Associations of Cerebral Small Vessel Disease on the Features of Hematoma and Hematoma Expansion in Intracerebral Hemorrhage.

INTRODUCTION: Several early noncontrast CT (NCCT) signs of spontaneous intracerebral hemorrhage (ICH) can predict hematoma expansion (HE). However, the associations of underlying cerebral small vessel disease (SVD) on early NCCT signs and HE have been less explored. METHODS: We conducted an analysis of all patients with spontaneous supratentorial ICH and received follow-up imaging between 2016 and 2020 at a stroke center. The early NCCT signs were categorized as shape or density signs. HE was defined as an increase in hematoma volume ≥6 mL or 33% from baseline. The severity of SVD was assessed by both a 3-point CT-based and a 4-point magnetic resonance imaging (MRI)-based SVD score. Regression models were used to examine the associations between SVD score and hematoma volume, NCCT signs, and HE. RESULTS: A total of 328 patients (median age: 64 years; 38% female) were included. The median baseline ICH volume was 8.6 mL, with 38% of the patients had shape signs and 52% had density signs on the initial NCCT. Higher MRI-SVD scores were associated with smaller ICH volumes (p = 0.0006), fewer shape (p = 0.001), or density signs (p = 0.0003). Overall, 16% of patients experienced HE. A higher MRI-SVD score was inversely associated with HE (adjusted odds ratio 0.71, 95% CI: 0.53-0.96). Subgroup analysis revealed that this association was primarily observed in patients who were younger (<65 years), male, had deep hemorrhage, or did not meet the criteria for cerebral amyloid angiopathy diagnosis. CONCLUSIONS: In patients with spontaneous ICH, a more severe SVD was associated with smaller hematoma volume, fewer NCCT signs, and a lower risk of HE. Further research is required to investigate why a higher burden of severely diseased cerebral small blood vessels is associated with less bleeding.

Outcome prediction of cardiac arrest with automatically computed gray-white matter ratio on computed tomography images.

BACKGROUND: This study aimed to develop an automated method to measure the gray-white matter ratio (GWR) from brain computed tomography (CT) scans of patients with out-of-hospital cardiac arrest (OHCA) and assess its significance in predicting early-stage neurological outcomes. METHODS: Patients with OHCA who underwent brain CT imaging within 12 h of return of spontaneous circulation were enrolled in this retrospective study. The primary outcome endpoint measure was a favorable neurological outcome, defined as cerebral performance category 1 or 2 at hospital discharge. We proposed an automated method comprising image registration, K-means segmentation, segmentation refinement, and GWR calculation to measure the GWR for each CT scan. The K-means segmentation and segmentation refinement was employed to refine the segmentations within regions of interest (ROIs), consequently enhancing GWR calculation accuracy through more precise segmentations. RESULTS: Overall, 443 patients were divided into derivation N=265, 60% and validation N=178, 40% sets, based on age and sex. The ROI Hounsfield unit values derived from the automated method showed a strong correlation with those obtained from the manual method. Regarding outcome prediction, the automated method significantly outperformed the manual method in GWR calculation (AUC 0.79 vs. 0.70) across the entire dataset. The automated method also demonstrated superior performance across sensitivity, specificity, and positive and negative predictive values using the cutoff value determined from the derivation set. Moreover, GWR was an independent predictor of outcomes in logistic regression analysis. Incorporating the GWR with other clinical and resuscitation variables significantly enhanced the performance of prediction models compared to those without the GWR. CONCLUSIONS: Automated measurement of the GWR from non-contrast brain CT images offers valuable insights for predicting neurological outcomes during the early post-cardiac arrest period.

A direct healthcare cost analysis of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

PURPOSE: We have previously published a retrospective matched-case control study comparing the effect of recombinant LH (r-hLH) versus highly purified human menopausal gonadotropin (hMG) supplementation on the follicle-stimulating hormone (FSH) during controlled ovarian hyperstimulation (COH) in the GnRH-antagonist protocol. The result from that study showed that the cumulative live birth rate (CLBR) was significantly higher in the r-hLH group (53% vs. 64%, p = 0.02). In this study, we aim to do a cost analysis between these two groups based on our previous study. METHODS: The analysis consisted of 425 IVF and ICSI cycles in our previous study. There were 259 cycles in the r-hFSH + hMG group and 166 cycles in the r-hFSH + r-hLH group. The total cost related to the treatment of each patient was recorded. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed and created. RESULTS: The total treatment cost per patient was significantly higher in the r-hFSH + r-hLH group than in the r-hFSH + hMG group ($4550 ± 798.86 vs. $4290 ± 734.6, p = 0.003). However, the mean cost per live birth in the r-hFSH + hMG group was higher at $8052, vs. $7059 in the r-hFSH + r-hLH group. The CEAC showed that treatment with hFSH + r-hLH proved to be more cost-effective than treatment with r-hFSH + hMG. Willingness-to-pay was evident when considering a hypothetical threshold of $18,513, with the r-hFSH + r-hLH group exhibiting a 99% probability of being considered cost-effective. CONCLUSION: The cost analysis showed that recombinant LH is more cost-effective than hMG supplementation on r-hFSH during COH in the GnRH-antagonist protocol.

Cerebral Venous Reflux and Cerebral Amyloid Angiopathy: An Magnetic Resonance Imaging/Positron Emission Tomography Study.

BACKGROUND: Cerebral venous outflow alterations contribute to central nervous system pathology in aging and neurodegenerative disorders and are potentially linked to underlying cerebral microangiopathy. We investigated whether cerebral venous reflux (CVR) is more closely associated with cerebral amyloid angiopathy (CAA) than hypertensive microangiopathy in intracerebral hemorrhage (ICH) survivors. METHODS: This cross-sectional study included 122 patients of spontaneous ICH with magnetic resonance and positron emission tomography imaging studies (2014-2022) in Taiwan. The presence of CVR was defined as abnormal signal intensity in the dural venous sinus or internal jugular vein on magnetic resonance angiography. Cerebral amyloid load was measured using the Pittsburgh compound B standardized uptake value ratio. Clinical and imaging characteristics associated with CVR were evaluated in univariable and multivariable analyses. In the subset of patients with CAA, we applied univariable and multivariable linear regression analyses to evaluate the association between CVR and cerebral amyloid retention. RESULTS: Compared with patients without CVR (n=84, 64.5±12.1 years), patients with CVR (n=38, 69.4±11.5 years) were significantly more likely to have CAA-ICH (53.7% versus 19.8%; P<0.001) and had a higher cerebral amyloid load (standardized uptake value ratio [interquartile range], 1.28 [1.12-1.60] versus 1.06 [1.00-1.14]; P<0.001). In a multivariable model, CVR was independently associated with CAA-ICH (odds ratio, 4.81 [95% CI, 1.74-13.27]; P=0.002) after adjustment for age, sex and conventional small vessel disease markers. In CAA-ICH, higher PiB retention was observed in patients with CVR than patients without CVR (standardized uptake value ratio [interquartile range], 1.34 [1.08-1.56] versus 1.09 [1.01-1.26]; P<0.001). In multivariable analysis after adjustment for potential confounders, the presence of CVR was independently associated with a higher amyloid load (standardized ß=0.40; P=0.001). CONCLUSIONS: In spontaneous ICH, CVR is associated with CAA and a higher amyloid burden. Our results suggest venous drainage dysfunction potentially plays a role in CAA and cerebral amyloid deposition.

The Extent of Tumor Invasion and Therapeutic Embolization Are Associated with Recurrent Hemorrhage in Patients with External Carotid Artery Blowout Syndrome.

PURPOSE: To explore the optimal strategies of therapeutic embolization for patients with carotid blowout syndrome in the external carotid artery (ECA), who may also present with arterial tumor invasion or necrosis extending to the internal carotid artery (ICA) or common carotid artery (CCA). MATERIALS AND METHODS: The study included 110 patients with ECA blowout between 2005 and 2022. Antecedent cross-sectional imaging features were examined, including tumor size, extent of arterial invasion, and air-containing necrosis. Patients were divided into Groups 1 (n = 53, simultaneous ICA/CCA invasion + ECA therapeutic embolization), 2 (n = 18, simultaneous ICA/CCA invasion + ECA-ICA/CCA therapeutic embolization), and 3 (n = 39, no ICA/CCA invasion + ECA therapeutic embolization). Kaplan-Meier and multivariable Cox regression analyses were performed to evaluate associations of clinical, imaging, and therapeutic embolization characteristics with recurrent bleeding. RESULTS: Multivariable Cox regression revealed that Group 1 was independently associated with a higher risk of recurrent bleeding than that in Group 2 (adjusted hazard ratio, 6.3; 95% CI, 1.7‒23.4; P = .005) and Group 3 (adjusted hazard ratio, 3.8; 95% CI, 1.8‒8.3; P = .001). In the subgroup with simultaneous ICA/CCA invasion, air-containing necrosis around the ICA/CCA was independently associated with recurrent bleeding after therapeutic embolization of the ECA (adjusted hazard ratio, 5.0; 95% CI, 1.8‒13.6; P = .002). CONCLUSIONS: In patients with ECA blowout treated with therapeutic embolization, there was a lower risk of recurrent bleeding when the extents of arterial invasion and therapeutic embolization were concordant. Air-containing necrosis around the ICA/CCA was associated with recurrent bleeding, so extensive therapeutic embolization to the ICA/CCA should be evaluated in such patients.

Presence of endometrioma decreased blastocyst formation rate but not impair Assisted Reproductive Technology (ART) outcome.

PURPOSE: This study aims to assess the impact of endometrioma on patients who undergo ART treatment due to endometriosis. METHODS: A retrospective study was conducted on women ≤ 40 years of age who underwent ART treatment at an academic medical center between January 2014 and December 2020. Two-hundred-and-eight women had received IVF/ICSI treatment due to endometriosis and there were 89 patients presence of endometrioma. Patients were further divided into primary endometrioma, recurrent endometrioma and those having received cystectomy for endometrioma prior to IVF/ICSI. The control group included 624 infertile women without endometriosis. RESULTS: In the endometrioma subgroup (B) the blastocyst formation rate was significantly lower when compared with the endometriosis (A) and control groups (C). The cumulative live birth rates (CLBRs) (60.5% versus 49.4% versus 56.9%, p = 0.194 in A versus B, p = 0.406 in A versus C, p = 0.878 in B versus C) were comparable. Multiple logistic regression analysis revealed that female age, total FSH dose and blastocyst formation rate were the significant variables in predicting CLBR (OR 0.89, CI 0.80-0.99, p < 0.025, OR 0.68 CI 0.53-0.88, p = 0.003 and OR 30.04, CI 9.93-90.9, p < 0.001, respectively). The CLBRs were comparable at 47.1%, 60% and 57.9% in the primary endometrioma, s/p cystectomy and recurrent endometrioma group. CONCLUSION: Although the blastocyst formation rate was lower in the endometrioma group, CLBR was not worse than those who were in the endometriosis or control group. Cystectomy for endometrioma did not alter IVF/ICSI outcomes if the ovarian reserve was comparable. Recurrent endometrioma did not worsen IVF/ICSI outcomes than primary endometrioma.

Development of a Predictive Model for Optimization of Embryo Transfer Timing Using Blood-Based microRNA Expression Profile.

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

[Pelvic floor muscle rehabilitation training combined with psychological nursing intervention in the treatment of type â ¢B prostatitis].

OBJECTIVE: To investigate the clinical effect of pelvic floor muscle rehabilitation training combined with psychological nursing intervention in the treatment of intractable type ⅢB prostatitis. METHODS: We retrospectively analyzed the clinical data on 51 cases of intractable type ⅢB prostatitis treated from October 2020 to October 2022, which were randomly assigned to receive Tamsulosin medication (the control group, n = 24) or pelvic floor muscle rehabilitation training and psychological nursing in addition (the intervention group, n = 27), all for 8 weeks. We obtained NIH-CPSI, IIEF-5, Self-Rating Anxiety Scale (SAS) scores, Self-Rating Depression Scale (SDS) scores, the level of lecithin and the count of leukocytes in the prostatic fluid and the incidence of adverse events, and compared them between the two groups of patients before and after treatment. RESULTS: The total effectiveness rate was significantly higher in the intervention than in the control group (88.9% vs 62.5%, P < 0.05). Compared with the baseline, the NIH-CPSI, IIEF-5, SAS and SDS scores and the lecithin level were remarkably increased in both groups after treatment (P < 0.05), even more significantly in the intervention group than in the control (P < 0.05). No statistically significant difference was observed in the count of leukocytes before and after treatment (P > 0.05). CONCLUSION: On the basis of Tamsulosin medication, the application of pelvic floor rehabilitation training combined with psychological care can significantly enhance the therapeutic effect on type IIIB prostatitis, effectively relieve prostatitis pain, improve erectile function, lessen anxiety and depression symptoms, increase the level of lecithosomes and promote the recovery of prostatic function.

On-Table Catheter-Based Neurosalvage Performed by Cardiologists for Embolic Complication during an Endovascular Procedure.

Objectives: To report our experience and clinical results of neurosalvage techniques, performed by interventional cardiologists without moving the patient, to manage cerebral thromboembolic complications. Background: Iatrogenic emboli may be released during an endovascular procedure, causing permanent neurological complications and catastrophic outcomes. Methods: Between July 2013 and December 2017, a total of eight patients suffered from embolic complications during endovascular procedures (two radiofrequency catheter ablation, five coronary angiogram/angioplasty, and one subclavian artery angioplasty). Catheter-based neurosalvage was attempted by experienced interventional cardiologists promptly in the same catheterization room. Results: The embolized locations were the M1 segment of the middle cerebral artery in four patients, the M2/M3 segments in three, and the basilar artery in one. Access to the supra-aortic vessels was achieved. Local intra-arterial thrombolysis was given in five patients (63%) and balloon angioplasty in three (38%). Intra-arterial thrombectomy with a stent retriever was attempted in three patients but failed in one. A combination of different techniques was used in three patients (38%). Final thrombolysis in cerebral infarction grade 3 flow was achieved in seven patients (88%). Favorable clinical outcomes at 1-month follow-up (modified Rankin scale of 0-2) were observed in seven patients (88%), and none of the patients had died at 12 months. Conclusions: Our experience demonstrated that acute embolic complications during an endovascular procedure can be salvaged by interventional cardiologists with acceptable angiographic and clinical results.

Spatial distribution of cerebral microbleeds reveals heterogeneous pathogenesis in CADASIL.

OBJECTIVES: Radiological diagnosis of subtypes of cerebral small vessel diseases remains challenging. This study aimed to explore the spatial distribution of cerebral microbleeds (CMBs) in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) in contrast to cerebral amyloid angiopathy (CAA) in the lobar regions. METHODS: Thirty-two patients with CADASIL and 33 patients with probable CAA were prospectively and consecutively included. On 3-Tesla susceptibility-weighted magnetic resonance images, CMBs were analyzed for incidence and volume within atlas-based regions of interest, followed by voxel-wise analysis using risk mapping. The distribution of CMBs was correlated with the status of hypertension. Correlation and group differences with a p-value less than 0.05 were considered to be significant. RESULTS: As compared with the CAA group, the CADASIL group presents a larger CMB volume in hippocampus/amygdala and white matter (nonparametric analysis of covariance, p = 0.014 and 0.037, respectively), a smaller CMB volume in parietal lobe (p = 0.038), and a higher incidence in hippocampus/amygdala, white matter, and insula (logistic regression, p = 0.019, 0.024, and 0.30, respectively). As part of the exclusion criteria of probable CAA, thalamus, basal ganglia, and pons exhibit greater CMB volume/incidence in the CADASIL group. In CADASIL patients, hot spots of CMBs are identified in the putamen and posteromedial thalamus; hypertension is associated with larger CMB volumes in insula, basal ganglia, and pons. CONCLUSIONS: The spatial distribution of CMBs is differentiable between CADASIL and CAA in lobar regions. In CADASIL patients, hypertension has a region-dependent mediating effect on the CMB volume. KEY POINTS: • The topological distribution of lobar CMBs is differentiable between CADASIL and CAA. • In CADASIL patients, hypertension mediates CMB volume and the mediation is region dependent. • CMB risk mapping allows for voxel-wise exploration of CMB distribution and reveals hot spots in the putamen and posteromedial thalamus in CADASIL.

Comparison of clinical and neuroimaging features between NOTCH3 mutations and nongenetic spontaneous intracerebral haemorrhage.

BACKGROUND AND PURPOSE: The NOTCH3 mutation is a common cause of hereditary cerebral small vessel disease (CSVD) and may be a cause of spontaneous intracerebral haemorrhage (ICH). The aim was to investigate the clinical/imaging features for identifying the NOTCH3-mutation-related ICH. METHODS: The study was based on a cohort of 749 CSVD patients in Taiwan who received next-generation sequencing of CSVD genes including NOTCH3. Patients with a history of ICH (n = 206) were included for analysis. The CSVD neuroimaging markers were compared between the patients with NOTCH3 and those without known genetic mutations. RESULTS: After excluding patients with other causes of ICH (structural lesions, systemic/medication related or amyloid angiopathy) and those without neuroimaging, 45 NOTCH3 mutation patients and 109 nongenetic ICH patients were included. The NOTCH3 mutation patients were more likely to have thalamic haemorrhage, a family history of stroke and more severe CSVD neuroimaging markers. A five-point NOTCH3-ICH score was constructed and consisted of a history of stroke in siblings, thalamic haemorrhage, any deep nuclei lacunae, any hippocampal cerebral microbleed (CMB) and a thalamic CMB >5 (one point for each). A score ≥2 had a sensitivity of 88.9% and a specificity of 64.2% in identifying the NOTCH3 mutation. The NOTCH3 mutation patients had a higher risk of recurrent stroke (9.1 vs. 4.5 per 100 person-years, log-rank p = 0.03) during follow-up. CONCLUSION: The patients with NOTCH3-mutation-related ICH had a higher burden of CMBs in the hippocampus/thalamus and a higher recurrent stroke risk. The NOTCH3-ICH score may assist in identifying genetic causes of ICH.

Plasma soluble TREM2 is associated with white matter lesions independent of amyloid and tau.

Cerebral small vessel disease is one of the most common causes of cognitive decline and stroke. While several lines of evidence have established a relationship between inflammation and cerebrovascular pathology, the mechanistic link has not yet been elucidated. Recent studies suggest activation of immune mediators, including the soluble form of triggering receptor expressed on myeloid cells 2 (TREM2), may be critical regulators. In this study, we compared the plasma levels of soluble TREM2 and its correlations with neuroimaging markers and cerebral amyloid load in 10 patients with Alzheimer's disease and 66 survivors of spontaneous intracerebral haemorrhage with cerebral amyloid angiopathy or hypertensive small vessel disease, two of the most common types of sporadic small vessel disease. We performed brain MRI and 11C-Pittsburgh compound B PET for all participants to evaluate radiological small vessel disease markers and cerebral amyloid burden, and 18F-T807 PET in a subgroup of patients to evaluate cortical tau pathology. Plasma soluble TREM2 levels were comparable between patients with Alzheimer's disease and small vessel disease (P = 0.690). In patients with small vessel disease, plasma soluble TREM2 was significantly associated with white matter hyperintensity volume (P < 0.001), but not with cerebral amyloid load. Among patients with Alzheimer's disease and cerebral amyloid angiopathy, plasma soluble TREM2 was independently associated with a tau-positive scan (P = 0.001) and white matter hyperintensity volume (P = 0.013), but not amyloid load (P = 0.221). Our results indicate plasma soluble TREM2 is associated with white matter hyperintensity independent of amyloid and tau pathology. These findings highlight the potential utility of plasma soluble TREM2 as a strong predictive marker for small vessel disease-related white matter injury and hold clinical implications for targeting the innate immune response when treating this disease.

Long-term outcomes of moyamoya disease following indirect revascularization in middle adulthood: A prospective, quantitative study.

BACKGROUND/PURPOSE: Our previous study demonstrated that indirect revascularization is effective in the treatment of adult moyamoya patients. This prospective study aims to evaluate the long-term effectiveness of indirect revascularization in moyamoya patients in middle adulthood. METHODS: From January 2013 to June 2019, moyamoya patients more than 40 years of age underwent indirect revascularizations were studied. The hypoperfusion area of brains was revascularized. The cerebral angiography and time-to-peak (TTP) scoring (ranged 0-14) of the magnetic resonance perfusion study were used to evaluate the revascularization effect. RESULTS: During the study period, 50 consecutive adult moyamoya patients underwent indirect revascularization. Seventeen patients (27 cerebral hemispheres) more than 40 years of age were included. The mean age was 47.9 ± 6.4 years, and 13 patients were female. The pre-operative Suzuki stages were I, II, III, IV, V, and VI in 1, 1, 9, 13, 0, and 3 hemispheres, respectively. After a mean follow-up period of 52.5 ± 20.6 months, all patients had improvement or stabilization of their clinical conditions. Available post-operative angiography demonstrated Matsushima grading A in 18 of 20 hemispheres. The mean TTP score of all 27 hemispheres improved from 5.0 ± 3.3 pre-operatively to 12.0 ± 2.1 after surgery (p < 0.001). The post-operative mean TTP score of the 7 hemispheres without angiographic follow-up was 10.4 ± 1.8. One patient had persistent mild motor weakness after 56-month follow-up. Transient complications with full recovery occurred in 3 patients. CONCLUSION: Indirect revascularization is a safe method with satisfactory long-term results in moyamoya patient in middle adulthood.

Air-containing necrosis as the imaging predictor for imminent carotid blowout in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Carotid blowout syndrome (CBS) is a devastating complication of head and neck cancer (HNC). In this study, we describe radiological features that can predict imminent (<6 months) carotid blowout in patients with HNC. METHODS: Cross-sectional CT or MRI were interpreted from 25 treated HNC patients with acute CBS and 50 treated HNC patients without CBS (controls). The tumor size and the distance from the tumor to the carotid trunk was measured. The following imaging findings of the tumor were also recorded: carotid trunk involvement, enhancement pattern, and the presence of air-containing necrosis. The odds ratios of imminent CBS for each imaging finding were estimated using a multivariable logistic regression model. RESULTS: Compared to the controls, the CBS group had larger tumors (49 ± 18 mm vs. 38 ± 18 mm, p = 0.017), tumors closer to the carotid trunk (0.5 ± 1.7 mm vs. 8.2 ± 14.2 mm, p < 0.001), a higher prevalence of 360° involvement (60% vs. 18%, p < 0.001), more heterogeneous enhancement patterns (84% vs. 50% p < 0.001), and more air-containing necrosis (40% vs. 2% p < 0.001). After multivariable adjustment, the presence of air-containing necrosis remained a significant risk factor for imminent CBS (OR: 20.1, 95% CI: 1.98-204.00; p = 0.011). CONCLUSION: The presence of air-containing necrosis is associated with a higher risk of imminent CBS. This characteristic imaging finding should be evaluated in the follow-up CT or MRI of HNC patients for early warning.

[Using Multiple Strategies to Reduce the Incidence of Delirium in Older Adult Patients Receiving Surgery].

BACKGROUND & PROBLEMS: Older adult patients receiving surgery experience a relatively high rate of developing acute delirium due to factors related to the environment, surgery and anesthesia, pain, and indwelling line, which puts these patients at higher risk of patient safety incidents. The incidence of delirium among older patients receiving surgery in our ward was 12.3%. Moreover, in our ward, delirium-attributed self-extraction accounted for 84.2% of the "tubing events" reported via the Taiwan Patient-safety Reporting System and delirium-attributed falls accounted for 33.3% of the "fall events". Thus, delirium in this patient population had a serious effect on patient safety and increased medical expenses. PURPOSE: Reduce the incidence of delirium in older adult patients receiving surgery from 12.3% to 6.6%. METHODS: Strategies used included providing delirium care education and training to improve the delivery of delirium preventive treatments and the care implementation rate by care teams; formulating a surgical delirium high-risk factor assessment scale for the early screening of high-risk patients; adopting the "RADAR" delirium identification method for the rapid identification of cognition changes; establishing delirium prevention and treatment care guidelines for quality-of-care improvement; introducing bedside exercise equipment to increase patient mobility; and designating a dedicated delirium ward for these patients to provide high-quality delirium care services. RESULTS: The incidence rate of delirium in older adult patients receiving surgery was reduced to 6.5%. In addition, the implementation rate of delirium prevention treatment was increased to 98% in physicians and 100% in nurses. CONCLUSIONS: This project resulted in significantly improved outcomes and was expanded to the other surgical wards. The innovative concept of incorporating a designated delirium ward for older patients receiving surgery into other wards may be referenced in future ward planning and strategies for improving the quality of medical care.

Centrum Semiovale Perivascular Space and Amyloid Deposition in Spontaneous Intracerebral Hemorrhage.

Background and Purpose: We explored whether high-degree magnetic resonance imaging­visible perivascular spaces in centrum semiovale (CSO) are more prevalent in cerebral amyloid angiopathy (CAA) than hypertensive small vessel disease and their relationship to brain amyloid retention in patients with primary intracerebral hemorrhage (ICH). Methods: One hundred and eight spontaneous ICH patients who underwent magnetic resonance imaging and Pittsburgh compound B were enrolled. Topography and severity of enlarged perivascular spaces were compared between CAA-related ICH (CAA-ICH) and hypertensive small vessel disease­related ICH (non-CAA ICH). Clinical and image characteristics associated with high-degree perivascular spaces were evaluated in univariate and multivariable analyses. Univariate and multivariable models were performed to evaluate associations between the severity of perivascular spaces in CSO and amyloid retention in CAA-ICH and non­CAA-ICH cases. Results: Patients with CAA-ICH (n=29) and non­CAA-ICH (n=79) had similar prevalence of high-degree perivascular spaces in CSO (44.8% versus 36.7%; P=0.507) and in basal ganglia (34.5% versus 51.9%; P=0.131). High-degree perivascular spaces in CSO were independently associated with the presence of lobar microbleed (odds ratio, 3.0 [95% CI, 1.1­8.0]; P=0.032). The amyloid retention was higher in those with high-degree than those with low-degree CSO-perivascular spaces in CAA-ICH (global Pittsburgh compound B standardized uptake value ratio, 1.55 [1.33­1.61] versus 1.13 [1.01­1.48]; P=0.003) but not in non­CAA-ICH. In CAA-ICH, the association between cerebral amyloid retention and the degree of perivascular spaces in CSO remained significant after adjustment for age and lobar microbleed number (P=0.004). Conclusions: Although high-degree magnetic resonance imaging­visible perivascular spaces are equally prevalent between CAA-ICH and non­CAA-ICH in the Asian cohort, the severity of magnetic resonance imaging­visible CSO-perivascular spaces may be an indicator of higher brain amyloid deposition in patients with CAA-ICH.

Peri-radiosurgical administration of bevacizumab improves radiographic response to single and fractionated stereotactic radiosurgery for large brain metastasis.

INTRODUCTION: Stereotactic radiosurgery (SRS) is a standard of care for brain metastases (BM) patients, yet large BM are at a greater risk for radionecrosis and local progression (LP). Concomitant bevacizumab and radiotherapy has been shown to improve outcomes in primary and metastatic brain tumors. This retrospective study investigated the efficacy and safety of concurrent bevacizumab and SRS for large BM. METHODS: From 2015 to 2019, patients with a BM diameter ≥ 2 cm who received either combination therapy (n = 49, SRS + BVZ group), or SRS alone (n = 73, SRS group) were enrolled. Bevacizumab was given peri-radiosurgically with a 2-week interval. Radiographic response was assessed using the RECIST version 1.1. Competing risk and logistic regression analysis were performed to evaluate prognostic factors. RESULTS: Radiographic response was achieved in 41 patients (84%) in the SRS + BVZ group and 37 patients (51%) in the SRS group (p = 0.001). In the multivariate regression analysis, concurrent bevacizumab was independently associated with a better radiographic response (p = 0.003). The cumulative incidences of LP and ≥ grade 2 radionecrosis at 12 months between the SRS + BVZ group and SRS group were 2% versus 6.8%, and 14.3% versus 14.6%, respectively. For patients with BM size ≥ 3 cm, the cumulative incidence of LP was significantly lower in the SRS + BVZ group (p = 0.03). No ≥ grade 4 toxicity was observed in either group. CONCLUSIONS: Concurrent bevacizumab and SRS for large BM is highly effective, with a better radiographic response and minimal excessive treatment-related toxicities. Peri-radiosurgical bevacizumab preferentially reduced the risk of LP, especially for BM size ≥ 3 cm.

Design and synthesis of 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives with anti-acetylcholinesterase activities.

Twelve novel 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives were synthesized via iodine-mediated oxidative cyclisation and confirmed by 1H NMR, 13C NMR and HRMS. The result of these derivatives' activities inhibiting acetylcholinesterase in vitro showed that 4 g and 4i had moderate inhibitory activities with 69.19% and 65.06%, respectively. The preliminary structure-activity relationships revealed that introduction of halogen atom on the para-position of phenyl of 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives could enhance their activities. Molecular docking study suggested that 4 g possessed an optimal docking pose with interactions inside AChE.

Superficial Cerebellar Microbleeds and Cerebral Amyloid Angiopathy: A Magnetic Resonance Imaging/Positron Emission Tomography Study.

Background and Purpose- The differentiation between cerebral amyloid angiopathy (CAA) and hypertensive small vessel disease in primary intracerebral hemorrhage is mainly based on hemorrhagic neuroimaging markers in the supratentorial regions, and the cause for cerebellar microbleeds remains unknown. Our aim was to investigate whether superficial cerebellar microbleeds are more likely to be related to CAA rather than hypertensive small vessel disease. Methods- Two hundred seventy-five consecutive patients with intracerebral hemorrhage were retrospectively reviewed from a prospectively maintained hospital-based stroke registry. Eighty-five (33.1%) patients had cerebellar microbleeds and were categorized into superficial (gray matter, vermis), deep (white matter, deep nucleus, cerebellar peduncle), or mixed type based on the location of cerebellar hemorrhagic lesions. Amyloid imaging was obtained using 11C-Pittsburgh Compound B-positron emission tomography in a subgroup of patients. The associations between cerebellar microbleed locations and the type of small vessel disease (CAA versus hypertensive small vessel disease) based on distribution of supratentorial hemorrhagic lesions as well as other magnetic resonance imaging and positron emission tomography markers were analyzed. Results- The presence of cerebellar microbleed was independently associated with supratentorial microbleed and lacunar infarcts (both P<0.01). Strictly superficial cerebellar microbleeds were significantly related to CAA-intracerebral hemorrhage, cortical superficial siderosis and high-grade enlarged perivascular space in centrum semiovale (all P<0.05); deep or mixed cerebellar microbleeds were related to hypertension and deep microbleed (all P<0.05). In multivariable models, superficial cerebellar microbleeds were independently associated with CAA-intracerebral hemorrhage (P=0.03). Of 33 patients assessed by amyloid positron emission tomography, cerebral and cerebellar amyloid load (standardized uptake value ratio) was higher in patients with superficial cerebellar microbleeds compared with deep/mixed cerebellar microbleeds (cerebrum standardized uptake value ratio [reference: cerebellum] 1.33±0.24 versus 1.05±0.09, P<0.001; cerebellum standardized uptake value ratio [reference: pons] 0.58±0.08 versus 0.51±0.09, P=0.03). Conclusions- Patients with strictly superficial cerebellar microbleeds are associated with a clinicoradiological diagnosis of CAA as well as increased cerebral and cerebellar amyloid deposition on Pittsburgh Compound B-positron emission tomography, suggesting underlying CAA pathology.

Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL.

BACKGROUND: Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients. METHODS: Sixty-three CADASIL patients (mean age 58.9 ± 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up. RESULTS: Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06-3.87) and ICH (odds ratio 2.06, 95% CI 1.26-3.35) at baseline, respectively. Within a mean follow-up period of 3.1 ± 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19-3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21-6.53) predicted incident ICH. CONCLUSIONS: In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.