Citations

OBJECTIVE Antifibrinolytics, such as tranexamic acid (TXA), have been shown to decrease intraoperative blood loss across multiple surgical disciplines. However, they carry the theoretical risk of thromboembolic events secondary to induced hypercoagulability. Therefore, the aim of this study was to systematically review the available literature and perform a meta-analysis on the use of TXA in meningioma resection to assess thromboembolic risks. METHODS The PubMed, Web of Science, and Google Scholar databases were reviewed for all randomized controlled trials presenting primary data on TXA use during resection of intracranial meningiomas. Data were gathered on operative duration, venous thromboembolic complications, deep venous thrombosis, use of allogeneic blood transfusion, estimated blood loss (EBL), and postoperative hemoglobin. Patients who received TXA were compared with controls who did not receive TXA intraoperatively using random-effects models. RESULTS A total of 508 unique articles were identified, of which 493 underwent full-text review. Ultimately, 6 studies with 381 total patients (190 receiving TXA) were included in the final analysis. All 6 trials were randomized, blinded, and placebo controlled with a TXA administration rate of a 20-mg/kg load followed by a 1-mg/kg/hr infusion. All studies were performed in lower-middle-income countries. There were no reported instances of venous thromboembolism (VTE) in the TXA and non-TXA cohorts. Patients receiving TXA exhibited fewer allogeneic transfusions (21.5% vs 41.6% [OR 0.26, 95% CI 0.09–0.77], p = 0.02) and lower EBL (MD −282.48 mL [95% CI −367.77 to −197.20 mL], p < 0.001) compared with patients who did not receive TXA, and they also had lower rates of perioperative complications (10.7% vs 19.9% [OR 0.47, 95% CI 0.2–0.95], p = 0.04). CONCLUSIONS Current literature suggests that TXA is not associated with increased risk for VTE when administered during resection of intracranial meningioma. TXA appears to decrease intraoperative blood loss and allogeneic transfusion requirements during meningioma resection and thus may improve the safety of surgical management of this pathology.

Importance Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR ( NCT01737398 ; March 2013–November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo (“placebo”) group. Interventions Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main Outcomes and Measures Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, –22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, –4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was −81.7% with eplontersen and −11.2% with placebo (difference, −70.4% [95% CI, −75.2% to −65.7%]; P &amp;lt; .001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, −24.8 [95% CI, −31.0 to −18.6; P &amp;lt; .001) and for Norfolk QoL-DN (−5.5 vs 14.2; difference, −19.7 [95% CI, −25.6 to −13.8]; P &amp;lt; .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and Relevance In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial Registration ClinicalTrials.gov Identifier: NCT04136184 ; EU Clinical Trials Register: EudraCT 2019-001698-10

Context.— Respiratory infections complicate lung transplantation and increase the risk of allograft dysfunction. Allograft lungs may have different susceptibilities to infection than native lungs, potentially leading to different disease severity in lungs of single lung transplant recipients (SLTRs). Objective.— To study whether infections affect allograft and native lungs differently in SLTRs but similarly in double LTRs (DLTRs). Design.— Using an institutional database of LTRs, medical records were searched, chest computed tomography studies were systematically reviewed, and histopathologic features were recorded per lung lobe and graded semiquantitatively. A multilobar-histopathology score (MLHS) including histopathologic data from each lung and a bilateral ratio (MLHSratio) comparing histopathologies between both lungs were calculated in SLTRs and compared to DLTRs. Results.— Six SLTRs died of infection involving the lungs. All allografts showed multifocal histopathologic evidence of infection, but at least 1 lobe of the native lung was uninvolved. In 4 of 5 DLTRs, histopathologic evidence of infection was seen in all lung lobes. On computed tomography, multifocal ground-glass and/or nodular opacities were found in a bilateral distribution in all DLTRs but in only 2 of 6 SLTRs. In SLTRs, the MLHSAllograft was higher than MLHSNative (P = .02). The MLHSratio values of SLTR and DLTR were significantly different (P &lt; .001). Conclusions.— Allograft and native lungs appear to harbor different susceptibilities to infections. The results are important for the management of LTRs.

Abstract Introduction The American Association of Neurological Surgeons (AANS), North American Skull Base Society (NASBS), American Rhinologic Society (ARS), and American Neurotology Society (ANS) fellowship directories are important information repositories for skull base surgical fellowship programs. However, there is limited research on the amount and depth of information available through these resources. The objective of the present study is to assess Web site accessibility and information availability for individual fellowship programs listed within the AANS, NASBS, ARS, and ANS fellowship directories. Methods Lists of all accredited skull base surgical programs were obtained from the AANS and NASBS fellowship directories. Duplications in listed programs were removed, and systematic queries via an online search engine were conducted to identify fellowship Web sites. From each available Web site, information pertaining to 24 different variables was collected and organized into two categories—recruitment and education. Differences in the availability of information on recruitment and education were then compared across Web sites and contextualized relative to other surgical specialties. Results After excluding duplicates, 113 fellowship programs were identified, of which 99 (87.6%) had accessible Web sites. Of the 48 listed by the NASBS, direct Web site links were available for 33 (68.8%), email contacts were accessible for 32 (66.7%), and phone numbers were listed for 6 (12.5%). Of the 39 programs listed by the AANS, none included Web site links, 38 (97.4%) provided an email contact, and 39 (100%) listed a departmental contact telephone number. All 28 (100%) programs listed by the ANS provided a phone and email contact in addition to a Web site link to each institutional Web site. Of the 33 programs listed by the ARS, 29 (88%) had a departmental contact telephone number, 31 (94%) had an email contact available, and 4 (12%) had a program Web site link directly available from the database Web site. Of the 99 total programs, fellowship Web sites displayed an average of 5.46 (42.0%) of the 13 recruitment features and 4.80 (42.6%) of the 11 education features. Programs in the geographic Northeast were significantly less likely to present information pertaining to recruitment (p = 0.023). Furthermore, programs in geographic Northeast and West were significantly less likely to present information focused on surgical training and/or education (p = 0.006). Conclusion Although many skull base fellowship programs have maintained comprehensive program Web sites, certain critical aspects remain deficient, and some programs provide little to no information. Providing more detailed information about programs can prove mutually beneficial for fellowship program directors and candidates.

Abstract Background Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. Methods We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). Results Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, −14%; 95% CI, −19% to −8%; P &lt; .001; I 2 = 0%; relative risk, 0.58; 95% CI, .37–.92, P = .02, I 2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. Conclusions Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity—findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.

Study Design: Systematic review and meta-analysis. Objective: To perform a systematic review of the clinical symptoms, radiographic findings, and outcomes after spinal decompression in B-cell lymphoma. Summary of Background Data: B-cell lymphoma is a potential cause of spinal cord compression that presents ambiguously with nonspecific symptoms and variable imaging findings. Surgical decompression is a mainstay for both diagnosis and management, especially in patients with acute neurological deficits; however, the efficacy of surgical intervention compared with nonoperative management is still unclear. Methods: The databases of Medline, PubMed, and the Cochrane Database of Systemic Reviews were queried for all articles reporting spinal B-cell lymphoma. Data on presenting symptoms, treatments, survival outcomes, and histologic markers were extracted. Using the R software “survival” package, we generated bivariate and multivariate Cox survival regression models and Kaplan-Meier curves. Results: In total, 65 studies were included with 72 patients diagnosed with spinal B-cell lymphoma. The mean age was 56.22 (interquartile range: 45.00–70.25) with 68% of patients being males and 4.2% of patients being immunocompromised. Back pain was the most common symptom (74%), whereas B symptoms and cauda equina symptoms were present in 6% and 29%, respectively. The average duration of symptoms before presentation was 3.81 months (interquartile range: 0.45–3.25). The most common location was the thoracic spine (53%), with most lesions being hyperintense (28%) on T2 magnetic resonance imaging. Surgical resection was performed in 83% of patients. Symptoms improved in 91% of patients after surgery and in 80% of patients treated nonoperatively. For all 72 patients, the overall survival at 1 and 5 years was 85% (95% CI: 0.749–0.953; n = 72) and 66% (95% CI: 0.512–0.847; n = 72), respectively. Conclusion: Although surgery is usually offered in patients with acute spinal cord compression from B-cell lymphoma, chemotherapy and radiation alone offer a hopeful alternative to achieve symptomatic relief, particularly in patients who are unable to undergo surgery.

OBJECTIVE Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to guide diagnostic localization of imaging-negative adrenocorticotropic hormone (ACTH)–secreting pituitary microadenomas. However, the efficacy of IPSS has been suboptimal at accurately lateralizing the adenoma, reducing surgical cure rates and leading to unintended pituitary dysfunction due to the added exploration. One rationale for the occasional imprecision is the existence of additional petrosal sinus collateral channels that connect the IPS bilaterally, which may lead to false localization results during sampling. The aim of this study was to explore a potential connection between normal anatomical variation in the angioarchitecture of the IPSs and the ACTH results obtained in subsequent IPSS tests. METHODS A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPSS for radiographically equivocal pituitary microadenomas. Cases were reviewed for tumor laterality noted on either operative or pathology reports, as well as the presence of angiographic evidence of cross-filling between the sinuses. In addition, ACTH levels from the right and left IPSs were documented at baseline and at 2, 5, and 10 minutes after corticotropin-releasing hormone (CRH) administration. A ratio of the change in ACTH levels measured at the time of maximal response (10 minutes) versus the levels measured at the initial response (2 minutes) was computed for each patient and compared between patients by their angiographic cross-filling status. RESULTS There were 41 patients with a histopathologically confirmed right- or left-sided ACTH-secreting pituitary microadenoma who underwent preoperative IPSS. Among these patients, 28 (68%) showed angiographic evidence of cross-filling between the IPSs, and 13 showed no cross-filling. On average, ACTH levels increased by a factor of 3.91 ± 0.77 in the contralateral IPS in patients with angiographic cross-filling, compared with a factor increase of only 1.80 ± 0.27 in patients without cross-filling (p = 0.014). In comparison, ACTH levels increased by a factor of 2.01 ± 0.57 in the ipsilateral IPS in patients with cross-filling, and by 8.78 ± 7.30 in those without cross-filling (p = 0.373). CONCLUSIONS The presence of angiographic cross-filling, suggestive of a greater degree of vascular channel networking between the right and left IPS, is a significant factor influencing the measured rates of change of ACTH in IPSS and may impact the specificity of this test to accurately determine microadenoma laterality in the preoperative setting.

Abstract Optic pathway gliomas (OPG) are generally low-grade lesions arising from the astrocytes of the visual pathway, most commonly of the optic nerves and chiasm. Uncertainty remains regarding the optimal management of this patient population. We sought to leverage population-level data from the Surveillance, Epidemiology, and End Results program database to develop a predictive calculator for overall survival (OS) amongst pediatric patients with OPG. A total of 1,052 patients who had been diagnosed with OPG were included. Multivariate cox proportional hazard model demonstrated patients of “other” race (hazard ratio [HR]=4.109, 95% confidence interval [CI] 1.076-15.694, p=0.039) exhibited a decreased overall survival, while patients with a median household income ≥$55,000 (HR=0.172, 95% CI 0.065-0.457, &lt;0.001) and those who underwent subtotal resection (HR=3.549, 95% CI 1.092-13.364, p=0.047) had a higher overall survival rate. An online, interactive survival prediction tool (https://spine.shinyapps.io/optic_glioma/) was created to estimate 5-, 10-, and 15-year overall survival probability as well as median survival months. C-index was 0.722 (95% CI 0.642-0.776) for the training set and 0.745 (95% CI 0.661-0.790) for the validation set. Good concordance between the predicted probability and the actual probability of the dataset was also observed. This calculator may serve as a useful clinical tool during patient counseling. Further investigations aimed at developing calculators of visual acuity preservation and progression-free survival are merited; progress toward this end will benefit from continued multicenter collaborations.