Performance of the 2019 ACR/EULAR Classification Criteria for IgG4-Related Disease in a Large Chinese Cohort.

OBJECTIVE: The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings. METHODS: Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD. RESULTS: A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers. CONCLUSIONS: The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.

T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese.

Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version - T2T-CHM13 - reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploid. The quality of T2T-YAO is much better than all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, a truly accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

Development of a 3D Printed Lung Model Made of Synthetic Materials for Simulation.

BACKGROUND: Considering the complexity of lung structures and the difficulty of thoracoscopic surgery, simulation-based training is of paramount importance for junior surgeons. Here, we aim to design a high-fidelity lung model through utilizing the three-dimensional (3D) printing technology combined with synthetic materials to mimic the real human lung. METHODS: The 3D printed lung model was manufactured based on the computed tomography images of a randomly selected male patient. Synthetic materials were used for the construction of lung parenchyma, blood vessels, and bronchi. Then, the model was assessed in terms of its visual, tactile, and operational features by participants (the senior surgeons, junior surgeons, and medical students), who were asked to complete the specially designed survey-questionnaires. RESULTS: A 3D printed model of the right lung made of synthetic materials was successfully fabricated. Thirty subjects participated in our study (10 senior surgeons, 10 junior surgeons, and 10 medical students). The average visual evaluation scores for senior surgeons, junior surgeons, and medical students were 3.97 ± 0.61, 4.56 ± 0.58, 4.76 ± 0.49, respectively. The average tactile evaluation scores were 3.40 ± 0.50, 4.13 ± 0.68, 4.00 ± 0.64, respectively. The average operation evaluation scores were 3.33 ± 0.83, 3.93 ± 0.66, 4.03 ± 0.66, respectively. Significant lower scores were obtained in the group of the senior surgeons compared with the other two groups. CONCLUSION: A high level of fidelity was exhibited in our 3D printed lung model and it could be applied as a promising simulator for the surgical training in the future.

Malignancy Risk of Immunoglobin G4-Related Disease: Evidence from a Large Cohort Multicenter Retrospective Study.

INTRODUCTION: The aim of this work was to evaluate the prevalence of malignancies in a multicenter cohort of Chinese patients with immunoglobulin G4-related disease (IgG4-RD) and to identify the related risk factors of malignancy in IgG4-RD patients. METHODS: We retrospectively analyzed 602 IgG4-RD patients who were recruited in five medical centers from 2009 to 2020. Standardized prevalence ratios (SPRs) against the general Chinese population were calculated along with 95% confidence intervals (CIs). We identified the risk factors of malignancy in IgG4-RD and calculated the odds ratios (ORs) of different factors. We then developed and validated a prediction model for malignancy risk of IgG4-RD based on our cohort. RESULTS: We observed a significantly increased prevalence of total malignancies in this cohort compared to the general Chinese population (SPR 8.66 [95% CI 5.84, 12.31]). Logistic regression analysis indicated that eosinophil percentage (OR 1.096 [95% CI 1.019-1.179], P = 0.016), serum albumin-to-globulin ratio (AGR) (OR 0.185 [95% CI 0.061-0.567], P = 0.002) and autoimmune pancreatitis (OR 2.400 [95% CI 1.038-5.549], P = 0.041) were three potential risk factors of malignancy in IgG4-RD patients. Four predictors were included in our final prediction model: age at IgG4-RD diagnosis, eosinophil percentage, AGR and autoimmune pancreatitis. The nomogram performed well in the internal validation cohort, with a concordance index (C-index) of 0.738. CONCLUSIONS: A significantly increased prevalence of total malignancies was observed in our multicenter cohort. Eosinophil percentage and autoimmune pancreatitis are risk factors, whereas AGR is negatively associated with malignancy in IgG4-RD. A prediction model for malignancy risk of IgG4-RD was first developed and validated in our study.

Needle biopsy compared with surgical biopsy: pitfalls of small biopsy in histologial diagnosis of IgG4-related disease.

OBJECTIVE: The growing utilization of needle biopsy has challenged the current pathology consensus of IgG4-related disease (IgG4-RD). The aims of this study were to identify the histological characteristics of needle biopsy and surgical specimens and evaluate the ability of needle biopsy in histological diagnosis of IgG4-RD. METHODS: Biopsies from patients who were referred to as IgG4-RD by the 2019 ACR/EULAR IgG4-RD classification criteria in Peking University People's Hospital from 2012 to 2019 were re-evaluated. Typical histological features and diagnostic categories were compared between needle biopsy and surgical biopsy. RESULTS: In total, 69 patients met the 2019 ACR/EULAR classification criteria and 72 biopsies of them were re-evaluated. All cases showed lymphoplasmacytic infiltrate, while storiform fibrosis and obliterative phlebitis were only present in 35 (48.6%) and 23 (31.9%) specimens, respectively. Storiform fibrosis was more likely to be seen in retroperitoneum lesion (P = 0.033). Surgical biopsy showed significantly higher IgG4+ plasma cells/high-power field (IgG4/HPF) count (P < 0.01) and higher proportion of IgG4/HPF > 10 (P < 0.01). No significant difference was observed with regard to the ratio of IgG4+ plasma cells/IgG+ plasma cells (IgG4/IgG) (P = 0.399), storiform fibrosis (P = 0.739), and obliterative phletibis (P = 0.153). According to the 2011 comprehensive diagnostic criteria, patients who performed a needle biopsy were less likely to be probable IgG4-RD (P = 0.045). Based on the 2011 pathology consensus, needle biopsy was less likely to be diagnosed as IgG4-RD (P < 0.01), especially to be highly suggestive IgG4-RD (P < 0.01). Only 1/18 (5.6%) needle salivary specimens fulfilled the cutoff of IgG4/HPF > 100, which was significantly less than 15/23 (65.2%) of surgical ones (P < 0.01). CONCLUSIONS: Needle biopsy shows an inferiority in detecting IgG4/HPF count but not in IgG4/IgG ratio, storiform fibrosis, and obliterative phlebitis. Compared with surgical samples, needle biopsy is less likely to obtain a histological diagnosis of IgG4-RD. A different IgG4/HPF threshold for needle biopsy of the salivary glands may be considered.

What Predicts the Prognosis of Spinal Metastases in Separation Surgery Procedures?

BACKGROUND: Separation surgery is performed to provide a safe gap between the epidural tumor and spinal cord for postoperative stereotactic body radiotherapy (SBRT) in cases of spinal metastases. However, there is a gap in evidence regarding sufficient tumor resection in separation surgery. We describe the prognoses according to the extent of resection in separation surgery. METHODS: This retrospective study included 36 consecutive patients who underwent separation surgery and postoperative SBRT between December 2016 and December 2019 at a single center. Local control (LC), overall survival (OS), distance of separation (DS), and quality-of-life parameters were analyzed. P values <0.05 were considered statistically significant. RESULTS: Patients were assigned to the aggressive resection group (ARG, n = 18) or moderate resection group (MRG, n = 18), with estimated LC and OS at 1 year of 79.0% and 75.9%, respectively. There were no significant differences between ARG and MRG in estimated LC (85.9% vs. 72.2%; P = 0.317) or OS (69.3% vs. 80.9%, P = 0.953) at 1 year. All 5 patients in MRG who developed local progression had less satisfactory tumor resection with DS <3 mm. A borderline significant difference in estimated LC at 1 year was noted between individuals with DS <3 mm and those with DS ≥3 mm (51.9% vs. 100.0%; P = 0.053) in MRG. There was no statistical difference between ARG and MRG in quality-of-life parameters. CONCLUSIONS: Moderate resection of ventral dural mass did not significantly reduce patients' prognosis in separation surgery. However, the minimal distance between the postoperative residual epidural tumor and spinal cord should be ≥3 mm.

Activity of fibroblast-like synoviocytes in rheumatoid arthritis was impaired by dickkopf-1 targeting siRNA.

BACKGROUND: Fibroblast-like synoviocytes (FLSs), resident mesenchymal cells of synovial joints, play an important role in the pathogenesis of rheumatoid arthritis (RA). Dickkopf-1 (DKK-1) has been proposed to be a master regulator of bone remodeling in inflammatory arthritis. Here, potential impairation on the activity of FLSs derived from RA to small interfering RNAs (siRNAs) targeting DKK-1 was investigated. METHODS: siRNAs targeting DKK-1 were transfected into FLSs of patients with RA. Interleukin (IL)-1ß, IL-6, IL-8, matrix metalloproteinase (MMP) 2, MMP3, MMP9, transforming growth factor (TGF)-ß1, TGF-ß2 and monocyte chemoattractant protein (MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Invasion assay and H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation, respectively. Western blotting was performed to analyze the expression of nuclear factor (NF)-κB, interleukin-1 receptor-associated kinase (IRAK)1, extracellular regulated protein kinases (ERK)1, Jun N-terminal kinase (JNK) and ß-catenin in FLSs. RESULTS: DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs (P < 0.01). siRNAs induced a significant reduction of the levels of IL-6, IL-8, MMP2, MMP3 and MMP9 in FLSs compared to the control group (P < 0.05). DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs (P < 0.05). Important molecules of pro-inflammatory signaling in FLSs, including IRAK1 and ERK1, were decreased by the inhibition of DKK-1 in FLSs. In contrast, ß-catenin, a pivotal downstream molecule of the Wnt signaling pathway was increased. CONCLUSIONS: By inhibiting DKK-1, we were able to inhibit the proliferation, invasion and pro-inflammatory cytokine secretion of FLSs derived from RA, which was mediated by the ERK or the IRAK-1 signaling pathway. These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA.