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Background Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection., Graphical abstract Image 1

Introduction High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding. Aim To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA). Methods SPACE was a 6-month, prospective, multicenter, observational outcomes study (NCT02190149). Enrolled patients received an eDiary application and a wearable activity tracker, which recorded physical activity, rAHF infusion, and occurrence of bleeding. Physical activity risks were ranked using National Hemophilia Foundation criteria. Results Fifty-four patients aged 11–58 years (n = 47 prophylaxis, n = 7 on-demand) were included in the analysis. Patients had a mean (SD) 8.14 (10.94) annualized bleeding rate, and recorded 4980 intervals between an rAHF infusion and physical activity; 1759 (35.3%) of these intervals were ≤24 hours. Analysis of recorded eDiary data showed that the risk of activity-related bleeding did not significantly increase with time between last infusion and activity, but did increase with higher-risk physical activities. Analysis of activity tracker recorded data showed that the risk of bleeding reported by patients as spontaneous increased with prolonging time (≤24 to >24 hours) from last infusion to physical activity start (odds ratio 2.65, p < 0.05). Joint health data collected at baseline were not included in the regression analysis because of small sample size; therefore the study could not assess whether patients with more joint disease at baseline were at higher risk of injury-related and reported spontaneous occurrence of bleeding. Conclusion These results show that activities with a high risk of collision lead to an increased risk of bleeding. Further investigation is warranted to explore potential benefits of FVIII infusion timing to reduce the risks of activity-related occurrence of bleeding.

Ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC); however, inadequate treatment response (ITR) is common. The UK-PBC Consortium developed the modified UDCA Response Score (m-URS) to predict ITR (using alkaline phosphatase [ALP] > 1.67 times the upper limit of normal [*ULN]) at 12 months post-UDCA initiation). Using data from the US-based Fibrotic Liver Disease Consortium, we assessed the m-URS in our multi-racial cohort. We then used a dynamic modeling approach to improve prediction accuracy. Using data collected at the time of UDCA initiation, we assessed the m-URS using the original formula; then, by calibrating coefficients to our data, we also assessed whether it remained accurate when using Paris II criteria for ITR. Next, we developed and validated a dynamic risk prediction model that included post-UDCA initiation laboratory data. Among 1578 patients (13% men; 8% African American, 9% Asian American/American Indian/Pacific Islander; 25% Hispanic), the rate of ITR was 27% using ALP > 1.67*ULN and 45% using Paris II criteria. M-URS accuracy was “very good” (AUROC = 0.87, sensitivity = 0.62, and specificity = 0.82) for ALP > 1.67*ULN and “moderate” (AUROC = 0.74, sensitivity = 0.57, and specificity = 0.70) for Paris II. Our dynamic model significantly improved accuracy for both definitions of ITR (ALP > 1.67*ULN: AUROC = 0.91; Paris II: AUROC = 0.81); specificity approached 100%. Roughly 9% of patients in our cohort were at the highest risk of ITR. Early identification of patients who will not respond to UDCA treatment using a dynamic prediction model based on longitudinal, repeated risk factor measurements may facilitate earlier introduction of adjuvant treatment.

Objective To estimate relative suicidality risk associated with binge‐eating disorder (BED). Methods Retrospective study of patients identified as having BED (N = 1042) and a matched general population cohort (N = 10,420) from the Optum electronic health record database between January 2009 and September 2015. Patients had ≥1 outpatient encounter with a provider who recognized BED during the 12‐month baseline preceding entry date. Incidence and relative risk of suicidality were assessed. Results Incidence per 1000 person‐years (95% CI) of suicidal ideation and suicide attempts, respectively, was 31.1 (23.1, 41.0) and 12.7 (7.9, 19.4) in the BED cohort and 5.8 (4.7, 7.1) and 1.4 (0.9, 2.2) in the comparator cohort. Risk of suicidal ideation and suicide attempts was greater in the BED cohort (HR [95% CIs], 6.43 [4.42, 9.37]) than in the comparator cohort (HR [95% CI], 9.47 [4.99, 17.98]) during follow‐up. After adjusting for psychiatric comorbidities, associations of suicidal ideation and suicide attempts with BED remained elevated in patients with BED having histories of suicidality. Conclusions Findings suggest that history of suicidality may result in an increased risk of suicidal ideation and suicide attempts in patients with BED relative to the general population. Psychiatric comorbidity burden may explain the elevated risk of these conditions in BED.

There are limited data examining the relationship between psychosocial factors and receipt of direct‐acting antiviral (DAA) treatment among patients with hepatitis C in large health care organizations in the United States. We therefore sought to determine whether such factors were associated with DAA initiation. We analyzed data from an extensive psychological, behavioral, and social survey (that incorporated several health‐related quality of life assessments) coupled with clinical data from electronic health records of patients with hepatitis C enrolled at four health care organizations during 2017‐2018. Of 2,681 patients invited, 1,051 (39.2%) responded to the survey; of 894 respondents eligible for analysis, 690 (77.2%) initiated DAAs. Mean follow‐up among respondents was 9.2 years. Compared with DAA recipients, nonrecipients had significantly poorer standardized scores for depression, anxiety, and life‐related stressors as well as poorer scores related to physical and mental function. Lower odds of DAA initiation in multivariable analysis (adjusted by age, race, sex, study site, payment provider, cirrhosis status, comorbidity status, and duration of follow‐up) included Black race (adjusted odds ratio [aOR], 0.59 vs. White race), perceived difficulty getting medical care in the preceding year (aOR, 0.48 vs. no difficulty), recent injection drug use (aOR, 0.11 vs. none), alcohol use disorder (aOR, 0.58 vs. no alcohol use disorder), severe depression (aOR, 0.42 vs. no depression), recent homelessness (aOR, 0.36 vs. no homelessness), and recent incarceration (aOR, 0.34 vs. no incarceration). Conclusion: In addition to racial differences, compared with respondents who initiated DAAs, those who did not were more likely to have several psychological, behavioral, and social impairments. Psychosocial barriers to DAA initiation among patients in care should also be addressed to reduce hepatitis C‐related morbidity and mortality., Even among persons with access to care, receipt of direct‐acting antiviral treatment for hepatitis C is suboptimal. We therefore conducted a detailed psychological, behavioral, and social survey among hepatitis C patients in care to determine whether such factors were associated with DAA initiation. Compared with respondents who initiated DAAs, those who did not were more likely to have several psychological, behavioral, and social impairments, suggesting that such factors should be addressed to reduce hepatitis C‐related morbidity and mortality.

Supplemental Digital Content is available in the text., Goals: This US-based, retrospective claims study aimed to investigate disease burden and treatment patterns in patients with eosinophilic esophagitis (EoE), and to compare health care resource use (HCRU) in patients with EoE and matched controls without EoE. Materials and Methods: Patients with a diagnosis of EoE and ≥12 months of prediagnosis data were identified from the Truven Health MarketScan Research databases (January 2008 to September 2016) and followed up from the diagnosis date until termination of eligibility for a health plan. Patient clinical characteristics and HCRU were recorded in the 12 months before diagnosis; HCRU and treatment patterns were recorded during follow-up. HCRU in patients with EoE and matched controls was compared during the 12-month postdiagnosis period. Results: Among the 23,003 patients with EoE (mean age: 34.3 y; 64.8% male), gastroesophageal reflux disease was the most common prediagnosis condition (34.6%). After diagnosis, the most common off-label, first-line treatments were proton pump inhibitor monotherapy (52.8%) and topical corticosteroid monotherapy (21.5%). Overall, 3336 patients (14.5%) received at least 3 lines of off-label pharmacotherapy. Outpatient visits (recorded in 99.9% of patients on and postdiagnosis) were most frequently to gastroenterologists/pediatric gastroenterologists (49.5% prediagnosis, 72.6% on and postdiagnosis). Inpatient admissions and outpatient and emergency room visits were more likely in patients with EoE than in matched controls (P

Phloretin, a dihydrochalcone, widely exists in the fruits of apple trees and crabapple trees (Malus prunifolia) with multiple biological activities. Presently, we studied the function of phloretin on the attenuation of hepatic steatosis and further explored the underlying mechanisms both in vitro and in vivo. Male C57BL/6J mice were fed a normal diet or high fat diet (HFD) with or without phloretin (100 mg kg-1) for 12 weeks. HepG2 cells were induced by 200 μM palmitic acid (PA) and co-incubated with phloretin (50 μM) for 24 h. The results showed that phloretin treatment significantly decreased the accumulation of lipids in the liver of the HFD-fed C57BL/6J mice and PA-induced HepG2 cells. Also, phloretin effectively ameliorated hepatic steatosis via promoting fatty acid β-oxidation (FAO). This biological activity of phloretin was closely related to its capacity to improve mitochondrial dysfunction, including the promotion of mitochondrial biosynthesis and inhibition of mitochondrial swelling through the AMPK-dependent SIRT1/PGC-1α and SIRT3/CypD signaling pathways, respectively. These results demonstrate that phloretin effectively improves mitochondrial function and ameliorates HFD-induced hepatic steatosis through an AMPK-dependent signaling pathway.

Author(s): Lu, Mei; Bowlus, Christopher L; Lindor, Keith; Rodriguez-Watson, Carla V; Romanelli, Robert J; Haller, Irina V; Anderson, Heather; VanWormer, Jeffrey J; Boscarino, Joseph A; Schmidt, Mark A; Daida, Yihe G; Sahota, Amandeep; Vincent, Jennifer; Li, Jia; Trudeau, Sheri; Rupp, Loralee B; Gordon, Stuart C; FOLD Investigators | Abstract: BackgroundBiopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients.MethodsHistological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and g100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis.ResultsAmong 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively).ConclusionAn algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients' cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.

Background Changing US demographics and evolving chronic hepatitis B (CHB) treatments may affect longitudinal trends in CHB-related complications. We studied trends in the prevalence of cirrhosis (past or present) and incidence of all-cause mortality, stratified by patient age, sex, race, and antiviral treatment status, in a sample from US health care systems. Methods Joinpoint and Poisson regression (univariate and multivariable) were used to estimate the annual percent change in each outcome from 2006 to 2016. Results Among 5528 CHB patients, cirrhosis prevalence (including decompensated cirrhosis) rose from 6.7% in 2006 to 13.7% in 2016; overall mortality was unchanged. Overall rates of cirrhosis and mortality were higher among treated patients, but adjusted annual percent changes (aAPC) were significantly lower among treated than untreated patients (cirrhosis: aAPC +2.4% vs. +6.2%, mortality: aAPC -3.9% vs. +4.0%). Likewise, among treated patients, the aAPC for mortality declined -3.9% per year whereas among untreated patients, mortality increased +4.0% per year. Conclusions From 2006 to 2016, the prevalence of cirrhosis among CHB patients doubled. Notably, all-cause mortality increased among untreated patients but decreased among treated patients. These results suggest that antiviral treatment attenuates the progression of cirrhosis and the risk of death among patients with CHB.

Background Genome‐wide association studies have identified over 100 single‐nucleotide polymorphisms (SNPs) associated with prostate cancer (PrCa), and polygenic risk scores (PRS) based on their combined genotypes have been developed for risk stratification. We aimed to assess the contribution of PRS to PrCa risk in a large multisite study. Methods The sample included 1972 PrCa cases and 1919 unaffected controls. Next‐generation sequencing was used to assess pathogenic variants in 14 PrCa‐susceptibility genes and 72 validated PrCa‐associated SNPs. We constructed a population‐standardized PRS and tested its association with PrCa using logistic regression adjusted for age and family history of PrCa. Results The mean age of PrCa cases at diagnosis and age of controls at testing/last clinic visit was 59.5 ± 7.2 and 57.2 ± 13.0 years, respectively. Among 1740 cases with pathology data, 57.4% had Gleason score ≤ 6, while 42.6% had Gleason score ≥ 8. In addition, 39.6% cases and 20.1% controls had a family history of PrCa. The PRS was significantly higher in cases than controls (mean ± SD: 1.42 ± 1.11 vs 1.02 ± 0.76; P

Our previous studies demonstrated that axonal remodeling of the corticospinal tract (CST) contributes to neurological recovery after stroke in rodents. The present study employed a novel non-invasive peripheral approach, to over-express tPA in denervated spinal motor neurons via recombinant adeno-associated virus (AAV) intramuscular injection in transgenic mice subjected to permanent middle cerebral artery occlusion (MCAo), in which the CST axons are specifically and completely labeled with yellow fluorescent protein (YFP). One day after surgery, mice were randomly selected to receive saline, AAV5-RFP, or tPA (1 × 1010viral particles) injected into the stroke-impaired forelimb muscles ( n = 10/group). Functional deficits and recovery were monitored with foot-fault and single pellet reaching tests. At day 28 after MCAo, mice received intramuscular injection of PRV-614-mRFP (1.52 × 107pfu) as above, and were euthanized four days later. Compared with saline or AAV-RFP-treated mice, AAV-tPA significantly enhanced behavioral recovery ( p

Purpose To perform radiomic analysis of primary tumors extracted from pretreatment contrast-enhanced computed tomography (CE-CT) images for patients with oropharyngeal cancers to identify discriminant features and construct an optimal classifier for the characterization and prediction of human papilloma virus (HPV) status. Materials and methods One hundred and eighty seven patients with oropharyngeal cancers with known HPV status (confirmed by immunohistochemistry-p16 protein testing) were retrospectively studied as follows: Group A: 95 patients (19HPV- and 76HPV+) from the MICAII grand challenge. Group B: 92 patients (52HPV- and 40HPV+) from our institution. Radiomic features (172) were extracted from pretreatment diagnostic CE-CT images of the gross tumor volume (GTV). Levene and Kolmogorov-Smirnov's tests with absolute biserial correlation (>0.48) were used to identify the discriminant features between the HPV+ and HPV- groups. The discriminant features were used to train and test eight different classifiers. Area under receiver operating characteristic (AUC), positive predictive and negative predictive values (PPV and NPV, respectively) were used to evaluate the performance of the classifiers. Principal component analysis (PCA) was applied on the discriminant feature set and seven PCs were used to train and test a generalized linear model (GLM) classifier. Results Among 172 radiomic features only 12 radiomic features (from 3 categories) were significantly different (P 0.48) between the HPV+ and HPV- groups. Among the eight classifiers trained and applied for prediction of HPV status, the GLM showed the highest performance for each discriminant feature and the combined 12 features: AUC/PPV/NPV = 0.878/0.834/0.811. The GLM high prediction power was AUC/PPV/NPV = 0.849/0.731/0.788 and AUC/PPV/NPV = 0.869/0.807/0.870 for unseen test datasets for groups A and B, respectively. After eliminating the correlation among discriminant features by applying PCA analysis, the performance of the GLM was improved by 3.3%, 2.2%, and 1.8% for AUC, PPV, and NPV, respectively. Conclusions Results imply that GTV's for HPV+ patients exhibit higher intensities, smaller lesion size, greater sphericity/roundness, and higher spatial intensity-variation/heterogeneity. Results are suggestive that radiomic features primarily associated with the spatial arrangement and morphological appearance of the tumor on contrast-enhanced diagnostic CT datasets may be potentially used for classification of HPV status.

10% of all pediatric brain tumors arise in the brainstem. Amongst these gliomas are the most common while other entities are rare and infrequently described in the literature. In this study we investigated the prevalence of non-gliomatous tumors in the brainstem. Amongst the 1323 embryonal tumours received at the RBTC, we identified 17 cases of ETMRs (17/165) that presented as brainstem primaries. Previously grouped within CNS-PNETs, ETMR, is a new WHO diagnostic entity, characterized by C19MC alterations. ETMR is a disease of infancy, the clinical spectrum of which is poorly understood. ETMRs arise at multiple CNS locations including cerebrum being most common (60%,) followed by cerebellum (18%) and midline structures (6%); notably 10% were brainstem primaries, mimicking DIPG radiologically. All patients presented with a short history of progressive neurological symptoms, with most common signs and symptoms of cranial neuropathies, long tract signs and gait disturbance. Median age at diagnosis was 27 months (range 16-75months) with a male to female ratio of 0.9:1. Predominantly localized (M0-94%, M2-3 -6%) majority of patients underwent upfront biopsy or partial resection (15/17:88%), while complete tumor resection was achieved in 2 cases. All patients received heterogenous combination of chemotherapy with and without radiotherapy. Majority of patients progressed rapidly with median time to progression of 4 months and overall survival of < 13 months. The only long-term surviving patient had complete resection dose intensified chemotherapy and radiation (OS 202months). Primary ETMRs in the brainstem are under recognised entities and carry a dismal prognosis. Although rapidly progressive, prompt recognition, maximal resection and management with multimodal adjuvant therapy should be considered in cases with brainstem disease.

Purpose To analyze clinical toxicity and quality-of-life (QOL) outcomes among patients with stage I non-small cell lung cancer (NSCLC) after stereotactic body radiation therapy (SBRT) as a function of radiation dose and volume parameters. Methods and Materials In this institutional review board–approved study, 55 patients with stage I NSCLC who received SBRT (12 Gy × 4) and completed QOL forms were analyzed. Clinical symptoms and QOL outcomes were measured at baseline and at 3, 6, 12, 18, 24, and 36 months after SBRT. Clinical toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Lung-Trial Outcome Index (FACT-L-TOI) instrument. Dosimetric parameters including the mean lung radiation dose and the volume of normal lung receiving greater than 5, 10, 13, or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student t tests and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxic effects. The Kaplan-Meier method was used to estimate rates of local control (LC), disease-free survival (DFS), and overall survival (OS). Results With a median follow-up of 24 months, the 3-year LC, DFS, and OS were 93%, 65%, and 84%, respectively, with a 5.5% rate of grade-3 toxic effects and no grade 4 or 5 toxic effects. Clinically meaningful declines in patient-reported QOL (FACT-L-TOI, lung cancer subscale, physical well-being, and/or functional well-being) posttreatment significantly correlated with increased dosimetric parameters such as V10, V13, and V20. Conclusion Although lung SBRT was associated with excellent LC and minimal clinical toxic effects for early-stage NSCLC, clinically meaningful declines in QOL were significantly correlated with increasing lung dose and volume parameters.

Bullous pemphigoid (BP), the most frequent blistering dermatosis in the elderly, is associated with increased mortality. The severity of BP can be assessed by detecting the anti-BP180 immunoglobulin G (IgG) concentration, but the lab test is not available in many community clinics. BP patients are usually in a hypercoagulable state with increased levels of D-dimer and fibrin degradation products (FDPs). We aimed to evaluate the use of D-dimer and FDPs in assessing BP severity. We compared the levels of plasma D-dimer, plasma FDPs, eosinophil counts, eosinophil cationic protein, and serum anti-BP180 IgG concentration between 48 typical BP patients and 33 Herpes zoster (HZ) patients (control group). Correlational analyses were conducted to determine the relationships between the lab values and common BP severity markers. The plasma D-dimer and FDP levels were higher in BP patients than in HZ controls (D-dimer: 3297 ± 2517 µg/L vs. 569.70 ± 412.40 µg/L; FDP: 9.74 ± 5.88 mg/L vs. 2.02 ± 1.69 mg/L, respectively,P r = 0.3928,P = 0.0058; FDP:r = 0.4379,P = 0.0019] and eosinophil counts [D-dimer:r = 0.3625,P = 0.0013; FDP:r = 0.2880,P = 0.0472]) in BP patients. We also found an association between FDP and urticaria/erythema lesions (r = 0.3016,P = 0.0372), but no other BPDAI components. In 19 BP patients with complete remission after systemic glucocorticoid treatment, D-dimer and FDP levels decreased post-therapy (D-dimer: 5559 ± 7492 µg/L vs. 1738 ± 1478 µg/L;P P = 0.0003), whereas they did not in BP patients with treatment resistant. Plasma D-dimer and FDP are convenient markers to evaluate BP severity assistant on BPDAI and eosinophil counts. FDP is also helpful for inflammatory lesions in BP patients.

Abiola Oladapo,1 Yanyu Wu,2 Mei Lu,3 Sepehr Farahbakhshian,3 Bruce Ewenstein2 1Baxalta US Inc., a Takeda Company, Cambridge, MA, USA; 2Takeda Development Center Americas, Inc., Cambridge, MA, USA; 3Takeda Development Center Americas, Inc., Lexington, MA, USACorrespondence: Yanyu WuTakeda Development Center Americas, Inc., 40 Landsdowne Street, Cambridge, MA, 02139, USATel +1 617-955-6408Email yanyu.wu@takeda.comPurpose: To estimate the incremental economic burden of major surgeries in patients with von Willebrand disease (VWD).Patients and Methods: This was a retrospective analysis of the IBM Health MarketScan® database (2008– 2018). Patients with at least two healthcare visits for VWD in the database who had undergone at least one major surgery unrelated to VWD (identified via International Classification of Diseases, Ninth and Tenth Revisions procedure codes) were included. Patients without VWD with major surgeries were selected from a 1% random database sample. All patients had ≥ 12 months of continuous healthcare plan enrollment before and following their first major surgery. Patients with VWD were matched (1:1) with patients without VWD using propensity score matching. Regression models compared healthcare resource utilization and costs between the matched cohorts over a 12-month period after patients’ index major surgery.Results: After propensity score matching, 2972 pairs were selected. Musculoskeletal and digestive surgeries were the two most common major surgeries (patients with VWD, 39.6% and 25.0%; without VWD, 37.1% and 23.4%, respectively). Patients with VWD were significantly more likely (p< 0.0001) to have an inpatient admission (odds ratio = 1.71; 95% confidence interval [CI] 1.52– 1.92) or emergency room visit (odds ratio = 1.41; 95% CI 1.25– 1.59) than patients without VWD. The numbers of inpatient admissions (incidence rate ratio [IRR] = 1.47; 95% CI 1.35– 1.60), emergency room visits (IRR = 1.44; 95% CI 1.31– 1.59), and outpatient visits (IRR = 1.16; 95% CI 1.11– 1.21) per patient were also significantly greater for patients with VWD than for those without VWD (p< 0.0001). Patients with VWD incurred significantly higher (p< 0.0001) total healthcare costs (medical and pharmacy) per patient than patients without VWD ($50,733.89 versus $30,154.84, respectively).Conclusion: Healthcare resource utilization and associated costs among patients undergoing major surgeries were significantly higher for those with VWD than for patients without VWD.Keywords: bleeding, healthcare costs, retrospective studies, healthcare resource utilization

Rare Brain Tumor Registry., [Background] Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease., [Methods] Paediatric patients with primary ETMRs and tissue available for analyses were identified from the Rare Brain Tumor Consortium global registry. The institutional histopathological diagnoses were centrally re-reviewed as per the current WHO CNS tumour guidelines, using histopathological and molecular assays. Only patients with complete clinical, treatment, and survival data on Nov 30, 2019, were included in clinicopathological analyses. Among patients who received primary multi-modal curative regimens, event-free survival and overall survival were determined using Cox proportional hazard and log-rank analyses. Univariate and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) with 95% CIs for clinical, molecular, or treatment-related prognostic factors., [Findings] 159 patients had a confirmed molecular diagnosis of primary ETMRs (median age at diagnosis 26 months, IQR 18–36) and were included in our clinicopathological analysis. ETMRs were predominantly non-metastatic (94 [73%] of 128 patients), arising from multiple sites; 84 (55%) of 154 were cerebral tumours and 70 (45%) of 154 arose at sites characteristic of other brain tumours. Hallmark C19MC alterations were seen in 144 (91%) of 159 patients; 15 (9%) were ETMR not otherwise specified. In patients treated with curative intent, event-free survival was 57% (95% CI 47–68) at 6 months and 31% (21–42) at 2 years; overall survival was 29% (20–38) at 2 years and 27% (18–37) at 4 years. Overall survival was associated with non-metastatic disease (HR 0·48, 95% CI 0·28–0·80; p=0·0057) and non-brainstem location (0·42 [0·22–0·81]; p=0·013) on univariate analysis, as well as with gross total resection (0·30, 0·16–0·58; p=0·0014), high-dose chemotherapy (0·35, 0·19–0·67; p=0·0020), and radiotherapy (0·21, 0·10–0·41; p, [Interpretation] Prompt molecular diagnosis and post-surgical treatment with intensive multi-modal therapy tailored to patient-specific risk features could improve ETMR survival., Canadian Institute of Health Research, Canada Research Chair Awards, Australian Lions Childhood Cancer Research Foundation, Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía, Miracle Marnie, Phoebe Rose Rocks, Tali's Funds, Garron Cancer Centre, Grace's Walk, Meagan's Hug, Brainchild, Nelina's Hope, and Jean Martel Foundation.

From our clinical practice, it was found that, using the back-shu acupoints as the main ones together with the symptomized acupoints according to the different syndromes, the therapeutic effect in the treatment of arrhythmia was good. Our experience in acupuncture treatment for arrhythmia is introduced as follows with two cases attached.

The role of ribavirin (RBV) in the era of direct-acting antivirals (DAA) is not clear, and DAA studies have been largely genotype- and regimen-specific. Using data from the Chronic Hepatitis Cohort Study, we evaluated the role of RBV and increased DAA treatment duration among patients with chronic hepatitis C (HCV) in routine clinical care. We performed multivariable analysis of data from 4133 patients receiving any of the following: sofosbuvir (SOF); daclatasvir + SOF; grazoprevir + elbasvir; paritaprevir/ritonavir + ombitasvir; simeprevir + SOF; and SOF + ledipasvir; SOF + velpatasvir ± voxilaprevir; and glecaprevir + pibrentasvir—all with/ without RBV. Inverse probability treatment weighting was used to adjust for treatment selection bias. Sustained virological response (SVR) was defined by undetectable HCV RNA 12 weeks after end of therapy. The overall SVR rate was 95%. Mean treatment duration was 12 ± 4.5 weeks. The final model included treatment duration and diabetes, as well as the interaction of RBV with previous treatment status (treatment naïve, interferon treatment failure [TF] or previous DAA TF), cirrhosis status, and HCV genotype (GT). Each one-month increment of treatment duration increased odds of SVR by 99% (aOR = 1.99). Diabetes, previous DAA TF, and decompensated cirrhosis significantly reduced odds of SVR. RBV significantly increased the likelihood of SVR among patients with decompensated cirrhosis (aOR = 5.05), previous DAA treatment failure (aOR = 5.43), and GT3 (aOR = 13.28). Among RBV-free regimens, patients with GT3 were less likely to achieve SVR than those with GT1 or 2 (aOR 0.07). Diabetes, decompensated cirrhosis, and prior DAA TF independently reduced the likelihood of SVR. Longer treatment duration increased likelihood of SVR. Conclusion: RBV increased likelihood of SVR among patients with GT3, previous DAA TF, or decompensated cirrhosis.

Background Hepatitis E virus (HEV) infection is a leading cause of acute hepatitis worldwide, and results in high morbidity and mortality rates among elderly people in China. The hepatitis E vaccine, Hecolin®, has been shown to be safe and highly efficacious among healthy adults aged 16–65 years old. However, there is no data about Hecolin® vaccination in elderly people older than 65 years (y). Methods An open-labeled, controlled trial was conducted to evaluate the safety and immunogenicity of Hecolin® among the elderly aged >65 y. A total of 601 eligible participants were enrolled. Among them, 200 elderly people aged >65 y and 201 adults aged 18–65 y were assigned to the Hecolin® groups and vaccinated at day 0, month 1 and month 6. Serum samples were collected for anti-HEV IgG determination at day 0 prior to immunization and at month 7. The remaining 200 elderly people aged >65 y were assigned to the safety control group and received no intervention but were instructed to report any adverse events that occurred during the whole study period in the same way as those in the Hecolin® groups. Results After receiving 3 doses of Hecolin® with the standard schedule, most (96.7%) of the vaccinated elderly people aged >65 y seroconverted at one month after the final dose (month 7). At month 7, the geometric mean concentrations of anti-HEV IgG were 5.36 (95% CI, 3.88–7.41) and 19.65 (95% CI, 16.81–22.98) among the baseline seronegative and seropositive elderly, respectively. Of the vaccinated elderly, 97.3% (177/182) had anti-HEV IgG levels higher than 1.0 WU/ml at month 7. Hecolin® was very well tolerated in this population. No vaccine-related SAEs were reported. Conclusions Hecolin® is immunogenic and well tolerated in elderly people aged greater than 65 years.

PURPOSE The current diagnostic testing algorithm for Lynch syndrome (LS) is complex and often involves multiple follow-up germline and somatic tests. We aimed to describe the results of paired tumor/germline testing performed on a large cohort of patients with colorectal cancer (CRC) and endometrial cancer (EC) to better determine the utility of this novel testing methodology. MATERIALS AND METHODS We retrospectively reviewed a consecutive series of patients with CRC and EC undergoing paired tumor/germline analysis of the LS genes at a clinical diagnostic laboratory (N = 702). Microsatellite instability, MLH1 promoter hypermethylation, and germline testing of additional genes were performed if ordered. Patients were assigned to one of five groups on the basis of prior tumor screening and germline testing outcomes. Results for each group are described. RESULTS Overall results were informative regarding an LS diagnosis for 76.1% and 60.8% of patients with mismatch-repair–deficient (MMRd) CRC and EC without and with prior germline testing, respectively. LS germline mutations were identified in 24.8% of patients in the group without prior germline testing, and interestingly, in 9.5% of patients with previous germline testing; four of these were discordant with prior tumor screening. Upon excluding patients with MLH1 promoter hypermethylation and germline mutations, biallelic somatic inactivation was seen in approximately 50% of patients with MMRd tumors across groups. CONCLUSION Paired testing identified a cause for MMRd tumors in 76% and 61% of patients without and with prior LS germline testing, respectively. Findings support inclusion of tumor sequencing as well as comprehensive LS germline testing in the LS testing algorithm. Paired testing offers a complete, convenient evaluation for LS with high diagnostic resolution.

Although repetitive transcranial magnetic stimulation (rTMS) has been considered a potentially effective treatment for cognitive impairment in patients with Alzheimer's disease (AD), previous studies have produced inconsistent results. The objective of this meta-analysis was to evaluate the effects of rTMS on cognitive function in patients with AD.PubMed, EMBASE, Web of Science, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant terms. Abstracts of all papers were carefully reviewed, followed by data extraction, quality assessment, data synthesis and subgroup analyses.A total of 12 studies with 231 patients were included, with 8 randomized controlled studies and 4 self-controlled studies. Eleven studies used high frequency rTMS (≥ 5 Hz), but only one study directly compared the difference between low-frequency (1 Hz) and high-frequency (20 Hz). Random-effects analysis revealed that rTMS could significantly improve cognition compared with sham-rTMS (SMD: 0.60, 95% CI: 0.35-0.85, P .0001). In subgroup analyses, the effect for stimulation at a single target was 0.13 (95% CI: -0.35-0.62) and multiple targets 0.86 (95% CI: 0.18-1.54). Treatment for ≤3 sessions produced an effect of 0.29 (95% CI: -1.04-1.62), whereas treatment for ≥5 sessions produced an effect of 2.77 (95% CI: 2.22-3.32). No differences were found for rTMS combined with medication or cognitive training.rTMS can significantly improve cognitive ability in patients with mild to moderate AD. Stimulation of multiple sites and long-term treatment are better at improving AD-associated cognitive performance. Furthermore, some novel interventional targets, like precuneus (PC), may be a more effective therapeutic site to improve memory in AD.

Cardiovascular complications are common after traumatic brain injury (TBI) and are associated with increased morbidity and mortality. In this study, we investigated the possible role of the immune system in mediating cardiac dysfunction post-TBI in mice. Adult male C57BL/6J mice were subjected to a TBI model of controlled cortical impact (CCI) with or without splenectomy (n = 20/group). Splenectomy was performed immediately prior to induction of TBI. Cardiac function was measured using echocardiography prior to and after TBI. Neurological and cognitive functional tests and flow cytometry and immunostaining were performed. TBI mice exhibited significant cardiac dysfunction identified by decreased left ventricular ejection fraction and fractional shortening at 3 and 30 days post-TBI. In addition, these mice exhibited significantly increased cardiomyocyte apoptosis, inflammation, and oxidative stress at 3 and 30 days post-TBI, as well as cardiac hypertrophy and fibrosis and ventricular dilatation at 30 days after TBI. TBI mice subjected to splenectomy showed significantly improved cardiac function, and decreased cardiac fibrosis, oxidative stress, cardiomyocyte apoptosis, and infiltration of immune cells and inflammatory factor expression in the heart compared with TBI control mice. TBI mice exhibited severe neurological and cognitive function deficits. However, splenectomy did not improve neurological and cognitive functional outcome after TBI compared with the TBI control group. TBI induces immune cell infiltration and inflammatory factor expression in the heart as well as cardiac dysfunction. Splenectomy decreases heart inflammation and improves cardiac function after TBI. Immune response may contribute to TBI-induced cardiac dysfunction.

PURPOSE/OBJECTIVE(S) To investigate the potential predictive value of patient clinical factors versus radiomic features extracted from CT images for characterization of Human Papilloma Virus (HPV) status for patients with oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS/METHODS One hundred twenty-eight OPSCC patients with known HPV-status (60-HPV+ and 68-HPV-, confirmed by immunohistochemistry-P16-protein testing) were retrospectively studied. Radiomic features (11 feature-categories) were extracted in 3D from contrast-enhanced (CE)-CT images of gross-tumor-volumes using 'in-house' software (ROdiomX) developed and validated following the image-biomarker-standardization-initiative (IBSI) guidelines. Six categories of clinical factors were investigated: Age-at-Diagnosis, Gender, Total-Charlson comorbidity score, Alcohol-Use, Smoking-History, and T-Stage, according to AJCC 7th-edition. An Elastic Net technique combined with a Generalized-Linear-Model (Lasso-GLM) were applied to perform L1 and L2 regularizations in the radiomic and clinical feature spaces to identify and rank the optimal feature subsets with most representative information for prediction of HPV. Elastic-Net GLM classifiers based on clinical factors only, radiomics only, and combined clinical and radiomics (ensemble/integrated) were constructed using random-permutation-sampling. Tests of significance (One-way ANOVA), average Area-Under-Receiver-Operating-Characteristic (AUC), and Positive and Negative Predictive values (PPV and NPV) were computed to estimate the generalization-error and prediction performance of the classifiers. RESULTS Five clinical factors, including T-stage, smoking status, and age; and 21 radiomic features, including tumor morphology, textural information, and intensity contrast were found to be statistically significant discriminators between HPV positive and negative cohorts. Performances for prediction of HPV status for the 3 classifiers were: Radiomics Elastic-Net-GLM: AUC/PPV/NPV = 0.799/0.775/0.802; Clinical Elastic-Net-GLM: 0.673/0.738/0.679, and Integrated/Ensemble Elastic-Net-GLM: 0.912/0.884/0.860. Results imply that the radiomics-based classifier significantly outperforms that using clinical factors only, and that the combination of both radiomics and clinical factors yields even higher predictive performance. CONCLUSION Albeit subject to confirmation in a larger cohort, this pilot study presents encouraging results in support of the role of radiomic features towards characterization of HPV in patients with OPSCC.

Purpose. To utilize radiomic features extracted from CT images to characterize Human Papilloma Virus (HPV) for patients with oropharyngeal cancer squamous cell carcinoma (OPSCC). Methods. One hundred twenty-eight OPSCC patients with known HPV-status (60-HPV + and 68-HPV-, confirmed by immunohistochemistry-P16-protein testing) were retrospectively studied. Radiomic features (11 feature-categories) were extracted in 3D from contrast-enhanced (CE)-CT images of gross-tumor-volumes using ‘in-house’ software (‘ROdiomiX’) developed and validated following the image-biomarker-standardization-initiative (IBSI) guidelines. Six clinical factors were investigated: Age-at-Diagnosis, Gender, Total-Charlson, Alcohol-Use, Smoking-History, and T-Stage. A Least-Absolute-Shrinkage-and-Selection-Operation (Lasso) technique combined with a Generalized-Linear-Model (Lasso-GLM) were applied to perform regularization in the radiomic and clinical feature spaces to identify the ranking of optimal feature subsets with most representative information for prediction of HPV. Lasso-GLM models/classifiers based on clinical factors only, radiomics only, and combined clinical and radiomics (ensemble/integrated) were constructed using random-permutation-sampling. Tests of significance (One-way ANOVA), average Area-Under-Receiver-Operating-Characteristic (AUC), and Positive and Negative Predictive values (PPV and NPV) were computed to estimate the generalization-error and prediction performance of the classifiers. Results. Five clinical factors, including T-stage, smoking status, and age, and 14 radiomic features, including tumor morphology, and intensity contrast were found to be statistically significant discriminators between HPV positive and negative cohorts. Performances for prediction of HPV for the 3 classifiers were: Radiomics-Lasso-GLM: AUC/PPV/NPV = 0.789/0.755/0.805; Clinical-Lasso-GLM: 0.676/0.747/0.672, and Integrated/Ensemble-Lasso-GLM: 0.895/0.874/0.844. Results imply that the radiomics-based classifier enabled better characterization and performance prediction of HPV relative to clinical factors, and that the combination of both radiomics and clinical factors yields even higher accuracy characterization and predictive performance. Conclusion. Albeit subject to confirmation in a larger cohort, this pilot study presents encouraging results in support of the role of radiomic features towards characterization of HPV in patients with OPSCC.

Stroke induces cardiac dysfunction which increases post stroke mortality and morbidity particularly in aging population. Here, we investigated the effects of inflammatory responses as underlying mediators of cardiac dysfunction after stroke in adult mice. Adult (eight-to-nine months) male C57BL/6 mice were subjected to photothrombotic stroke. To test whether immunoresponse to stroke leads to cardiac dysfunction, splenectomy was performed with stroke. Immunohistochemistry, flow cytometry, PCR, ELISA and echocardiography were performed. We found marginal cardiac dysfunction at acute phase and significant cardiac dysfunction at chronic phase of stroke as indicated by significant decrease of left ventricular ejection fraction (LVEF) and shortening fraction (LVSF). Stroke significantly increases macrophage infiltration into the heart and increases IL-1β, IL-6, MCP-1, TGF-β and macrophage-associated inflammatory cytokine levels in the heart as well as induces cardiac-fibrosis and hypertrophy. Splenectomy with stroke significantly reduces macrophage infiltration into heart, decreases inflammatory factor expression in the heart, decreases cardiac hypertrophy and fibrosis, as well as significantly improves cardiac function compared to non-splenectomized adult stroke mice. Therefore, cerebral ischemic stroke in adult mice induces chronic cardiac dysfunction and secondary immune response may contribute to post stroke cardiac dysfunction.

Background Patients with hemophilia and inhibitors generally face greater disease burden compared to patients without inhibitors. While raising awareness of relative burden may improve the standard of care for patients with inhibitors, comparative data are sparse. Analyzing data drawn from the Cost of Haemophilia across Europe – a Socioeconomic Survey (CHESS) study, the aim of this study was to compare the clinical burden of disease in patients with severe hemophilia with and without inhibitors. Hemophilia specialists (N = 139) across five European countries completed an online survey between January–April 2015, providing demographic, clinical and 12-month ambulatory/secondary care activity data for 1285 patients. Patients with hemophilia who currently presented with inhibitors and those who never had inhibitors were matched on baseline characteristics via propensity score matching. Outcomes were compared between the two cohorts using a paired t-test or Wilcoxon signed-rank or McNemar’s test. Results The proportion of patients who currently presented with inhibitors was 4.5% (58/1285). Compared to PS-matched patients without inhibitors, patients with inhibitors experienced more than twice the mean annual number of bleeds (mean ± standard deviation, 8.29 ± 9.18 vs 3.72 ± 3.95; p

Objective To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus (T2DM). Methods PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception up to July 2020, to identify randomised controlled trials (RCTs) that enrolled patients with T2DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs alone. The primary outcomes were haemoglobin A1c (HbA1c) and fasting blood glucose (FBG). The secondary outcomes included 2-h blood glucose (2hBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), and acupuncture-related adverse events. Mean difference (MD) and 95% confidence interval (CI) were used as the effect measure in the meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Results Twenty-one RCTs (n=1,188) were included. The meta-analytic results showed that the acupuncture group had greater reductions in FBG (MD -6.46 mg/dL, 95% CI -11.95 to -0.98; moderate-quality evidence) and HOMA-IR (MD -1.23, 95% CI -2.16 to -0.31; low-quality evidence), but comparable changes in HbA1c (MD -0.39%, 95% CI -0.84 to 1.61; very-low-quality evidence), 2hBG (MD -4.99 mg/dL, 95% CI -20.74 to 10.76; low-quality evidence), and FINS (MD -1.32 µIU/mL, 95% CI -3.76 to 1.12; low-quality evidence). No data on the incidence of diabetic complications were found. All acupuncture-related adverse events reported were mild. Conclusions The current evidence suggests that acupuncture, as a complementary therapy to antidiabetic drugs, has a small but statistically significant effect on decreasing FBG and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and FINS remain uncertain. Acupuncture is generally safe in patients with mild diabetes. More evidence for the long-term effects of acupuncture on T2DM is needed. (Trial registration No. CRD42018115639).

Reporting is critical for establishing the value of randomized controlled trials (RCTs). This study evaluated the adherence of bariatric surgery RCT reporting to the CONsolidated Standards Of Reporting Trials (CONSORT) statement 2010 and its 2017 extension for non-pharmacologic treatments (NPT extension). We identified all RCTs comparing bariatric surgery with conservational therapy or alternative bariatric surgery up to June 30, 2020. Reporting quality was assessed using criteria developed from the CONSORT statement and the NPT extension and scored as a percentage. The factors associated with reporting quality were explored by univariate and multivariate analysis. In total, 102 RCTs of bariatric surgery were included. The median scores according to the CONSORT statement and NPT extension were 63.3 and 26.8 of a maximum possible 100, respectively. Two-thirds of NPT extension items were reported in less than 25% of the RCTs. The median score improved over time for the CONSORT statement but not the NPT extension. A higher CONSORT score was associated with publication in core clinical journals, protocol registration, and funding. No factors associated with the NPT extension score were identified. Substantial efforts are warranted from authors, journals, registration platforms, and funders to overcome the flaws in the reporting of bariatric surgery RCTs.

Background: Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) often leads to incomplete reperfusion. There is a compelling need to develop therapies to enhance the perfusion and to improve neurological outcomes. Methods: Using rat models of embolic middle cerebral artery occlusion (eMCAO) and transient MCAO (tMCAO), we investigated the effect of small extracellular vesicles (sEVs) derived from healthy rat cerebral endothelial cells (CECs) administered intravenously in combination with tPA (CECs/tPA) and as an acute intraarterial adjunct therapy with mechanical reperfusion on stroke outcomes. Recanalization, cerebral blood flow (CBF), and blood-brain barrier (BBB) permeability were analyzed. MicroRNAs (miRs) and proteins were analyzed in CECs harvested from ischemic rats by RT-PCR and Western blots. Transmission electron microscopy was employed to analyze the brain distribution of CEC-sEVs. The effect of sEVs derived from clots acquired from patients undergone thrombectomy was tested on human CEC permeability. Results: CEC-sEVs/tPA given 4h after eMCAO or CEC-sEVs given upon reperfusion after 2h tMCAO significantly reduced infarct volume by ~36% and ~43%, respectively, and robustly improved neurological outcomes compared with tPA or ischemia/reperfusion alone (n=10 rats/group). CEC-sEVs/tPA and upon reperfusion after eMCAO or tMCAO, resepectively, significantly increased recanalization of the occluded MCA, enhanced CBF and reduced BBB leakage. CEC-sEVs/tPA substantially reduced a network of microRNAs and proteins that mediate thrombosis, coagulation and inflammation in CECs. Moreover, CEC-sEVs intravenously administered crossed the BBB and were internalized by CECs cells, astrocytes, and neurons. Stroke patient-clot derived exosomes impaired human CEC permeability and upregulated pro-inflammatory and -coagulatant proteins, which were blocked by CEC-sEVs. Conclusion: CEC-sEVs have a therapeutic effect on acute ischemic stroke in rats by reducing neurovascular damage. Suppressing the network of pro-thrombotic, -coagulant and -inflammatory microRNAs and proteins in CECs by CEC-sEVs likely contributes to the therapeutic effect of CEC-sEVs.

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

ObjectiveAlthough research suggests a close association between maternal thyroid function and birth outcomes, no clear conclusion has been reached. We aimed to explore this potential association in a retrospective cohort study.MethodsThis study included 8985 mother–child dyads. The maternal serum free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPO Ab) concentrations and birth outcome data were reviewed from medical records. Subjects with TPO Ab concentrations of >34 and ≤34 IU/ml were classified into the TPO Ab positivity (+) and TPO Ab negativity (−) groups, respectively.ResultsCompared with subjects in the normal group (0.1 ≤ TSH < 2.5 mIU/L and TPO Ab−), those with TSH concentrations of 2.5–4.0 mIU/L and TPO Ab− had a 0.65-fold lower risk of low birth weight (LBW). In contrast, those with TSH concentrations of >4.0 mIU/L, regardless of the TPO Ab status, had a 2.01-fold increased risk of LBW. Subclinical hypothyroidism, regardless of the TPO Ab status, was associated with a 1.94-fold higher risk of LBW when compared with that in subjects with euthyroidism and TPO Ab−. No other significant associations were observed.ConclusionA maternal TSH concentration of 2.5–4.0 mIU/L was associated with a lower risk of LBW when combined with TPO Ab−, whereas subjects with a TSH concentration of >4.0 mIU/L had an increased risk of LBW. Subclinical hypothyroidism appears to be associated with a higher risk of LBW.

BACKGROUND: von Willebrand disease (VWD) can lead to serious, life-threatening bleeding events associated with substantial clinical and economic burden. OBJECTIVE: To estimate the prevalence, healt...

Background TDF and ETV are first-line treatments for CHB virus infection. A recent analysis of nationwide insurance data from Korea suggested that the risk of HCC may vary by type of CHB treatment; however, this finding was based on a limited follow-up period following TDF approval in Korea in 2012 and has not been replicated in large datasets outside of Asia. The objective of this analysis was to explore the long-term risk of HCC with TDF vs. ETV in treatment naive (TN) CHB patients in a US administrative claims dataset. Methods Among 158,272 patients with evidence of CHB and administrative medical claims between January 2006 and September 2018, we identified TN patients exposed to TDF (N=6,145) or ETV (N=4,046) with at least 1 year of continuous enrollment prior to cohort entry. Exclusion criteria included coinfection with HCV, HDV, or HIV; prior exposure to peginterferon or nucleos(t)ide analogues; HCC or liver transplant prior or up to 6 months after initiating treatment. Absolute rates and corresponding 95% CIs were determined for each treatment group, Cox proportional hazards methods were used to estimate the risk of incident HCC associated with TDF vs ETV. To account for the effects of potential differences in demographics and baseline health status, we incorporated multivariable adjustment and weighting based on treatment propensity scores. Results Median follow-up duration was comparable in TDF- vs ETV-treated patients among TDF-treated CHB patients, the absolute rate of HCC was approximately half that of patients treated with ETV (0.32 per 100 PY (CI: 0.23 – 0.43) vs 0.61 per 100 PY (CI: 0.45 – 0.80)). After adjustment for age group, sex, baseline health conditions and propensity score weighting, TDF remained associated with a significantly decreased risk of HCC compared to treatment with ETV (HR: 0.56, CI: 0.37 – 0.86). Conclusions In this analysis of commercially insured, TN CHB patients in the US, the absolute rate of HCC was lower in those treated with TDF than with ETV. After adjustment, treatment with TDF remained associated with a significantly decreased long term risk of HCC, consistent with recent findings from Asia.

Using electronic health records, we found that hepatitis C virus (HCV) reporting on death certificates of 2901 HCV-infected decedents from 4 US healthcare organizations during 2011–2017 was documented in only 50% of decedents with hepatocellular carcinoma and less than half with decompensated cirrhosis. National figures likely underestimate the US HCV mortality burden.

BackgroundETMRs are a newly recognized rare paediatric brain tumor with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and limited clinical data, disease features and determinants of outcome are poorly defined. We performed an integrated clinico-pathologic and molecular analyses of 159 primary ETMRs to define clinical phenotypes, identify predictors of survival and critical treatment modalities for this orphan disease.MethodsPrimary ETMR patients were identified from the Rare Brain Tumor Consortium (rarebraintumorconsortium.ca) global registry using histopathologic and molecular assays. Event-Free (EFS) and Overall Survival (OS) for 108 patients treated with curative multi-modal regimens were determined using Cox proportional hazard and log rank analyses.FindingsETMRs were predominantly non-metastatic (73%) tumors arising from multiple sites; 55% were cerebral tumors, 45% arose at sites characteristic of other brain tumors. Hallmark C19MC alterations were seen in 91%; 9% were ETMR-NOS. Survival and hazard analyses showed a 6 month median EFS and 2-4yr OS of 27-29% with metastatic disease (HR=0.44, 95% CI 0.26-0.74; p=0.002) and brainstem location (HR=0.40, 95% CI 0.021-0.75; p=0.005) correlating with adverse OS. Gross total resection (GTR: HR=0.38, 95% CI 0.21-0.68; p=0.001), high dose chemotherapy (HDC: HR=0.55, 95% CI 0.31-0.97; p=0.04) and radiation (RT: HR=0.32, 95% CI 0.16-0.60; p=InterpretationPrompt molecular diagnosis and post-surgical treatment with multi-modal therapy tailored to patient-specific risk features improves ETMR survival.FundingThis work was supported by the Canadian Institute of Health Research Grant No. 137011, Canada Research Chair Awards to AH. Funds from Miracle Marnie, Phoebe Rose Rocks, Tali’s Funds, Garron Cancer Centre, Grace’s Walk, Meagan’s Walk, Nelina’s Hope and Jean Martel Foundation are gratefully acknowledged. SK and PS were respectively supported by the Australian Lions Children’s Cancer Foundation and the Spanish Society of Pediatrics, Consejería de Salud y Familias de la Junta de Andalucía Project EF-0451-2017.

Introduction Despite recognized differences in the rates of cardiovascular and renal disease between men and women in the general population, studies of the downstream effects of antiviral treatment for hepatitis C (HCV) have not investigated differences in outcomes based on sex. We analyzed sex differences in risk of acute coronary syndrome (ACS), end-stage renal disease (ESRD), and ischemic stroke by treatment and response in a large US-based multisite cohort of HCV patients. Methods Observation started at the HCV diagnosis date (untreated) or last antiviral treatment start (treated). Treatment selection bias was addressed using an inverse probability-weighting approach. We estimated the effect of treatment on the cumulative incidence of outcomes using the Fine-Gray method (subdistribution hazard ratios [sHR] and 95% confidence intervals [95% CI]). Death was a competing risk. Results Roughly 40% of 15,295 HCV patients were women. After controlling for other risk factors, sustained virological response (SVR) (interferon-based [IFN] or direct-acting antiviral [DAA]) significantly reduced risk of all outcomes, particularly among female patients. Female patients who achieved SVR after IFN-based treatment had significantly lower risk of ACS compared with male patients with SVR from either treatment type (sHR 0.45 [95% CI 0.35-0.59] vs 0.81 [95% CI 0.69-0.96, for DAA SVR] and sHR 0.72 [95% 0.62, 0.85, for IFN SVR]). Successful treatment seemed to be most protective against ESRD; female patients who achieved SVR were at 66%-68% lower risk than untreated patients (sHR 0.32 [95% CI 0.17-0.60 for DAA SVR] and 0.34 [95% CI 0.20-0.58 for IFN SVR]), whereas men were at 38%-42% lower risk (sHR 0.62 [95% CI 0.46-0.85 for DAA SVR] and 0.58 [95% CI 0.43-0.76 for IFN SVR]). IFN treatment failure significantly increased risk of all outcomes by 50%-100% among female patients. Compared with no treatment, female patients who experienced IFN treatment failure were at 63% increased risk of ACS (sHR 1.63 [95% CI 1.35-1.96]), almost twice the risk of ESRD (sHR 1.95 [95% CI 1.43-2.66]) and 51% increased risk of stroke (sHR 1.49 [95%CI 1.11-2.00]). Discussion SVR reduced the risk of extrahepatic complications, particularly in females. The significantly increased risk associated with IFN TF in women-a subset who represented roughly 10% of that group-underscores the importance of prioritizing these patients for DAA treatment irrespective of the fibrosis stage.

Objectives Convulsive status epilepticus (CSE) is a life-threatening neurologic emergency, which is defined by the International League Against Epilepsy (ILAE) as bilateral tonic–clonic seizure activity lasting longer than 5 min, while absence status epilepticus (SE) and focal SE are specified as exceeding 10 min. Epidemiological evidence on SE is currently lacking, and the incidence is not well-known, especially in light of changes in the ILAE criteria for SE. The objectives of this systematic literature review were to describe the epidemiology of SE in the US population and the associated burden of illness. Methods A systematic review, including literature and pragmatic searches, was conducted. Literature searches were performed using MEDLINE, Embase, BIOSIS, and Web of Science electronic databases from inception to February 2019. Pragmatic searches of the gray literature were carried out using Google, Google Scholar, conference proceedings, and ClinicalTrials.gov to identify additional sources. Only US-based studies or multinational studies reporting US data of interest were included. Results In total, 69 sources were identified. The incidence of all SE in patients of all ages in the USA ranged from 18.3 to 41 per 100,000 people per year. Incidence of all-age CSE rose from 3.5 (1979) to 12.5 (2010) per 100,000 people per year. Status epilepticus incidence followed a bimodal (U-shaped) distribution, with the highest estimates in the first years of life (0–4 years) and after 60 years. Mortality associated with SE varied from 21% over 30 days to 31.2% over 10 years. For CSE, two studies reported similar in-hospital mortalities (9.2% and 10.7%). Median healthcare costs related to SE admission were approximately US$14,500 per adult (17–45 years) and US$8000 per child (0–16 years). Conclusions There is a lack of recent data on the epidemiology and healthcare burden associated with SE. Reports of SE incidence in the USA are highly variable and predate the 2015 ILAE definition of SE. However, the available data suggest a high burden of illness.

Normal ranges of serum alanine aminotransferase (ALT) may vary by race. However, results from research studies are contradictory, and many of these studies have included only small numbers of African Americans. We investigated ALT values in patients without evidence of liver disease to determine whether normal ranges differ across race groups. We also evaluated whether a race- and sex-dependent upper limit of normal (ULN) would improve the ability of ALT to predict liver disease compared to the sex-dependent ULN currently in use. We identified ICD9 codes for liver conditions and diabetes in medical records from a sample of 6719 patients. Analysis of variance (ANOVA) was used to assess differences in ALT log-transformed distributions by race. Logistic regression was used to evaluate whether the addition of race to the current sex-dependent ULN improves the ability of ALT to predict liver disease (assessed by area under the receiver operating characteristic curve (AUROC)). Among 1200 patients with BMI 18.5

Goals To determine the proportion and characteristics of adults with hepatitis C at health care organizations in 4 US states who initiated direct-acting antivirals (DAAs). Background There are almost no data to assess the penetrance of treatment of the hepatitis C population in general US health care settings. Study We conducted a prospective observational study using electronic clinical, pharmacy, and mortality data to determine the fraction of patients who initiated DAAs between January 2014 and December 2017, by start date and regimen. We used stepwise multivariate logistic regression analysis to identify sociodemographic and clinical characteristics associated with receipt of DAAs. Results Of 8823 patients, 2887 (32.7%) received DAAs. Quarterly (Q) uptake ranged from 1.1% in Q3 2014 to a high of 5.6% in Q2 2015. Characteristics associated with receipt of DAAs included age 51 to 70 years, higher income, pre-2014 treatment failure, and higher noninvasive fibrosis score (FIB4); however, over one half of patients with FIB4 scores >3.25, consistent with severe liver disease, were not treated. A lower likelihood of initiation was associated with Medicaid coverage. Of 5936 patients who did not initiate treatment, 911 (15.3%) had died and 2774 (46.7%) had not had a clinical encounter in ≥12 months by the end of the study. Fewer than 1% of DAA prescriptions originated from nonspecialty providers. Conclusions During 4 calendar years of follow-up, one third of patients initiated DAAs. Large fractions of untreated patients had advanced liver disease, died, or were lost to follow-up. Even among patients in integrated health care systems, receipt of DAAs was limited.

Previous studies have revealed the serious human health risk effects of organic pollutants-polychlorinated biphenyls (PCBs). However, the roles of circulating PCBs on stroke risk have not been elucidated. The purpose of this study was to examine whether serum PCBs could increase the risk for stroke among Chinese participants. A total of 241 patients with stroke and age- (5-year interval) and gender-matched controls were recruited in Tianjin, China. Concentrations of 17 PCB congeners were measured by using high-resolution gas chromatography with mass spectrometric detection. Conditional logistic regression models were applied to assess the odds ratio (OR) and 95% confidential interval (CI). Significant positive associations were observed between serum total PCBs and dioxin-like PCBs and the risk for stroke (all p trends

Background: Migraine is the most common acute primary headache in children and adolescents. In 2014, topiramate became the first preventive drug for migraine, approved by the Food and Drug Administration (FDA) for adolescents. This meta-analysis was aimed to evaluate the efficacy and safety of topiramate in the prevention of pediatric migraine.Methods: We searched the PubMed, EMBASE, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) databases up to June 2019 for eligible randomized controlled trials (RCTs). The primary outcomes were mean migraine days per month, ≥50% reduction rate, and Pediatric Migraine Disability Assessment Scale (PedMIDAS) scores. RevMan5.3 software was performed for statistical analysis.Results: Overall, 5 RCTs recruiting 531 patients (6–17 years of age) were included in the meta-analysis. The target dose of topiramate was 2 mg/kg (the maintenance phase was 12 weeks), 2–3 mg/kg, 50 mg/day, and 100 mg/day (maintaining for 16 weeks), respectively, in the included studies. Our results demonstrate that participants receiving topiramate had a significant advantage in remitting the monthly migraine days than those receiving placebo, with a mean difference (MD) of −0.78 (n = 531; 95% CI, −1.23 to −0.32; Z = 3.37; P = 0.0008). Topiramate could also reduce the mean PedMIDAS scores (n = 238; 95% CI, −16.53 to −0.49; Z = 2.43; P = 0.04). However, there was no significant difference in the percentage of patients experiencing a ≥50% reduction in monthly headache days between topiramate and placebo groups (n = 531; 95% CI, 0.94–1.77; Z = 1.58; P = 0.11). Topiramate was associated with higher rates of side effects such as weight decrease (n = 395; 95% CI, 2.73–22.98; Z = 3.81; P < 0.01) and paresthesia (n = 531; 95% CI, 3.05–13.18; Z = 4.94; P < 0.01).Conclusions: Topiramate can significantly decrease monthly headache days and migraine-related burden in migraine patients

Introduction: Despite the recent advances in the acute stroke care, treatment options for long-term disability are limited. RPh201 is a botany-derived bioactive compound that has been shown to exert beneficial effects in various experimental models of neural injury. However, the effect of RPh201 on stroke recovery has not been investigated. The present study evaluated the effect of RPh201 on functional recovery after stroke. Methods: Young adult Wistar rats subjected to embolic middle cerebral artery occlusion (MCAO) were randomized into the following experimental groups stratified by sex (n=20/group): 1) RPh201 treatment, and 2) vehicle (cottonseed oil). RPh201 (20 μl) or vehicle were subcutaneously administered twice a week for 16 consecutive weeks starting at 21 days after MCAO. An array of behavioral tests were performed during 120 days after treatment initiation. Results: Male, but not female, ischemic rats treated with RPh201 exhibited significant (p Conclusions: Our data demonstrated that RPh201 has a therapeutic effect on improvement of functional recovery in male ischemic rats even when the treatment was initiated 21 days post stroke. Enhanced axonal and myelination densities by RPh201 in ischemic brain may contribute to improved stroke recovery.

Background We used data from the Fibrotic Liver Disease Consortium to evaluate the impact of ursodeoxycholic acid (UDCA) treatment across race/ethnicity, gender, and clinical status among patients with primary biliary cholangitis. Methods Data were collected from "index date" (baseline) through December 31, 2016. Inverse Probability of Treatment Weighting was used to adjust for UDCA treatment selection bias. Cox regression, focusing on UDCA-by-risk factor interactions, was used to assess the association between treatment and mortality and liver transplant/death. Results Among 4,238 patients with primary biliary cholangitis (13% men; 8% African American, 7% Asian American/American Indian/Pacific Island [ASINPI]; 21% Hispanic), 78% had ever received UDCA. The final multivariable model for mortality retained age, household income, comorbidity score, total bilirubin, albumin, alkaline phosphatase, and interactions of UDCA with race, gender, and aspartate aminotransferase/alanine aminotransferase ≥1.1. Among untreated patients, African Americans and ASINPIs had higher mortality than whites (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.08-1.67 and aHR = 1.40, 95% CI 1.11-1.76, respectively). Among treated patients, this relationship was reversed (aHR = 0.67, 95% CI 0.51-0.86 and aHR = 0.88, 95% CI 0.67-1.16). Patterns were similar for liver transplant/death. UDCA reduced the risk of liver transplant/death in all patient groups and mortality across all groups except white women with aspartate aminotransferase/alanine aminotransferase ≥1.1. As compared to patients with low-normal bilirubin at baseline (≤0.4 mg/dL), those with high-normal (1.0 > 0.7) and mid-normal bilirubin (0.7 > 0.4) had significantly higher liver transplant/death and all-cause mortality. Discussion African American and ASINPI patients who did not receive UDCA had significantly higher mortality than white patients. Among African Americans, treatment was associated with significantly lower mortality. Regardless of UDCA treatment, higher baseline bilirubin, even within the normal range, was associated with increased mortality and liver transplant/death compared with low-normal levels.

PURPOSE: Little is known about health-related quality of life (HRQoL) in patients with chronic hepatitis B virus (CHB) infection in the United States. Our goal is to understand factors associated with HRQoL in this population. METHODS: We conducted a survey to assess HRQoL and behavioral risks among patients with CHB infection from four large U.S. health care systems. Primary outcomes were generated from the SF-8 scale to assess HRQoL, as measured by the mental component scores (MCS) and physical component scores (PCS). The survey also measured socio-demographic information, hepatitis-related behavioral risk factors, treatment exposure/history, stress, and social support. We supplemented survey data with electronic health records data on patient income, insurance, disease severity, and comorbidities. Multivariate analysis was used to estimate and compare adjusted least square means of MCS and PCS, and examine which risk factors were associated with lower MCS and PCS. RESULTS: Nine hundred sixty-nine patients (44.6%) responded to the survey. Current life stressors and unemployment were associated with both lower MCS and PCS results in multivariate analyses. Lower MCS was also associated with White race and low social support, while lower PCS was also associated with Medicaid insurance. CONCLUSIONS: Stressful life events and unemployment were related to mental and physical health status of CHB patients. Those who have social support have better mental health; White and Medicaid patients are more likely to have poorer mental and physical health, respectively. Management of CHB patients should include stress management, social support, and financial or employment assistance.

Injury of oligodendrocytes (OLs) induces demyelination, and patients with neurodegenerative diseases exhibit demyelination concomitantly with neurological deficit and cognitive impairment. Oligodendrocyte progenitor cells (OPCs) are present in the adult central nervous system (CNS), and they can proliferate, differentiate, and remyelinate axons after damage. However, remyelination therapies are not in clinical use. Multiple sclerosis (MS) is a major demyelinating disease in the CNS. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic promise in animal models and in clinical trials of MS. Exosomes are nanoparticles generated by nearly all cells and they mediate cell-cell communication by transferring cargo biomaterials. Here, we hypothesize that exosomes harvested from MSCs have a similar therapeutic effect on enhancement of remyelination as that of MSCs. In the present study we employed exosomes derived from rhesus monkey MSCs (MSC-Exo). Two mouse models of demyelination were employed: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS; and 2) cuprizone (CPZ) diet model, a toxic demyelination model. MSC-Exo or PBS were intravenously injected twice a week for 4 weeks, starting on day 10 post immunization in EAE mice, or once a week for 2 weeks starting on the day of CPZ diet withdrawal. Neurological and cognitive function were tested, OPC differentiation and remyelination, neuroinflammation and the potential underlying mechanisms were investigated using immunofluorescent staining, transmission electron microscopy and Western blot. Data generated from the EAE model revealed that MSC-Exo cross the blood brain barrier (BBB) and target neural cells. Compared with the controls (p 0.05), treatment with MSC-Exo: 1) significantly improved neurological outcome; 2) significantly increased the numbers of newly generated OLs (BrdU

Objective Mobile health (mHealth) provides an innovative and effective approach to promote prevention and management of coronary heart disease. However, the magnitude of its effects is unclear. The aim of this systematic review was to examine the impact of mHealth-based cardiac rehabilitation outcomes among coronary heart disease patients. Methods Medline, CINAHL, Embase, PubMed, Google Scholar, NICE, and Cochrane library were searched for randomized controlled trials published between January 2002 and March 2017 which compared mHealth with conventional cardiac rehabilitation programs among coronary heart disease patients. Results Eight articles were included in this review. The impact of mHealth interventions on physical activity, medicine adherence, smoking cessation, level of anxiety, and quality of life was inconsistent among the articles. Conclusions Further research is needed to conclusively determine the impact of mHealth interventions on cardiac rehabilitation outcomes. The limitations of the included studies (e.g., inadequate sample size, failure to address the core components of cardiac rehabilitation programs, and lack of theory-based design) should be taken into account when designing future studies.

Background Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus. Anti-double-stranded (ds) DNA immunoglobulin G (IgG) plays a pivotal role in the pathogenesis of LN. Currently, there are various therapies for patients with LN; however, most of them are associated with considerable side effects. We confirmed previously that ALW (ALWPPNLHAWVP), a 12-amino acid peptide, inhibited the binding of polyclonal anti-dsDNA antibodies to mesangial cells and isolated glomeruli in vitro. In this study, we further investigate whether the administration of ALW peptide decreases renal IgG deposition and relevant damage in MRL/lpr lupus-prone mice. Methods Forty female MRL/lpr mice were randomly divided into four groups. The mice were intravenously injected with D-form ALW peptide (ALW group), scrambled peptide (PLP group), and normal saline (NaCl group) or were not treated (blank group). The IgG deposition, the histopathologic changes, and the expressions of profibrotic factors were analyzed in the kidney of MRL/lpr mice. Results Compared with the other groups, glomerular deposition of IgG, IgG2a, IgG2b, and IgG3 was decreased in the ALW group. Moreover, ALW administration attenuated renal histopathologic changes in MRL/lpr mice, including mesangial proliferation and infiltration of inflammatory cells. Furthermore, the expressions of profibrotic cytokines, such as transforming growth factor-beta1 (TGF-β1) and platelet-derived growth factor B (PDGF-B), decreased in the serum and kidney tissue of ALW-treated mice. Conclusions Our study demonstrated that ALW peptide ameliorates the murine model of LN, possibly through inhibiting renal IgG deposition and relevant tissue inflammation and fibrosis.