Unsupervised Machine Learning to Identify Risk Factors of Pyeloplasty Failure in Ureteropelvic Junction Obstruction.

Introduction: In adult patients with ureteropelvic junction obstruction (UPJO), little data exist on predicting pyeloplasty outcome, and there is no unified definition of pyeloplasty success. As such, defining pyeloplasty success retrospectively is particularly vulnerable to bias, allowing researchers to choose significant outcomes with the benefit of hindsight. To mitigate these biases, we performed an unsupervised machine learning cluster analysis on a dataset of 216 pyeloplasty patients between 2015 and 2023 from a multihospital system to identify the defining risk factors of patients that experience worse outcomes. Methods: A KPrototypes model was fitted with pre- and perioperative data and blinded to postoperative outcomes. T-test and chi-square tests were performed to look at significant differences of characteristics between clusters. SHapley Additive exPlanation values were calculated from a random forest classifier to determine the most predictive features of cluster membership. A logistic regression model identified which of the most predictive variables remained significant after adjusting for confounding effects. Results: Two distinct clusters were identified. One cluster (denoted as "high-risk") contained 111 (51.4%) patients and was identified by having more comorbidities, such as old age (62.7 vs 35.7), high body mass index (BMI) (26.9 vs 23.8), hypertension (66.7% vs 17.1%), and previous abdominal surgery (72.1% vs 37.1%) and was found to have worse outcomes, such as more frequent severe postoperative complications (7.2% vs 1.0%). After adjusting for confounding effects, the most predictive features of high-risk cluster membership were old age, low preoperative estimated glomerular filtration rate (eGFR), hypertension, greater BMI, previous abdominal surgery, and left-sided UPJO. Conclusions: Adult UPJO patients with older age, lower eGFR, hypertension, greater BMI, previous abdominal surgery, and left-sided UPJO naturally cluster into to a group that more commonly suffers from perioperative complications and worse outcomes. Preoperative counseling and perioperative management for patients with these risk factors may need to be thought of or approached differently.

Differences in Patient-Reported Outcome Measures in Patients With Cancer Six Months Before Death.

PURPOSE: Patient-reported outcome measures (PROMs) provide a direct report of the patient's perspective, complementary to clinician assessment. Currently, understanding the real-time changes in PROM scores near the end of life remains limited. This study evaluated differences in mean PROM scores between patients with cancer within 6 months before death compared with surviving patients with cancer. METHODS: This retrospective case-control study uses the National Institutes of Health's Patient-Reported Outcomes Measurement Information System computer adaptive testing instruments to assess pain interference, physical function, fatigue, and depression. Patients dying within 6 months of PROM completion were selected as cases and matched to controls 1:3 by age at PROM completion, sex, cancer disease site, and cancer stage at diagnosis. Generalized estimating equation models assessed the difference in mean PROM score in cases compared with controls. RESULTS: A total of 461 cases and 1,270 controls from September 2020 to January 2023 were included. After adjustment for ethnicity, Charlson Comorbidity Index, and census tract median household income, significant differences in mean scores were demonstrated. Physical function domain showed the largest difference, with cases averaging 6.52 points lower than controls (95% CI, -8.25 to -4.80). Fatigue and pain interference domains showed a rise in PROMs scores by 4.83 points (95% CI, 2.94 to 6.72) and 4.33 points (95% CI, 2.53 to 6.12), respectively. CONCLUSION: Compared with controls, patients dying within 6 months of PROM completion demonstrated worse PROM scores in the four domains assessed. These findings suggest the utility of routinely collected PROMs as a real-time indicator of the terminal stage of life among patients with cancer to allow for earlier intervention with supportive oncology services.

KEAP1-mutant atypical meningioma: illustrative case.

BACKGROUND: While genetic testing of tumors is commonly used to inform the selection of systemic therapies, there is limited evidence for the application of radiotherapy for brain cancer. Recent studies have shown that Kelch-like ECH-associated protein 1 (KEAP1), a key regulator of cellular responses to oxidative and electrophilic stress, is associated with radioresistance in multiple cancer types. Several studies have reported the clinical significance of KEAP1 mutation in brain metastasis; however, the effect of KEAP1 mutations on radioresponse in meningioma has never been reported. OBSERVATIONS: The authors present the case of a 40-year-old female with a KEAP1 mutation-positive atypical meningioma that was initially treated with resection followed by intensity-modulated radiation therapy (IMRT). Recurrence was observed at 15 months, requiring reoperation and adjuvant stereotactic radiosurgery (SRS). An excellent treatment response was observed at 7 months post-SRS with an improvement in reported symptoms, although bevacizumab was required for the resolution of radiation necrosis observed 2 months post-SRS. LESSONS: To the authors' knowledge, this is the first report of KEAP1-mutant meningioma, including its clinical course after comprehensive management. Notably, treatment included multimodal radiotherapy with IMRT followed by SRS. SRS led to an excellent treatment response at the 7-month follow-up. However, radiation necrosis developed after both radiotherapy treatments, suggesting that radiological modification can be beneficial in patients with KEAP1 mutations. https://thejns.org/doi/10.3171/CASE24387.

A Retrospective Review Comparing Renuvion Helium Plasma Radiofrequency with BodyTite Bipolar Radiofrequency after Liposuction or Body Contouring.

Background: Driven by demand for nonexcisional alternatives to address lax skin following liposuction, various energy-based technologies have become available. Helium plasma radiofrequency (RF) and bipolar RF have gained prominence. These technologies have distinctly different methods of action and indications, potentially influencing procedural safety and duration. Methods: Conducted to collect and evaluate real-world procedure and safety data, this retrospective, single-center, contiguous series study included patients who underwent either helium plasma RF or bipolar RF following a liposuction or body contouring procedure. Results: The helium plasma RF group (N = 229) averaged 4.9 concurrent procedures, whereas the bipolar RF group (N = 236) averaged 4.4 concurrent procedures. The total treatment time, including concurrent procedures, was 182 minutes for the helium plasma RF group and 196 minutes for the bipolar RF group. The findings from the subanalysis group (n = 9) indicated that the treatment time for the helium plasma RF side of the body was 50% shorter than the bipolar RF side. A statistically significant difference in adverse events by group was observed. There were 45 events in 34 patients for helium plasma RF and 93 events in 62 patients for bipolar RF. Notably, fewer occurrences of burns, hematoma, hypertrophic scar, and seroma were reported for helium plasma RF compared with bipolar RF. Conclusions: The analysis reveals a notable difference in the occurrence of adverse events, with statistically significantly fewer incidents observed for helium plasma RF compared with bipolar RF. Data suggests that helium plasma RF exhibits shorter durations in the operating room compared with bipolar RF, suggesting increased procedural efficiency.

Stereotactic body radiotherapy for painful spinal metastases: a decade of experience at a single institution.

OBJECTIVE: This study aimed to retrospectively evaluate the efficacy of stereotactic body radiotherapy (SBRT) for pain relief in patients with painful spinal bone metastases (SBMs) and to identify key factors contributing to treatment outcomes. METHODS: The authors conducted a retrospective analysis of adult patients who underwent SBRT for painful solid tumor SBMs between March 2012 and January 2023. During this period, SBRT was performed adhering to the International Spine Radiosurgery Consortium guidelines and international consensus recommendations for target volume delineation. To be included, patients needed to experience persistent pain directly associated with SBMs, warranting regular opioid treatment. Positive pain relief post-SBRT was defined by three criteria: 1) a decrease in the severity of pain; 2) reduction in opioid dosage; and 3) concurrent improvement in daily activities. The revised Tokuhashi score and Spine Instability Neoplastic Score were used to identify crucial factors influencing treatment outcomes. RESULTS: This study included 377 patients, covering 576 lesions across 759 vertebrae. Of these, 332 lesions showed significant pain relief within 3 months following SBRT. Lower pain relief rates were observed in patients with a revised Tokuhashi score of 0-8 or in patients with diabetes mellitus. In contrast, higher relief rates were linked to treating a single painful SBM in 1 SBRT course, and greater contouring of the involved sectors according to International Spine Radiosurgery Consortium guidelines and international consensus recommendations. The highest pain relief rate was observed in patients with prostate cancer (73.8%), whereas the lowest rate was observed in patients with hepatocellular carcinoma (36.4%). The presence of pre-SBRT vertebral fractures, the dosage and fraction of SBRT, and the use of concurrent systemic cancer therapies or antiresorptive agents, including bisphosphonates and denosumab, did not notably influence the pain relief efficacy of SBRT. Comprehensive medical records 6 months after SBRT treatment were available for only 362 lesions. The overall rate of pain relief observed was 32.6%. CONCLUSIONS: SBRT is an effective treatment approach for managing painful SBMs, achieving a pain relief rate of 57.6% within 3 months and maintaining a rate of 32.6% at 6 months after treatment. The transition to osteoblastic lesions may potentially improve the stability of SBMs, indicated by lower Spine Instability Neoplastic Score, which in turn could extend pain relief management.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

Bilateral Multiple Orbital Metastases Successfully Treated with Standalone Stereotactic Radiosurgery: Clinical Image.

Bilateral orbital metastases are extremely rare, and no previous literature has reported bilateral multiple orbital metastases treated with stereotactic radiosurgery (SRS). We present the impressive images of a patient with history of metastatic leiomyosarcoma with newly diagnosed bilateral multiple orbital metastases. The pre-SRS magnetic resonance imaging (MRI) showed 1 right and 2 left orbital metastatic lesions. The patient underwent SRS, and the post-SRS MRI at 2 months showed a decrease in size of the treated lesions. The positron emission tomography scan at 5 months after the treatment showed no avid F-fluorodeoxyglucose uptakes in the 3 orbital metastases. The presenting symptoms were all improved after the treatment with no adverse effects from the SRS. Our interesting images show the presence of multiple lesions in the orbital spaces with excellent treatment response post SRS. This is the first report of a patient who has bilateral and multiple orbital metastases that were successfully treated with standalone SRS.

Stereotactic Radiosurgery for Residual, Recurrent, and Metastatic Hemangiopericytomas: A Single-Institution Retrospective Experience.

BACKGROUND AND OBJECTIVES: Hemangiopericytomas are infrequent vascular tumors originating from Zimmermann pericytes. The conventional treatment involves gross total resection, followed by adjuvant radiotherapy. Nevertheless, their tendency to infiltrate dural sinuses, high vascularity, and anatomic complexity pose challenges for radical resection, leading to a significant risk of recurrence. Stereotactic radiosurgery (SRS) has emerged as a promising adjuvant therapy to address these challenges. Our study provides the largest single-institutional retrospective, aiming to evaluate the effectiveness and safety of SRS as a treatment modality for residual, recurrent, and metastatic hemangiopericytomas. METHODS: From 1998 to 2023, 27 patients with 101 tumors underwent CyberKnife SRS at Stanford University Medical Center. The median age was 51 years at the time of treatment. The median follow-up period from SRS was 103 months (range: 6-250). All patients underwent upfront surgical resection. The median tumor volume was 1.5 cc. The median single-fraction equivalent dose was 19 Gy. The SRS was administered at the 76% of the median isodose line (range: 64-89). RESULTS: Of the 101 treated tumors, 24 (23.8%) progressed with a median time to recurrence of 30 months. At 10 years, the rates of local tumor control (LTC), overall survival (OS), and progression-free survival (PFS) were 74.3%, 80.8%, and 67%, respectively. In patients with metastatic lesions, the LTC rates were significantly greater when compared with those with residual or recurrent tumors. There was no significant difference between patients with residual, recurrent, and metastatic hemangiopericytomas in OS and PFS. Notably, no cases of radiation-induced adverse events were detected. CONCLUSION: SRS leads to excellent LTC, PFS, and OS at 10 years with negligible risk for adverse events. Therefore, it is an effective and safe management modality for patients with residual, recurrent, and metastatic hemangiopericytomas.

Recurrent choroid plexus carcinoma treated with CyberKnife radiosurgery: illustrative case.

BACKGROUND: Choroid plexus carcinomas (CPCs) are rare malignant brain tumors primarily affecting children younger than 2 years old. These tumors originate from the choroid plexus epithelium and are a subtype of choroid plexus tumors, which account for 1%-4% of pediatric brain tumors. Although CPCs often show a notably high recurrence rate after surgery, the standard treatment approach remains gross-total resection (GTR) of the tumor, given the lack of clinical data supporting the effectiveness of adjunct treatment options such as radiotherapy or chemotherapy. OBSERVATIONS: A 16-year-old female with a history of a recurrent cranial CPC resistant to surgery and radiotherapy was treated with CyberKnife stereotactic radiosurgery (SRS), following resection. The procedures successfully maintained local disease control for 41 months; however, there was a subsequent recurrence, ultimately leading to the death of the patient. LESSONS: CPC treatment remains challenging. SRS can be used as a viable adjunct to surgery, which remains the gold standard, although it can also be considered for nonsurgical candidates or when GTR cannot be achieved. Nevertheless, it is crucial to conduct additional research to explore diverse approaches for radiosurgery, including its role as the primary treatment modality versus its combination with surgery, radiotherapy, or chemotherapy. https://thejns.org/doi/10.3171/CASE23748.

Cervicomedullary cavernous malformation of the C1 nerve root: illustrative case.

BACKGROUND: Cavernous malformations (CMs) originating from spinal nerve roots are rare but can present with rapidly progressing neurological deficits. Therefore, quick identification and treatment are essential. OBSERVATIONS: The authors present the case of a 52-year-old male presenting with headaches and gait disturbance, found to have a CM of the C1 nerve root. The patient underwent successful suboccipital craniectomy and C1 laminectomy, with complete resection of the lesion, preservation of the cervical spinal nerve roots, and symptomatic improvement postoperatively. LESSONS: This is the first presentation in the literature of a CM originating from the C1 nerve root. The authors show complete resection of the lesion with preservation of the C1 nerve root. Nerve root lesions usually show insidious symptomatic onset. Quick identification and resection are recommended to prevent permanent neurological disability. https://thejns.org/doi/10.3171/CASE2456.

Primary Stereotactic Body Radiotherapy for Spinal Bone Metastases From Lung Adenocarcinoma.

OBJECTIVE: This study aimed to assess the results of primary stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM) originating from lung adenocarcinoma (ADC). We considered the revised Tokuhashi score (rTS), Spinal Instability Neoplastic Score (SINS), and genetic characteristics. METHODS: We examined adult patients with lung ADC who underwent primary SBRT (using the CyberKnife System) for SBM between March 2012 and January 2023. RESULTS: We analyzed data from 99 patients, covering 152 SBM across 194 vertebrae. The overall local control (LC) rate was 77.6% for SBM from lung ADC, with a LC rate of 90.7% at 1 year. The median period for local progression (LP) occurrence was recorded at 10.0 (3-52) months. Additionally, Asian patients demonstrated higher LC rates than White patients. Utilizing the rTS and SINS as predictive tools, we revealed that a poor survival prognosis and an unstable spinal structure were associated with increased rates of LP. Furthermore, the presence of osteolytic bone destructions and pain complaints were significantly correlated with the occurrence of LP. In the cohort of this study, 108 SBM underwent analysis to determine the expression levels of programmed cell death ligand 1 (PD-L1). Additionally, within this group, 60 showed mutations in the epidermal growth factor receptor (EGFR) alongside PD-L1 expression. Nevertheless, these genetic differences did not result in statistically significant differences in the LC rate. CONCLUSION: The one-year LC rate for primary SBRT targeting SBM from lung ADC stood at 90.7%, particularly with the use of the CyberKnife System. Patients achieving LC exhibited significantly longer survival times compared to those with LP.

Digital twin mathematical models suggest individualized hemorrhagic shock resuscitation strategies.

BACKGROUND: Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting. METHODS: We sought to bridge this gap by linking preclinical data in a porcine model with clinical data from patients from the Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study via a three-compartment ordinary differential equation model of inflammation and coagulation. RESULTS: The mathematical model accurately predicts physiologic, inflammatory, and laboratory measures in both the porcine model and patients, as well as the outcome and time of death in the PROMMTT cohort. Model simulation suggests that resuscitation with plasma and red blood cells outperformed resuscitation with crystalloid or plasma alone, and that earlier plasma resuscitation reduced injury severity and increased survival time. CONCLUSIONS: This workflow may serve as a translational bridge from pre-clinical to clinical studies in trauma-associated hemorrhagic shock and other complex disease settings.

Research to improve survival in patients with severe bleeding after major trauma presents many challenges. Here, we created a computer model to simulate the effects of severe bleeding. We refined this model using data from existing animal studies to ensure our simulations were accurate. We also used patient data to further refine the simulations to accurately predict which patients would live and which would not. We studied the effects of different treatment protocols on these simulated patients and show that treatment with plasma (the fluid portion of blood that helps form blood clots) and red blood cells jointly, gave better results than treatment with intravenous fluid or plasma alone. Early treatment with plasma reduced injury severity and increased survival time. This modelling approach may improve our ability to evaluate new treatments for trauma-associated bleeding and other acute conditions.

The Role of CyberKnife Stereotactic Radiosurgery in Recurrent Cranial Medulloblastomas across Pediatric and Adult Populations.

Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. Methods: We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised eight pediatric patients (ages 3-18) and two adult patients (ages 19-75). The median age at the time of SRS was 13 years, the median tumor volume accounted for 1.9 cc, the median biologically equivalent dose (BED) was 126 Gy, and the single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. Results: Following a median follow-up of 39 months (range: 6-78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. Conclusions: Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (AREs) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial.

Stereotactic radiosurgery for facial nerve hemangioma: Case report and systematic review.

BACKGROUND: Facial nerve hemangiomas (FNHs) are rare tumors that primarily occur near the geniculate ganglion in the temporal bone. Despite their rarity, they can cause significant facial nerve dysfunction. The optimal management approach for FNHs remains uncertain, with surgery being the mainstay but subject to debate regarding the extent of resection and preservation of the facial nerve. METHODS: Systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We queried the PubMed/Medline (accessed on 5 March 2024) electronic database using combinations of the following search terms and words text: "geniculate ganglion hemangioma", "ganglional hemangioma", "hemangioma of the facial nerve", "facial hemangioma", and "intratemporal hemangioma". RESULTS: We identified a total of 30 literatures (321 patients). The most common site involved for the facial nerve hemangioma was the geniculate ganglion area followed by internal auditory canal, tympanic segment, labyrinthine segment and mastoid involvement. All patients were treated with conservative management or surgery. We report a 48-year-old female patient with HB grade 2 facial palsy and hemifacial spasm underwent SRS using Cyberknife technology. The treatment targeted the FNH in the left internal acoustic canal near the geniculate ganglion. Six months post-treatment, clinical improvement was evident, and lesion control was confirmed in a follow-up brain MRI. CONCLUSION: The rarity of FNHs contributes to the lack of consensus on optimal management. This illustrative case demonstrates the feasibility of SRS as a standalone treatment for FNHs.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

Treatment of Refractory Bipolar Depression With Stereotactic Radiosurgery Targeting the Subgenual Cingulate Cortex.

Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the neurobiology of depression. Deep brain stimulation in the SGC is thought to reduce and normalize local metabolism, causing normalization of circuit behavior and an improvement in depressive symptoms. We hypothesized that nonablative stereotactic radiosurgery (SRS) to the SGC would reduce local metabolism and reduce the severity of depression in patients with treatment-resistant bipolar depression. Methods Under the FDA's Humanitarian Device Exemption program, patients were screened for inclusion and exclusion criteria. Three volunteers meeting the criteria provided informed consent. Bilateral SGC targets were irradiated to a maximum dose of 75 Gy in one fraction. Subjects were followed for one year following the procedure with mood assessments (Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Young Mania Rating Scale), neurocognitive testing (Delis-Kaplan Executive Function System, Wechsler Adult Intelligence Scale III digit span, and California Verbal Learning Test II), and imaging. Further imaging was completed approximately two years after the procedure. Clinical improvement was defined as a ≥50% reduction in HDRS. Results Two of the three subjects showed clinical improvement in depressive symptoms during the follow-up period, while one subject showed no change in symptom severity. One of three subjects was hospitalized for the emergence of an episode of psychotic mania after discontinuing antipsychotic medications against medical advice but promptly recovered with the reinstitution of an antipsychotic. Sequential assessments did not reveal impairment in any cognitive domain assessed. For one of the three subjects, MRI imaging showed evidence of edema at 12 months post-SRS, which resolved at 22 months post-procedure. In a second of three patients, there was evidence of local edema at the target site at long-term follow-up. All imaging changes were asymptomatic. Conclusion Radiosurgical targeting of the SGC may be a noninvasive strategy for the reduction of severe depression in treatment-resistant bipolar disorder. Two out of three patients showed clinical improvement. While these results are promising, further study, including improvements in target selection and dosing considerations, is needed.

Experimental and Monte Carlo based dosimetric investigation of a novel 3 mm radiosurgery 3 MV beam using the microSilicon detector.

BACKGROUND: The ZAP-X system is a novel gyroscopic radiosurgical system based on a 3 MV linear accelerator and collimator cones with a diameter between 4 and 25 mm. Advances in imaging modalities to detect small and early-stage pathologies allow for an early and less invasive treatment, where a smaller collimator matching the anatomical target could provide better sparing of surrounding healthy tissue. PURPOSE: A novel 3 mm collimator cone for the ZAP-X was developed. This study aims to investigate the usability of a commercial diode detector (microSilicon) for the dosimetric characterization of this small collimator cone; and to investigate the underlying small field perturbation effects. METHODS: Profile measurements in five depths as well as PDD and output ratio measurements were performed with a microSilicon detector and radiochromic EBT3 films. In addition, comprehensive Monte Carlo simulations were performed to validate the measurement observations and to quantify the perturbation effects of the microSilicon detector in these extremely small field conditions. RESULTS: It is shown that the microSilicon detector enables an accurate dosimetric characterization of the 3 mm beam. The profile parameters, such as the FWHM and 20%-80% penumbra width, agree within 0.1 to 0.2 mm between film and detector measurements. The output ratios agree within the measurement uncertainty between microSilicon detector and films, whereas the comparisons of the PDD results show good agreement with the Monte Carlo simulations. The analysis of the perturbation factors of the microSilicon detector reveals a small field correction factor of approximately 3% for the 3 mm circular beam and a correction factor smaller than 1.5% for field diameters above 3 mm. CONCLUSIONS: It could be shown that the microSilicon detector is well-suitable for the characterization of the new 3 mm circular beam of the ZAP-X system.

Stereotactic Radiosurgery for Ependymoma in Pediatric and Adult Patients: A Single-Institution Experience.

BACKGROUND AND OBJECTIVES: Ependymoma is commonly classified as World Health Organization grade 2 with the anaplastic variant categorized as grade 3. Incomplete resection or anaplastic features can result in unfavorable outcomes. Stereotactic radiosurgery (SRS) provides a minimally invasive approach for recurrent ependymomas. Our study investigates the efficacy and safety of SRS for grade 2 and 3 ependymomas in pediatric and adult populations. METHODS: We conducted a retrospective analysis on 34 patients with 75 ependymomas after CyberKnife SRS between 1998 and 2023. Fourteen were pediatric (3-18 years), and 20 were adult (19-75 years) patients. The median age was 21 years, and the median tumor volume was 0.64 cc. The median single-fraction equivalent dose was 16.6 Gy, with SRS administered at 77% of the median isodose line. RESULTS: After a median follow-up of 42.7 months (range: 3.8-438.3), 22.7% of ependymomas progressed. The 5-year local tumor control rate was 78.1%, varying between 59.6% and 90.2% for children and adults, with grade 2 at 85.9% compared with 58.5% for grade 3 tumors. The 5-year overall survival rate was 73.6%, notably higher in adults (94.7%) than in children (41%), and 100% for grade 2 but decreased to 35.9% for grade 3 patients. The 5-year progression-free survival rate was 68.5%, with 78.3% and 49.2% for adults and children, respectively, and a favorable 88.8% for grade 2, contrasting with 32.6% for grade 3 patients. Symptom improvement was observed in 85.3% of patients. Adverse radiation effects occurred in 21.4% of pediatric patients. CONCLUSION: Our study supports SRS as a viable modality for pediatric and adult patients with grade 2 and 3 ependymomas. Despite lower local tumor control in pediatric and grade 3 cases, integrating SRS holds promise for improved outcomes. Emphasizing careful patient selection, personalized treatment planning, and long-term follow-up is crucial for optimal neurosurgical outcomes.

Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury.

Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.

Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial.

Importance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates. Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo. Design, Setting, and Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation. Intervention: Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days. Main Outcome and Measures: The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL. Results: Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, -1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, -6.3; 95% CI, -10.8 to -1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen. Conclusions and Relevance: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04291508.