Pleomorphic Xanthoastrocytoma: Multi-Institutional Evaluation of Stereotactic Radiosurgery.

BACKGROUND AND OBJECTIVES: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA. METHODS: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used. RESULTS: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS. CONCLUSION: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.

Pharmaceutical Modulation of Intracranial Aneurysm Development and Rupture.

Management of intracranial aneurysms (IAs) is determined by patient age, risk of rupture, and comorbid conditions. While endovascular and microsurgical interventions offer solutions to mitigate the risk of rupture, pharmacological management strategies may complement these approaches or serve as alternatives in appropriate cases. The pathophysiology of IAs allows for the targeting of inflammation to prevent the development and rupture of IAs. The aim of this review is to provide an updated summary of different pharmaceutical management strategies for IAs. Acetylsalicylic acid and renin-angiotensin-aldosterone system (RAAS) inhibitor antihypertensives have some evidence supporting their protective effect. Studies of selective cyclooxygenase-2 (COX-2) inhibitors, statins, ADP inhibitors, and other metabolism-affecting drugs have demonstrated inconclusive findings regarding their association with aneurysm growth or rupture. In this manuscript, we highlight the evidence supporting each drug's effectiveness.

Laparoscopy and thoracoscopy in small animal surgery: A 2020 survey of small animal diplomate and resident veterinary surgeons.

OBJECTIVE: To document the utilization and training of laparoscopic and thoracoscopic minimally invasive surgery (MIS) techniques within the American, European, Australian and New Zealand Colleges of Small Animal Veterinary Surgeons (ACVS, ECVS, and ANZCVS) in 2020. STUDY DESIGN: Observational study. SAMPLE POPULATION: Diplomates and residents of the ACVS, ECVS, and FANZCVS. METHODS: An electronic survey was sent using veterinary list servers. Questions were organized into categories evaluating (1) the demographics of the study population and the caseload, (2) comfort level with specific procedures, (3) motivating factors and limitations, and (4) surgical training and the role of the governing bodies. RESULTS: Respondents included 111 practicing surgeons and 28 residents. Respondents' soft-tissue MIS caseloads had increased since they first started performing MIS; however, most respondents were only comfortable performing basic laparoscopy. Over half of the respondents agreed on the patient benefits and high standard of care provided by MIS. Perceived adequate soft-tissue training in MIS during residency was strongly associated with perceived proficiency at the time of survey response. Most respondents agreed that the specialty colleges should take a more active role in developing standards for soft-tissue MIS, with residents agreeing that a required standardized course would be beneficial. CONCLUSION: Soft-tissue MIS is widely performed by diplomates and residents. Perceived adequate soft-tissue MIS training was strongly associated with perceived proficiency. CLINICAL SIGNIFICANCE: There is substantial underutilization of advanced MIS techniques in veterinary specialty surgical practice, which might be improved by a stronger focus on MIS training during residency.

Gamma knife radiosurgery for clival metastasis: case series and systematic review.

PURPOSE: Clival metastatic cancer is rare and has limited literature to guide management. We describe management of clival metastasis with Gamma Knife radiosurgery (GKRS). We augment our findings with a systematic review of all forms of radiation therapy for clival metastasis. METHODS: Records of 14 patients with clival metastasis who underwent GKRS at the University of Pittsburgh Medical Center from 2002 to 2023 were reviewed. Treatment parameters and clinical outcomes were assessed. A systematic review was conducted using evidence-based guidelines. RESULTS: The average age was 61 years with male predominance (n = 10) and average follow-up of 12.4 months. The most common primary cancers were prostate (n = 3) and lung (n = 3). The average time from cancer diagnosis to clival metastasis was 34 months. The most common presenting symptoms were headache (n = 9) and diplopia (n = 7). Five patients presented with abducens nerve palsies, and two presented with oculomotor nerve palsies. The median tumor volume was 9.3 cc, and the median margin dose was 15 Gy. Eleven patients achieved tumor control after one procedure, and three with progression obtained tumor control after repeat GKRS. One patient recovered abducens nerve function. The median survival from cancer diagnosis and GKRS were 49.7 and 15.3 months, respectively. The cause of death was progression of systemic cancer in six patients, clival metastasis in one, and unknown in four. The systematic review included 31 studies with heterogeneous descriptions of treatment and outcomes. CONCLUSION: Clival metastasis is rare and associated with poor prognosis. GKRS is a safe, effective treatment for clival metastasis.

Atlantoaxial facet fixation using cervical facet cage: technical case report and review of the literature.

In 1994, the use of interfacet spacer placement was for joint distraction, reduction, and fusion to supplement atlantoaxial or occipitocervical fixation. Here, we present a unique case of bilateral atlantoaxial interfacet fixation using cervical facet cages (CFC) in a pediatric patient with basilar invagination. In addition, we review the literature on atlantoaxial facet fixation. We present a 12-year-old boy with Wiedemann-Steiner syndrome who presented with multiple episodes of sudden neck jerking, described as in response to a sensation of being shocked, and guarding against neck motion, found to have basilar invagination with cervicomedullary compression. He underwent an occiput to C3 fusion with C1-C2 CFC fixation. We also conducted a literature review identifying all publications using the following keywords: "C1" AND "C2" OR "atlantoaxial" AND "facet spacer" OR "DTRAX." The patient demonstrated postoperative radiographic reduction of his basilar invagination from 6.4 to 4.1 mm of superior displacement above the McRae line. There was a 4.5 mm decrease in the atlantodental interval secondary to decreased dens retroflexion. His postoperative course was complicated by worsening of his existing dysphagia but was otherwise unremarkable. His neck symptoms completely resolved. We illustrate the safe use of CFC for atlantoaxial facet distraction, reduction, and instrumented fixation in a pediatric patient with basilar invagination. Review of the literature demonstrates that numerous materials can be safely placed as a C1-C2 interfacet spacer including bone grafts, titanium spacers, and anterior cervical discectomy and fusion cages. We argue that CFC may be included in this arsenal even in pediatric patients.

Single institution series describing external ventricular drain (EVD) placement and short- and long-term complications related to placement accuracy.

Background: The placement of an external ventricular drain (EVD) for the treatment of acute hydrocephalus is one of the most common life-saving procedures that neurosurgeons perform worldwide. There are many well-known complications associated with EVD placement, including tract hemorrhages, intra-parenchymal and subdural hemorrhages, infection, and catheter misplacement. Given the variety of complications associated with EVD placement and the inconsistent findings on the relationship of accuracy to complications, the present study reviewed short- and long-term complications related to EVD placement at our institution. Methods: A retrospective review was conducted for all consecutive patients who underwent bedside EVD placement for any indication between December 2020 and December 2021. Collected variables included demographic information, etiology of disease state, pre-and post-operative head computed tomography measurements, and post-procedural metrics (immediate and delayed complications). Results: A total of 124 patients qualified for inclusion in our study. EVDs that were non-functioning/exchanged were not significantly related to age, accuracy, ventriculomegaly, sex, disposition, laterality, type of EVD used, intraventricular hemorrhage (IVH), etiology, or Kakarla Grade (KG) (all P > 0.17). The need for a second EVD was similarly not related to age, accuracy, ventriculomegaly, sex, disposition, location, laterality, type of EVD used, IVH, etiology, or KG (all P > 0.130). Patients who died, however, were significantly more likely to have a second contralateral EVD placed (18.2% vs. 4.9% P = 0.029). We also found that left-sided EVDs were significantly more likely to fail within seven days of placement (29.4% vs 13.3%, P = 0.037; relative risk (RR) 1.93, 95% confidence interval: 1.09-3.43), unrelated to age, sex, etiology, type of EVD, IVH, location of the procedure, or accuracy (all P > 0.07). This remained significant when using a binary logistic regression to control for ventriculomegaly, accuracy, mortality, age, sex, and etiology (P = 0.021, B = 3.43). Conclusion: In our cohort, although a clear relationship between inaccuracy and complication rates was not found, our data did demonstrate that left-sided EVDs were more likely to fail within the immediate postoperative time point, and patients who died were more likely to have a second, contralateral EVD placed.

Multiplexed high-throughput immune cell imaging in patients with high-risk triple negative early breast cancer: Analysis from the International Breast Cancer Study Group (IBCSG) Trial 22-00.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype, with dismal prognosis and limited option in advanced settings, yet stromal tumor infiltrating lymphocytes (sTILs) in this subtype has a predictive role. PATIENTS AND METHODS: The International Breast Cancer Study Group (IBCSG) Trial 22-00 is a randomized phase III clinical trial testing the efficacy of low-dose metronomic oral Cyclophosphamide-Methotrexate (CM) maintenance following standard adjuvant chemotherapy treatment for early-stage hormone receptor-negative breast cancer patients. A case-cohort sampling was used. We characterized immune cells infiltrates in patients with TNBC by 6 plex immunofluorescence (IF) staining for CD4, FOXP3, CD3, cytokeratine and CD8 RESULTS: We confirmed that high immune CD3+ T cells as well as stromal and intra-epithelial Tregs (CD4+Foxp3+ T cells) infiltrates were associated with a better Distant Recurrence-Free Interval (DRFI), especially in LN+ patient, regardless of the treatment. More importantly, we showed that the spatial distribution of immune cells at baseline is crucial, as CM maintenance was detrimental for T cells excluded LN+ TNBC patients. CONCLUSIONS: immune spatial classification on immune cells infiltrates seems crucial and could help patients' selection in clinical trial and greatly improve responses to specific therapies.

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma.

BACKGROUND: The antibody-drug conjugates sacituzumab govitecan (SG) and enfortumab vedotin (EV) are standard monotherapies for metastatic urothelial carcinoma (mUC). Given the different targets and payloads, we evaluated the safety and efficacy of SG + EV in a phase I trial in mUC (NCT04724018). PATIENTS AND METHODS: Patients with mUC and Eastern Cooperative Oncology Group performance status ≤1 who had progressed on platinum and/or immunotherapy were enrolled. SG + EV were administered on days 1 + 8 of a 21-day cycle until progression or unacceptable toxicity. Primary endpoint was the incidence of dose-limiting toxicities during cycle 1. The number of patients treated at each of four pre-specified dose levels (DLs) and the maximum tolerated doses in combination (MTD) were determined using a Bayesian Optimal Interval design. Objective response, progression-free survival, and overall survival were secondary endpoints. RESULTS: Between May 2021 and April 2023, 24 patients were enrolled; 1 patient never started therapy and was excluded from the analysis. Median age was 70 years (range 41-88 years); 11 patients received ≥3 lines of therapy. Seventy-eight percent (18/23) of patients experienced grade ≥3 adverse event (AE) regardless of attribution at any DL, with one grade 5 AE (pneumonitis possibly related to EV). The recommended phase II doses are SG 8 mg/kg with EV 1.25 mg/kg with granulocyte colony-stimulating factor support; MTDs are SG 10 mg/kg with EV 1.25 mg/kg. The objective response rate was 70% (16/23, 95% confidence interval 47% to 87%) with three complete responses; three patients had progressive disease as best response. With a median follow-up of 14 months, 9/23 patients have ongoing response including 6 responses lasting over 12 months. CONCLUSIONS: The combination of SG + EV was assessed at different DLs and a safe dose for phase II was identified. The combination had encouraging activity in patients with mUC with high response rates, including clinically significant complete responses. Additional study of this combination is warranted.

Social Media, Public Health Research, and Vulnerability: Considerations to Advance Ethical Guidelines and Strengthen Future Research.

The purpose of this article is to build upon prior work in social media research and ethics by highlighting an important and as yet underdeveloped research consideration: how should we consider vulnerability when conducting public health research in the social media environment? The use of social media in public health, both platforms and their data, has advanced the field dramatically over the past 2 decades. Applied public health research in the social media space has led to more robust surveillance tools and analytic strategies, more targeted recruitment activities, and more tailored health education. Ethical guidelines when using social media for public health research must also expand alongside these increasing capabilities and uses. Privacy, consent, and confidentiality have been hallmarks for ethical frameworks both in public health and social media research. To date, public health ethics scholarship has focused largely on practical guidelines and considerations for writing and reviewing social media research protocols. Such ethical guidelines have included collecting public data, reporting anonymized or aggregate results, and obtaining informed consent virtually. Our pursuit of the question related to vulnerability and public health research in the social media environment extends this foundational work in ethical guidelines and seeks to advance research in this field and to provide a solid ethical footing on which future research can thrive.

Infant Rudimentary Meningocele with Tethering of the Cervical Cord: A Case Report.

Rudimentary meningoceles of the spine with dural extension are very rare and warrant surgical excision to prevent infection and long-term neurological deficits in pediatric patients. We present the case of a 5-month-old infant with a tethered spinal cord secondary to a rudimentary meningocele. The patient presented shortly after birth with a midline cervical dimple that was evaluated for a suspected dermal sinus tract. Magnetic resonance imaging scan of the spine showed a sinus tract with intradural extension to C2-3 and external opening at the level of spinous process C5. En bloc surgical excision and spinal cord release were successfully performed. Histological analysis of the specimen confirmed the presence of two blunt sinus tracts and staining was consistent with a rudimentary meningocele. Intradural rudimentary meningoceles in infants can successfully be managed with surgical intervention. Surgery is indicated to prevent future motor complications from spinal cord tethering and neoplastic growth from the rudimentary meningocele.

Association Between Pretreatment Chest Imaging and Immune Checkpoint Inhibitor Pneumonitis Among Patients With Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI treatment in 2% to 5% of patients; however, risk factors for developing ICI pneumonitis (ICI-p) remain undefined. METHODS: We conducted a retrospective cohort study of consecutive patients with lung cancer who received at least one dose of ICI from 2015 through 2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and a pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort. Univariate and multivariable survival analyses using the Fine-Gray competing risk model were used to examine the associations. RESULTS: A total of 471 patients with lung cancer were included, of which 402 had non-small cell lung cancer and 69 had small cell lung cancer; 39 (8%) patients in the overall cohort developed ICI-p. Preexisting interstitial abnormalities and prior chest radiation were both significantly associated with ICI-p on univariate analysis (hazard ratio [HR], 8.91; 95% CI, 4.69-16.92; P<.001; and HR, 2.81; 95% CI, 1.50-5.28; P=.001). On multivariable analyses, interstitial abnormalities remained a strong independent risk factor for ICI-p when controlling for chest radiation and type of immunotherapy (HR, 9.77; 95% CI, 5.17-18.46; P<.001). Among patients with ICI-p (n=39), those with severe (grade 3-5) pneumonitis had worse overall survival compared with those with mild (grade 1 or 2) pneumonitis (P=.001). Abnormal pulmonary function test results at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI-p. CONCLUSIONS: Preexisting interstitial abnormalities on chest CT and prior chest radiation are independent risk factors that are strongly associated with ICI-p in patients with lung cancer. These findings highlight a potential need for closer observation for ICI-p among patients with these risk factors.

Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023.

The 18th St Gallen International Breast Cancer Conference held in March 2023, in Vienna, Austria, assessed significant new findings for local and systemic therapies for early breast cancer with a focus on the evaluation of multimodal treatment options. The emergence of more effective, innovative agents in both the preoperative (primary or neoadjuvant) and post-operative (adjuvant) settings has underscored the pivotal role of a multidisciplinary approach in treatment decision making, particularly when selecting systemic therapy for an individual patient. The importance of multidisciplinary discussions regarding the clinical benefits of interventions was explicitly emphasized by the consensus panel as an integral part of developing an optimal treatment plan with the 'right' degree of intensity and duration. The panelists focused on controversies surrounding the management of common ductal/no special type and lobular breast cancer histology, which account for the vast majority of breast tumors. The expert opinion of the panelists was based on interpretations of available data, as well as current practices in their professional environments, personal and socioeconomic factors affecting patients, and cognizant of varying reimbursement and accessibility constraints around the world. The panelists strongly advocated patient participation in well-designed clinical studies whenever feasible. With these considerations in mind, the St Gallen Consensus Conference aims to offer guidance to clinicians regarding appropriate treatments for early-stage breast cancer and assist in balancing the realistic trade-offs between treatment benefit and toxicity, enabling patients and clinicians to make well-informed choices through a shared decision-making process.

Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.

Hepatitis B virus (HBV) chronically infects millions of people worldwide, which underscores the importance of discovering and designing novel anti-HBV therapeutics to complement current treatment strategies. An underexploited but attractive therapeutic target is ε, a cis-acting regulatory stem-loop RNA situated within the HBV pregenomic RNA (pgRNA). The binding of ε to the viral polymerase protein (P) is pivotal, as it triggers the packaging of pgRNA and P, as well as the reverse transcription of the viral genome. Consequently, small molecules capable of disrupting this interaction hold the potential to inhibit the early stages of HBV replication. The rational design of such ligands necessitates high-resolution structural information for the ε-P complex or its individual components. While these data are currently unavailable for P, our recent structural elucidation of ε through solution nuclear magnetic resonance spectroscopy marks a significant advancement in this area. In this review, we provide a brief overview of HBV replication and some of the therapeutic strategies to combat chronic HBV infection. These descriptions are intended to contextualize our recent experimental efforts to characterize ε and identify ε-targeting ligands, with the ultimate goal of developing novel anti-HBV therapeutics.

Different Scripts, Different Casts: A Crime Script Analysis Indicating Intimate Partner Violence Is Not All the Same.

Crime script analysis was used to analyze intimate partner violence diversity by identifying variables significantly associated with different script tracks. Qualitative thematic analysis using official police administrative data from Queensland, Australia, was used to develop an intimate partner violence protoscript (n = 40), followed by quantitative hierarchical cluster analysis and cross-tabulations to examine diversity within scripts. Four diverse script tracks were identified: "escalating jealousy," "persistently possessive," "controlling victim agency," and "enduring argument." Intimate partner diversity exists with divisions based on statistically significant variables. Implications for situational crime prevention and the use of mixed methods for strengthening crime script analysis are discussed.

Assessing the Mental Health Impact of the COVID-19 Pandemic on US Fire-Based Emergency Medical Services Responders: A Tale of Two Samples (The RAPID Study I).

OBJECTIVE: This study aimed to examine the COVID-19 pandemic's impact on fire service safety culture, behavior and morale, levers of well-being, and well-being outcomes. METHODS: Two samples (Stress and Violence against fire-based EMS Responders [SAVER], consisting of 3 metropolitan departments, and Fire service Organizational Culture of Safety [FOCUS], a geographically stratified random sample of 17 departments) were assessed monthly from May to October 2020. Fire department-specific and pooled scores were calculated. Linear regression was used to model trends. RESULTS: We observed concerningly low and decreasing scores on management commitment to safety, leadership communication, supervisor sensegiving, and decision-making. We observed increasing and concerning scores for burnout, intent to leave the profession, and percentage at high risk for anxiety and depression. CONCLUSIONS: Our findings suggest that organizational attributes remained generally stable but low during the pandemic and impacted well-being outcomes, job satisfaction, and engagement. Improving safety culture can address the mental health burden of this work.

Evidence for Spinozan "Unbelieving" in the Right Inferior Prefrontal Cortex.

Humans can think about possible states of the world without believing in them, an important capacity for high-level cognition. Here, we use fMRI and a novel "shell game" task to test two competing theories about the nature of belief and its neural basis. According to the Cartesian theory, information is first understood, then assessed for veracity, and ultimately encoded as either believed or not believed. According to the Spinozan theory, comprehension entails belief by default, such that understanding without believing requires an additional process of "unbelieving." Participants (n = 70) were experimentally induced to have beliefs, desires, or mere thoughts about hidden states of the shell game (e.g., believing that the dog is hidden in the upper right corner). That is, participants were induced to have specific "propositional attitudes" toward specific "propositions" in a controlled way. Consistent with the Spinozan theory, we found that thinking about a proposition without believing it is associated with increased activation of the right inferior frontal gyrus. This was true whether the hidden state was desired by the participant (because of reward) or merely thought about. These findings are consistent with a version of the Spinozan theory whereby unbelieving is an inhibitory control process. We consider potential implications of these results for the phenomena of delusional belief and wishful thinking.