Surgical outcomes and perioperative risk factors of patients with interstitial lung disease after pulmonary resection.

BACKGROUND: Patients of interstitial lung disease (ILD) combined with pulmonary lesions are increasingly common in clinical practice. Patients with ILD are at significantly higher risk for complications after pulmonary resection (including lobectomy and sublobar resection), especially acute exacerbations of ILD (AE-ILD). The purpose of this study is to summarize the short-term and long-term outcomes after pulmonary resection in ILD patients and to analyze the clinical factors affecting surgical safety. METHODS: From January 2004 to January 2022, a total of 78 patients who were diagnosed with ILD and underwent pulmonary resection at our center were enrolled in this study. Clinical data, pathological findings, surgical procedures, and intraoperative safety of these patients were collected retrospectively. Postoperative 90-day complications and mortality, long-term surgical outcomes from postoperative 90 days to 24 months, and changes in ILD condition were investigated. Logistic regression analysis was used to identify the risk factors associated with postoperative complications. RESULTS: The median age of patients was 66.5 (range 33-86) years, 82.1% (64/78) of patients were male, and 78.2% (61/78) of patients had comorbidities. Idiopathic ILD and secondary ILD accounted for 86% and 14%, thoracotomy and video-assisted thoracoscopic surgery accounted for 12.8% and 87.2%, and lobectomy and sublobar resection accounted for 37.2% and 62.8%, respectively. Postoperative 90-day complications occurred in 25.6% (20/78) of patients, with pulmonary complications and AE-ILD occurring in 15.4% and 9.0% of patients, respectively. The postoperative 90-day mortality rate was 5.1% (4/78), and the cause of death was AE-ILD. Exacerbation of ILD or other complications occurred in 12.8% (10/78) of patients from postoperative 90 days to 24 months. Univariate logistic regression analysis showed that comorbidity, extent of resection, systemic lymph node dissection, operation time, intraoperative blood loss, and pathology of pulmonary lesion were associated with postoperative 90-day complications. In multivariate logistic regression analysis, age-adjusted Charlson Comorbidity Index and intraoperative blood loss were identified as independent risk factors of postoperative 90-day complications. CONCLUSIONS: Patients with ILD have a significantly higher risk of postoperative 90-day complications and mortality after pulmonary resection, especially pulmonary complications and AE-ILD. After postoperative 90 days, the risk of deterioration of pulmonary status remains high, including exacerbation of ILD and complications associated with long-term use of glucocorticoids and immunosuppressant. Age, comorbidity and intraoperative blood loss are high risk factors for postoperative 90-day complications.

Postoperative clinical outcomes of patients with thymic epithelial tumors after over-3-year follow-up at a single-center.

BACKGROUND: To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation. METHODS: Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0. RESULTS: A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2-137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications. CONCLUSIONS: The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy.

Surgical treatment of intermediate to high grade thymic neuroendocrine neoplasms: case series of five patients and literature review.

Background: Thymic neuroendocrine neoplasms (Th-NENs) are extremely rare. Th-NENs are divided into four pathological subtypes: typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC). The latter three subtypes are highly aggressive with poor prognosis. There are limited reports on the optimal surgical strategies for Th-NENs. This study aims to report a case series of Th-NENs after surgical treatment and review the literatures. Methods: We report a case series of five patients diagnosed with Th-NENs and summarize their clinical characteristics. Literatures related to surgical treatment of Th-NENs were reviewed. Results: There were three males and two females, and mean age was 53.6 years. No myasthenia gravis or neuroendocrine symptoms were found. Three patients were diagnosed with AC and the other two were diagnosed with LCNEC. Two patients were stage II-b, one patient was stage III-a, and two patients were stage IV-b. One patient received preoperative chemotherapy, one patient received preoperative chemoradiotherapy, and three patients underwent surgery directly. Two patients underwent extended thymectomy via video-assisted thoracoscopic surgery (VATS), two patients underwent extended thymectomy via median sternotomy, and one patient underwent resection of anterior mediastinal tumor, sternal metastases, superior vena cava and partial right atrium via median sternotomy and cardiopulmonary bypass. R0 resection was achieved in 80% (4/5) of patients. There was no postoperative 90-day complication and death. One patient had no recurrence. One patient had lymph node metastases and was still alive after somatostatin analogue therapy. One patient had no recurrence of Th-NENs but died of other tumors. Two patients had distant metastases. Median overall survival (mOS) was 49 (range, 4-134) months. A total of 22 original studies related to surgical treatment of Th-NENs were retrieved. Conclusions: Th-NENs is a very rare and extremely aggressive malignancy. Early diagnosis and surgical resection are the most important methods to improve prognosis. Radical resection and lymph node dissection are recommended for accurate staging and better prognosis. Currently, there are few clinical data on Th-NENs and several important surgical issues remain unresolved. In the future, multi-center, large-sample database and clinical studies are urgently needed to explore better treatment modality.

Clinical characteristics of multicentric reticulohistiocytosis and distinguished features from rheumatoid arthritis: a single-center experience in China.

OBJECTIVE: To investigate the clinical features of multicentric reticulohistiocytosis (MRH). METHODS: The clinical manifestations, laboratory examination results and histologic characteristics of eleven patients with MRH were collected and compared with those of 33 patients with rheumatoid arthritis. RESULTS: In total, 72.7% of the MRH patients were women. The median age was 46 years (range 33-84 years). Diagnosed by specific pathologic features, all MRH patients exhibited cutaneous involvement. The dorsa of the hands, arms, face and auricle were the most commonly affected areas. Nodules were also located on the legs, scalp, trunk, neck, and even the hypoglossis and buccal mucosa. Ten MRH patients (90.9%) had symmetric polyarthritis. Compared with rheumatoid arthritis (RA) patients, MRH patients were more likely to have distal interphalangeal joint (DIP) involvement (63.6% vs 24.2%, P = 0.017) and less likely to have elbow (36.4% vs 72.7%, P = 0.003), ankle (45.5% vs 93.9%, P < 0.001) and metacarpophalangeal joint (MCP) (36.4% vs 78.8%, P = 0.009) involvement. Positivity for rheumatoid factor (RF) (36.4% vs 84.6%, P = 0.001) and anti-CCP antibody (9.1% vs 81.8%, P = 0.000), as well as the median RF titer [43.8 (31.7-61.0) vs 175.4 (21.3-940.3), P = 0.021], in MRH patients was lower than in RA patients. Elevation of the erythrocyte sedimentation rate (ESR) was also less common in MRH patients than in RA patients (36.4% vs 72.7%, P = 0.030). After treatment with median- to large-dose corticosteroids and disease-modifying antirheumatic drugs, 8 patients achieved complete remission and 2 patients partial remission (skin lesions ameliorated, joint lesions not ameliorated). CONCLUSION: Always pathologically diagnosed, MRH is a systemic disease involving RA-like erosive polyarthritis and a specific distribution of skin nodules characterized by "coral beads". More DIP involvement and less elbow, ankle and MCP involvement are seen in MRH than in RA. In addition, less positivity and lower-titer RF, uncommon presence of anti-CCP antibodies and ESR elevation may be helpful to distinguish MRH from RA.

Genome-wide DNA methylation patterns in monocytes derived from patients with primary Sjogren syndrome.

BACKGROUND: Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients. METHODS: A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips. RESULTS: In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients. CONCLUSION: Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.

Antagonizing miR-7 suppresses B cell hyperresponsiveness and inhibits lupus development.

OBJECTIVES: The objective of this study was to address the biological function of miR-7 in an animal model of systemic lupus erythematosus. METHODS: MRLlpr/lpr lupus mice were administrated antagomiR-7 or a scramble control by tail vein for 5weeks. Three groups of animals' tissues were assessed for lupus manifestations by immunofluorescence and immunohistochemistry, and serum was examined for levels of autoantibodies and inflammatory cytokines. Splenic B cell subsets were assessed for intracellular expression of PI3K signaling by FACS. Finally, the ability of the miR-7 antagomir to regulate the expansion of T follicular helper (Tfh) cells and B cell hyperresponsiveness was further explored. RESULTS: We found that miR-7 was up-regulated in MRLlpr/lpr lupus mice and directly targeted PTEN mRNA in B cells. Up-regulated miR-7 in MRLlpr/lpr lupus B cells was negatively correlated with PTEN expression. Notably, miR-7 antagomir treatment reduced lupus manifestations in MRLlpr/lpr lupus mice. miR-7-mediated down-regulation of PTEN/AKT signaling promoted B cell differentiation into plasmablasts/plasma cells and spontaneous germinal center (GC) formation, whereas miR-7 antagomir normalized splenic B cell subtypes. Besides suppressing the activation of B cells, miR-7 antagomir intervention also down-regulated STAT3 phosphorylation and production of IL-21 and reduced Tfh expansion. CONCLUSION: The above data have demonstrated the critical roles of miR-7 not only in regulating PTEN expression and also B cell and Tfh cell function in lupus-prone MRLlpr/lpr lupus mice. Furthermore, the disease manifestations in MRLlpr/lpr lupus mice are efficiently improved by miR-7 antagomir, indicating miR-7 as a potential treatment strategy in SLE.

Comparative study of three-dimensional versus two-dimensional video-assisted thoracoscopic two-port lobectomy.

BACKGROUND: The advantages and disadvantages of three-dimensional (3D) and two-dimensional (2D) two-port video-assisted thoracoscopic surgery (VATS) lobectomy and systematic dissection of mediastinal lymph nodes for lung cancer were investigated. METHODS: Between December 2013 and July 2015 at Beijing Hospital, 191 patients underwent lobectomy and systematic dissection of mediastinal lymph nodes for lung cancer. After applying the study criteria, a total of 165 patients were included and allocated to 3D (n = 76) and 2D (n = 89) groups. Variables of the study design, including duration of surgery, volume of intraoperative bleeding, numbers and groups of lymph nodes dissected, drainage volume after surgery, duration of drainage tube insertion, hospitalization time after surgery, hospitalization costs, and complications, were recorded and analyzed. Intergroup differences for all data were compared and statistically analyzed. RESULTS: No statistical difference was found between the two groups with respect to duration of surgery, volume of intraoperative bleeding, drainage volume after surgery, duration of drainage tube insertion, hospitalization time after surgery, hospitalization costs, and complications ( P > 0.05). Additionally, there was no significant difference in the numbers and groups of all lymph nodes or N 2 lymph nodes resected ( P > 0.05). CONCLUSION: Lobectomy with systematic lymph node dissection can be undertaken with two ports using a 3D thoracoscope, and presents similar results to the use of a traditional 2D thoracoscope, at no greater hospitalization cost but with better operational perception and sensitivity during surgery. Two-port lobectomy with systematic lymph node dissection using a 3D thoracoscope is a safe and effective surgical process for lung cancer treatment.

A single-nucleotide polymorphism of CCL21 rs951005 T>C is associated with susceptibility of polymyositis and such patients with interstitial lung disease in a Chinese Han population.

OBJECTIVES: Our objective was to better understand the roles of single nucleotide polymorphisms (SNPs) in the CCL21, ERBB3, and TERT genes region in the development of idiopathic inflammatory myopathies (IIMs), we explored the associations between SNPs in the mentioned three genes and IIMs susceptibility in a Chinese Han population. METHODS: Chinese polymyositis (PM) patients (n =291), dermatomyositis (DM) patients (n=526) and ethnically-matched healthy controls (n =968) were genotyped for the CCL21 region SNPs (rs951005 and rs2492358), ERBB3 (rs2292239 and rs11171739), and TERT (rs2853676 and rs10069690), by using the Sequenom MassArray system. RESULTS: Our study indicated strong allele and genotype associations between rs951005 (OR: 1.65, 95%CI: 1.18-2.30, Pc=0.015; Pc=0.041, respectively) in CCL21 gene and PM patients. Additionally, rs951005 was associated with interstitial lung disease (ILD) in PM patients (Pc =0.01), and was associated with PM patients in additive model. However, the Chinese Han PM/DM patients and controls had statistically similar frequencies of alleles, genotypes and different genetic models (additive, dominant, and recessive) of ERBB3 and TERT polymorphisms. CONCLUSIONS: This was the first study to demonstrate that the CCL21 gene SNP (rs951005) might confer genetic predisposition to PM patients or such patients with ILD in a Chinese Han population.

Adamantiades-Behcet's disease-complicated gastroenteropathy.

Adamantiades-Behcet's disease (ABD) is a chronic, relapsing, systemic vasculitis of unknown etiology. It is more prevalent in populations along the ancient Silk Road from Eastern Asia to the Mediterranean Basin, and most frequently affects young adults between the second and fourth decades of life. ABD-complicated gastroenteropathy is a significant cause of morbidity and mortality, with abdominal pain as the most common symptom. The ileocecal region is affected predominantly, with ulcerations that may lead to penetration and/or perforation, whereas other parts of the gastrointestinal system including the esophagus and stomach can also be affected. Endoscopy is useful to locate the site and extent of the lesions, and tissue biopsy is often warranted to examine the histopathology that is often suggestive of underlying vasculitis of small veins/venules or, alternatively in some cases, nonspecific inflammation. Bowel wall thickening is the most common finding on computed tomography scan. Treatment is largely empirical since well-controlled studies are difficult to conduct due to the heterogeneity of the disease, and the unpredictable course with exacerbation and remission. Corticosteroids with or without other immunosuppressive drugs, such as cyclophosphamide, azathioprine, sulfasalazine, tumor necrosis factor α antagonist or thalidomide should be applied before surgery, except in emergency.

[An open-label, multicentric clinical trial to evaluate the efficacy and impact on bone metabolism of recombinant human tumor necrosis factor-α receptor II IgG Fc fusion protein with methotrexate in active rheumatoid arthritis: 24-week clinical and radiographic results from ReABLE study].

OBJECTIVE: To evaluate the efficacy, radiographic changes and safety of the combination of recombinant human tumor necrosis factor-α receptor II IgG Fc fusion protein (rhTNFR:Fc) and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: 30 RA patients were treated with rhTNFR:Fc (25 mg subcutaneously twice weekly) and oral MTX (up to 15 mg weekly) in an open-label manner. Clinical response was assessed by American College of Rheumatology (ACR) criteria and Disease Activity Score in 28 joints (DAS28). Radiographs of hands and wrist were assessed by the modified Sharp score. RESULTS: At Week 24, ACR20, ACR50 and ACR70 responses were achieved by 90%, 76.67% and 46.67% respectively. At Week 24, the mean DAS28 was 3.65 ± 1.26 versus 6.41 ± 0.61 at baseline (P < 0.001). And 20% patients achieved remission and 16.67% patients had a low disease activity. At week 24, EULAR good and moderate responses were attained by 36.67% and 60% respectively. Similarly, Health Assessment Questionnaire (HAQ) improved significantly, declining from 1.12 at baseline to 0.36 at week 24 (P < 0.001). No radiographic progression (based on change of total Sharp score) was found in 27 cases. Adverse events were mild. CONCLUSION: rhTNFR:Fc in combination with MTX shows an excellent efficacy of reduced disease activity, improved function and slowed radiographic progression through 24 weeks. A combination therapy for 24 weeks can lead to disease remission and an inhibition of radiographic progression. Further study is warranted.

[The diagnostic value of anti-SSA antibody in primary Sjögren's syndrome].

OBJECTIVE: According to international classification criteria (2002) on Sjögren's syndrome, labial pathology was still considered as a major criterion for diagnosis. Standard labial biopsy was hard to be carried out in China. This study is to evaluate whether the invasive labial biopsy could be replaced by noninvasive detection of serum anti-SSA antibody. METHODS: 181 Chinese patients with the initial diagnosis of primary Sjögren's syndrome in Peking Union Medical College Hospital (PUMCH) were enrolled in Sjögren's International Collaborative Clinical Alliance (SICCA). All patients received standard labial biopsies (area of salivary gland tissue ≥ 4 mm²) and focal score (FS) of focal lymphatic sialadenitis were confirmed by pathologists from school of stomatology, University California of San Francisco (UCSF). Anti-SSA antibodies in sera of all patients were detected by double immunodiffusion (DID), Western blot in PUMCH and by enzyme-linked immunosorbent assay (ELISA) in central laboratory of SICCA. The correlation between labial pathological findings and serum anti-SSA antibody was studied by chi² test and the concordance was calculated by unweighted Kappa. RESULTS: (1) Bivariate analysis revealed strong associations of FS > 1 with the presence of anti-SSA antibody by DID (83.9% vs 42.0%, P < 0.0001). The accordance between FS and antibody detection by DID was fine with a kappa value of 0.432. However, there were 16.1% false-positive antibody reports and 42.0% false-negative antibody reports. (2) FS > 1 was strongly associated with the presence of anti-SSA antibody by Western blot (83.0% vs 51.7%, P < 0.0001). But the accordance between FS and antibody detection by Western blot was only fair with a kappa value of 0.316. There were 17.0% false-positive antibody reports and 51.7% false-negative antibody reports. (3) FS > 1 was strongly associated with the presence of anti-SSA antibody by ELISA (81.5% vs 38.6%, P < 0.0001). The accordance between FS and antibody detection by ELISA was fine with a kappa value of 0.427. There were 18.5% false-positive antibody reports and 38.6% false-negative antibody reports. CONCLUSION: In Sjögren's syndrome, labial biopsy with FS > 1 finding is strongly associated with anti-SSA antibody. Positive results of anti-SSA antibodies by DID or ELISA may indicate FS > 1, thus labial biopsy could relatively be avoided, negative results may need further standard labial biopsy procedure to confirm the diagnosis of Sjögren's syndrome.

Cloning and characterization of a GABA receptor from Plutella xylostella (Lepidoptera: Plutellidae).

A full-length cDNA, with an open reading frame (ORF) of 1,449 bp, encoding a subunit of the gamma-aminobutyric acid (GABA)-activated chloride channel was isolated from Plutella xylostella (L.) (Lepidoptera: Plutellidae) (GenBank accession no. EF156251). The subunit gene encoded a 483-amino acid polypeptide that showed 84% sequence identity with DmRdl subunit (U02042) (Drosophila melanogaster resistant to dieldrin). When expressed in Xenopus laevis oocytes, the subunit assembled as a functional homomeric complex activated by GABA and abamectin in a dose-dependent manner. The EC50 value of GABA was 0.49 mM (0.41-0.58) (n = 5). However, the responses to abamectin were very robust, with an EC50 of 4.85 microM (4.02-5.89) (n = 6), indicating that abamectin was > 100-fold more potent in activating chloride currents than GABA. The results suggest that this subunit is vital to the formation of a functional channel and contains the binding site of abamectin.