bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between the clinical remission and histological remission in repeat biopsy findings of quiescent proliferative lupus nephritis
Authors: Das Uttara , Patel Ravi , Guditi Swarnalatha , Taduri Gangadhar 
Published: February 2021

Background The optimal duration of maintenance therapy is controversial in proliferative lupus nephritis (LN). Discordance between clinical parameters of renal remission and histological findings has made repeat biopsy a compulsory tool to confirm the histological remission (HR), but the timing is debatable. Aim of this study was to find the correlation of sustained complete clinical remission (CR) in sever lupus nephritis with histological findings on repeat kidney biopsy and appropriate duration of treatment in maintenance phase after achieving complete clinical remission. Methods Repeated kidney biopsy (biopsy 2) was performed on patients of biopsy proven (biopsy 1) proliferative LN who had been in CR for at least 2-years. The clinical and histologic findings of these groups (biopsy 1 and biopsy 2) were compared. Total 29 patients were included for the final analysis. Group 2 was further divided as per the duration of sustained CR (>48 months & <48 months). Regression analysis were used to find predictors of the HR. Results Average time taken to achieve CR was 9(range 2–24) months. Average duration of follow up and maintenance therapy was 68 ± 17.8 and 62.5 ± 14.2 months respectively. In the repeat kidney biopsy, HR was observed in 93.1% patients. Immunofluorescence study (IF) was normal in 72% of the patients. Normal light microscopy (LM) findings were observed in 58% patients. Transformation from proliferative to nonproliferative LN was noted in 82% cases. Other than the duration of CR on maintenance therapy and blood pressure, rest of the variables failed to predict HR. In sustained remission for more than 48-months group, 100% patients achieved HR whereas only 84% in 24–48-months group. Conclusion Sustained CR on maintenance immunosuppressive therapy for more than 48-months duration predicts HR in repeat kidney biopsy findings in quiescent proliferative LN. Hence the minimum duration of maintenance therapy in proliferative LN should be at least for another 48 months after achieving CR.
New insights in gut-liver axis in wild-type murine imiquimod-induced lupus
Authors: Maalouly Georges , Hajal Joelle , Noujeim Charbel , Choueiry Michel , Nassereddine Hussein , Smayra Viviane , Saliba Youakim , Fares Nassim 
Published: February 2021

Background Intestinal and hepatic manifestations of lupus seem to be underestimated in comparison to other major organ lesions. Although recent data point to gut-liver axis involvement in lupus, gut permeability dysfunction and liver inflammation need to be more investigated. Objective This study aims to assess fecal calprotectin, intestinal tight junction proteins and liver inflammation pathway in wild-type murine imiquimod- induced lupus. Methods C57BL/6 mice were topically treated on their right ears with 1.25 mg of 5% imiquimod cream, three times per week for six weeks. Fecal calprotectin was collected at day 0, 22 and 45. Renal, liver and intestinal pathology, as well as inflammatory markers, intestinal tight junction proteins, and E. coli protein in liver were assessed at sacrifice. Results At six weeks, lupus nephritis was confirmed on histopathology and NGAL and KIM-1 expression. Calprotectin rise started at day 22 and persists at day 45. Protein expression of Claudine, ZO-1 and occludin was significantly decreased. E. coli protein was significantly increased in liver with necro-inflammation and increased TLR4, TLR7, and pNFκB/NFκB liver expression. Conclusion This study is the first to demonstrate early fecal calprotectin increase and liver activation of TLR4- NFκB pathway in wild-type murine imiquimod-induced lupus.
Breastfeeding in women affected by systemic lupus erythematosus: Rate, duration and associated factors
Authors: Orefice Valeria , Ceccarelli Fulvia , Pirone Carmelo , Galoppi Paola , Spinelli Francesca Romana , Alessandri Cristiano , Brunelli Roberto , Perrone Giuseppina , Conti Fabrizio 
Published: February 2021

Objective Breastfeeding is a crucial moment for both mothers and child, providing a beneficial effect on child survival, nutrition, development and on maternal health. Despite the prevalent involvement of childbearing women in systemic lupus erythematosus (SLE), breastfeeding is still a neglected topic. The objective of this study was to evaluate breastfeeding frequency, duration and associated factors in SLE women. Methods We consecutively enrolled SLE pregnant women reporting demographic, clinical, serological, gynaecological and obstetric data. Breastfeeding experience was evaluated by using a specific questionnaire. Disease activity was assessed before and during pregnancy as well as during postpartum. Results A total of 57 pregnancies in 43 SLE women were included in the present study. In almost all the pregnancies, mothers planned to breastfeed their child (96.5%) and forty-one (71.9%) actually did breastfeed. The median time of breastfeeding was 3 months (IQR 7). Non-breastfeeding women showed a more frequent caesarean section (p = 0.0001), IUGR occurrence (p = 0.004) and disease relapse (p = 0.0001) after pregnancy. When comparing patients according with breastfeeding duration (cut-off 6 months), we found a significant more frequent smoking habitus (p = 0.02), caesarean section (p = 0.009), and joint involvement during postpartum (p = 0.0001) in women breastfeeding for less than or equal to 6 months, together with higher median BMI (p = 0.0001). Moreover, breastfeeding duration was positively associated with disease duration and hydroxychloroquine (HCQ) treatment during disease history, pregnancy and postpartum. Conclusions SLE women didn’t show lower breastfeeding rate in comparison with general population but they presented higher prevalence of early discontinuation within three months. Early interruption was positively associated with smoking, BMI, joint involvement; meanwhile disease duration and HCQ treatment during postpartum were positively associated with a longer breastfeeding duration.
A Multi-Institutional Retrospective Analysis of Oncologic Outcomes for Patients With Locally Advanced Cervical Cancer Undergoing Platinum-Based Adjuvant Chemotherapy After Concurrent Chemoradiotherapy
Authors: Wu Ning , Su Xing , Song Honglin , Li Ying , Gu Fei , Sun Xiaoge , Li Xiaofan , Cheng Guanghui 
Published: February 2021

Objective: To evaluated the oncologic outcomes associated with platinum-based adjuvant chemotherapy following concurrent chemoradiotherapy (CCRT) in the management of patients with locally advanced cervical cancer (LACC). Methods: A total of 695 patients with FIGO stage IB2, IIA2, IIB-IVA LACC treated at 6 medical facilities were enrolled and divided into 2 groups: 478 were assigned to CCRT alone (CCRT group) and 217 to adjuvant chemotherapy after CCRT (CCRT-ACT group). The treatment outcomes were retrospectively compared and reported after the propensity score matching (PSM) analysis. Results: With a median follow-up of 56.4 months, no statistically significant differences were found in overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and distance metastasis-free survival (DMFS) between 2 groups. In CCRT-ACT group, patients with lymph nodes involvement or squamous cell carcinoma (SCC) had significantly longer DMFS, but no significant benefit in survival outcomes were observed with more than 2 cycles of adjuvant chemotherapy. Moreover, patients with a high level of CA125 (>20.5U/mL) or SCC-Ag (>22.8μg/L) had a relatively better DFS or PFS, and grade 3-4 acute hematological toxicity, late urinary and lower gastrointestinal complications and diarrhea symptom were more frequent in CCRT-ACT group. Conclusions: Adjuvant chemotherapy after CCRT has a potential role in further improving disease control for LACC patients with lymph nodal-metastasis or SCC with a high level of CA125 or SCC-Ag. Due to increased treatment-related complications and diarrhea symptom affecting the quality of life, post-CCRT adjuvant chemotherapy with excessive cycles was not be considered as the most appropriate choice in general.
Use of sublingual tacrolimus in adults undergoing hematopoietic cell transplant: A pilot study
Authors: May Heather P , Bartoo Gabriel T , Wolf Robert C , Shah Mithun V , Litzow Mark R , Hogan William J , Alkhateeb Hassan 
Published: February 2021

Introduction Orally administered tacrolimus is widely used in hematopoietic cell transplant patients, but multiple clinical situations may arise rendering oral administration infeasible. The undesirable sequelae of intravenous administration, including toxicity, challenges with administration and cost call for innovative solutions to conserve existing supply and optimize safety and efficacy of medication delivery. We sought to demonstrate feasibility of sublingual tacrolimus use and estimate a sublingual-to-oral (SL:PO) conversion ratio in the hematopoietic cell transplant setting. Methods Ten adults undergoing allogeneic hematopoietic cell transplant received tacrolimus 0.04 mg/kg/dose twice daily. Initial doses were given via sublingual route and a steady state trough level was collected after 4 consecutive doses. Participants were then switched to oral tacrolimus, the dose adjusted for a goal trough 8-12ng/mL, and another steady state trough was drawn. Total daily dose was divided by trough concentration for each route to determine the dosing ratio of SL:PO. Results Median trough level following sublingual administration was 11.3 ng/mL. Three of these were within goal, 3 were low (4.7–6.4 ng/mL) and 4 were elevated (15.9–18.6 ng/mL). Median SL:PO ratio was 1.02. In 5 participants the SL:PO ratio was <1 (range 0.57–0.94) and in 5 the ratio was ≥1 (range 1.10–1.92). No significant barriers or intolerance to sublingual tacrolimus use were noted. Conclusions Results demonstrate reliable absorption with sublingual tacrolimus use in patients undergoing hematopoietic cell transplant. Sublingual administration may allow for avoidance of the undesirable complications of IV tacrolimus, such as increased toxicities, required hospitalization for continuous infusion, risk of dose conversion and dilution errors and increased cost. Trial Registry name: Use of Sublingual Tacrolimus in Adult Blood and Marrow Transplant Patients, NCT04041219 https://clinicaltrials.gov/ct2/show/NCT04041219?term=NCT04041219&draw=2&rank=1
Switching to intravitreal fluocinolone acetonide implant for refractory diabetic macular edema: 12- and 24-month results
Authors: Chronopoulos Argyrios , Chronopoulos Panagiotis , Ashurov Agharza , Korb Christina , Pfeiffer Norbert , Hattenbach Lars-Olof 
Published: February 2021

Purpose: To report visual and anatomical outcomes of chronic/refractory diabetic macular edema (DME) treated with intravitreal fluocinolone acetonide implant. Setting: Retrospective, one arm, multicentric study. Method: Between 2013 and 2018, 27 consecutive eyes of 25 patients with chronic/refractory DME were treated with a fluocinolone acetonide intravitreal implant. Best registered visual acuity (BRVA), central retinal thickness (CRT), and Goldmann tonometry intraocular pressure (IOP) were assessed at 12 and 24 months. The need for IOP lowering treatment as well as top-up therapy during the follow-up were also assessed. Results: The duration of DME prior to treatment in our study was 54 ± 24 months. The baseline mean BRVA of 0.7 ± 0.34 logMAR improved to 0.5 ± 0.3 ( p = 0.01) at 12 months and 0.46 ± 0.3 ( p = 0.04) at 24 months. At 12 months, BRVA improved in 14 eyes (52%), stabilized in 5 eyes (20%), and decreased in 3 eyes (11%). At 24 months, BRVA improved further in 6 eyes (24%), stabilized in 3 eyes (12%), and decreased in 6 eyes (24 %). Mean CRT decreased from 497 ± 176 to 349 ± 186 μm at 12 months ( p = 0.0005) and to 267 ± 104 μm at 24 months ( p = 0.001). Only five eyes required additional treatment for DME and only three eyes required treatment for raised IOP. Discussion: Our results show that the visual and the anatomical improvements achieved by a single injection of a fluocinolone acetonide implant were maintained up to 24 months with minimal additional therapy even in eyes with a long and heavy history; however, IOP monitoring remains essential.
Detection of EGFR Activating and Resistance Mutations by Droplet Digital PCR in Sputum of EGFR-Mutated NSCLC Patients
Authors: Hackner Klaus , Buder Anna , Hochmair Maximilian J , Strieder Matthaeus , Grech Christina , Fabikan Hannah , Burghuber Otto C. , Errhalt Peter , Filipits Martin 
Published: February 2021

Background: Proof of the T790M resistance mutation is mandatory if patients with EGFR-mutated non-small cell lung cancer (NSCLC) progress under first- or second-generation tyrosine kinase inhibitor therapy. In addition to rebiopsy, analysis of plasma circulating tumor DNA is used to detect T790M resistance mutation. We studied whether sputum is another feasible specimen for detection of EGFR mutations. Methods: Twenty-eight patients with advanced EGFR-mutated NSCLC were included during stable and/or progressive disease. The initial activating EGFR mutations (exon 19 deletions or L858R mutations) at stable disease and at progressive disease (together with T790M) were assessed in simultaneously collected plasma and sputum samples and detected by droplet digital polymerase chain reaction (ddPCR). Results: Activating EGFR mutations were detected in 47% of the plasma samples and 41% of sputum samples during stable disease, and in 57% of plasma samples and 64% of sputum samples during progressive disease. T790M was detected in 44% of the plasma samples and 66% of the sputum samples at progressive disease. In ddPCR T790M-negative results for both specimens (plasma and sputum), negativity was confirmed by rebiopsy in 5 samples. Concordance rate of plasma and sputum for T790M was 0.86, with a positive percent agreement of 1.0 and a negative percent agreement of 0.80. Conclusions: We demonstrated that EGFR mutation analysis with ddPCR is feasible in sputum samples. Combination of plasma and sputum analyses for detection of T790M in NSCLC patients with progressive disease increases the diagnostic yield compared with molecular plasma analysis alone.
Substance Use Disorders and Associated Factors Among Adult Psychiatric Patients in Jimma Town, Southwest Ethiopia, 2017. Community-Based Cross-Sectional Study
Authors: Dawud Badiru , Yeshigeta Eyerusalem , Negash Alemayehu , Mamaru Almaz , Agenagnew Liyew , Tolosa Daniel , Kerebih Habtamu , Mekuriaw Birhanie , Abdisa Eba , Abera Mubarek , Hailesilassie Hailemariam , Soboka Matiwos 
Published: February 2021

Background: Substance use disorders are more common among people with mental illness than in the general population. It makes recovery from mental illness more difficult, leads to frequent thoughts of suicide and re-hospitalization. Objective: Aimed to assess the prevalence of substance use disorders and associated factors among adult psychiatric patients in Jimma Town, Southwest, Ethiopia, 2017. Methods: A community-based cross-sectional study was conducted on a total of 300 patients with mental illness using the case tracing method. Participants were interviewed using the alcohol use disorder identification test questionnaire to assess Alcohol Use Disorder (AUD). Fagerstrom test tool for nicotine dependence and structured questionnaires were utilized to assess the socio-demographic characteristics of participants. Data were analyzed using SPSS version 20. The variable that showed association with AUD and nicotine dependence at P < .25 in the bivariate analysis was entered into multivariable logistic regressions to control confounders for both outcome variables independently. The significance of association was determined by P < .05 and strength was described using an adjusted odds ratio at a 95% confidence level. Results: The prevalence of alcohol use disorder and nicotine dependence was 14.3% and 23.3%, respectively. Female gender (AOR 0.15, 95% CI = 0.04-0.57), starting treatment within the first month of the onset of the illness (AOR 0.20, 95% CI = 0.05-0.82) and nicotine dependence(AOR 4.84, 95% CI = 1.85-12.67) associated with AUD. Additionally, being female (AOR 0.04, 95% CI = 0.01-0.25), joblessness (AOR 3.05, 95% CI = 1.30-7.16), absence of relapse of illness (AOR 0.18, 95% CI = 0.065-0.503), no improvement in illness (AOR 5.3, 95% CI = 1.70-16.50), and current khat use (AOR 3.09, 95% CI = 1.21-7.90) were associated with nicotine dependence. Conclusion: This study revealed a high prevalence of substance use disorders among psychiatric patients in the community. Being female, experiencing a shorter duration of illness before initiating treatment, and nicotine-dependence were significantly associated with AUD. On the other hand, female sex and absence of relapse of illness were negatively associated with nicotine dependence whereas, joblessness, less improvement of illness, and khat chewing were positively associated with it. Therefore, services on substance use disorders have to be extended to the community level with wide-scale training for the town’s health care providers, including health extension workers who have direct contact with these individuals. Accordingly, comprehensive and suitable interventions were advised to be provided on factors contributing to substance use disorders in general.
Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis
Authors: Harroud Adil , Marrie Ruth Ann , Fitzgerald Kathryn C , Salter Amber , Lu Yi , Patel Mitulkumar , Kowalec Kaarina 
Published: February 2021

Background: Major depressive disorder (MDD) is common in multiple sclerosis (MS) and its incidence rises before MS diagnosis. However, the causality and direction of this association remain unclear. Objective: The objective is to investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR). Methods: We selected genetic instruments associated with risk of MDD ( n = 660,937 cases; 1,453,489 controls) and MS ( n = 47,429 cases; 68,374 controls). Using two-sample MR, we examined putative causal effects in either direction, with sensitivity analyses to assess pleiotropy. Also, we adjusted for body mass index (BMI) in multivariable MR. Results: We found no effect of genetic liability to MDD on the odds of MS (OR = 1.07/doubling in odds, 95% CI = 0.90–1.28). Similarly, our findings did not support a causal effect of genetic liability to MS on MDD (OR = 1.00/doubling in odds, 95% CI = 0.99–1.01). Despite heterogeneity, sensitivity analyses indicated that bias from pleiotropy was unlikely. Conversely, genetic predisposition toward higher BMI increased the odds of MS (OR = 1.34/SD increase, 95% CI = 1.09–1.65) and MDD (OR = 1.08, 95% CI = 1.01–1.15). Conclusion: This study does not support a causal association between MDD genetic liability and MS susceptibility, and vice versa. Genetic evidence suggesting commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis.
Multi-layer analysis of quantitative 7 T magnetic resonance imaging in the cortex of multiple sclerosis patients reveals pathology associated with disability
Authors: Lema Dopico Alfonso , Choi Seongjin , Hua Jun , Li Xu , Harrison Daniel M 
Published: February 2021

Background: Cortical demyelination is a relevant aspect of tissue damage in multiple sclerosis (MS). Microstructural changes may affect each layer in the cortex differently. Objectives: To evaluate the sensitivity of quantitative magnetic resonance imaging (qMRI) measurements on cortical layers as clinically accessible biomarkers of grey matter (GM) pathology. Methods: Forty-five participants with MS underwent 7 T magnetic resonance imaging (MRI) of the brain. Magnetization prepared two rapid acquisition gradient echoes (MP2RAGE) was processed for T1-weighted images and a T1 map. Multi-echo gradient echo images were processed for quantitative susceptibility and R2* maps. Cortical GM volumes were segmented into four cortical layers, and relaxometry metrics were calculated within and between these layers. Results: Significant correlations were found for disability scales and multi-layer metrics, for example, Expanded Disability Status Scale (EDSS) and peak height (PH) in the subpial (T1: ρ = −0.372, p < 0.050) and inner (R2*: ρ = −0.359, p < 0.050) cortical layers. Multivariate regression showed interdependency between atrophy and cortical metrics in some instances, but an independent relationship between cortical metrics and disability in others. Conclusion: Cortical layer 7 T qMRI analyses reveal layer-specific relationships with disability in MS and allow emergence of clinically relevant associations that are hidden when analysing the full cortex.
The relative contributions of obesity, vitamin D, leptin, and adiponectin to multiple sclerosis risk: A Mendelian randomization mediation analysis
Authors: Harroud Adil , Manousaki Despoina , Butler-Laporte Guillaume , Mitchell Ruth E , Davey Smith George , Richards J Brent , Baranzini Sergio E 
Published: February 2021

Background: Obesity is associated with increased risk of multiple sclerosis (MS); however, the underlying mechanisms remain unclear. Objective: To determine the extent to which decreased vitamin D bioavailability and altered levels of adiponectin and leptin mediate the association between obesity and MS. Methods: We performed Mendelian randomization (MR) analyses to estimate the effects on MS of body mass index (BMI), 25-hydroxyvitamin D (25OHD), adiponectin, and leptin levels in a cohort of 14,802 MS cases and 26,703 controls. We then estimated the proportion of the effect of obesity on MS explained by these potential mediators. Results: Genetic predisposition to higher BMI was associated with increased MS risk (odds ratio (OR) = 1.33 per standard deviation (SD), 95% confidence interval (CI) = 1.09–1.63), while higher 25OHD levels reduced odds of MS (OR = 0.72 per SD, 95% CI = 0.60–0.87). In contrast, we observed no effect of adiponectin or leptin. In MR mediation analysis, 5.2% of the association between BMI and MS was attributed to obesity lowering 25OHD levels (95% CI = 0.3%–31.0%). Conclusions: This study found that a minority of the increased risk of MS conferred by obesity is mediated by lowered vitamin D levels, while leptin and adiponectin had no effect. Consequently, vitamin D supplementation would only modestly reverse the effect of obesity on MS.