non-MS Group Research Articles

Cyclophosphamide for severe acute forms of central nervous system inflammatory disorders

Cyclophosphamide (CYC) may be an effective treatment in patients who fail first line therapy for severe central nervous system (CNS) inflammatory disorders including CNS vasculitis, neuromyelitis optica, autoimmune encephalitis, tumefactive and aggressive multiple sclerosis (MS). We performed a retrospective analysis of 46 patients treated with CYC after failing first line therapy for severe CNS inflammatory conditions. Primary outcomes included modified Rankin Scale (mRS) for patients classified into a non-MS group, Expanded Disability Status Score (EDSS) for MS patients, and Targeted Neurological Deficit score (TND) for all patients. Secondary outcome included neuroimaging studies following CYC treatment. By the second follow up period (average of 7 months) mRS in the non-MS group improved from 3.7 to 2.2 and EDSS in the MS group improved from 5.6 to 3.8. Average TND score at 7 months was 2.8 (mild-marked improvement). At first follow up (average 5.6 months), 76.2% (32/42) patients had either stable or improving imaging, and 83.3% (30/36) patients had stable or improving imaging at second follow up (average 13.6 months). Adverse events were reported by 31.9% of patients with most common being nausea and vomiting, headache, alopecia, and hyponatremia. Treatment with CYC can result in disease stabilization of severe CNS inflammatory diseases and is generally well tolerated.

Polymorphisms -374 T/A and -429 T/C of the Receptor for Advanced Glycation End-Products (RAGE) and Serum Levels of RAGE (sRAGE) Are Not Associated with Metabolic Syndrome.

RAGE is a multi-ligand transmembrane glycoprotein that promotes biological signals associated with inflammatory responses and degenerative diseases. sRAGE is a soluble variant, proposed as an inhibitor of RAGE activity. -374 T/A and -429 T/C polymorphisms of the advanced glycation end products receptor AGER gene are associated with the development of some diseases, such as type of cancer, cardiovascular disease, and micro and macrovascular disease in diabetes among others but their role in metabolic syndrome (MS) is still unknown. We studied 80 healthy men without MS, and 80 men with MS according to the harmonized criteria. -374 T/A and -429 T/C polymorphisms were genotyped by RT-PCR, and sRAGE was measured by ELISA. Allelic and genotypic frequencies did not differ between Non-MS and MS groups (-374 T/A p = 0.48, p = 0.57 and -429 T/C p = 0.36, p = 0.59). Significant differences were found in fasting glucose levels and diastolic blood pressure among the genotypes of the -374 T/A polymorphism in the Non-MS group (p < 0.01 and p = 0.008). Glucose levels were different between -429 T/C genotypes in the MS group (p = 0.02). sRAGE levels were similar in both groups, but in the Non-MS group showed a significant difference between individuals with only 1 or 2 components of the metabolic syndrome (p = 0.047). However, no associations of any SNP with MS were found (recessive model p = 0.48, dominant model p = 0.82 for -374 T/A; recessive model p = 0.48, dominant model p = 0.42 for -429 T/C). -374 T/A and -429 T/C polymorphisms are not associated with MS in Mexican population and have no influence on serum sRAGE levels.

Washed microbiota transplantation improves patients with metabolic syndrome in South China.

Metabolic syndrome (MS) is a growing public health problem worldwide. The clinical impact of fecal microbiota transplantation (FMT) from healthy donors in MS patients is unclear, especially in southern Chinese populations. This study aimed to investigate the effect of washed microbiota transplantation (WMT) in MS patients in southern China. The clinical data of patients with different indications receiving 1-3 courses of WMT were retrospectively collected. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared, such as fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c)), high-density lipoprotein cholesterol (HDL-c), non-high-density lipoprotein (non-HDL-c), systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. At the same time, comprehensive efficacy evaluation and atherosclerotic cardiovascular disease (ASCVD) grade assessment were performed on MS patients. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of MS patients before and after transplantation. A total of 237 patients were included, including 42 in the MS group and 195 in the non-MS group. For MS patients, WMT significantly improved the comprehensive efficacy of MS in short term 40.48% (p<0.001), medium term 36.00% (p=0.003), and long term 46.15% (p=0.020). Short-term significantly reduced FBG (p=0.023), TG (p=0.030), SBP (p=0.026) and BMI (p=0.031), and increased HDL-c (p=0.036). The medium term had a significant reduction in FBG (p=0.048), TC (p=0.022), LDL-c (p=0.043), non-HDL-c (p=0.024) and BMI (p=0.048). WMT had a significant short term (p=0.029) and medium term (p=0.011) ASCVD downgrading effect in the high-risk group of MS patients. WMT improved gut microbiota in MS patients. WMT had a significant improvement effect on MS patients and a significant downgrade effect on ASCVD risk in the high-risk group of patients with MS. WMT could restore gut microbiota homeostasis in MS patients. Therefore, the regulation of gut microbiota by WMT may provide a new clinical approach for the treatment of MS.

Factors Related to the Progression of Clinically Isolated Syndrome to Multiple Sclerosis: A Retrospective Study in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a demyelinating disease which usually manifests as clinically isolated syndrome (CIS). Approximately 70% of patients with CIS progress to MS. Therefore, there is a pressing need to identify the most accurate predictive factors of CIS developing into MS, some of which could be a clear clinical phenotype of early MS as well as lesions in magnetic resonance imaging (MRI), pathological findings in cerebrospinal fluid (CSF) and evoked potentials (EP) tests. The problem is of outstanding importance since early MS diagnosis and treatment prevents long-term disability. The aim of our study is to analyze the factors that could influence the progression of CIS to MS. Materials and Methods: This study is a retrospective data analysis which included patients with their primary CIS diagnosis between 1st January 2015 and 1st January 2020. The prevalence and predictive value of clinical symptoms, MRI lesions, pathological CSF and EP findings were evaluated in accordance with the final diagnosis and compared between the sexes and age groups. Results: Out of 138 CIS patients, 49 (35.5%) patients progressed to MS. MS patients were more likely to have a diminished sense of vibration and proprioception (χ2 = 9.033, p = 0.003) as well as spinal cord MRI lesions (χ2 = 7.209, p = 0.007) in comparison with the non-MS group. Positive oligoclonal bands (OCBs) in CSF (χ2 = 34.859, p ≤ 0.001) and pathological brainstem auditory evoked potential (BAEP) test findings (χ2 = 10.924, p ≤ 0.001) were more prevalent in the MS group. Diminished sense of vibration and proprioception increased the risk for developing MS by 13 times (p = 0.028), whereas positive OCBs in CSF increased the risk by 100 times (p < 0.001). MS patients that were older than 50 years were more likely to exhibit positive Babinski’s reflex (χ2 = 6.993, p = 0.03), decreased muscle strength (χ2 = 13.481, p = 0.001), ataxia (χ2 = 8.135, p = 0.017), and diminished sense of vibration and proprioception (χ2 = 7.918, p = 0.019) in comparison with both younger age groups. Conclusions: Diminished sense of vibration and proprioception, spinal cord MRI lesions, positive OCBs and pathological BAEP test findings were more common among patients that developed MS. Diminished sense of vibration and proprioception along with positive CSF OCBs are predictors of CIS progressing to MS. Older patients that develop MS have more symptoms in general, such as positive Babinski’s reflex, decreased muscle strength, ataxia, and diminished sense of vibration and proprioception.

Health-related quality of life of patients with multiple sclerosis: Analysis of ten years of national data

BackgroundMultiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system. Both the physical and mental burden of MS affect patients’ health-related quality of life (HRQoL). However, there is limited research at the national level evaluating the humanistic burden among MS patients. ObjectivesThis study evaluated the HRQoL and functional limitations among MS patients using ten years of national survey data. MethodsGuided by the conceptual framework of the Wilson and Cleary model, this study compared HRQoL between adults diagnosed with MS (Clinical Classification Code= “080″) and non-MS adults using the 2006–2015 Medical Expenditure Panel Survey (MEPS) data. The humanistic burden included HRQoL and functional limitations. The HRQoL was evaluated using physical component summary (PCS) and mental component summary (MCS) based on the Short Form Health Survey (SF-12). The study applied the multivariable Generalized Linear Models (GLM) to estimate the marginal differences in PCS and MCS based on the SF-12. In addition, seeking help for activities of daily living (ADL) and instrumental activities of daily living (IADL) were modeled with multivariable logistic regression. ResultsAccording to the MEPS, the estimated annual prevalence of MS was 0.52 million (95% Confidence Interval [CI]: 0.42–0.60). MS patients were mainly female (71.90%), middle aged (50–64 years, 40.21%), non-Hispanic whites (78.29%), and enrolled in private insurance plans (68.93%). The average PCS scores in MS and non-MS groups were 35.70 and 49.48, respectively. The average MCS scores were 45.58 and 51.25 for MS and non-MS groups, respectively. In addition, 18.26% of MS patients sought help for ADL, and 27.08% sought help for IADL. After adjusting for individual, biological, and environmental characteristics, the multivariable GLM with Poisson distribution indicated that the marginal difference of PCS score was 11.10 (95% CI: 9.50–12.61) units lower, and the MCS score was 4.89 (95% CI: 3.44–6.30) units lower among MS patients. In addition, MS patients were 17.32 (95% CI: 11.61–25.84) and 14.43 (95% CI: 10.09–20.65) times more likely to request assistance for ADL and IADL, respectively. ConclusionsMS was associated with lower physical and mental HRQoL than their non-MS counterparts and MS patients were more likely to request help for ADL and IADL. More work is needed to evaluate the effect of treatment strategies on improving the HRQoL and functional limitations in MS.

Impact of Metabolic Syndrome and Its Components on Clinical Severity and Long-Term Prognosis in Patients With Premature Myocardial Infarction.

BackgroundThe effects of metabolic syndrome (MS) on premature myocardial infarction (PMI) are not clear to date. This study aimed to investigate the impact of MS and its components on clinical severity and long-term prognosis in patients with PMI.MethodsWe enrolled 772 patients aged ≤45 years old who were diagnosed with acute myocardial infarction (AMI) at our hospital consecutively between 2015 and 2020. The patients were divided into an MS group and non-MS group. The parameters of clinical severity were compared using regression analysis. Patients were followed for median of 42 months for major adverse cardiovascular events (MACE).ResultsHyperglycemia was associated with multi-vessel disease [odds ratio(OR)=1.700, 95% confidence interval (CI)=1.172-2.464, P=0.005] and Syntax score ≥33 (OR=2.736, 95% CI=1.241-6.032, P=0.013). Increased MACE were observed in the MS group(17.9% vs 10.3%, P=0.004).The Kaplan-Meier curve also showed significant differences (P< 0.001). MS was an independent risk factor for MACE. Of each component of MS, BMI ≥28 kg/m2 (hazard ratio [HR]=2.022, 95% CI =1.213-3.369, P=0.007] and hyperglycemia (HR=2.904, 95% CI=1.847-4.567, P<0.001) were independent risk factors for MACE.ConclusionsIn patients with PMI, 1) hyperglycemia usually indicates more severe lesions; 2) MS as a whole was an independent risk factor for MACE; 3) BMI ≥28.0 kg/m2 and hyperglycemia were associated with MACE.

Efficacy and Safety of Left Atrial Appendage Occlusion in Mild Mitral Stenosis Patients with High Bleeding Risk.

Atrial fibrillation (AF) is highly prevalent in patients with mitral stenosis (MS), but the efficacy of left atrial appendage occlusion (LAAO) in these patients remains unclear.The aim of this study was to evaluate the efficacy and safety of LAAO in patients with MS complicated by AF at high risk of bleeding.We recruited patients from September 2015 to September 2018. We compared the 3-year outcomes of LAAO in 21 patients with AF complicated by MS and 42 sex- and age-matched patients with AF without MS.The MS group had more cases of peripheral arterial embolism (28.6% versus 2.4%, P = 0.004), more spontaneous echo contrast (47.6% versus 9.5%, P = 0.001), a larger LAA orifice diameter (P < 0.01), and a slower LAA flow (P < 0.05) than the Non-MS group. The mean size of the selected occluder device was bigger for patients with MS than for patients with Non-MS (29.2 ± 3.7 versus 26.9 ± 3.1 mm, P = 0.014). In the first 45 follow-up days, 2 (9.5%) patients with MS had device-related thrombi (DRT); one of them had transient ischemic attack 24 hours postoperatively. From 45 days to 6 months, one patient in each group had DRT. After 6 months, two patients in the Non-MS group still had residual leaks; one of them had a stroke, with a small DRT. The proportion of dual antiplatelet therapy was higher in the Non-MS group than in the MS group (33.3% versus 4.8%, P = 0.012), but this population had an increased bleeding risk.LAAO is relatively effective and safe for preventing embolic events in patients with MS complicated by AF, at high risk of bleeding.

Association of Serum Vitamin D and Estradiol Levels with Metabolic Syndrome in Rural Women of Northwest China: A Cross-Sectional Study.

Objectives: We aimed to determine the association of serum vitamin D and estradiol levels with metabolic syndrome (MS) in rural women of northwest China. Methods: This research is a cross-sectional study. MS was defined according to the updated China Diabetes Society (CDS) criteria. Fasting serum 25-hydroxyvitamin D [25(OH)D] and estradiol levels were measured using a chemiluminescence immunoassay. Differences between variables were analyzed using the chi-square test and t-test. Logistic regression analysis models were used to estimate the odds ratios (ORs) and 95% confidence intervals. Results: In total, 1893 women participated, of whom 641 (33.9%) had MS. The serum levels of 25(OH)D and estradiol were higher in the non-MS group. There was no significant association between 25(OH)D and estradiol levels. After adjusting for potential confounders, we compared first, second, and third quartiles with the highest quartile. Adjusted ORs for MS with respect to 25(OH)D level quartiles were 1.555, 1.281, and 1.568, respectively. Adjusted ORs for MS with respect to estradiol level quartiles were 0.671, 0.785, and 0.996, respectively. In the vitamin D-deficient (VD-deficient) group, adjusted ORs for MS with respect to estradiol level quartiles were 0.635, 0.753, and 0.918, respectively. Conclusions: There is a negative correlation between MS and vitamin D level and a positive correlation between MS and estradiol level. Low estradiol concentrations increased the risk of MS in the VD-deficient group. The results suggest a potential synergism between low 25(OH)D concentration and estradiol in MS in women.

The central vein sign is present in most infratentorial multiple sclerosis plaques

Background and purposeThere is growing evidence supporting the presence of the central vein sign (CVS) in the supratentorial brain as an imaging biomarker for multiple sclerosis (MS) diagnosis. Recently, using optimized susceptibility-weighted angiography (SWAN-venule), we detected CVS in 86% of supratentorial white matter lesions (WMLs) in the clinical setting on images obtained in a 3T MRI scanner. Despite the relevance of the infratentorial compartment, CVS prevalence in infratentorial MS plaques has not been investigated in detail. Our objective was to determine the proportion of MS infratentorial lesions showing CVS positivity. Materials and methodsWe included subjects with MS and other brain diseases showing at least one infratentorial lesion larger than 3 mm on 3D-FLAIR. Patients were scanned in a 3T MRI scanner (GE Medical Systems, discovery-MR750), applying a comprehensive protocol including post-contrast 3D-FLAIR and SWAN-venule sequences. CVS presence was confirmed by two trained raters. ResultsThirty MRIs of subjects with MS were analyzed. One hundred and one infratentorial lesions were detected on FLAIR, and 86% were centered by a vein. Fifteen MRIs from the non-MS group were analyzed, 19 lesions were visible ion FLAIR and 16% were positive for the CVS. ConclusionsSWAN-venule detects infratentorial lesions and highlights the central vein in MS plaques at 3T MRI. As occurs in the supratentorial brain, most infratentorial lesions are perivenular.

Metabolic Syndrome is an Independent Risk Factor for Fuhrman Grade and TNM Stage of Renal Clear Cell Carcinoma.

BackgroundMore and more evidences show that metabolic syndrome (MS) is closely related to clear cell renal cell carcinoma (ccRCC), but the impact of MS on Fuhrman grade and TNM stage of ccRCC is rarely reported.PurposeTo explore the relationship between MS and its components of Fuhrman grade and TNM stage in ccRCC.ObjectiveThe clinical data of 247 patients with ccRCC diagnosed in our hospital from January 2016 to November 2020 were retrospectively collected and analyzed. Based on diagnostic criteria of MS, the patients were divided into MS and non-MS group. Logistic regression analysis was used to analyze the independent risk factors of ccRCC.ResultsThe incidence of MS was 32.79% (81/247). There was no significant difference in age, gender, smoking and drinking between MS group and non-MS group (P > 0.05). In MS group, BMI ≥25kg/m2, hypertension, diabetes, hyperlipidemia, tumor diameter, poorly differentiated renal cancer, high-stage renal cancer, triglyceride, fasting blood glucose, glycated hemoglobin, fasting insulin and homeostasis model assessment index were significantly higher than those in non-MS group (P < 0.001), while in high density lipoprotein cholesterol (p < 0.005), islet beta cell secretory index (P < 0.001), well-differentiated renal cell carcinoma (P= 0.009), and low-stage renal cell carcinoma (P = 0.019) were significantly lower than that of non-MS group. Logistic regression analysis showed that hypertension (P = 0.005), diabetes (P = 0.012), hyperlipidemia (P = 0.021) are independent risk factors for Fuhrman grade of ccRCC, while diabetes (P = 0.002), hyperlipidemia (P = 0.007) are independent risk factors for TNM staging of ccRCC.ConclusionThe patients with ccRCC and MS had higher Fuhrman grade and TNM stage. MS is an independent risk factor for Fuhrman grade and TNM stage of ccRCC.

Predictive Value of Serum Lipoprotein-Associated Phospholipase A2 for Type 2 Diabetes Mellitus Complicated with Metabolic Syndrome in Elderly Patients

The aim was to investigate the predictive value of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) for type 2 diabetes mellitus (T2DM) complicated with metabolic syndrome (MS) in elderly patients. A total of 296 patients with T2DM admitted from January 2019 to January 2021 were enrolled and assigned to MS group (n = 181) and non-MS group (n = 115). Their clinical data and laboratory test results were compared. Logistic regression analysis was employed to identify independent risk factors for MS in T2DM patients. Spearman's analysis was utilized to explore the correlations between serum Lp-PLA2 level and detection indicators. The predictive value of Lp-PLA2 for MS was analyzed by plotting receiver operating characteristic (ROC) curve, and Cox regression model was applied to explore the correlation of serum Lp-PLA2 level with MS. The results of data subjected to multivariate analysis were used to construct prediction models. The incidence rate of MS was 61.15% in T2DM patients. MS group had a significantly higher serum level of Lp-PLA2 than non-MS group (p < 0.05). Serum Lp-PLA2 was significantly positively correlated to FBG, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), FINS, and HOMA-IR, but significantly negatively associated with LDL-C (p < 0.05). The area under the ROC curve of Lp-PLA2 for predicting MS in T2DM patients was 0.724 (95% CI: 0.625 - 0.826, p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of Lp-PLA2 with an optimal cutoff value of 82.96 ng/mL were 73.7%, 85.4%, 77.56%, and 93.24%, respectively. TC, TG, HDL-C, HbA1c, and Lp-PLA2 were independent risk factors for MS (p < 0.05). The area under the ROC curve of the risk prediction model established based on these indicators was 0.823, and the cutoff value, Youden index, sensitivity, and specificity were 0.219, 0.656, 78.87%, and 87.66%, respectively, indicating higher predictive value. Increased serum Lp-PLA2 level is an independent risk factor for MS in T2DM patients. Lp-PLA2 (82.87 ng/mL) has high predictive value for MS.

Assessing Cognitive Function in Multiple Sclerosis With Digital Tools: Observational Study.

BackgroundCognitive impairment (CI) is one of the most prevalent symptoms of multiple sclerosis (MS). However, it is difficult to include cognitive assessment as part of MS standard care since the comprehensive neuropsychological examinations are usually time-consuming and extensive.ObjectiveTo improve access to CI assessment, we evaluated the feasibility and potential assessment sensitivity of a tablet-based cognitive battery in patients with MS.MethodsIn total, 53 participants with MS (24 [45%] with CI and 29 [55%] without CI) and 24 non-MS participants were assessed with a tablet-based cognitive battery (Adaptive Cognitive Evaluation [ACE]) and standard cognitive measures, including the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). Associations between performance in ACE and the SDMT/PASAT were explored, with group comparisons to evaluate whether ACE modules can capture group-level differences.ResultsCorrelations between performance in ACE and the SDMT (R=–0.57, P<.001), as well as PASAT (R=–0.39, P=.01), were observed. Compared to non-MS and non-CI MS groups, the CI MS group showed a slower reaction time (CI MS vs non-MS: P<.001; CI MS vs non-CI MS: P=.004) and a higher attention cost (CI MS vs non-MS: P=.02; CI MS vs non-CI MS: P<.001).ConclusionsThese results provide preliminary evidence that ACE, a tablet-based cognitive assessment battery, provides modules that could potentially serve as a digital cognitive assessment for people with MS.Trial RegistrationClinicalTrials.gov NCT03569618; https://clinicaltrials.gov/ct2/show/NCT03569618

MONISEDA Project: Improving Analgosedation Monitoring in Spanish Pediatric Intensive Care Units.

Background: Analgosedation (AS) assessment using clinical scales is crucial to follow the international recommendations about analgosedation. The Analgosedation workgroup of the Spanish Society of Pediatric Intensive Care (SECIP) carried out two surveys in 2008 and 2015, which verified the gap in analgosedation assessment in Spanish pediatric intensive care unit (PICUs). The objective of the study was to analyze how analgosedation assessment by clinical scales changed after a multicenter intervention program.Methods: This is a multicenter pre–post study comparing the use of sedation, analgesia, withdrawal, and delirium scales before and after the MONISEDA project. Results were also compared with a control group formed by non-participating units. A survey about analgosedation management and monitoring was filled out before (year 2015) and after (year 2020) the implementation of the MONISEDA project in 2016. Results were compared not only between those periods of time but also between participant and non-participant PICUs in the MONISEDA project (M-group and non-M group, respectively). Data related to analgosedation of all patients admitted to a MONISEDA-participant PICU were also collected for 2 months.Results: Fifteen Spanish PICUs were enrolled in the MONISEDA project and another 15 non-participant PICUs formed the control group. In the M-group, the number of PICUs with a written analgosedation protocol increased from 53 to 100% (p = 0.003) and withdrawal protocol from 53 to 100% (p = 0.003), whereas in the non-M group, the written AS protocol increased from 80 to 87% and the withdrawal protocol stayed on 80%. The number of PICUs with an analgosedation team increased from 7 to 47% in the M-group (p = 0.01) and from 13 to 33% in the non-M group (p = 0.25). In the M-group, routine use of analgosedation clinical scales increased from 7 to 100% (p < 0.001), withdrawal scales from 7% to 86% (p = 0.001), and delirium scales from 7 to 33% (p = 0.125). In the non-M group, the number of PICUs using AS scales increased from 13 to 100% (p < 0.001), withdrawal scales from 7 to 27% (p = 0.125), and delirium scales from 0 to 7% (p = 1).Conclusions: The development of a specific training program improves monitoring and management of analgosedation in PICUs.

Serum Levels of HCY, MIF, and hs-CRP Correlate with Glycolipid Metabolism in Adults with Never-Medicated First-Episode Schizophrenia.

Objective It has been reported that the prevalence of metabolic syndrome (MS) in multiepisode patients with schizophrenia is 35.3%, which is 2- to 4-fold higher than in the general population. The study is designed to compare the glycolipid metabolism in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls to investigate changes in serum levels of homocysteine (Hcy), macrophage migration inhibitory factor (MIF), and high-sensitive C-reactive protein (hs-CRP) and their relationships with the glycolipid metabolism in patients with FES. Methods His case-control study included 88 patients diagnosed with FES and 88 sex- and age-matched healthy controls. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and 17-item Hamilton Rating Scale for Depression (HAMD-17). Patients with FES were classified into MS and non-MS groups. Results There were significant differences in the education level, body mass index (BMI), and waist circumference between the patients with FES and healthy controls (all p > 0.05). The patients with FES had higher levels of FPG and blood glucose at the oral glucose tolerance test (OGTT) (2 h glucose) concomitant with higher proportion of impaired glucose tolerance (IGT) and homeostasis model assessment of insulin resistance (HOMA2-IR) than healthy controls (all p < 0.001). It was revealed that the patients with FES showed higher serum levels of Hcy, MIF, and hs-CRP than healthy controls (all p < 0.001). The serum level of Hcy shared positive correlations with the score of PANSS totals (r = 0.551) and the negative syndrome of the PANSS scale (r = 0.494). The serum levels of MIF and hs-CRP was only positively correlated with the negative syndrome of the PANSS scale (r = 0.320 and r = 0.446). The level of Hcy shared positive correlations with the levels of FPG, 2 h glucose, and HOMA2-IR; the level of MIF was only positively correlated with the level of HOMA2-IR; the level of hs-CRP had a positive correlation with both levels of FPG and 2 h glucose (all p < 0.001). The levels of Hcy, MIF, and hs-CRP all shared positive correlations with the TG level and negative correlations with the HDL-C level (all p < 0.001). There were remarkable differences between the MS and non-MS groups with regard to BMI, waist circumference, negative subscale of the PANSS scale, FPG, TG, and HDL-C (all p < 0.05). Elevated levels of Hcy, MIF, and hs-CRP were detected in the MS group compared to the non-MS group (all p < 0.05). Conclusion These findings suggest that increased concentrations of HCY, MIF, and hs-CRP may contribute to the abnormal glycolipid metabolism in the context of schizophrenia.

MRI-based thalamic volumetry in multiple sclerosis using FSL-FIRST: Systematic assessment of common error modes.

FSL's FMRIB's Integrated Registration and Segmentation Tool (FSL-FIRST) is a widely used and well-validated tool. Automated thalamic segmentation is a common application and an important longitudinal measure for multiple sclerosis (MS). However, FSL-FIRST's algorithm is based on shape models derived from non-MS groups. As such, the present study sought to systematically assess common thalamic segmentation errors made by FSL-FIRST on MRIs from people with multiple sclerosis (PwMS). FSL-FIRST was applied to generate thalamic segmentation masks for 890 MR images in PwMS. Images and masks were reviewed systematically to classify and quantify errors, as well as associated anatomical variations and MRI abnormalities. For cases with overt errors (n = 362), thalamic masks were corrected and quantitative volumetric differences were calculated. In the entire quantitative volumetric group, the mean volumetric error of FSL-FIRST was 2.74% (0.360 ml): among only corrected cases, the mean volumetric error was 6.79% (0.894 ml). The average percent volumetric error associated with seven error types, two anatomical variants, and motions artifacts are reported. Additional analyses showed that the presence of motion artifacts or anatomical variations significantly increased the probability of error (χ2 =18.14, p<.01 and χ2 =64.89, p<.001, respectively). Finally, thalamus volume error was negatively associated with degree of atrophy, such that smaller thalami were systematically overestimated (r = -.28, p<.001). In PwMS, FSL-FIRST thalamic segmentation miscalculates thalamic volumetry in a predictable fashion, and may be biased to overestimate highly atrophic thalami. As such, it is recommended that segmentations be reviewed and corrected manually when appropriate for specific studies.

Predictive Ability of the Estimate of Fat Mass to Detect Early-Onset Metabolic Syndrome in Prepubertal Children with Obesity.

Body mass index (BMI), usually used as a body fatness marker, does not accurately discriminate between amounts of lean and fat mass, crucial factors in determining metabolic syndrome (MS) risk. We assessed the predictive ability of the estimate of FM (eFM) calculated using the following formula: FM = weight − exp(0.3073 × height2 − 10.0155 ×d-growth-standards/standards/body-mass-index-for-age-bmi-for-age weight− 1 + 0.004571 × weight − 0.9180 × ln(age) + 0.6488 × age0.5 + 0.04723×male + 2.8055) (exp = exponential function, score 1 if child was of black (BA), south Asian (SA), other Asian (AO), or other (other) ethnic origin and score 0 if not, ln = natural logarithmic transformation, male = 1, female = 0), to detect MS in 185 prepubertal obese children compared to other adiposity parameters. The eFM, BMI, waist circumference (WC), body shape index (ABSI), tri-ponderal mass index, and conicity index (C-Index) were calculated. Patients were classified as having MS if they met ≥ 3/5 of the following criteria: WC ≥ 95th percentile; triglycerides ≥ 95th percentile; HDL-cholesterol ≤ 5th percentile; blood pressure ≥ 95th percentile; fasting blood glucose ≥ 100 mg/dL; and/or HOMA-IR ≥ 97.5th percentile. MS occurred in 18.9% of obese subjects (p < 0.001), with a higher prevalence in females vs. males (p = 0.005). The eFM was correlated with BMI, WC, ABSI, and Con-I (p < 0.001). Higher eFM values were present in the MS vs. non-MS group (p < 0.001); the eFM was higher in patients with hypertension and insulin resistance (p < 0.01). The eFM shows a good predictive ability for MS. Additional to BMI, the identification of new parameters determinable with simple anthropometric measures and with a good ability for the early detection of MS, such as the eFM, may be useful in clinical practice, particularly when instrumentation to estimate the body composition is not available.

Association of Dynamic Changes in Metabolic Syndrome Status with the Risk of Parkinson’s Disease: A Nationwide Cohort Study

The longitudinal association between dynamic changes in the metabolic syndrome (MS) status and Parkinson's disease (PD) has been poorly studied. We examined whether dynamic changes in MS status are associated with altered risk for PD. This study was a nationwide retrospective cohort study. We enrolled 5,522,813 individuals aged≥40 years who had undergone health examinations under the National Health Insurance Service between 2009 and 2010 (two health examinations with a 2-year interval). Participants were followed up until the end of 2017. The participants were categorized into four groups according to MS status changes over 2 years: non-MS, improved MS, incident MS, and persistent MS groups. Multivariable Cox hazard regression was performed. During the 7-year median follow-up, there were 20,524 cases of newly developed PD. Compared with non-MS group, improved, incident, and persistent MS groups for 2 years were significantly associated with higher risks of PD (model 3; hazard ratio: 1.12, 95%confidence interval: 1.06-1.19 [improved MS]; 1.15, 1.09-1.22 [incident MS]; and 1.25, 1.20-1.30 [persistent MS]). Individuals with incident and persistent abdominal obesity, low levels of high-density lipoprotein cholesterol, hypertriglyceridemia, and hyperglycemia had a significantly increased risks of PD compared with those without either condition over 2 years. Persistent and incident MS and its components may be risk factors for incident PD. Ever exposure to MS may also be associated with PD risk. Appropriate intervention for preventing and improving MS may be crucial in decreasing the PD incidence.

Utility of paramagnetic rim lesions on 1.5-T susceptibility phase imaging for the diagnosis of pediatric multiple sclerosis.

Studies have suggested that paramagnetic rim lesions on 7-tesla (T) and 3-T susceptibility-based brain MRI are specific features of multiple sclerosis (MS) lesions in adults. The aim of this study was to investigate whether the presence of paramagnetic rim lesions on 1.5-T phase images can help discriminate pediatric patients with MS from those with other demyelinating diseases. In this retrospective study we reviewed brain MRIs performed on 1.5-T scanners that included susceptibility-weighted imaging (SWI) sequences with phase images in children younger than 18years diagnosed with MS and other acquired demyelinating syndromes. In each case, five white matter lesions were selected using T2/fluid-attenuated inversion recovery images for further paramagnetic rim evaluation on SWI. Two researchers performed independent assessments of the presence of paramagnetic rim lesions. Discrepancies between them were settled by consensus, with input from a senior neuroradiologist. We included 13 children diagnosed with MS and 16 children diagnosed with non-MS demyelinating diseases and analyzed a total of 132 focal white matter lesions. Seventy-one percent of the lesions in the MS group had paramagnetic rims, while none of the lesions in the non-MS group had rims. All but one of the children with MS had at least one lesion with a paramagnetic rim. The presence of one lesion with a paramagnetic rim on 1.5-T phase-contrast images resulted in 70% sensitivity and 100% specificity for MS. Paramagnetic rim lesions detected on 1.5-T phase-contrast MR images can help discriminate MS from other acquired demyelinating syndromes in the pediatric population.

Clinical characteristics and risk factors of mirror syndrome: a retrospective case-control study

BackgroundMirror syndrome (MS) is a rare obstetric disorder complicated with high maternal morbidity and fetal mortality. MS is often misdiagnosed or underdiagnosed due to the low incidence and lack of awareness of its diverse features. This study aimed to summarise the etiology, clinical characteristics, and risk factors of MS among mothers with fetal hydrops.MethodsThis retrospective case-control study included 37 pregnant women with fetal hydrops in the second and third trimesters from 58,428 deliveries performed at the Third Affiliated Hospital of Sun Yat-Sen University between January 2012 and December 2020. Cases were categorized as MS and non-MS according to the presence or absence of maternal mirroring symptoms. Binary logistic regression was performed for analysis.ResultsFourteen women developed MS with an overall incidence of 0.024% (14/58,428) and 37.8% (14/37) in the fetal hydrops cases. Among the 11 MS cases with known associated etiologies, seven had alpha thalassemia major. Onset of fetal hydrops was later (27.8 vs. 23.0 weeks) and the rate of placental thickening was higher (85.7% vs. 34.8%) in the MS group than in the non-MS group (P < 0.05). Regarding maternal characteristics, the MS group had higher maternal morbidity (85.7% vs. 8.7%), more weight gain (9.0 vs. 5.5 kg), higher rates of hypertension (35.7 vs. 0%) and proteinuria (64.3% vs. 4.3%), and lower levels of hemoglobin (88 vs. 105 g/L) and serum albumin (25.8 vs. 35.0 g/L) than the non-MS group (P < 0.05). Logistic regression analysis showed that onset of fetal hydrops at ≥24 weeks and placental thickening were associated with the risk of MS among fetal hydrops cases (OR 15.83, 95% CI 1.56–160.10 and OR 8.63, 95% CI 1.29–57.72, respectively).ConclusionsMS is relatively common among fetal hydrops cases in the late second and third trimesters, and alpha thalassemia major is the main etiology for fetal hydrops and also MS in this population. Complicated with high maternal morbidity, the key maternal features of MS include more weight gain, hemodilution, and hypertension. Among those with fetal hydrops, the onset time of ≥24 weeks and placental thickening are risk factors for MS.

Clinical features and risk factors of metabolic syndrome in adult hypopituitary patients

Objective: To investigate the clinical features and risk factors of metabolic syndrome (MS) in adult hypopituitary patients (HP). Methods: Patients diagnosed with HP in the outpatient or inpatient department of the endocrinology department in West China Hospital from January,2012 to December,2019 were selected as the experimental group (HP group), and patients with normal pituitary function treated for saddle lesions were selected as the control group. HP patients with or without MS were divided into MS group and non-MS group HP patients were divided into four groups according to the level of growth hormone by the quartile method (GH>0.35 μg/L、0.13 μg/L<GH≤0.35 μg/L、0.05 μg/L<GH≤0.13 μg/L and GH≤0.05 μg/L). And then we compared the differences in clinical characteristics between groups. Results: A total of 264 patients with HP (136 males, 51.5%) and 53 patients with normal pituitary function (22 males, 41.5%) were included. There were no significant differences between the two groups in age[(41±13)vs(40±12) years old] and body mass index(BMI)[(23.3±4.5)vs(23.1±3.9) kg/m2]. Delays in diagnosis and treatment were common in HP, and less than 50% of HP patients received standard alternative therapy. The prevalence of MS (39.4% vs 24.4%) and non-alcoholic fatty liver disease (30.9% vs 12.5%), waist circumference [(87.2±10.6) vs (82.2±12.6) cm], triglyceride [M(Q1,Q3)1.81(1.15, 2.83) vs 1.14(0.80, 1.69) mmol/L] in HP group were higher than those in control group (P<0.05). Blood pressure [systolic blood pressure:(112±19) vs (124±16) mmHg; diastolic blood pressure:(70±12) vs (81±12) mmHg; 1 mmHg=0.133 kPa] and HDL cholesterol [1.06(0.83, 1.35) vs 1.49(1.14, 1.78) mmol/L] in HP group were lower than those in control group (P<0.05). The levels of GH [0.11 (0.03, 0.35) vs 0.20 (0.05, 0.41) μg/L] and IGF-1 [58.33 (38.12, 76.03) vs 65.54 (51.78, 101.76) μg/L] in MS group were lower than those in non-MS group (P<0.05). The lower the GH level(GH>0.35 μg/L、0.13 μg/L<GH≤0.35 μg/L、0.05 μg/L<GH≤0.13 μg/L and GH≤0.05 μg/L) in patients with HP, the higher the prevalence of MS (25.5%, 30.0%, 42.9%, 48.6%, P=0.031). Conclusions: The prevalence of MS in adult HP patients is higher than in patients with normal pituitary function. Abdominal obesity and dyslipidemia are the main components of MS, and GH deficiency is related to MS in HP patients.