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Background: Quantitative susceptibility mapping (QSM) is a post-processing technique that creates brain susceptibility maps reflecting metal burden through tissue magnetic susceptibility. We assessed topographic differences in magnetic susceptibility between participants with and without Wilson's disease (WD), correlating these findings with clinical severity, brain volume, and biofluid copper and iron indices. Methods: A total of 43 patients with WD and 20 unaffected controls, were recruited. QSM images were derived from a 3T MRI scanner. Clinical severity was defined using the minimal Unified Wilson's Disease Rating Scale (M-UWDRS) and Montreal Cognitive Assessment scoring. Differences in magnetic susceptibilities between groups were evaluated using general linear regression models, adjusting for age and sex. Correlations between the susceptibilities and clinical scores were analyzed using Spearman's method. Results: In age- and sex-adjusted analyses, magnetic susceptibility values were increased in WD patients compared with controls, including caudate nucleus, putamen, globus pallidus, and substantia nigra (all p < 0.01). Putaminal susceptibility was greater with an initial neuropsychiatric presentation (n = 25) than with initial hepatic dysfunction (n = 18; p = 0.04). Susceptibility changes correlated negatively with regional brain volume in almost all topographic regions. Serum ferritin, but not serum copper or ceruloplasmin, correlated positively with magnetic susceptibility level in the caudate nucleus (p = 0.04), putamen (p = 0.04) and the hippocampus (p = 0.03). The dominance of magnetic susceptibility in cortical over subcortical regions correlated with M-UWDRS scores (p < 0.01). Conclusion: The magnetic susceptibility changes could serve as a surrogate marker for patients with WD.

Objective: Our aim is to demonstrate a rare cause of hemoperitoneum without vaginal bleeding resulting from the rupture of a uterine artery pseudoaneurysm after uncomplicated vaginal delivery. Case report: A 39-year-old woman who had experienced a normal vaginal delivery 8 days previously to being seen in our hospital, was presented to the emergency room with hypovolemic shock. Computed tomography angiography (CTA) showed massive internal bleeding and a ruptured pseudoaneurysm arising from the left uterine artery. The patient was successfully treated through transcatheter arterial embolization (TAE). Conclusion: A pseudoaneurysm is a rare disease which can occur during an uncomplicated vaginal delivery. The clinical presentation can vary from asymptomatic, vaginal bleeding or hemoperitoneum. The diagnosis can be made by using Doppler sonography, CTA or Magnetic Resonance Imaging. The use of TAE is now the most common treatment option and possesses a high success rate.

IntroductionThis study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS).Materials and methodsA retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR.ResultsWe analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p

Abstract Lobar cerebral microbleeds are a characteristic neuroimaging finding in cerebral amyloid angiopathy (CAA) but can also be found in hypertensive arteriolosclerosis. We aimed to investigate whether CAA is more associated with intracortical lobar microbleeds than hypertensive arteriosclerosis. Ninety-one survivors of spontaneous intracerebral hemorrhage with at least one lobar microbleed were included and underwent brain MRI and amyloid PET. We categorized lobar microbleeds as intracortical, juxtacortical, or subcortical. We assessed the associations between the lobar microbleed categories and microangiopathy subtypes or cerebral amyloid load based on the Pittsburgh Compound-B PET standardized uptake value ratio (SUVR). Patients with CAA had a higher prevalence of intracortical lobar microbleeds (80.0% vs. 50.8%, P = 0.011) and lower prevalence of subcortical lobar microbleeds (13.3% vs. 60.1%, P

Abstract Objective This study aimed to explore the clinical significance of brain imaging signatures in the context of clinical neurological deficits in association with upper and lower motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Methods We performed brain MRI examinations to quantitatively evaluate (1) gray matter volume and (2) white matter tract fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Image‐derived indices were correlated with (1) global neurological deficits of MRC muscle strength sum score, revised amyotrophic lateral sclerosis functional rating scale (ALSFRS‐R), and forced vital capacity (FVC), and (2) focal scores of University of Pennsylvania Upper motor neuron score (Penn score) and the summation of compound muscle action potential Z scores (CMAP Z sum score). Results There were 39 ALS patients and 32 control subjects matched for age and gender. Compared to controls, ALS patients had a lower gray matter volume in the precentral gyrus of the primary motor cortex, which was correlated with FA of corticofugal tracts. The gray matter volume of the precentral gyrus was correlated with FVC, MRC sum score, and CMAP Z sum score, while the FA of the corticospinal tract was linearly associated with CMAP Z sum score and Penn score on multivariate linear regression model. Interpretation This study indicated that clinical assessment of muscle strength and routine measurements on nerve conduction studies provided surrogate markers of brain structural changes for ALS. Furthermore, these findings suggested parallel involvement of both upper and lower motor neurons in ALS.

ObjectiveThe aim of this study is to investigate the clinical value of radiomics based on non-enhanced head CT in the prediction of hemorrhage transformation in acute ischemic stroke (AIS).Materials and methodsA total of 140 patients diagnosed with AIS from January 2015 to August 2022 were enrolled. Radiomic features from infarcted areas on non-enhanced CT images were extracted using ITK-SNAP. The max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select features. The radiomics signature was then constructed by multiple logistic regressions. The clinicoradiomics nomogram was constructed by combining radiomics signature and clinical characteristics. All predictive models were constructed in the training group, and these were verified in the validation group. All models were evaluated with the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).ResultsOf the 140 patients, 59 experienced hemorrhagic transformation, while 81 remained stable. The radiomics signature was constructed by 10 radiomics features. The clinicoradiomics nomogram was constructed by combining radiomics signature and atrial fibrillation. The area under the ROC curve (AUCs) of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the training group were 0.64, 0.86, and 0.86, respectively. The AUCs of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the validation group were 0.63, 0.90, and 0.90, respectively. The DCA curves showed that the radiomics signature performed well as well as the clinicoradiomics nomogram. The DCA curve showed that the clinical application value of the radiomics signature is similar to that of the clinicoradiomics nomogram.ConclusionThe radiomics signature, constructed without incorporating clinical characteristics, can independently and effectively predict hemorrhagic transformation in AIS patients.

Abstract Although numerous studies have attempted to establish the relationship between adenomyosis and infertility, no consensus has emerged. Our aim was to investigate whether adenomyosis and endometriosis affected IVF outcomes in our patients. This was a retrospective study of 1720 patients from January 2016 to December 2019. In total, 1389 cycles were included: 229 cycles in the endometriosis group (group E), 89 cycles in the adenomyosis group (group A), 69 cycles in the endometriosis and adenomyosis group (group EA), and 1002 cycles in the control group (group C). Most patients in groups A and EA received GnRH agonist treatment before FET. The 1st FET live birth rates (LBR) were 39.3%, 32.1%, 25% and 48.1% in groups E, A, EA, and C. The miscarriage rates were 19.9%, 34.7%, 39%, and 17.6%. The per retrieval cycle cumulative live birth rates (cLBRs) in patients

Abstract Background To investigate the association between cerebral amyloid deposition and long‐term cognitive outcomes in patients with hemorrhagic small vessel disease (SVD) and survivors of intracerebral hemorrhage (ICH). Methods Patients experiencing an ICH without overt dementia were prospectively recruited (n = 68) for brain MRI and Pittsburgh compound B (PiB) positron emission tomography scans at baseline. Cognitive function was assessed using the mini‐mental status examination (MMSE) and clinical dementia rating after an overall median follow‐up of 3.8 years. A positive amyloid scan was defined as a global PiB standardized uptake value ratio >1.2. Associations between follow‐up cognitive outcomes and neuroimaging markers were explored using multivariable Cox regression models. Results PiB(+) patients were older (72.1 ± 7.8 vs. 59.9 ± 11.7, p = .002) and more frequently had cerebral amyloid angiopathy (CAA) (63.6% vs. 15.8%, p = .002) than PiB(−) patients. PiB(+) was associated with a higher risk of dementia conversion (32.9 vs. 4.0 per 100‐person‐years, hazard ratio [HR] = 15.7 [3.0–80.7], p = .001) and MMSE score decline (58.8 vs. 9.9 per 100‐person‐years, HR = 6.2 [1.9–20.0], p = .002). In the non‐CAA subgroup (n = 52), PiB(+) remained an independent predictor of dementia conversion, p = .04). In the Cox models, PiB(+) was an independent predictor of dementia conversion (HR = 15.8 [2.6–95.4], p = .003) and MMSE score decline (HR = 5.7 [1.6–20.3], p = .008) after adjusting for confounders. Conclusions Cerebral amyloid deposition potentially contributes to long‐term cognitive decline in SVD‐related ICH.

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

Background and Purpose Cerebral venous flow alterations potentially contribute to age-related white matter changes, but their role in small vessel disease has not been investigated. Methods This study included 297 patients with hypertensive intracerebral hemorrhages (ICH) who underwent magnetic resonance imaging. Cerebral venous reflux (CVR) was defined as the presence of abnormal signal intensity in the dural venous sinuses or internal jugular vein on time-of-flight angiography. We investigated the association between CVR, dilated perivascular spaces (PVS), and recurrent stroke risk. Results CVR was observed in 38 (12.8%) patients. Compared to patients without CVR those with CVR were more likely to have high grade (>20 in the number) dilated PVS in the basal ganglia (60.5% vs. 35.1%; adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.25 to 5.60; P=0.011) and large PVS (>3 mm in diameter) (50.0% vs. 18.5%; aOR, 3.87; 95% CI, 1.85 to 8.09; P

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 (

IntroductionThe primary factor for cardiovascular disease and upcoming cardiovascular events is atherosclerosis. Recently, carotid plaque texture, as observed on ultrasonography, is varied and difficult to classify with the human eye due to substantial inter-observer variability. High-resolution magnetic resonance (MR) plaque imaging offers naturally superior soft tissue contrasts to computed tomography (CT) and ultrasonography, and combining different contrast weightings may provide more useful information. Radiation freeness and operator independence are two additional benefits of M RI. However, other than preliminary research on MR texture analysis of basilar artery plaque, there is currently no information addressing MR radiomics on the carotid plaque.MethodsFor the automatic segmentation of MRI scans to detect carotid plaque for stroke risk assessment, there is a need for a computer-aided autonomous framework to classify MRI scans automatically. We used to detect carotid plaque from MRI scans for stroke risk assessment pre-trained models, fine-tuned them, and adjusted hyperparameters according to our problem.ResultsOur trained YOLO V3 model achieved 94.81% accuracy, RCNN achieved 92.53% accuracy, and MobileNet achieved 90.23% in identifying carotid plaque from MRI scans for stroke risk assessment. Our approach will prevent incorrect diagnoses brought on by poor image quality and personal experience.ConclusionThe evaluations in this work have demonstrated that this methodology produces acceptable results for classifying magnetic resonance imaging (MRI) data.

Early identification of vertebral compression fractures (VCFs) is crucial for successful secondary fracture prevention. Tomosynthesis, a low-dose tomographic imaging technique, may facilitate the evaluation and long-term follow-up of VCFs in patients with osteoporosis. Herein, we compared the performances of plain radiography and tomosynthesis for VCF diagnosis and healing assessment in patients enrolled in fracture liaison services in our hospital. Forty-nine patients with new VCFs at the T10–L5 levels were prospectively recruited between August 2018 and May 2020; all patients underwent thoracolumbar plain radiography and tomosynthesis. We evaluated the accuracy of the VCF diagnosis, image quality, and VCFs healing process. Tomosynthesis identified 90 levels of VCF in 49 patients, while plain radiography revealed only 87.8% (79/90) of them. There were 44.9% (22/49) patients with neglected chronic VCFs as seen on tomosynthesis. Tomosynthesis images had improved VCF diagnostic accuracy up to 12.2% and showed significantly more anatomic details than plain radiography. For diagnosis of VCFs, the performance of plain radiographs was poorer than that of tomosynthesis images (plain radiographs: sensitivity 84%, specificity 93.5%, false positive rate 6.5%, and false negative rate 16%; tomosynthesis: sensitivity 93.2%, specificity 100%, false positive rate 0%, and false negative 6.8%), using magnetic resonance imaging (MRI) as gold standard. The Kappa coefficient between Tomosynthesis and MRI is 0.956 while between radiography and MRI is 0.704. Tomosynthesis showed significantly more anatomic details than plain radiography and all the examiners revealed a clear preference for tomosynthesis. Tomosynthesis scored 3.3 times higher on the fracture healing assessment at the 3-month follow-up than plain radiographs. Tomosynthesis is a promising tool for VCF screening and diagnosis in patients with osteoporosis and for monitoring fracture healing status at a low radiation dose and cost.

BackgroundThe role of luteinizing hormone (LH) in controlled ovarian hyperstimulation (COH) requires more evidence for its efficacy. Several studies compared recombinant human LH (r-hLH) or human menopausal gonadotropin (hMG) in combination with recombinant human follicle-stimulating hormone (r-hFSH) but lack the results with GnRH-antagonist protocol and in Asians.MethodsThis is a retrospective, single-center study inspecting women receiving GnRH antagonist protocol and r-hFSH+hMG or r-hFSH+r-hLH regimen for over five days for COH in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in Taiwan from 2013 to 2018. The outcomes of IVF/ICSI cycles were analyzed after propensity score matching between the two groups. A subgroup analysis was conducted in cycles in which women underwent their first embryo transfer (ET), including fresh ET and frozen ET (FET).ResultsWith a total of 503 cycles, the results revealed that the r-hFSH+r-hLH group performed better in terms of numbers of oocytes retrieved (r-hFSH+hMG vs. r-hFSH+r-hLH, 11.7 vs. 13.7, p=0.014), mature oocytes (8.7 vs. 10.9, p=0.001), and fertilized oocytes (8.3 vs. 9.8, p=0.022), while other outcomes were comparable. The analysis of first ET cycles also showed similar trends. Although the implantation rate (39% vs. 43%, p=0.37), pregnancy rate (52% vs. 53%, p=0.90), and live birth rate (39% vs. 45%, p=0.19) were not significantly different, the miscarriage rate was higher in the r-hFSH+hMG group than the r-hFSH+r-hLH group (26% vs. 15%, p

Object: We have previously reported that cumulative live birth rates (CLBRs) are higher in the freeze-all group compared with controls (64.3% vs. 45.8%, p = 0.001). Here, we aim to determine if the freeze-all policy is more cost-effective than fresh embryo transfer followed by frozen-thawed embryo transfer (FET). Materials and methods: The analysis consisted of 704 ART (Assisted reproductive technology) cycles, which included in IVF (In vitro fertilisation) and ICSI (Intra Cytoplasmic Sperm Injection) cycles performed in Taichung Veterans General Hospital, Taiwan between January 2012 and June 2014. The freeze-all group involved 84 patients and the fresh Group 625 patients. Patients were followed up until all embryos obtained from a single controlled ovarian hyper-stimulation cycle were used up, or a live birth had been achieved. The total cost related to treatment of each patient was recorded. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-all strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed. Results: The total treatment cost per patient was significantly higher for the freeze-all group than in the fresh group (USD 3419.93 ± 638.13 vs. $2920.59 ± 711.08 p

Abstract Background Optimization of vascular risk factor control is emerging as an alternative approach to improve cognitive outcomes in Alzheimer’s disease, although its efficacy is still under debate. We aimed to investigate the contribution of vascular risk factors on Alzheimer’s biomarkers and conversion rate to dementia in subjects with mild cognitive impairment (MCI) with low cerebral small vessel disease burden. Methods Two hundred ninety-five newly diagnosed MCI subjects were enrolled from March 2005 to May 2017 for a cross-sectional assessment of vascular risk factors and Alzheimer’s plasma and imaging biomarkers, followed by a cognitive outcome assessment 24 months after enrollment. The association between vascular risk factors and Alzheimer’s biomarkers were tested using multivariable linear regression models adjusted with age, gender, education, and APOE ε4 allele. The association between vascular risk factors and conversion to dementia was tested using multivariable logistic regression models adjusted with age, gender, education, and baseline Mini-Mental State Examination (MMSE) score. Results At baseline, higher low-density lipoprotein (LDL) cholesterol level was associated with more advanced plasma biomarkers, including Aβ42/Aβ40 ratio (P = 0.012) and tau level (P = 0.001). A history of hypertension was associated with more advanced white matter hyperintensity (P = 0.011), while statin therapy for dyslipidemia was associated with less advanced white matter hyperintensity (P = 0.002). At 24 months, individual vascular risk factor was not significantly associated with cognitive outcome. By contrast, statin therapy for dyslipidemia was associated with reduced conversion to dementia (adjusted OR = 0.191, 95% CI = 0.062~0.586, P = 0.004). Conclusions For MCI subjects, dyslipidemia may contribute to AD-related neurodegeneration while hypertension may contribute to vascular pathology. The association between statin therapy for dyslipidemia and reduced conversion to dementia supports further interventional study to evaluate the potential beneficial effect of statin in MCI subjects.

Abstract 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.

Objective: Microbial contamination of ART culture media is rare but serious. We examined our own experience and conducted a review of the literature with a view to preventing its occurrence and recurrence. Case report: A total of 12 cases were recorded during January 2006 to March 2019. The contaminations were caused by semen and were shown to be bacteria that were resistant to the prophylactic antibiotics used in the medium. After the procedures were cancelled due to contaminations, nine husbands received antibiotic treatment, while nine couples changed over to the ICSI program. Eventually, eight couples concluded the study with live birth deliveries, and there was no recurrence of contamination. Conclusion: ART laboratories should preserve all sperm suspension samples until embryo transfer has been completed for the purpose of checking whether contamination has occurred. In addition to antibiotic treatment, implementation of the ICSI procedure during the next ART cycle has already been proven to be effective. In the future, the zona-removal technique may be considered as another potential option.

Progressive multifocal leukoencephalopathy (PML) is a rare viral demyelinating disease of central nervous system. Immunosuppression is a significant risk factor for the disease. Previously, PML developed more commonly in patients of hematological malignancy and acquired immune deficiency syndrome (AIDS). In the era of biological disease modifying anti-rheumatic drugs, PML is more frequently reported in patients of autoimmune diseases. However, for its rarity and unspecific clinical presentations, accurate diagnosis and immediate immune restoration might be difficult in clinical practice, and the outcome might thus be miserable. Herein we present a 27-year-old lady of systemic lupus erythematosus (SLE) – rheumatoid arthritis overlap syndrome with suspected involvement of central nervous system. Neuropsychiatric SLE was suspected first. However, after intensive immunosuppressive treatment, the condition kept deteriorating. An alternative diagnosis was thus considered. PML was suspected for her immunosuppressive status and suggestive radiological findings, and the diagnosis was confirmed by a polymerase chain reaction of JC virus from cerebrospinal fluid. After restoring the immune status by decreasing the dose of immunosuppressants, the condition of the patient improved significantly. We report this case to raise the importance of clinical alertness for the rare but possibly underdiagnosed disease. Keywords: Antirheumatic agents, Rheumatoid arthritis, Immunosuppressive agents, Progressive multifocal leukoencephalopathy, Systemic lupus erythematosus

Fisetin, a naturally occurring flavonoid in fruits, nuts and vegetables possess antioxidant and anti-inflammatory properties. This study shows that fisetin exerts preventive and therapeutic effects on hypertension associated cardiac abnormalities in H9c2 cells and Spontaneously Hypertensive Rats (SHRs). For In vitro analysis, H9c2 cells were challenged with AngII and Fisetin (50 µM/mL) was administered either before 2 h or after 12 h of AngII challenge. For In vivo studies, SHRs received oral fisetin (10 mg/kg, twice a week for 6 weeks) and their cardiac function was analyzed by echocardiography. Histological studies and Western blotting were performed to assess the severity and the mechanism of the underlying cardiac abnormality. Fisetin effectively suppressed calcineurin-NFATC3 involved cellular hypertrophic effects as observed in H9c2 cells and in SHR hearts. Fisetin also enhanced cardiac function and restored cardiac morphology and therefore, fisetin is a potential agent against hypertension associated hypertrophy and cardiac deterioration.

Objective: Cerebrovascular reactivity (CVR) represents the phenomenon where cerebral vessels dilate or constrict in response to vasoactive stimuli. CVR impairment may contribute to brain injury due to cerebral small vessel disease (SVD). We aimed to determine the CVR in hypertensive intracerebral hemorrhage (ICH) and to identify its vascular dysfunction.Methods: A total of 21 patients with spontaneous hypertensive ICH (strictly deep or mixed deep and lobar hemorrhages, mean age 62.5 ± 11.3 years) and 10 control subjects (mean age 66.1 ± 6.0 years) were enrolled for CVR measurement at least 3 months after the symptomatic ICH event. Each participant underwent a brain MRI study, and CVR was calculated as the cerebral blood flow (CBF) reduction using arterial spin labeling (ASL) between baseline and 10 min after an intravenous dipyridamole injection (0.57 mg/kg). Traditional MRI markers for SVD were also evaluated, including cerebral microbleed, white matter hyperintensity, lacune, and MRI-visible enlarged perivascular space, which were used to determine the total small vessel disease score.Results: Compared to control subjects, hypertensive ICH patients showed reduced CVR in the basal ganglia (CBF reduction 22.4 ± 22.7% vs. 41.7 ± 18.3, p = 0.026), the frontal lobe (15.1 ± 11.9 vs. 26.6 ± 9.9, p = 0.013), and the temporal lobe (14.7 ± 11.1 vs. 26.2 ± 10.0, p = 0.010). These differences remained significant in multivariable models after adjusting for age and sex. Within ICH groups, the CBF reduction in the basal ganglia was significantly correlated with the total small vessel disease score (R = 0.58, p = 0.006), but not with individual MRI markers.Conclusion: Patients with advanced hypertensive SVD demonstrated impaired vasoconstriction after dipyridamole challenge in the basal ganglia and the frontal and temporal lobes. Our findings provide safe approaches for whole-brain CVR mapping in SVD and identify a potential physiological basis for vascular dysfunction in hypertensive SVD.

Objective: There are increasing concerns regarding the adverse effects associated with control ovarian hyperstimulation (COH) in both endometrial and uterine environments. With the “segmentation treatment policy” of assisted reproductive techniques (ART), endometrial problems may be obviated through embryo cryopreservation. However, it remains unclear if the “freeze-all policy” offers a better outcome when compared with fresh embryo transfer (ET). To clarify this, we compared the cumulative live birth rates (CLBRs) between these two patient populations. Materials and methods: This is a retrospective study on 853 patients undergoing ovarian stimulation and ART (including IVF/ICSI) during the period from January 2012 to June 2014 in Taichung Veterans General Hospital, Taiwan, ROC. We followed up with these patients through to November 2016. Patients whose embryos were not completely transferred back were excluded. The study group ('freeze-all') included 84 patients whose cycles were performed initially without fresh ET, but were later given frozen-thawed ET. The control group (‘fresh ET’) had 625 patients whose cycles were performed with fresh ET, followed by frozen-thawed ET. Basic parameters and CLBRs were statistically compared between these two groups. Results: The CLBRs in the study group were significantly higher than those in the control group (64.3% vs. 45.8%, p = 0.001). Subgroup analysis revealed that when the number of oocyte pick up (OPU) is between 4 and 15, the CLBRs in the study group were significantly better (58.3% vs. 40.9%, p = 0.042). For those with OPU 15 the CLBRs were similar in these two groups (OPU 15: study vs. control 85.7% vs. 80.8% respectively, p = 0.625) Conclusion: The Freeze-all policy improved the ART outcome for normal responders.

Objective: The purpose of this study was to describe our preliminary experience of the efficacy and safety of a conservative strategy for abnormally invasive placenta. Materials and Methods: A retrospective review of eight pregnant women with abnormally invasive placenta (one with placenta previa accrete, three with placenta previa increta, and four with previa percreta) was performed. The diagnosis was made by prenatal ultrasonography, and was confirmed by operative and histopathological findings. Patients who desired future fertility or who had extensive diseases were selected as candidates after panel meeting. Conservative management after obtaining informed consent was defined by a primary cesarean delivery before 35 weeks of gestation with the abnormally adherent placenta left in situ, partially or totally. The primary outcome was successful uterine preservation. The secondary outcome was severe maternal morbidity including sepsis, coagulopathy, immediate or delayed hemorrhage bladder injury, and fistula. Results: Among the eight patients, the mean age was 34 ± 3 years (range, 30–40 years). All women had risk factors, such as placental previa, previous cesarean delivery and/or dilation & curettage, for abnormally invasive placenta. Seven women underwent planned cesarean delivery at the mean gestation age of 34 weeks (range, 31–37 weeks). One woman received hysterotomy at 18 weeks. In our series, the uterus was preserved in only two cases (25%), one who received hysterotomy at a relatively young gestational age and another who had mild disease. Mean maternal blood loss during primary cesarean delivery was 528 ± 499 ml (range, 100 ml–1,500 ml). Severe maternal morbidity was recorded in seven out of eight patients (87.5%). Conclusion: In this small series, we observed a low successful uterine preservation rate and a high maternal complication rate. We recommend that primary cesarean hysterectomy should be used as the treatment of choice for mild to severe abnormally invasive placenta. Conservative management should be reserved for women with a strong fertility desire and women with extensive disease that precludes primary hysterectomy due to surgical difficulty.

Abstract Chronic kidney disease has been linked to cognitive impairment and morphological brain change. However, less is known about the impact of kidney functions on cerebral cortical thickness. This study investigated the relationship between kidney functions and global or lobar cerebral cortical thickness (CTh) in 259 non-demented elderly persons. Forty-three participants (16.7%) had kidney dysfunction, which was defined as either a glomerular filtration rate (GFR) of

Abstract Patients with asymptomatic occlusion in the internal carotid arteries (ICA) have been shown to have a better preserved hemodynamic status of the brain as compared to patients with symptoms. This study was aimed to explore the cerebral perfusion alterations in asymptomatic patients using multi-parametric arterial spin-labeling (ASL) magnetic resonance (MR) imaging. Forty-two patients diagnosed with asymptomatic ICA stenosis/occlusion were prospectively included and divided into high-grade (ultrasonographic stenosis ≥70%, N = 20) and low-grade groups (N = 22). On a 3-Tesla clinical MR scanner, pseudo-continuous ASL was performed to measure cerebral blood flow CBF, arterial transit time ATT, and flow territory. Fisher’s exact test indicates that the high-grade group has higher frequency in asymmetric ATT (p

Background: Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer’s disease (AD), while the role of brain amyloid deposition in the clinical manifestation or brain atrophy remains unresolved. We aimed to explore the relation between brain amyloid deposition, cortical thickness, and plasma biomarkers.Methods: We used 11C-Pittsburgh compound B-positron emission tomography to assay brain amyloid deposition, magnetic resonance imaging to estimate cortical thickness, and an immunomagnetic reduction assay to measure plasma biomarkers. We recruited 39 controls, 25 subjects with amnesic mild cognitive impairment (aMCI), and 16 subjects with AD. PiB positivity (PiB+) was defined by the upper limit of the 95% confidence interval of the mean cortical SUVR from six predefined regions (1.0511 in this study).Results: All plasma biomarkers showed significant between-group differences. The plasma Aβ40 level was positively correlated with the mean cortical thickness of both the PiB+ and PiB- subjects. The plasma Aβ40 level of the subjects who were PiB+ was negatively correlated with brain amyloid deposition. In addition, the plasma tau level was negatively correlated with cortical thickness in both the PiB+ and PiB- subjects. Moreover, cortical thickness was negatively correlated with brain amyloid deposition in the PiB+ subjects. In addition, the cut-off point of plasma tau for differentiating between controls and AD was higher in the PiB- group than in the PiB+ group (37.5 versus 25.6 pg/ml, respectively). Lastly, ApoE4 increased the PiB+ rate in the aMCI and control groups.Conclusion: The contributions of brain amyloid deposition to cortical atrophy are spatially distinct. Plasma Aβ40 might be a protective indicator of less brain amyloid deposition and cortical atrophy. It takes more tau pathology to reach the same level of cognitive decline in subjects without brain amyloid deposition, and ApoE4 plays an early role in amyloid pathogenesis.

Midline shift (MLS) of the brain is an important feature that can be measured using various imaging modalities including X-ray, ultrasound, computed tomography, and magnetic resonance imaging. Shift of midline intracranial structures helps diagnosing intracranial lesions, especially traumatic brain injury, stroke, brain tumor, and abscess. Being a sign of increased intracranial pressure, MLS is also an indicator of reduced brain perfusion caused by an intracranial mass or mass effect. We review studies that used the MLS to predict outcomes of patients with intracranial mass. In some studies, the MLS was also correlated to clinical features. Automated MLS measurement algorithms have significant potentials for assisting human experts in evaluating brain images. In symmetry-based algorithms, the deformed midline is detected and its distance from the ideal midline taken as the MLS. In landmark-based ones, MLS was measured following identification of specific anatomical landmarks. To validate these algorithms, measurements using these algorithms were compared to MLS measurements made by human experts. In addition to measuring the MLS on a given imaging study, there were newer applications of MLS that included comparing multiple MLS measurement before and after treatment and developing additional features to indicate mass effect. Suggestions for future research are provided.

Objective: In 1991, researchers reported that a modest preovulatory increase in serum progesterone levels is associated with lower pregnancy rates and higher incidence of pregnancy loss in in vitro fertilization (IVF). We wonder whether embryo transfer (ET) in assisted reproductive technology (ART) cycles in patients with premature progesterone rise (PPR) have a negative impact on the clinical pregnancy rates (CPRs) and/or live birth rates (LBRs) in our series. Consequently, will blastocyst transfer reverse the negative impact? Materials and methods: This noninterventional, retrospective, observational tertiary center study was conducted between January 2010 and December 2012. All fresh ET cycles with serum progesterone levels measured (n = 599) on the day of hCG administration were analyzed. Results: Sera lutenizing hormone (LH), E2, and progesterone (P) were measured and analyzed. The CPRs of cycles in patients with p ≤ 1.5 ng/mL (low) versus those with p > 1.5 ng/mL (high) were 37.04% versus 41.03% [odds ratio (OR) = 1.18, 95% confidence interval (CI): 0.728–1.920; p = 0.50). The LBRs of cycles in patients with low progesterone level versus those with PPR were 30.52% versus 34.62% (OR = 1.21, 95% CI: 0.729–1.992; p = 0.47). No statistically significant association was detected. We further analyzed the outcomes according to different stages of ET and found that blastocyst (D5) ET significantly increase the LBRs as compared with cleavage stage (D2/D3) ET in the PPR group (44.44% versus 21.43%; p = 0.043). Conclusion: PPR did not significantly compromise the clinical outcomes in this series. However, shifting to blastocyst transfer probably could increase the live birth in cycles with PPR.

Ameloblastomas are benign but locally invasive odontogenic epithelial tumors. They have a high tendency to recur, but a low incidence of metastasis. This is the first reported case presenting a perineural spread of metastasis in ameloblastoma. This is the case of a 74-year-old man with left mandibular granular cell type ameloblastoma diagnosed in 1978. Local recurrence occurred 26 years after tumor excision, and he again received surgical treatment. Distant metastasis with intracranial perineural spread along the sixth cranial nerve occurred 9 years after the second operation. The diagnosis was confirmed by excisional biopsy of the intracranial lesion and a needle biopsy of the left mandibular tumor. Only 5 patients have been previously reported with metastasized granular cell type ameloblastoma. We herein have presented a characterization of granular cell type ameloblastomas and a possible mechanism for perineural spread.

Background: Mitochondrial dysfunction is linked to the pathogenesis of Parkinson′s disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population. Methods: Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population. Results: Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082-0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030-0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112-11.523, P = 0.033), other haplogroups also did not show significant differences in the group. Conclusions: Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese.

The cerebral hypoperfusion caused by chronic progressive stenosis or occlusion of intracranial arteries in moyamoya disease can be treated by direct bypass or indirect revascularization procedures. The extent of collaterals from the external carotid artery (ECA) after indirect revascularization surgery is the key point of angiographic follow-up, and the invasiveness of angiography impelled us to investigate the role of ultrasonography in the evaluation of collaterals. We hypothesized that the collaterals shown on angiography might produce corresponding hemodynamic changes in color Doppler ultrasonography. We prospectively recruited moyamoya patients who underwent indirect revascularization surgery and received both preoperative and postoperative angiography and color Doppler ultrasound studies. The collaterals on angiography were graded according to Matsushima method. A total of 21 patients (age, 17 ± 10.2 years) with 24 operated hemispheres were enrolled. Patients who showed better collateral establishment by angiography had higher end-diastolic velocity (EDV), lower resistance index (RI), and larger flow volume in the superficial temporal artery (STA) and ECA (all p < 0.05). In STA, increase of EDV greater than 13.5 cm/sec or reduction of RI greater than 0.19 after operation corresponded to 94% of Matsushima grade A+B. In ECA, post-operative EDV greater than 22 cm/sec or increase of EDV greater than 6.4 cm/sec also corresponded to 94% of Matsushima grade A+B. Our findings revealed potential roles of color Doppler ultrasonography in identifying patients with poor collaterals after indirect revascularization procedures.

PURPOSE:To assess the inter session reproducibility of automatic segmented MRI-derived measures by FreeSurfer in a group of subjects with normal-appearing MR images. MATERIALS AND METHODS:After retrospectively reviewing a brain MRI database from our institute consisting of 14,758 adults, those subjects who had repeat scans and had no history of neurodegenerative disorders were selected for morphometry analysis using FreeSurfer. A total of 34 subjects were grouped by MRI scanner model. After automatic segmentation using FreeSurfer, label-wise comparison (involving area, thickness, and volume) was performed on all segmented results. An intraclass correlation coefficient was used to estimate the agreement between sessions. Wilcoxon signed rank test was used to assess the population mean rank differences across sessions. Mean-difference analysis was used to evaluate the difference intervals across scanners. Absolute percent difference was used to estimate the reproducibility errors across the MRI models. Kruskal-Wallis test was used to determine the across-scanner effect. RESULTS:The agreement in segmentation results for area, volume, and thickness measurements of all segmented anatomical labels was generally higher in Signa Excite and Verio models when compared with Sonata and TrioTim models. There were significant rank differences found across sessions in some labels of different measures. Smaller difference intervals in global volume measurements were noted on images acquired by Signa Excite and Verio models. For some brain regions, significant MRI model effects were observed on certain segmentation results. CONCLUSIONS:Short-term scan-rescan reliability of automatic brain MRI morphometry is feasible in the clinical setting. However, since repeatability of software performance is contingent on the reproducibility of the scanner performance, the scanner performance must be calibrated before conducting such studies or before using such software for retrospective reviewing.

Objective To investigate the value of multiplex ligation⁃dependent probe amplification (MLPA) method in the prenatal diagnosis of spinal muscular atrophy (SMA). Methods Six SMA pedigrees, which included 7 patients, 12 parents and 6 fetuses, were admitted in our hospital. MLPA was used to detect the survival motor neuron (SMN) and other modifier genes, according to steps of hybridization, ligation, PCR reaction, fragment separation by capillary electrophoresis and peak pattern evaluation. Synchronously, the deletion of SMN1 gene was detected by polymerase chain reaction⁃restriction fragment length polymorphism (PCR⁃RFLP). The DNA samples of fetuses were collected by centrifuging the amniotic fluid as well as derived from amniotic cell culture. Results According to MLPA, 7 patients and 1 fetus were detected to carry homozygous deletion of survival motor neuron 1 (SMN1) gene, which was also detected by PCR⁃PFLP. In addition, 11 parents and 5 fetuses carried one copy of SMN1 gene, while 1 parent who was also a carrier of SMA carried two copies of SMN1 gene. Furthermore, after being analyzed by MLPA, 10 cases carried one copy of SMN2 gene, while 15 cases had two copies of SMN2 gene. After detecting the neuronal apoptosis inhibitory protein (NAIP) gene, 3 cases had the deletion of NAIP gene while others showed normal. Conclusion MLPA can detect the deletion and quantify the copy numbers of SMN and other modifier genes, improving the efficiency and stability of genetic diagnosis. It is adequate for detecting patients and carriers of SMA, as well as providing reliable evidence for genetic counseling. DOI：10.3969/j.issn.1672⁃6731.2012.03.012

Objective: The purpose of this study was to determine the diagnostic capability of sequential two-dimensional (2D) and adjunctive three-dimensional (3D) ultrasonography (US) in identifying the location and extent of placental invasion of the bladder. Materials and Methods: Forty-five patients at risk of placenta previa were examined sequentially with 2D US and then with a targeted scan of the region of interest with adjunctive 3D US to determine whether those patients suspected of having advanced invasive placentation by conventional ultrasonographic evidence had placental invasion of the bladder. The images were coded as positive, negative or indeterminate (equivocal) for bladder invasion. Follow-up postoperative outcomes were obtained. Results: Seven of the 45 patients exhibited characteristic ultrasonographic findings for placenta increta/percreta. Among these seven patients with advanced invasive placentation, a targeted scan with adjunctive 3D US correctly provided additional corroborative information to the 2D US indeterminate diagnosis in patients who were found with variable degrees of bladder wall involvement at surgery. Conclusion: 3D US may be a useful adjunctive tool in refining 2D ultrasonographic techniques to identify the extent and degree of placental invasion of the bladder. The advantages of 3D US are: (1) a multiplanar image display allows viewing of sections from sagittal, coronal and axial planes at the same time, thereby more accurately determining the location and extent of placental invasion; (2) the viewing planes of the spatial angioarchitecture network can be arbitrarily manipulated to better delineate the aberrant vessels protruding into the bladder; (3) 3D reconstruction images can be clearly displayed by live 3D in a rotation mode for a better illustrative effect.

Objective: We describe the serial computed tomography (CT) findings of extensive hepatic infarction and successful plasma exchange therapy in a severe preeclamptic woman with postpartum HELLP syndrome. Case Report: A 38 year-old woman presented with elevated blood pressure of 140–180/90–120 mmHg and 3+ proteinuria at 28 weeks of gestation. Two days after admission, the patient suddenly complained of severe epigastric pain and headache. Her blood pressure rose sharply to 195/120 mmHg. A 980 g female was delivered by emergency cesarean section. Following delivery, the patient's clinical condition and laboratory values deteriorated, with progressive liver insufficiency (peak AST level = 4246 IU/L, ALT = 3685 IU/L, LDH = 6237 IU/L, platelets = 72,000/mm3). Two consecutive plasma exchanges (PEX) were undertaken on the 3rd and 4th postpartum day. A contrast-enhanced CT of the abdomen performed 8 days postpartum showed geographically wedge-shaped areas of low attenuation, with a mottled appearance in the right hepatic lobe. Shortly thereafter, the patient recovered and all laboratory parameters gradually normalized 3 weeks after delivery. Follow-up CT-scan of the liver 2 months postpartum showed no evidence of infarction, with complete recovery. Conclusion: We recommend that severely ill patients with HELLP syndrome having epigastric pain should undergo CT imaging of the liver. A trial of postpartum PEX therapy should be considered for treatment of the HELLP syndrome complicated with hepatic infarction, which is recalcitrant to conventional medical management, and fails to abate within 72–96 hours of delivery.

Background and purpose NOTCH3 p.R544C mutation accounts for 5% of spontaneous intracerebral haemorrhage (ICH) in East Asian patients. We investigated whether certain CT features are associated with NOTCH3-related ICH.Methods Patients with spontaneous ICH from a prospective stroke registry were screened for NOTCH3 p.R544C mutation. The neuroimaging features on the initial non-contrast CT scans selected to predict NOTCH3 p.R544C mutation, including burden of white matter lesion (WML), degree of brain atrophy, number of lacunes, prominent juxtacortical WML and prominent lobar lacunes, were analysed by neuroradiologists blinded to the mutation status.Results Of 299 patients with spontaneous ICH (mean age, 61 years; male, 68%; ICH volumes, 14.1±17.8 mL), 13 patients (4.3%) carried NOTCH3 p.R544C mutation. The clinical features, haematoma size and location were similar between NOTCH3 p.R544C mutation carriers and non-carriers. The CT scan revealed that patients with NOTCH3 p.R544C mutation had more severe WML and more frequently had prominent juxtacortical WML (69.2% vs 17.8%, p