Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report.

BACKGROUND: No reports have shown histological changes before and after anti-C5 monoclonal antibody treatment in patients with atypical hemolytic uremic syndrome (aHUS). Here, we report a rare case of complement-mediated aHUS with a complement factor H (CFH) mutation and anti-CFH antibodies who underwent multiple kidney biopsies. CASE PRESENTATION: A 53-year-old woman developed aHUS with CFH gene mutation [c.3572C > T (p. Ser1191 Leu)] and anti-CFH antibodies. Her father had succumbed to acute kidney injury (AKI) in his 30 s. She exhibited AKI, thrombocytopenia, and hemolytic anemia with schistocytes. After improving the platelet count with one session of plasma exchange, a kidney biopsy was performed one month after the onset of symptoms. Blood vessel thrombosis, obvious endothelial swelling, endocapillary hypercellularity, and subendothelial exudative lesions in the glomeruli and arterioles were detected. Anti-C5 monoclonal antibody treatment with eculizumab immediately improved disease activity. A second biopsy 3 months later revealed marked improvement of endothelial injuries with residual membrane double contours and exudative lesions. A third biopsy at 17 months after gradual improvement of kidney function showed a further decrease of double contours along with alterations of the exudative lesions to fibrous intimal thickening. CONCLUSIONS: This is the first report showing the pathophysiology of aHUS in the kidneys and the efficacy of anti-C5 monoclonal antibody treatment by presenting serial kidney pathological features before and after anti-C5 monoclonal antibody treatment. Since her CFH mutation was considered the most important pathological condition, treatment centered on eculizumab was administered, resulting in a good long-term prognosis. In addition, kidney pathological resolution in aHUS occurred over 1 year after anti-C5 monoclonal antibody treatment.

Investigation of Clinical Features and Association between Vascular Endothelial Injury Markers and Cytomegalovirus Infection Associated with Thrombotic Microangiopathy in Patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: Case-Based Research.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) can occasionally trigger thrombotic microangiopathy (TMA). Cytomegalovirus (CMV) may be reactivated during intensive immunosuppressive therapy for AAV and cause TMA. Therefore, we aimed to evaluate the clinical features of and the association between vascular endothelial injury markers and TMA due to CMV in patients with AAV. A 61-year-old female was diagnosed with AAV and severe kidney injury. Immunosuppressive therapy gradually improved her symptoms and laboratory findings. However, 2 weeks after induction therapy initiation, she exhibited altered consciousness, a significant decrease in platelet count, and hemolytic anemia, resulting in a TMA diagnosis. Plasma exchange did not improve TMA findings and routine screening test revealed CMV infection. Ganciclovir injection improved the infection and TMA findings. Consequently, we diagnosed her with CMV-induced TMA. Both AAV and CMV may induce severe vascular endothelial injury, potentially leading to TMA development. CMV-induced TMA should be considered when TMA develops during induction therapy against AAV. Moreover, of the three serum markers of vascular injury-serum sulfatides, soluble thrombomodulin, and pentraxin 3-serum sulfatides may be associated with the development of TMA, and a high level of soluble thrombomodulin may be associated with the development of CMV viremia during the clinical course of AAV.

Advances in Derivatization Techniques Enabled by DABCO for Novichok Agent Analysis in Biofluids Using LC-MS.

The characterization of Novichoks (NVs), a new group of nerve agents that have been implicated in two recent poisonings, has not been extensively conducted. Here, we present a novel method for analyzing NV hydrolysates using liquid chromatography-tandem mass spectrometry (LC-MS/MS) enabled by pentafluorobenzyl (PFB) derivatization followed by reaction with 1,4-diazabicyclo[2.2.2]octane (DABCO). This approach enabled efficient, simultaneous screening of six NV hydrolysates, with 1-2 orders improvement in the limit of detection in relation to that achieved through previous methods. A straightforward pretreatment using DABCO and filtration was employed for biological samples, mitigating instrument damage and allowing LC-MS/MS after a reaction with highly hydrophobic PFB bromide (PFBBr). In addition, the use of pralidoxime (PAM) significantly enhanced the detection of NV hydrolysates from NV-surrogate-spiked serum. While PAM is not a proven NV antidote, its effectiveness as an analytical reagent to aid in the detection of NV hydrolysates was demonstrated for the first time. Understanding the proposed mechanism of DABCO-mediated derivatization reagent removal in this research could broaden the range of compounds amenable to derivatization LC, thereby enhancing the capabilities of conventional derivatization techniques.

Dimethoxytriadinylation LC-MS/MS of Novichok A-Series Degradation Products in Human Urine.

Novichok A-series compounds, novel nerve agents, pose an increasing threat to citizens worldwide; however, no analytical methods have been reported for detecting their hydrolysis products. Herein, a screening method was developed to detect and identify Novichok A-series degradation products (hydrolysates of A230, A232, A234, A262, and one related compound) and alkyl methylphosphonic acids (RMPAs, conventional nerve agent hydrolysates) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified a suitable derivatization reagent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), and optimized the reaction conditions. The derivatized esters of Novichok A-series degradation products were stable and easily detected. We used this derivatization to achieve the first analytical method for Novichok hydrolysis products in urine (0.40-4.0 ng/mL). The detection limits of the RMPAs (0.1-0.4 ng/mL) were comparable to those presented in previous reports involving pentafluorobenzylation or direct LC-MS/MS. The applicability of the newly developed method was evaluated by analyzing urine samples from the OPCW Fifth Biomedical Proficiency Test.

A diagnostic index based on quantitative susceptibility mapping and voxel-based morphometry may improve early diagnosis of Alzheimer's disease.

OBJECTIVES: Voxel-based morphometry (VBM) is widely used to quantify the progression of Alzheimer's disease (AD), but improvement is still needed for accurate early diagnosis. We evaluated the feasibility of a novel diagnosis index for early diagnosis of AD based on quantitative susceptibility mapping (QSM) and VBM. METHODS: Thirty-seven patients with AD, 24 patients with mild cognitive impairment (MCI) due to AD, and 36 cognitively normal (NC) subjects from four centers were included. A hybrid sequence was performed by using 3-T MRI with a 3D multi-echo GRE sequence to obtain both a T1-weighted image for VBM and phase images for QSM. The index was calculated from specific voxels in QSM and VBM images by using a linear support vector machine. The method of voxel extraction was optimized to maximize diagnostic accuracy, and the optimized index was compared with the conventional VBM-based index using receiver operating characteristic analysis. RESULTS: The index was optimal when voxels were extracted as increased susceptibility (AD > NC) in the parietal lobe and decreased gray matter volume (AD < NC) in the limbic system. The optimized proposed index showed excellent performance for discrimination between AD and NC (AUC = 0.94, p = 1.1 × 10-10) and good performance for MCI and NC (AUC = 0.87, p = 1.8 × 10-6), but poor performance for AD and MCI (AUC = 0.68, p = 0.018). Compared with the conventional index, AUCs were improved for all cases, especially for MCI and NC (p < 0.05). CONCLUSIONS: In this preliminary study, the proposed index based on QSM and VBM improved the diagnostic performance between MCI and NC groups compared with the VBM-based index. KEY POINTS: • We developed a novel diagnostic index for Alzheimer's disease based on quantitative susceptibility mapping (QSM) and voxel-based morphometry (VBM). • QSM and VBM images can be acquired simultaneously in a single sequence with little increasing scan time. • In this preliminary study, the proposed diagnostic index improved the discriminative performance between mild cognitive impairment and normal control groups compared with the conventional VBM-based index.

Comparison of the factors associated with the short-term prognosis between elderly and non-elderly patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective observational study.

OBJECTIVES: The difference in factors associated with the prognosis between elderly and non-elderly patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is uncertain. We aimed to elucidate the clinical factors associated with the short-term prognosis (within 6 months from the start of the treatment) and investigate the differences in the associated factors between elderly and non-elderly individuals. METHODS: We performed a dual centre retrospective observational study of patients newly treated with AAV (eosinophilic granulomatous with polyangiitis was excluded). The primary outcome was all-cause death, and the secondary outcome was end-stage renal disease (ESRD) and infectious complications within 6 months after the start of treatment. We analysed factors associated with these outcomes using logistic regression analyses. RESULTS: Of the 79 patients, patients aged ≥75 years were defined as elderly (n=41), whereas those aged <75 years were de¬fined as non-elderly (n=38). In elderly patients, age was significantly associated with all-cause mortality. In the non-elderly patients, the geriatric nutritional risk index was significantly associated with all-cause death. The estimated glomerular filtration rate (eGFR) before the start of treatment was significantly associated with ESRD in elderly and non-elderly patients. In elderly patients, the Birmingham vasculitis score 3, eGFR, methylprednisolone pulse use, and cyclophosphamide use were significantly associated with infectious complications. Factors other than the serum albumin level were not significantly associated with infectious complications in the non-elderly population. CONCLUSIONS: The factors associated with all-cause death and infectious complications differed between elderly and non-elderly patients. Awareness of these differences may contribute to better management of AAV.

Relationship between glomerular number in fresh kidney biopsy samples and light microscopy samples.

BACKGROUND: On-site evaluation of fresh kidney biopsy (FKB) samples at the time of biopsy is useful to verify that adequate specimens are acquired. However, some cases present poor correlation between glomerular number in FKB samples and light microscopy (LM) samples. We examined the usefulness of such on-site evaluation. METHODS: We conducted a retrospective cross-sectional observational study (n = 129) to assess the correlation between glomerular number in FKB samples and LM samples and the associated factors hindering the evaluation. RESULTS: There was a significant positive correlation between glomerular number in FKB samples and LM samples. The median ratio of glomerular number (LM samples/FKB samples) was 0.74. According to this ratio, cases were divided into three groups: reasonable estimation (65 cases), underestimation (32 cases), and overestimation (32 cases). Comparing the reasonable and underestimation groups, significant differences were detected in the extent of interstitial fibrosis and tubular atrophy (IFTA) and interstitial inflammation. Logistic regression analysis demonstrated that IFTA and interstitial inflammation were significantly associated with the underestimation. Moreover, the cortex length of FKB samples correlated with glomerular number in LM samples regardless of tubulointerstitial lesions. CONCLUSIONS: Glomerular number determined during on-site evaluation can be a reference for the actual number of glomeruli in LM samples. Since tubulointerstitial lesions make it difficult to recognize glomeruli in FKB samples, the possibility of underestimation for cases with possibly severe tubulointerstitial lesions should be considered. In such cases, evaluation of cortex length of FKB samples may substitute for evaluating glomeruli on-site.

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Developing Pancreatic Lesion and Diabetes Mellitus: A Case Report and Review of the Literature.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small blood vessels and causes severe systemic organ injury commonly affecting the lungs and kidney. However, gastrointestinal, especially pancreatic, lesions are rare. We report the case of a 67-year-old Japanese man diagnosed with myeloperoxidase (MPO) AAV who developed pancreatic lesions and diabetes mellitus. The patient was admitted to our hospital due to fever, cough, and weight loss. He developed progressive glomerulonephritis, lung nodules, and pancreatic swelling and mass. Additionally, laboratory examination revealed positive MPO-ANCA and elevated glycated hemoglobin A1c, which were suggestive of diabetes mellitus. Renal biopsy revealed necrotizing crescentic glomerulonephritis and vasculitis in the small arteries. Endoscopic ultrasound-guided fine needle aspiration of the pancreas was performed, and histological findings suggested the possibility of pancreatic vasculitis and parenchymal injury. The patient was diagnosed with AAV, which was managed with glucocorticoids. This improved the renal function and pancreatic lesions. Furthermore, blood glucose levels improved despite treatment with glucocorticoids. These findings suggest that AAV-related pancreatic lesions worsened glycemic control. However, glucocorticoid therapy improved vasculitis and pancreatic lesions, which resulted in improved glycemic control.

Cholesterol Emboli Co-Existing with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in a 76-Year-Old Woman.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis injures small vessels and causes severe systemic organ injury. Main target antigens of ANCA are myeloperoxidase and proteinase 3. ANCA strongly associates with the development and progression of the vasculitis. Its manifestations include rapidly progressive glomerulonephritis, interstitial pneumonitis, alveolar hemorrhage, purpura, and neurological disorder. Most patients with ANCA-associated vasculitis in Japan are elderly and have atherosclerotic risk factors. Cholesterol emboli are systemic vascular inflammation triggered by cholesterol crystals. Cholesterol emboli cause kidney dysfunction and ischemia of the intestines, brain, heart, skin, and peripheral nerves. Diabetes mellitus, hypertension, hyperlipidemia, and history of cardiovascular diseases are risk factors of the development of cholesterol emboli. We report a case of ANCA-associated vasculitis coexisting with cholesterol emboli. A 76-year-old woman was diagnosed with ANCA-associated interstitial pneumonitis. She rapidly developed progressive glomerulonephritis, purpura, and peripheral sensory nerve disorder. A kidney biopsy revealed that renal dysfunction was caused by vasculitis of the interlobular arteries and cholesterol emboli. A skin biopsy revealed that purpura was caused by cholesterol emboli. Glucocorticoid and statin therapies were administered. Thereafter, the renal function and other symptoms improved and stabilized. The representative symptoms of ANCA-associated vasculitis and cholesterol emboli are closely similar, and it is difficult to distinguish between these diseases when they coexist. Because the background characteristics of patients with ANCA-associated vasculitis and risk factors of cholesterol emboli overlap, at the time of diagnosing ANCA-associated vasculitis, clinicians should consider the possibility of cholesterol emboli coexistence.

Convergent Total Synthesis of Asimicin via Decarbonylative Radical Dimerization.

Asimicin (1) exhibits potent antitumor activity and comprises a central C2 -symmetric bis-tetrahydrofuran and two aliphatic side-chains, one of which terminates with (S)-methyl-2(5H)-furanone. This work reports a convergent total synthesis of 1 in 17 steps from d-gulose derivative 4. Decarbonylative radical-radial homo-coupling of α-alkoxyacyl telluride 12 a efficiently produced the C2 -symmetric core 3-SS, which was transformed into 1 through stepwise attachment of the two side-chains and functional group manipulations.

Technical Performance and Clinical Effectiveness of Drop Type With Adjustable Concentrator-Cell Free and Concentrated Ascites Reinfusion Therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is a very useful treatment method for refractory ascites but is difficult for many hospitals to employ due to its need for specialized equipment. We have therefore developed drop-type with adjustable concentrator CART (DC-CART) that uses a drop-type filtration mechanism and requires only a simple pump and pressure monitor for its concentration process. Easy adjustment of ascites concentration is possible through a recirculation loop, and filter membrane washing is aided by DC-CART's external pressure-type filtration to enable the processing of any quality or quantity of ascites. Moreover, the absence of a roller pump before filtration avoids inflammatory substance release from compressed cells. A total of 268 sessions of DC-CART using ascites from 98 patients were performed with good clinical results at our hospitals between January 2012 and June 2016. This report presents the detailed methods of DC-CART and summarizes its clinical effectiveness using patient ascites and blood data obtained from 59 sessions between March 2015 and February 2016. This novel technique successfully processed refractory ascites in numerous diseases with no serious adverse events. DC-CART could concentrate large amounts of ascites (from median weight: 4900 g [max: 20 200 g] to median weight: 695 g; median concentration ratio: 7.4), and a high amount of protein (median weight: 73 g [max: 294 g]) could be reinfused. Serum albumin levels were significantly increased (P = 0.010) and kidney function and systemic hemodynamics were well maintained in treated subjects. Additional concentration of ascites and adjustment of ascites volume were easily performed by recirculation (from median weight: 615 g to median weight: 360 g; median concentration ratio: 1.5). Time was needed during DC-CART for filter membrane cleaning, especially for viscous ascites. Overall, DC-CART represents a safe and useful treatment method for various forms of refractory ascites that can be performed at a wide range of health care institutions.

Identification of chronic kidney disease patient characteristics influencing the renoprotective effects of febuxostat therapy: a retrospective follow-up study.

BACKGROUND: The ability of antihyperuricemic therapy to exert renoprotective effects in patients with chronic kidney disease (CKD) is controversial. In the present study, we studied patient characteristics that may mask favorable impact of antihyperuricemic therapy on the progression of CKD. METHODS: This was a single-center, retrospective, follow-up study. One-hundred and seventy-eight CKD patients with hyperuricemia who received febuxostat therapy were included in this study. Mean serum uric acid (mUA) level after treatment and changes in estimated glomerular filtration rate (ΔeGFR) over 6 months were measured and their correlation was examined. Patients were divided into two groups based on mUA, and their ΔeGFR were compared. These analyses were evaluated in various subgroups. RESULTS: Febuxostat therapy markedly decreased UA level in any CKD stage patients without resulting in serious adverse events. eGFRs of CKD patients in the mUA < 6.0 mg/dl group were maintained, whereas those in the mUA ≥ 6.0 mg/dl group decreased. A significant inverse correlation was observed between mUA and ΔeGFR (r = -0.16, p = 0.019). The renoprotective effects of febuxostat were significant in the following subgroups: male patients, age < 70 years, systolic blood pressure < 130 mmHg, normal cholesterol levels, and absence of diabetes. Coexisting vascular risk factors appear to exert additive masking effects against febuxostat renoprotection. CONCLUSIONS: The results of this study suggest that various vascular risk factors markedly attenuate the renoprotective effects of febuxostat.

Outcomes of critically ill patients with liver failure who require mechanical ventilation: A retrospective, single-center study.

Background and Aims: Critically ill patients with liver failure have high mortality. Besides the management of organ-specific complications, liver transplantation constitutes a definitive treatment. However, clinicians may hesitate to introduce mechanical ventilation for patients on liver transplantation waitlists because of poor prognosis. This study investigated the outcomes of intensive care and ventilation support therapy effects in patients with liver failure. Methods: This single-center study retrospectively enrolled 32 consecutive patients with liver failure who were admitted to the intensive care unit from January 2014 to December 2020. The medical records were reviewed and analyzed retrospectively for Acute Physiologic and Chronic Health Evaluation (APACHE)-II. The model for end-stage liver disease scores, 90-day mortality, and survival was assessed using the Kaplan-Meier method. Results: The average patient age was 45.5 ± 20.1 years, and 53% of patients were women. On intensive care unit admission, APACHE-II and model for end-stage liver disease scores were 20 and 28, respectively. Among 13 patients considered for liver transplantation, 4 received transplants. Thirteen patients (40.6%) were intubated and mechanically ventilated in the intensive care unit. The 90-day mortality rate of patients with and without mechanical ventilation in the intensive care unit (13, 61.5% vs. 19, 47.4%, p = 0.4905) was similar. APACHE-II score >21 was an independent predictor of mechanical ventilation requirement in patients with liver failure during intensive care unit stay. Conclusion: Although critically ill patients with liver failure are at risk of multiorgan failure with poor outcomes, mechanical ventilation did not negatively affect the 90-day mortality or performance rates of liver transplantation. Clinicians should consider mechanical ventilation-based life support in critically ill patients with liver failure who are awaiting liver transplantation.

Simultaneous analysis of degradation products of Novichok agents and conventional nerve agents in human urine by ion chromatography-tandem mass spectrometry using ammonium regeneration solution.

An ion chromatography (IC)-tandem mass spectrometry (MS/MS) method to analyze nerve agent degradation products in human urine was developed. Six degradation products of conventional nerve agents and six Novichok agent degradation products were analyzed simultaneously despite their differences in hydrophilicity and acidity. Using ammonium regeneration solution improved the peak shapes greatly compared with the results obtained with the ordinary IC-MS/MS configuration. For urine samples, a simple pretreatment method of dilution with water and ultrafiltration was used. The detection limits of the nerve agent degradation products were sufficiently low (10-250 ng/mL) and the calibration curves showed acceptable linearity. Due to the absence of a derivatization step, throughput was higher than for our previous derivatization-liquid chromatography-MS/MS method.

Analysis of degradation products of Novichok agents in human urine by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

PURPOSE: The detection of hydrolysis products of Novichok agents in biological samples from victims is important for confirming exposure to these agents. However, Novichok agents are new class of nerve agent and there have been only few reports on analyses of Novichok agent degradation products. Here, we developed hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry (MS/MS) methods to detect Novichok agent degradation products in human urine with simple pretreatment and high sensitivity. METHODS: A Poroshell 120 HILIC-Z column was used to analyze six Novichok agent degradation products. For urine samples, we used a simple pretreatment method, which consisted of deproteinization with acetonitrile and microfiltration. We calculated the pKa values of the OH groups, the log P values, and the molecular weights to investigate the difference in chromatographic behaviors of the Novichok agent degradation products and the degradation products of conventional nerve agents. RESULTS: Six Novichok agent degradation products, including N-(bis-(diethylamino)methylidene)-methylphosphonamidic acid (MPGA), which could not be detected by our previous method, could be analyzed with sufficient peak shape and mutual separation. The detection limits of six Novichok agent degradation products were sufficiently low (1-50 ng/mL) and the calibration curves showed sufficient linearity. The physicochemical parameters of Novichok agent degradation products were different from those of conventional nerve agent degradation products, and this explains the difference in chromatographic behaviors. CONCLUSION: Six Novichok agent degradation products were successfully analyzed by HILIC-MS/MS. Due to the absence of a derivatization step, throughput performance was higher than our previous derivatization-liquid chromatography-MS/MS method.

Predictive Factors of Cytomegalovirus Viremia during the Clinical Course of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Single Center Observational Study.

We aim to elucidate factors to aid in the prediction of cytomegalovirus viremia during the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We conducted a single-center, retrospective, observational study of 35 patients with newly diagnosed AAV. Factors associated with the development of CMV viremia were investigated via a logistic regression analysis. The CMV antigenemia test was performed in 25 patients (71%), of whom 15 (60%) were diagnosed with CMV viremia. Of these 15 patients, 5 developed a CMV infection. The total protein, hemoglobin, platelet count and lymphocyte counts at the time of the CMV antigenemia test were significantly lower in patients who developed CMV viremia. In addition, total protein, hemoglobin, platelet count and lymphocyte count also presented significantly decreasing trends in the following order: patients who did not develop CMV viremia, patients who developed CMV viremia without any symptoms, and patients who developed CMV infection. All patients with CMV recovered. In conclusion, the total protein, hemoglobin, platelet count and lymphocyte count may be useful markers for the prediction of CMV viremia and infection after the start of induction of immunosuppressive therapy for patients with AAV.

Prediction of amyloid positron emission tomography positivity using multiple regression analysis of quantitative susceptibility mapping.

PURPOSE: To develop a method for predicting amyloid positron emission tomography (PET) positivity based on multiple regression analysis of quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: This prospective study included 39 patients with suspected dementia from four centers. QSM images were obtained through a 3-T, three-dimensional radiofrequency-spoiled gradient-echo sequence with multiple echoes. The cortical standard uptake value ratio (SUVR) was obtained using amyloid PET with 18F-flutemetamol, and susceptibility in the brain regions was obtained using QSM. A multiple regression model to predict cortical SUVR was constructed based on susceptibilities in multiple brain regions, with the constraint that cortical SUVR and susceptibility were positively correlated. The discrimination performance of the Aß-positive and Aß-negative cohorts was evaluated based on the predicted SUVR using the area under the receiver operating characteristic curve (AUC) and Mann-Whitney U test. RESULTS: The correlation coefficients between true and predicted SUVR were increased by incorporating the constraint, and the AUC to discriminate between the Aß-positive and Aß-negative cohorts reached to 0.79 (p < 0.01). CONCLUSION: These preliminary results suggest that a QSM-based multiple regression model can predict amyloid PET positivity with fair accuracy.

Efficacy of Quantitative Susceptibility Mapping with Brain Surface Correction and Vein Removal for Detecting Increase Magnetic Susceptibility in Patients with Alzheimer's Disease.

PURPOSE: Studies on quantitative susceptibility mapping (QSM) have reported an increase in magnetic susceptibilities in patients with Alzheimer's disease (AD). Despite the pathological importance of the brain surface areas, they are sometimes excluded in QSM analysis. This study aimed to reveal the efficacy of QSM analysis with brain surface correction (BSC) and/or vein removal (VR) procedures. METHODS: Thirty-seven AD patients and 37 age- and sex-matched, cognitively normal (CN) subjects were included. A 3D-gradient echo sequence at 3T MRI was used to obtain QSM. QSM images were created with regularization enabled sophisticated harmonic artifact reduction for phase data (RESHARP) and constrained RESHARP with BSC and/or VR. We conducted ROI analysis between AD patients and CN subjects who did or did not undergo BSC and/or VR using a t-test, to compare the susceptibility values after gray matter weighting. RESULTS: The susceptibility values in RESHARP without BSC were significantly larger in AD patients than in CN subjects in one region (precentral gyrus, 8.1 ± 2.9 vs. 6.5 ± 2.1 ppb) without VR and one region with VR (precentral gyrus, 7.5 ± 2.8 vs. 5.9 ± 2.0 ppb). Three regions in RESHARP with BSC had significantly larger susceptibilities without VR (precentral gyrus, 7.1 ± 2.0 vs. 5.9 ± 2.0 ppb; superior medial frontal gyrus, 5.7 ± 2.6 vs. 4.2 ± 3.1 ppb; putamen, 47,8 ± 16.5 vs. 40.0 ± 15.9 ppb). In contrast, six regions showed significantly larger susceptibilities with VR in AD patients than in CN subjects (precentral gyrus, 6.4 ± 1.9 vs. 4.9 ± 2.7 ppb; superior medial frontal gyrus, 5.3 ± 2.7 vs. 3.7 ± 3.3 ppb; orbitofrontal cortex, -2.1 ± 2.7 vs. -3.6 ± 3.2 ppb; parahippocampal gyrus, 0.1 ± 3.6 vs. -1.7 ± 3.7 ppb; putamen, 45.0 ± 14.9 vs. 37.6 ± 14.6 ppb; inferior temporal gyrus, -3.4 ± 1.5 vs. -4.4 ± 1.5 ppb). CONCLUSION: RESHARP with BSC and VR showed more regions of increased susceptibility in AD patients than in CN subjects. This study highlights the efficacy of this method in facilitating the diagnosis of AD.

Serum Sulfatide Levels as a Biomarker of Active Glomerular Lesion in Patients with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single Center Pilot Study.

Sulfatides are glycosphingolipids that are associated with coagulation and platelet aggregation. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) activates platelet function and often leads to thrombotic complications. These facts suggest an association between serum sulfatides and AAV. We aimed to clarify the significance of serum sulfatide levels in patients with AAV. We conducted a retrospective, single-center, observational pilot study that included 35 patients who developed AAV and 10 control patients who were candidates for living-donor kidney transplantation. We compared serum sulfatide levels between the control and AAV patients. We analyzed the differences in serum sulfatide levels among four classes (focal, crescentic, mixed, and sclerotic class) of glomerular lesions that were categorized by histopathologic classification of ANCA-associated glomerulonephritis. Serum sulfatide levels in patients with AAV were significantly lower than those in the controls. Serum sulfatide levels were significantly different between the four classes. Additionally, serum sulfatide levels in the crescentic class were significantly lower than those in the other classes. Serum sulfatide levels were significantly correlated with albumin, cholesterol, C-reactive protein, and pentraxin 3. In conclusion, serum sulfatide levels are significantly correlated with inflammation, reflecting crescentic glomerulonephritis, which is an active glomerular lesion in AAV patients.