Comparison of Repeat Versus Initial Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: A Retrospective Multicenter Matched Cohort Study.

BACKGROUND AND OBJECTIVES: Studies comparing neurological and radiographic outcomes of repeat to initial stereotactic radiosurgery (SRS) intracranial arteriovenous malformations are scarce. Our aim was to perform a retrospective matched comparison of patients initially treated with SRS with those undergoing a second radiosurgical procedure. METHODS: We collected data from arteriovenous malformations managed in 21 centers that underwent initial and repeated radiosurgery from 1987 to 2022. Based on arteriovenous malformations volume, margin dose, deep venous drainage, deep, and critical location, we matched 1:1 patients who underwent an initial SRS for treatment-naive arteriovenous malformations and a group with repeated SRS treatment. RESULTS: After the selection process, our sample consisted of 328 patients in each group. Obliteration in the initial SRs group was 35.8% at 3 and 56.7% at 5 years post-SRS, while the repeat SRS group showed obliteration rates of 33.9% at 3 years and 58.6% at 5 years, without statistically significant differences (P = .75 and P = .88, respectively). There were no statistically significant differences between the 2 groups for obliteration rates (hazard ratio = 0.93; 95% CI, 0.77-1.13; P = .5), overall radiation-induced changes (RIC) (OR = 1.1; 95% CI, 0.75-1.6; P = .6), symptomatic RIC (OR = 0.78; 95% CI, 0.4-1.5; P = .4), and post-SRS hemorrhage (OR = 0.68; 95% CI; P = .3). CONCLUSION: In matched cohort analysis, a second SRS provides comparable outcomes in obliteration and RIC compared with the initial SRS. Dose reduction on repeat SRS may not be warranted.

PPAR-γ agonist pioglitazone and the risks of malignancy among type2 diabetes mellitus patients.

AIMS: PPAR-gamma shows promise in inhibiting malignancy cell progression. However, pioglitazone, the sole current PPAR-gamma agonist, was reported to have risks of bladder cancer in previous clinical researches. This study is aimed to assess the influence of pioglitazone on the development of tumors. METHODS: By using Taiwan's National Health Insurance Research Database, this nested case-control study identified incident type2 diabetes initiating metformin treatment between 2000 and 2014, and then categorized into two groups based on whether they developed malignancies after enrollment or not. The index date was defined as the date of malignancy diagnosis in the cancer group or a matched date in the non-cancer group. We analyzed the exposure to pioglitazone preceding the index date. RESULTS: 47,931 patients in the cancer group and 47,931 patients in the matched non-cancer group were included. The non-cancer group exhibited a significantly higher rate of pioglitazone prescription before the index date for overall malignancies (odds ratios for pioglitazone use were 0.91, 0.92, 0.94, and 0.93 in the first, second, third, and fourth years before the index date). For breast cancer and prostate cancer, pioglitazone was frequently prescribed in the non-cancer group, whereas for pancreatic cancer, pioglitazone use was more common in the cancer group. CONCLUSIONS: PPAR-gamma agonists may be associated with reduced risks of overall malignancies, particularly for breast and prostate cancers. However, it may be linked to an elevated risk of pancreatic cancer.

Stereotactic radiosurgery for anterior cranial fossa dural arteriovenous fistulas.

OBJECTIVE: Anterior cranial fossa (ACF) dural arteriovenous fistulas (DAVFs) are notoriously malignant vascular abnormalities, and their drainage into the cortical vein poses a high risk of intracranial hemorrhage (ICH). Stereotactic radiosurgery (SRS) is increasingly seen as an alternative to microsurgery or embolization for the treatment of DAVFs; however, researchers have yet to report on its applicability to ACF DAVFs. This paper summarizes the authors' experience in the use of SRS for ACF DAVFs. The authors' objective was to gain a preliminary overview of SRS outcomes in the treatment of ACF DAVFs. METHODS: This retrospective study examined all patients who underwent SRS for ACF DAVFs at a single academic medical center between November 2000 and November 2023. Demographic data, DAVF characteristics, and clinical outcomes were obtained from medical records. RESULTS: A total of 12 patients diagnosed with ACF DAVFs were treated using SRS. One patient was lost to follow-up. The mean age was 54.8 years and men comprised 82% of the cohort. The most common presenting symptoms included headache (n = 5), ocular symptoms (n = 3), seizure (n = 2), anosmia (n = 1), and tinnitus (n = 1). Two patients were asymptomatic. Four patients (36%) initially presented with ICH. Nine patients exhibited DAVF Cognard type IV, and 2 patients exhibited Cognard type III. DAVF obliteration in 7 of the 11 patients (64%) was confirmed by brain MR angiography (n = 4) or digital subtraction angiography (n = 3). No post-SRS episodes of ICH were reported. Most of the patients (10 of 11) reported improvements in clinical symptoms. CONCLUSIONS: SRS appears to be a viable alternative treatment for ACF DAVFs, particularly for patients who are not suitable candidates for surgery or those with an unfavorable angioarchitecture.

Stereotactic radiosurgery for brain metastases from human epidermal receptor 2 positive breast Cancer: an international, multi-center study.

PURPOSE: To report patient outcomes and local tumor control rates in a cohort of patients with biopsy-proven HER-2 positive breast cancer treated with stereotactic radiosurgery (SRS) for brain metastases (BM). METHODS: This international, retrospective, multicenter study, included 195 female patients with 1706 SRS-treated BM. Radiologic and clinical outcomes after SRS were determined and prognostic factors identified. RESULTS: At SRS, median patient age was 55 years [interquartile range (IQR) 47.6-62.0], and 156 (80%) patients had KPS ≥ 80. The median tumor volume was 0.1 cm3 (IQR 0.1-0.5) and the median prescription dose was 16 Gy (IQR 16-18). Local tumor control (LTC) rate was 98%, 94%, 93%, 90%, and 88% at six-, 12-, 24-, 36- and 60-months post-SRS, respectively. On multivariate analysis, tumor volume (p = < 0.001) and concurrent pertuzumab (p = 0.02) improved LTC. Overall survival (OS) rates at six-, 12-, 24-, 36-, 48-, and 60-months were 90%, 69%, 46%, 27%, 22%, and 18%, respectively. Concurrent pertuzumab improved OS (p = 0.032). In this patient subgroup, GPA scores ≥ 2.5 (p = 0.038 and p = 0.003) and rare primary tumor histologies (p = 0.01) were associated with increased and decreased OS, respectively. Asymptomatic adverse radiation events (ARE) occurred in 27 (14.0%) and symptomatic ARE in five (2.6%) patients. Invasive lobular carcinoma primary (p = 0.042) and concurrent pertuzumab (p < 0.001) conferred an increased risk for overall but not for symptomatic ARE. CONCLUSION: SRS affords effective LTC for selected patients with BM from HER-2 positive breast cancer. Concurrent pertuzumab improved LTC and OS but at the same time increased the risk for overall, but not symptomatic, ARE.

Stereotactic Radiosurgery With Versus Without Neoadjuvant Endovascular Embolization for Brain Arteriovenous Malformations With Associated Intracranial Aneurysms.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) with neoadjuvant embolization is a treatment strategy for brain arteriovenous malformations (AVMs), especially for those with large nidal volume or concomitant aneurysms. The aim of this study was to assess the effects of pre-SRS embolization in AVMs with an associated intracranial aneurysm (IA). METHODS: The International Radiosurgery Research Foundation AVM database from 1987 to 2018 was retrospectively reviewed. SRS-treated AVMs with IAs were included. Patients were categorized into those treated with upfront embolization (E + SRS) vs stand-alone SRS (SRS). Primary end point was a favorable outcome (AVM obliteration + no permanent radiation-induced changes or post-SRS hemorrhage). Secondary outcomes included AVM obliteration, mortality, follow-up modified Rankin Scale, post-SRS hemorrhage, and radiation-induced changes. RESULTS: Forty four AVM patients with associated IAs were included, of which 23 (52.3%) underwent pre-SRS embolization and 21 (47.7%) SRS only. Significant differences between the E + SRS vs SRS groups were found for AVM maximum diameter (1.5 ± 0.5 vs 1.1 ± 0.4 cm3, P = .019) and SRS treatment volume (9.3 ± 8.3 vs 4.3 ± 3.3 cm3, P = .025). A favorable outcome was achieved in 45.4% of patients in the E + SRS group and 38.1% in the SRS group (P = .625). Obliteration rates were comparable (56.5% for E + SRS vs 47.6% for SRS, P = .555), whereas a higher mortality rate was found in the SRS group (19.1% vs 0%, P = .048). After adjusting for AVM maximum diameter, SRS treatment volume, and maximum radiation dose, the likelihood of achieving favorable outcome and AVM obliteration did not differ between groups (P = .475 and P = .820, respectively). CONCLUSION: The likelihood of a favorable outcome and AVM obliteration after SRS with neoadjuvant embolization in AVMs with concomitant IA seems to be comparable with stand-alone SRS, even after adjusting for AVM volume and SRS maximum dose. However, the increased mortality among the stand-alone SRS group and relatively low risk of embolization-related complications suggest that these patients may benefit from a combined treatment approach.

Electronic Alert Systems for Patients With Acute Kidney Injury: A Systematic Review and Meta-Analysis.

Importance: The acute kidney injury (AKI) electronic alert (e-alert) system was hypothesized to improve the outcomes of AKI. However, its association with different patient outcomes and clinical practice patterns remains systematically unexplored. Objective: To assess the association of AKI e-alerts with patient outcomes (mortality, AKI progression, dialysis, and kidney recovery) and clinical practice patterns. Data Sources: A search of Embase and PubMed on March 18, 2024, and a search of the Cochrane Library on March 20, 2024, to identify all relevant studies. There were no limitations on language or article types. Study Selection: Studies evaluating the specified outcomes in adult patients with AKI comparing AKI e-alerts with standard care or no e-alerts were included. Studies were excluded if they were duplicate cohorts, had insufficient outcome data, or had no control group. Data Extraction and Synthesis: Two investigators independently extracted data and assessed bias. The systematic review and meta-analysis followed the PRISMA guidelines. Random-effects model meta-analysis, with predefined subgroup analysis and trial sequential analyses, were conducted. Main Outcomes and Measures: Primary outcomes included mortality, AKI progression, dialysis, and kidney recovery. Secondary outcomes were nephrologist consultations, post-AKI exposure to nonsteroidal anti-inflammatory drugs (NSAID), post-AKI angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker (ACEI/ARB) prescription, hospital length of stay, costs, and AKI documentation. Results: Thirteen unique studies with 41 837 unique patients were included (mean age range, 60.5-79.0 years]; 29.3%-48.5% female). The risk ratios (RRs) for the AKI e-alerts group compared with standard care were 0.96 for mortality (95% CI, 0.89-1.03), 0.91 for AKI stage progression (95% CI, 0.84-0.99), 1.16 for dialysis (95% CI, 1.05-1.28), and 1.13 for kidney recovery (95% CI, 0.86-1.49). The AKI e-alerts group had RRs of 1.45 (95% CI, 1.04-2.02) for nephrologist consultation, 0.75 (95% CI, 0.59-0.95) for post-AKI NSAID exposure. The pooled RR for post-AKI ACEI/ARB exposure in the AKI e-alerts group compared with the control group was 0.91 (95% CI, 0.78-1.06) and 1.28 (95% CI, 1.04-1.58) for AKI documentation. Use of AKI e-alerts was not associated with lower hospital length of stay (mean difference, -0.09 [95% CI, -0.47 to 0.30] days) or lower cost (mean difference, US $655.26 [95% CI, -$656.98 to $1967.5]) but was associated with greater AKI documentation (RR, 1.28 [95% CI, 1.04-1.58]). Trial sequential analysis confirmed true-positive results of AKI e-alerts on increased nephrologist consultations and reduced post-AKI NSAID exposure and its lack of association with mortality. Conclusions and Relevance: In this systematic review and meta-analysis, AKI e-alerts were not associated with a lower risk for mortality but were associated with changes in clinical practices. They were associated with lower risk for AKI progression. Further research is needed to confirm these results and integrate early AKI markers or prediction models to improve outcomes.

Gamma Knife Radiosurgery for Hypothalamic Hamartoma: A Multi-Institutional Retrospective Study on Safety, Efficacy, and Complication Profile.

BACKGROUND AND OBJECTIVES: Gamma knife radiosurgery (GKRS) is a safe and effective treatment option for hypothalamic hamartomas (HH), but there is no consensus opinion on its timing, dosage, and follow-up. The aim of this study was to define the safety, efficacy, outcome, and complication profile of GKRS in this patient population. METHODS: This retrospective multicentric study involved 39 patients with the mean age of 16 ± 14.84 years. Early seizures resulted in an earlier age of diagnosis in 97% of patients. At baseline, no endocrine abnormalities were seen in 75% of patients while 18.9% showed precocious puberty (PP). The median target volume was 0.55 cc (0.1-10.00 cc), and a median margin dose of 16 Gy (8.1-20.0 Gy) was delivered in a single session. All patients were evaluated for clinical, endocrinological, and radiological outcomes. RESULTS: The median follow-up was 5 (0.1-15) years. The median target volume of the cohort was 0.55 (0.35-1.77) cc. The largest HH was of 10 cc. 24/39 (61.5%) were small HH (Regis I-III). At presentation, 94.8% patients suffered from seizures (87.18% with gelastic seizures). 7/39 patients (17.9%) were presented with both PP and epilepsy. Only one (2.6%) patient presented with PP alone. 29 patients had more than 3-year follow-up. All received ≥16 Gy targeting complete HH. 28% of patients showed regression in HH volume. Patients with Regis grade I-III and longer follow-up (>75 months) showed gradual improvement in seizures. 16/29 patients (55.2%) achieved good seizure control (Engel I/II) while 13 (44.8%) were in Engel III/IV status. Nine patients needed adjuvant treatment because of poor seizure control. Eight patients suffered from transient increase in seizures. One patient developed poikilothermia, and 2 patients developed new onset hormonal deficiency. CONCLUSION: GKRS is a safe and effective modality for treatment of HH with significant improvement in seizure control with minimal disruption of endocrine profile. It provides an excellent safety, efficacy, and complication profile, especially for small HH. Latency of results and its adjuvant nature remain the areas of research and breakthroughs among contemporary treatment options.

Risk of new tumor, carotid stenosis, and stroke after Stereotactic Radiosurgery for Pituitary Tumor: A multicenter study of 2254 patients with imaging follow-up.

BACKGROUND: Higher risk of secondary brain tumor, carotid stenosis and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion and stroke after SRS. METHODS: In this multicentric retrospective study, 2,254 patients with PitNET were studied, 1,377 in the exposed group and 877 in the control group. RESULTS: There were 9,840.1 patient-years at risk for the SRS and 5,266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95%CI:0.5%, 4.1%) for SRS and 3.7% (95%CI:0%, 8.7%) for the control group (p=0.6), with an incidence rate of 1.32 per 1,000 and 0.95 per 1,000, respectively. SRS was not associated with increased risk of tumorigenesis when stratified by age (HR: 1.59 [95%CI: 0.57, 4.47], p=0.38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95%CI: 0.2, 1.6) in the SRS and 2% (95%CI: 0, 4.4) in the control group (p=0.8). The 15-year probability of stroke was 2.6% (95%CI: 0.6%, 4.6%) in the SRS and 11.1% (95%CI: 6%, 15.9%) in the control group (p<0.001). In cox multivariate analysis stratified by age, SRS (HR 1.85[95%CI:0.64, 5.35], p=0.26) was not associated with risk of new stroke. CONCLUSION: No increased risk of long-term secondary brain tumor, new stenosis or occlusion and stroke was demonstrated in SRS group compared to control in this study with imaging surveillance.

Utilizing Raman spectroscopy for urinalysis to diagnose acute kidney injury stages in cardiac surgery patients.

BACKGROUND: The successful treatment and improvement of acute kidney injury (AKI) depend on early-stage diagnosis. However, no study has differentiated between the three stages of AKI and non-AKI patients following heart surgery. This study will fill this gap in the literature and help to improve kidney disease management in the future. METHODS: In this study, we applied Raman spectroscopy (RS) to uncover unique urine biomarkers distinguishing heart surgery patients with and without AKI. Given the amplified risk of renal complications post-cardiac surgery, this approach is of paramount importance. Further, we employed the partial least squares-support vector machine (PLS-SVM) model to distinguish between all three stages of AKI and non-AKI patients. RESULTS: We noted significant metabolic disparities among the groups. Each AKI stage presented a distinct metabolic profile: stage 1 had elevated uric acid and reduced creatinine levels; stage 2 demonstrated increased tryptophan and nitrogenous compounds with diminished uric acid; stage 3 displayed the highest neopterin and the lowest creatinine levels. We utilized the PLS-SVM model for discriminant analysis, achieving over 90% identification rate in distinguishing AKI patients, encompassing all stages, from non-AKI subjects. CONCLUSIONS: This study characterizes the incidence and risk factors for AKI after cardiac surgery. The unique spectral information garnered from this study can also pave the way for developing an in vivo RS method to detect and monitor AKI effectively.

Shortened Cerebral Circulation Time Predicts Resistance to Obliteration in High-Flow Brain Arteriovenous Malformations After Stereotactic Radiosurgery.

BACKGROUND AND OBJECTIVES: Treatment selection for brain arteriovenous malformations (BAVMs) is complicated by BAVM size, location, and hemodynamics. Quantitative digital subtraction angiography is used to quantify the hemodynamic impact of BAVMs on cerebral circulation. This study investigated the association between cerebral circulation time and the complete obliteration (CO) rate of BAVMs after stereotactic radiosurgery (SRS). METHODS: We analyzed the data of 143 patients who underwent SRS for BAVMs between January 2011 and December 2019 in our institute. Their pre-SRS magnetic resonance imaging and angiography images were analyzed to acquire BAVM characteristics and quantitative digital subtraction angiography parameters. Modified cerebral circulation time (mCCT) was defined as the time difference between the bolus arrival time of the ipsilateral cavernous internal carotid artery and that of the parietal vein, as determined from the lateral view of images obtained using digital subtraction angiography. Cox regression with hazard ratios and Kaplan-Meier analyses were conducted to determine the associations between the parameters and BAVM CO after SRS. RESULTS: Of the 143 patients, 101 (70.6%) achieved BAVM CO. According to the multivariate analyses, an increased mCCT (hazard ratio: 1.24, P = .041) was the independent factor associated with BAVM CO after adjustment for age, sex, hemorrhagic presentation, a BAVM volume of >5 cm3, and a margin dose of >18 Gy. Individuals with an mCCT of ≤2.32 s had a lower 36-month probability of BAVM CO than did those with an mCCT of >2.32 s (44.1% ± 6.8% vs 63.3% ± 5.6%, P = .034). CONCLUSION: The hemodynamic impact of high-flow BAVM demonstrated by a shortened mCCT is associated with a lower BAVM CO rate after SRS.

Stereotactic radiosurgery for brain metastasis from cholangiocarcinoma.

OBJECTIVE: Accounting for approximately 15% of primary liver cancers and 3% of gastrointestinal malignancies, cholangiocarcinoma (CCA) poses a serious health concern given its high mortality rate. Managing brain metastases (BMs) from CCA is challenging because of their rarity and poor prognosis, with little guidance on treatment from the literature. In this study, the authors aimed to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in managing BMs from CCA. METHODS: This multicenter retrospective study included 13 CCA patients with 41 BMs treated with SRS from October 2006 to April 2022 at eight institutions affiliated with the International Radiosurgery Research Foundation. Inclusion criteria were a CCA diagnosis, an age over 18 years, no other malignancies, single-fraction SRS treatment for BMs, and at least one follow-up image. Data on demographics, tumor characteristics, treatment details, and outcomes were collected. The primary endpoints were local control (LC), intracranial progression-free survival (PFS), and overall survival (OS). The secondary endpoint was the development of adverse radiation effects (AREs). RESULTS: The median radiological follow-up was 5 months (range 1-18 months). At the last follow-up, LC was achieved in 39 (95.1%) of 41 BMs. New distant metastases were observed in 3 patients (23.1%), and the mean intracranial PFS was 9.4 months (95% CI 6.5-12.3 months). Six-month and 1-year OS rates were 38.5% and 11.5%, respectively, and the median OS was 6 months (95% CI 4.9-7.2 months). Concurrent immunotherapy was associated with a high risk of local failure (HR 29.665, 95% CI 1.799-489.206, p = 0.018), and the absence of systemic chemotherapy before SRS was linked to reduced OS (HR 6.658, 95% CI 1.173-37.776, p = 0.032). Regarding AREs, only 1 patient (7.7%) experienced right hemiparesis and was treated with corticosteroid therapy. CONCLUSIONS: SRS is an effective option for managing BMs in CCA patients, showing promise in LC and a high safety profile.

Long-Term Clinical Outcomes of Acute Kidney Disease in Patients Receiving Extracorporeal Membrane Oxygenation.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is widely used; however, studies on the long-term outcomes of ECMO are scarce. We investigated the long-term clinical outcomes of acute kidney disease (AKD) in patients receiving ECMO. METHODS: Electronic data (2009-2018) were retrospectively collected from a multicenter database. Patients were divided into two groups (AKD and non-AKD) according to their AKD status 8-90 days after the initiation of ECMO. Inverse probability of treatment weighting was used to balance baseline covariates between the two groups. The primary outcomes were major adverse kidney events (MAKEs) and major adverse cardiovascular events (MACEs), and the secondary outcomes were all-cause readmission, sepsis-related readmission, infection-related readmission, and dementia. RESULTS: Totally, 395 patients were eligible for analysis; of them, 160 patients (40.5%) developed AKD. The AKD group had a higher risk of MAKEs (hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.68-2.53) than did the non-AKD group. Subgroup analysis revealed that the observed unfavorable effect of AKD on the risk of MAKEs was more pronounced in patients receiving venovenous ECMO than in those receiving venoarterial ECMO (HR: 5.69 vs. 1.85, respectively; p for interaction = 0.004). AKD group had a higher risk of MACE during the initial 3-year post-ECMO in comparison to those without (HR: 1.68; 95% CI: 1.22-2.30). Moreover, the risks of all-cause, sepsis-related, and infection-related readmissions were high in AKD survivors. CONCLUSIONS: AKD is associated with an increased risk of long-term MAKEs and initial 3-year MACE in ECMO recipients. In addition, AKD is associated with increased risks of all-cause, infection-related, and sepsis-related readmissions.

Identification of Endothelial Cell Protein C Receptor by Urinary Proteomics as Novel Prognostic Marker in Non-Recovery Kidney Injury.

Acute kidney injury is a common and complex complication that has high morality and the risk for chronic kidney disease among survivors. The accuracy of current AKI biomarkers can be affected by water retention and diuretics. Therefore, we aimed to identify a urinary non-recovery marker of acute kidney injury in patients with acute decompensated heart failure. We used the isobaric tag for relative and absolute quantification technology to find a relevant marker protein that could divide patients into control, acute kidney injury with recovery, and acute kidney injury without recovery groups. An enzyme-linked immunosorbent assay of the endothelial cell protein C receptor (EPCR) was used to verify the results. We found that the EPCR was a usable marker for non-recovery renal failure in our setting with the area under the receiver operating characteristics 0.776 ± 0.065; 95%CI: 0.648-0.905, (p < 0.001). Further validation is needed to explore this possibility in different situations.

Distributed source modeling of stereoencephalographic measurements of ictal activity.

OBJECTIVES: Stereoelectroencephalography (SEEG) can define the epileptogenic zone (EZ). However, SEEG is susceptible to the sampling bias, where no SEEG recording is taken within a circumscribed EZ. METHODS: Nine patients with medically refractory epilepsy underwent SEEG recording, and brain resection got positive outcomes. Ictal neuronal currents were estimated by distributed source modeling using the SEEG data and individual's anatomical magnetic resonance imaging. Using a retrospective leave-one-out data sub-sampling, we evaluated the sensitivity and specificity of the current estimates using MRI after surgical resection or radio-frequency ablation. RESULTS: The sensitivity and specificity in detecting the EZ were indistinguishable from either the data from all electrodes or the sub-sampled data (rank sum test: rank sum = 23719, p = 0.13) when at least one remaining electrode contact was no more than 20 mm away. CONCLUSIONS: The distributed neuronal current estimates of ictal SEEG data can mitigate the challenge of delineating the boundary of the EZ in cases of missing an electrode implanted within the EZ and a required second SEEG exploration. SIGNIFICANCE: Distributed source modeling can be a tool for clinicians to infer the EZ by allowing for more flexible planning of the electrode implantation route and minimizing the number of electrodes.

Fibrate and the risk of cardiovascular disease among moderate chronic kidney disease patients with primary hypertriglyceridemia.

Introduction: Hypertriglyceridemia is the most prevalent dyslipidemia in patients with chronic kidney disease (CKD). However, research about fibrate treatment in CKD patients is limited, and assessing its benefits becomes challenging due to the frequent concurrent use of statins. Thus, this study is aimed to investigate the role of fibrate in CKD stage 3 patients with hypertriglyceridemia who did not receive other lipid-lowering agents. Methods: This study enrolled patients newly diagnosed CKD3 with LDL-C<100mg/dL and had never received statin or other lipid-lowering agents from Chang Gung Research Database. The participants were categorized into 2 groups based on the use of fibrate: fibrate group and non-fibrate group (triglyceride >200mg/dL but not receiving fibrate treatment). The inverse probability of treatment weighting was performed to balance baseline characteristics. Results: Compared with the non-fibrate group (n=2020), the fibrate group (n=705) exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (MACCEs) (10.4% vs. 12.8%, hazard ratios [HRs]: 0.69, 95% confidence interval [CI]: 0.50 to 0.95), AMI (2.3% vs. 3.9%, HR: 0.52, 95% CI: 0.37 to 0.73), and ischemic stroke (6.3% vs. 8.0%, HR: 0.67, 95% CI: 0.52 to 0.85). The risk of all-cause mortality (5.1% vs. 4.5%, HR: 1.09, 95% CI: 0.67 to 1.79) and death from CV (2.8% vs. 2.3%, HR: 1.07, 95% CI: 0.29 to 2.33) did not significantly differ between the 2 groups. Conclusion: This study suggests that, in moderate CKD patients with hypertriglyceridemia but LDL-C < 100mg/dL who did not take other lipid-lowering agents, fibrates may be beneficial in reducing cardiovascular events.

Glucose Metabolism of Hippocampal Subfields in Medial Temporal Lobe Epilepsy.

PURPOSE: Reduced glucose metabolism in the hippocampus is commonly observed in cases of medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS). Glucose metabolism among the various hippocampal subfields has not been thoroughly investigated. PATIENTS AND METHODS: This study examined 29 patients (18 females; 15-58 years) diagnosed with HS who underwent surgery for drug-resistant epilepsy. FreeSurfer 7.1.1 was used in the processing of MRI data and 18 F-FDG PET scans to derive volumetric data and the FDG SUVr in the whole hippocampus and hippocampal subfields, including the CA1, CA2-4, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), and subiculum. Asymmetries in the volume and SUVr between the 2 sides from the subfields of the hippocampus were defined in terms of an asymmetry index. Comparisons of the asymmetry index among these regions were performed. The correlations between asymmetry index values and postoperative outcomes and presurgical neuropsychological test results were also evaluated. RESULT: The CA1, CA2-4, subiculum, GC-ML-DG, and whole hippocampus presented reductions in volume and hypometabolism ipsilateral to MTLE. Asymmetries in volume and SUVr were significantly less pronounced in the CA1 and subiculum than in the CA2-4 or GC-ML-DG. Postoperative seizure outcomes were not correlated with the asymmetry index for volume or SUVr in any hippocampal subfield. In cases of left MTLE, scores of immediate logical memory and delayed logical memory were positively correlated with the asymmetry index for SUVr in the following subfields: CA1 ( R = 0.829, P = 0.021; R = 0.770, P = 0.043), CA2-4 ( R = 0.825, P = 0.022; R = 0.894, P = 0.007), subiculum ( R = 0.882, P = 0.009; R = 0.853, P = 0.015), GC-ML-DG ( R = 0.850, P = 0.015; R = 0.796, P = 0.032), and whole hippocampus ( R = 0.841, P = 0.018; R = 0.822, P = 0.023). In cases of right MTLE, the scores for delayed face memory were positively correlated with the asymmetry index for SUVr in the subiculum ( R = 0.935, P = 0.006). CONCLUSIONS: In cases of HS, changes in glucose metabolism levels varied among the hippocampal subfields. Asymmetries in glucose metabolism among the CA-1, CA2-4, subiculum, and GC-ML-DG subregions were correlated with scores for verbal memory among patients with left MTLE. Asymmetric glucose metabolism in the subiculum was also correlated with visual memory scores among patients with right MTLE.

Vascular compactness of unruptured brain arteriovenous malformation predicts risk of hemorrhage after stereotactic radiosurgery.

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm3 versus 20-40 cm3 versus > 40 cm3; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV-V compared with grade I-III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm3) bAVMs and the diffuse Spetzler-Martin IV-V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs.