Supplementary Material for: Contribution of IVIM to Conventional Dynamic Contrast-Enhanced and Diffusion-Weighted MRI in Differentiating Benign from Malignant Breast Masses

<p><b><i>Background:</i></b> The aim of this study was to determine whether the indicators obtained from intravoxel incoherent motion (IVIM) imaging can improve the characterization of benign and malignant breast masses compared with conventional dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted magnetic resonance imaging (DW-MRI). <b><i>Patients and Methods:</i></b> This study included 23 benign and 31 malignant breast masses of 48 patients. Main indicators were initial enhancement ratio (IER), time-signal intensity curve (TIC), apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f). The discriminative abilities of the different models were compared by means of receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) analysis. <b><i>Results:</i></b> D had the highest AUC (0.980), sensitivity (93.55%), specificity (100%), and diagnostic accuracy (96.36%). Both D and TIC could provide the independent predicted features for malignant breast masses. The combination of D and TIC had an AUC of up to 0.990. <b><i>Conclusion:</i></b> D of IVIM can effectively complement existing conventional DCE-MRI and DW-MRI in differentiating malignant from benign breast masses. IVIM combined with DCE-MRI is a robust means of evaluating breast masses.</p

Supplementary Material for: Hearing Restoration for Adults with Vestibular Schwannoma in the Only Hearing Ear: Ipsilateral or Contralateral Cochlear Implantation?

<i>Objective:</i> To explore auditory outcomes following cochlear implantation (CI) in patients with vestibular schwannoma (VS) in the only hearing ear. <i>Methods:</i> Three patients, all with a long history of hearing loss on one side and with newly diagnosed VS on the other side, underwent ipsilateral or contralateral CI. Their clinical data were collected retrospectively. Postoperative hearing outcomes were measured during follow-up and compared with the preoperative test results. A thorough search of the English-language literature was performed. <i>Results:</i> Patients 1 and 2 underwent CI in the ipsilateral and contralateral ear, respectively, without tumor removal; patient 3 underwent CI after tumor resection. At the last follow-up, the result of pure-tone audiometry was 25, 45, and 25 dB, respectively. An open-set speech discrimination score was achieved in all 3 patients, with monosyllabic word recognition of 60, 30, and 75%, respectively. Besides the patients included in our study, 28 CI cases with VS in the only hearing ear have been reported up to now. <i>Conclusions:</i> In patients with VS in the only hearing ear, significant hearing deterioration with no obvious tumor growth is a good indication for ipsilateral CI. Long-term deafness in the tumor-free ear is not an absolute contraindication for CI

Supplementary Material for: Circulating Leptin Concentrations in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> Weight loss is a clinically important risk factor indicating a poor prognosis in chronic obstructive pulmonary disease (COPD). Leptin is an important regulator of food intake and energy expenditure. <b><i>Objectives:</i></b> To conduct a meta-analysis to determine whether the level of leptin is related to the disease status of COPD. <b><i>Methods:</i></b> Studies published before December 2012 were identified by searching PubMed, Embase and the Cochrane Database. Observational studies comparing circulating leptin levels between COPD patients and healthy controls were included. Data were independently extracted by two investigators and analyzed using Stata 12.0 software. <b><i>Results:</i></b> Ten articles were included in the meta-analysis. Circulating leptin levels were correlated with the body mass index (BMI) as well as percent fat mass in stable COPD patients. The correlation coefficient tended to be weaker during exacerbation. A positive correlation between leptin and tumor necrosis factor (TNF)-α levels was found in COPD exacerbations, while it disappeared in patients with stable disease. Most studies indicated that circulating leptin levels in stable COPD patients were not significantly different from those in healthy controls when adjusted for gender and BMI, whilst leptin levels tended to elevate in exacerbation groups. <b><i>Conclusions:</i></b> The normal regulatory mechanism of leptin is maintained in stable COPD patients despite weight loss. The additional correlation between leptin and TNF-α during exacerbations may support the closer association of leptin with changes in nutritional parameters and suggests its valuable role in the evaluation of systemic inflammatory responses in COPD patients during exacerbation, which merits further study

Supplementary Material for: Oxidative Balance Score and the Risk of End-Stage Renal Disease and Cardiovascular Disease

<p><b><i>Background:</i></b> Oxidative balance score (OBS) is a composite measure of oxidative stress-related exposures. The aim of this study was to investigate the association between OBS, end-stage renal disease (ESRD), and cardiovascular disease (CVD). <b><i>Methods:</i></b> Using data from the Chronic Renal Insufficiency Cohort, we calculated the main exposure OBS by summing up 12 apriori-defined pro- and antioxidant factors obtained from the diet history questionnaire and lifestyle assessment. We divided OBS into quartiles (Q1-Q4), with Q1 (predominance of pro-oxidants) as the reference. We analyzed OBS quartiles as an ordinal variable. Crude and adjusted hazards ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models for time to ESRD and CVD. <b><i>Results:</i></b> Compared to Q1, Q4 (high antioxidant) was associated with ESRD in the crude model (HR 1.35, 95% CI 1.08-1.69) and adjusting for age, sex, and race (HR 1.36, 95% CI 1.09-1.71) but not in the fully adjusted model (HR 1.12, 95% CI 0.84-1.51). HR of ESRD increased as the OBS quartiles increased in the crude model (<i>p</i>_trend < 0.05) but not in the fully adjusted model (<i>p</i>_trend = 0.30). Compared to Q1, Q4 was associated with CVD in the crude (HR 1.33, 95% CI 1.06-1.68) but not adjusted models. The HR of CVD increased with an increase in OBS quartiles in the crude model (<i>p</i>_trend < 0.05). <b><i>Conclusion:</i></b> The reverse association between OBS and progression to ESRD suggests that perhaps the effect of oxidative balance-related exposure is different in the setting of established chronic kidney disease.</p

PowerPoint Slides for: Oxidative Balance Score and the Risk of End-Stage Renal Disease and Cardiovascular Disease

<p><b><i>Background:</i></b> Oxidative balance score (OBS) is a composite measure of oxidative stress-related exposures. The aim of this study was to investigate the association between OBS, end-stage renal disease (ESRD), and cardiovascular disease (CVD). <b><i>Methods:</i></b> Using data from the Chronic Renal Insufficiency Cohort, we calculated the main exposure OBS by summing up 12 apriori-defined pro- and antioxidant factors obtained from the diet history questionnaire and lifestyle assessment. We divided OBS into quartiles (Q1-Q4), with Q1 (predominance of pro-oxidants) as the reference. We analyzed OBS quartiles as an ordinal variable. Crude and adjusted hazards ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models for time to ESRD and CVD. <b><i>Results:</i></b> Compared to Q1, Q4 (high antioxidant) was associated with ESRD in the crude model (HR 1.35, 95% CI 1.08-1.69) and adjusting for age, sex, and race (HR 1.36, 95% CI 1.09-1.71) but not in the fully adjusted model (HR 1.12, 95% CI 0.84-1.51). HR of ESRD increased as the OBS quartiles increased in the crude model (<i>p</i>_trend < 0.05) but not in the fully adjusted model (<i>p</i>_trend = 0.30). Compared to Q1, Q4 was associated with CVD in the crude (HR 1.33, 95% CI 1.06-1.68) but not adjusted models. The HR of CVD increased with an increase in OBS quartiles in the crude model (<i>p</i>_trend < 0.05). <b><i>Conclusion:</i></b> The reverse association between OBS and progression to ESRD suggests that perhaps the effect of oxidative balance-related exposure is different in the setting of established chronic kidney disease.</p

Supplementary Material for: Baseline Clinical Characteristics and Complement Biomarkers of Patients with C3 Glomerulopathy Enrolled in Two Phase 2 Studies Investigating the Factor D Inhibitor Danicopan

Introduction: C3 glomerulopathy (C3G) is a rare, progressive kidney disease resulting from dysregulation of the alternative pathway (AP) of complement. Biomarkers at baseline were investigated in patients with C3G who participated in two phase 2 studies with the factor D (FD) inhibitor, danicopan. Methods: Patients with biopsy-confirmed C3G, proteinuria ≥500 mg/day, and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 were enrolled into two studies (NCT03369236 and NCT03459443). Biomarker analysis was performed for patients with C3G confirmed by central pathology laboratory re-evaluation. Complement and clinical biomarkers, biopsy composite score, and activity and chronicity indices were assessed at baseline and analyzed by pairwise Spearman correlation analysis. Results: Twenty-nine patients were included in the analysis (median [interquartile range] age: 24.0 [10.0] years). Systemic complement AP activation was evident by reduced median concentrations of C3 and C5, elevated sC5b-9, and normal C4, relative to reference ranges. C3 showed strong pairwise correlations with C5 and sC5b-9 (r = 0.80 and −0.73, respectively; p r = −0.83 and −0.87, respectively; p r = 0.69 and r = 0.83, respectively; p r = −0.76, p r = −0.57, p = 0.0021). Conclusion: Associations among complement biomarkers, kidney function, and kidney histology may add to the current understanding of C3G and assist with the characterization of patients with this heterogenous disease