BackgroundRenal interstitial fibrosis is one of the most common pathways in the progression of chronic kidney disease (CKD). Noninvasive evaluation of interstitial fibrosis would help monitoring CKD progression and prognosis prediction.PurposeTo evaluate the severity of renal interstitial fibrosis by diffusion‐relaxation correlation spectrum imaging (DR‐CSI).Study TypeProspective.SubjectsForty patients with CKD and 10 healthy controls (average age 49.2 ± 14.8 years, 18 females).Field Strength/Sequence3‐T, DR‐CSI with 36 axial spin‐echo echo‐planar diffusion‐weighted images (6 b‐values, 6 echo times).AssessmentInterstitial fibrosis level (IFL) was assessed from biopsy results (IFL = 1, fibrosis percentage <25%, defined as mild; IFL = 2, 25%–50%, moderate; IFL = 3, >50%, severe). Estimated glomerular filtration rate (eGFR) was calculated using serum creatinine. The regions of interest included cortex for both kidneys. The diffusivity‐T2 spectrum was assessed considering three compartments (threshold: T2 30–40 msec, diffusivity 5–9 μm2/msec, according to visible peaks): A (low diffusivity, short T2), B (low diffusivity, long T2), and C (high diffusivity). Volume fractions Vi (i = A, B, C) were calculated.Statistical TestsIntra‐class coefficient (ICC, >0.6 as good) to assess inter‐reader agreement of DR‐CSI Vi. Spearman's correlation to assess relationship of Vi to IFL and eGFR. Receiver operating characteristic analyses with the area under the curve (AUC) to discriminate patients with moderate‐severe fibrosis from mild ones. Statistical significance criteria: P‐value <0.05.ResultsICCs were good for all Vi. Correlations were found between IFL and VB (r = 0.424, significant) and VC (r = −0.400, significant), and between eGFR and VB (r = −0.303, P = 0.058) and VC (r = 0.487, significant). Regarding VB and VC, the AUCs were 0.903 and 0.824.Data ConclusionDR‐CSI help distinguish patients with moderate or severe renal interstitial fibrosis from mild ones.Evidence Level: 2Technical Efficacy: Stage 2

BackgroundNeuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC–MSCs) in treating NMOSD.MethodsThe trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC—MSCs. Patients will be treated with three different doses of hUC–MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years.DiscussionAlthough hUC–MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC–MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC–MSC in treating NMOSD and might be able to determine the optimal dose of hUC–MSC for NMOSD patients.Trial registrationThe study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.

<div>AbstractPurpose:<p>We investigated the safety and preliminary efficacy of anti–PD-L1 antibody (ZKAB001) as maintenance therapy for localized patients with high-grade osteosarcoma to reduce the risk of recurrence and metastasis.</p>Patients and Methods:<p>This open-label Phase I/II study was divided into dose-escalation Phase I and expansion Phase II. Phase I used a 3+3 design with ZKAB001 at three escalating doses ranging: 5, 10, 15 mg/kg every 2 weeks in 9 patients with localized high-grade osteosarcoma and Phase II tested 10 mg/kg in 12 patients for up to 24 cycles. Primary endpoints were safety and tolerability assessed using CTCAE4.0.3.</p>Results:<p>Between October 2018 and 2019, 21 eligible patients were enrolled and accepted ZKAB001 treatment: 9 in the dose-escalation phase, and 12 in expansion phase. Six patients with disease progression withdrew from this study and follow-up is ongoing. The MTD was not defined in Phase I. All doses had a manageable safety profile. The recommended dose in Phase II was set at 10 mg/kg. Most frequent immune-related adverse events were thyroiditis (76.2%) and dermatitis (42.9%). Only 1 (4.8%) of 21 patients had a Grade 3 skin rash. The median 3-year event-free survival (EFS) and overall survival (OS) were not established; however, 24-month EFS was 71.4% (95% confidence interval, 47.2–86.0) and 2-year OS was 100%. Preliminary efficacy data showed EFS benefits in patients with PD-L1 positive or an MSI-H sub-population.</p>Conclusions:<p>Switching to maintenance using ZKAB001 showed an acceptable safety profile and provided preliminary evidence of clinical activity in localized patients with osteosarcoma.</p></div>

<p>Summary of Exposure to ZKAB001, All Treated Patient Population</p>