performed using multivariable linear regression, with the outcome as the pooled mortality by country and the covariates as the adjusted parameters. RESULTS: Our search yielded 14 376 records of which 101 were included in the final analysis, totaling 59 197 patients and representing 31 LMICs. The pooled TBI-related mortality was 16.7% (95% CI: 13.7%-20.3%) without significant differences comparing pediatrics vs adults. Pooled severe TBI-related mortality was significantly higher than mild. Multivariable analysis showed a significant association between TBI-related mortality and median income ( P = .04), population percentage below poverty line ( P = .02), primary school enrollment ( P = .01), and poverty head ratio ( P = .04). CONCLUSION: TBI-related mortality in LMICs is 3-fold to 4-fold higher than that reported in high-income countries. Within LMICs, parameters associated with poorer outcomes after TBI include factors recognized as social determinants of health. Addressing social determinants of health in LMICs might expedite the quest to close the care delivery gap after TBI.

"Footprint-free" human induced pluripotent stem cell-derived astrocytes for in vivo cell-based therapy.

The generation of human induced pluripotent stem cells (hiPSC) from somatic cells has enabled the possibility to provide patient-specific hiPSC for cell-based therapy, drug discovery, and other translational applications. Two major obstacles in using hiPSC for clinical application reside in the risk of genomic modification when they are derived with viral transgenes and risk of teratoma formation if undifferentiated cells are engrafted. In this study, we report the generation of "footprint-free" hiPSC-derived astrocytes. These are efficiently generated, have anatomical and physiological characteristics of fully differentiated astrocytes, maintain homing characteristics typical of stem cells, and do not give rise to teratomas when engrafted in the brain. Astrocytes can be obtained in sufficient numbers, aliquoted, frozen, thawed, and used when needed. Our results show the feasibility of differentiating astrocytes from "footprint-free" iPSC. These are suitable for clinical cell-based therapies as they can be induced from patients' specific cells, do not require viral vectors, and are fully differentiated. "Footprint-free" hiPSC-derived astrocytes represent a new potential source for therapeutic use for cell-based therapy, including treatment of high-grade human gliomas, and drug discovery.