[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[Malignant peripheral nerve sheath tumor: a clinicopathological analysis].

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

[Safety and efficacy of transcatheter aortic valve replacement using the "All in One" single artery/vessel technique].

Objective: To explore the safety and efficacy of transcatheter aortic valve replacement (TAVR) using the "All in One" single-artery/vessel technique. Methods: This is a retrospective study. A total of 30 consecutive patients underwent TAVR using the single artery/vascular technique in Beijing Anzhen Hospital from August to December 2021 were included. Baseline clinical data, operative situation, postoperative outcomes, and incidence of adverse events during hospitalization and at one month post TAVR were analyzed. Results: Mean age was (72.6±9.7) years, 16 were male patients, STS score was (4.73±3.12)%. Four patients were diagnosed as isolated aortic regurgitation (all with tricuspid aortic valves), and 26 patients were diagnosed as aortic stenosis (AS), 10 of whom with tricuspid aortic valves and 16 of whom with bicuspid aortic valves. The single-vessel technique was applied in 3 aortic stenosis cases; the single-artery technique was applied in 27 cases. Echocardiography was performed immediately after procedure and results showed no or trace perivalvular leak in 27 cases and small perivalvular leak in 3 cases; the mean aortic transvalvular gradient of 26 AS patients decreased from (50.4±16.0) mmHg (1 mmHg=0.133 kPa) to (9.4±3.2) mmHg (P<0.001). The procedure time was (64.8±18.9) min. There were no intraoperative death, valve displacement, conversion to surgery, coronary artery occlusion in all 30 patients. There were no major cardiac adverse events such as myocardial infarction or stroke occurred during hospitalization or at follow-up. One-month follow-up echocardiography indicated prosthesis works well. The symptoms were significantly alleviated, and the Kansas City Cardiomyopathy Score (KCCQ score) of all patients increased from 48.1±18.4 to 73.5±17.6 (P<0.001). Conclusions: TAVR using the single artery/vessel technique is safe and feasible. This technique is related to reduced access complications and worthy of wide application.

[Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR].

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

Implementation and evaluation of the public health emergency response to the 2019 outbreak of e-cigarette and vaping product use-associated lung injury in Massachusetts,USA.

OBJECTIVES: In 2019, an outbreak of e-cigarette/vaping product use-associated lung injury (EVALI) across the United States was responsible for acute harm, hospitalizations, and mortality among individuals using vape products, including youth and young adults. The objective of this study is to describe and evaluate the public health surveillance and emergency response activities that occurred in Massachusetts during the 2019 EVALI outbreak. STUDY DESIGN: Descriptive process and policy evaluation. METHODS: Between September and December 2019, the Massachusetts Department of Public Health temporarily removed access to e-cigarettes in stores, conducted tobacco retailer educational activities, and promoted tobacco cessation communications. The public health response was monitored through online adult panel surveys, in-school youth surveys, retailer compliance checks, and existing tobacco control program surveillance. RESULTS: Massachusetts residents indicated high awareness of the EVALI outbreak and the corresponding public health response. Tobacco retailers were compliant with the temporary state prohibition on the sale of e-cigarettes. In response to reduced access to vaping products in stores, both adult and youth survey respondents reported reduced use, increased quit attempts, or complete e-cigarette cessation. CONCLUSION: Emergency action undertaken by state public health programs and other governmental agencies corresponded with reduced availability of e-cigarettes and an increase in self-reported quit behaviors. Existing public health infrastructure at the state and local levels in Massachusetts facilitated an environment in which emergency and permanent protective measures could be implemented.

Janus kinase inhibitors for treating active ankylosing spondylitis: a meta-analysis of randomized controlled trials.

OBJECTIVE: In this study, we aimed to assess the safety and efficacy of Janus kinase (JAK) inhibitors in patients with ankylosing spondylitis (AS). METHODS: We conducted a Bayesian network meta-analysis using direct and indirect data from randomized controlled trials (RCTs), and examined the safety and efficacy of JAK inhibitors in active AS patients exhibiting inadequate response or intolerance to two or more non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: RCTs included a total of 406 patients (203 experimental subjects and 203 controls) from three studies on upadacitinib, filgotinib, and tofacitinib. Assessment of SpondyloArthritis International Society 20% improvement (ASAS20), ASAS40, and ASAS5/6 responses were significantly higher in the JAK inhibitor group than in the placebo group. Other efficacy outcomes, such as ASAS partial remission, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), Ankylosing Spondylitis Disease Activity Score (ASDAS), Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) scores, and Bath Ankylosing Spondylitis Functional Index (BASFI) were also significantly higher in the JAK inhibitor group compared to the placebo group. The JAK inhibitors significantly improved disease activity (ASAS partial remission, BASDAI50, ASDAS), function (BASFI), and MRI outcomes (SPARCC MRI spine). However, the incidence of adverse events (AEs) and serious adverse events (SAEs), and the rate of withdrawal attributed to AEs did not differ between the JAK inhibitor and placebo groups. CONCLUSION: JAK inhibitors were effective in active AS patients exhibiting an inadequate response or intolerance to two or more NSAIDs, without the risk of SAEs; this suggests that based on our data, studies are warranted to further investigate the use of JAK inhibitors for treating AS.

BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells.

BACKGROUND: The preservation of biological and physiological vitality as well as the formation of dentin are among the main tasks of human dental pulp for a life time. Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) exhibits the capacity of dental pulp regeneration and dentin complex rebuilding. Exploration of the mechanisms regulating differentiation and proliferation of hDPSCs may help to investigate potential clinical applications. BTB and CNC homology 1 (BACH1) is a transcription repressor engaged in the regulation of multiple cellular functions. This study aimed to investigate the effects of BACH1 on the proliferation and odontoblastic differentiation of hDPSCs in vitro. METHODS: hDPSCs and pulpal tissues were obtained from extracted human premolars or third molars. The distribution of BACH1 was detected by immunohistochemistry. The mRNA and protein expression of BACH1 were examined by qRT-PCR and Western blot analysis. BACH1 expression was regulated by stable lentivirus-mediated transfection. Cell proliferation and cell cycle were assessed by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine assay and flow cytometry. The expression of mineralization markers, alkaline phosphatase (ALP) activity and alizarin red S staining were conducted to assess the odontoblastic differentiation ability. RESULTS: BACH1 expression was stronger in the odontoblast layer than in the cell rich zone. The total and nuclear protein level of BACH1 during odontoblastic differentiation was downregulated initially and then upregulated gradually. Knockdown of BACH1 greatly inhibited cell proliferation, arrested cell cycle, upregulated the heme oxygenase-1 (HO-1) expression and attenuated ALP activity, decreased calcium deposits and downregulated the expression of mineralization markers. Treatment of Tin-protoporphyrin IX, an HO-1 inhibitor, failed to rescue the impaired odonto/osteogenic differentiation capacity. Overexpression of BACH1 increased cell proliferation, ALP activity and the expression of mineralization markers. CONCLUSIONS: Our findings suggest that BACH1 is an important regulator of the proliferation and odontoblastic differentiation of hDPSCs in vitro. Manipulation of BACH1 expression may provide an opportunity to promote the regenerative capacity of hDPSCs.

[Effect of rotigotine on the quality of emergence from general anesthesia in patients undergoing deep brain stimulation].

Objective: To investigate the effect of rotigotine on the quality of emergence from general anesthesia in patients undergoing deep brain stimulation (DBS). Methods: A total of 42 patients (31 males and 11 females, aged 55-85 years) undergoing DBS surgery under general anesthesia in the First Affiliated Hospital of Zhengzhou University from March 2020 to October 2021 were selected. The patients were divided into non-rotigotine group (n=21) and rotigotine group (n=21) by using a random number table according to whether rotigotine patch was used. Postoperative recovery time, extubation time, length of postanesthesia care unit (PACU) stay, and grades of muscle tension, swallowing function and salivary secretion during recovery were compared between the two groups. Meanwhile, the incidence of adverse events during extubation was also compared. Results: The postoperative recovery time, extubation time and length of PACU stay in rotigotine group were (20.3±2.6) min, (30.6±3.1) min and (46.4±3.9) min, respectively, which were shorter than those of non-rotigotine group [(29.0±5.8) min, (42.6±10.0) min and (63.0±18.9) min, respectively] (all P<0.05). The grades of postoperative muscle tension, swallowing function and salivary secretion in rotigotine group [M(Q1, Q3)] were 1(1, 2), 1(1, 2) and 1(1, 1), respectively, which were lower than those of non-rotigotine group [2(2, 3), 2(2, 2) and 2(1, 2), respectively] (P=0.001, 0.002 and 0.011). The incidence of adverse events during anesthesia extubation in rotigotine group was 14.3% (3/21), which was lower than that of non-rotigotine group [42.9% (9/21), P=0.040]. Conclusion: Rotigotin patch is helpful to improve the quality of emergence from general anesthesia in patients undergoing DBS and reduce the occurrence of adverse events during extubation.

[Chronic active Epstein-Barr virus infection in the gastrointestinal tract: a clinicopathological study of three cases].

Objective: To study the clinicopathological features of chronic active Epstein-Barr virus infection (CAEBV) in the digestive tract and to discuss its differential diagnosis. Methods: The clinical data of 3 cases of CAEBV in the digestive tract diagnosed in Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), Nanjing, China from December 2018 to August 2020 were collected. Three cases of CAEBV were evaluated using histology, immunohistochemistry and in situ hybridization. The related literature was reviewed. Results: Three patients were all males, aged 33, 32 and 31 years, respectively. All patients had a history of intermittent fever and repeated diarrhea for the past years with persistent increase in EB viral load (DNA copies) in peripheral blood. Endoscopically, intestinal tract was involved in all cases with ulcers, and esophagus was involved concurrently in 1 case showing nodular lesions. Microscopically, there were moderate polymorphic inflammatory infiltrate with lymphoid component displaying no or mild atypia in all cases and deep fissuring ulcers in one case (case 3). All tumor cells were positive for CD3 and TIA-1, and negative for CD56 and CD5. Cases 1 and 2 showed CD4-/CD8-, whereas case 3 displayed CD4+/CD8-. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in all 3 cases. Follow-up data showed that cases 1 and 2 were free of disease progression at the end of follow-up (16 months and 17 months, respectively). However, case 3 progressed to extranodal NK/T-cell lymphoma 22 months after the initial diagnosis. Conclusions: CAEBV of the digestive tract is a rare lymphoid proliferative disorder with potential transformation to extranodal NK/T-cell lymphoma. It is a great mimicker of inflammatory bowel disease, especially in small biopsy specimens. It is important to integrate clinicopathological, radiological and laboratory data to avoid misdiagnosis.

[Clinicopathological features of ectopic meningothelial hamartoma].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of ectopic meningothelial hamartoma (EMH). Methods: Three cases of EMH diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2020 were enrolled. All cases were evaluated by clinical and imaging features, HE and immunohistochemical staining, and the relevant literature was reviewed. Results: There were one male and two female patients, aged 2, 67 and 19 years, respectively. Clinically, they presented as skin masses in the head and face region (two cases) and sacro-coccygeal region (one case). Grossly, the lesions ranged in size from 1.6 cm to 8.9 cm. Microscopically, the lesions were ill-defined, and located in the dermis and subcutis, and showed pseudovascular channels lined by monolayer of cuboidal to flattened epithelium with mild atypia, with variable cystic cavity formation. There was prominent interstitial fibrosis. Concentric, lamellated, onion skin-like arrangement with short spindle or ovoid cells and psammoma bodies were noted. Immunohistochemically, these cells were strongly positive for SSTR2, EMA, vimentin and progesterone receptor. Ki-67 positive index was low, approximately 1%. Conclusions: EMH is uncommon. Definitive diagnosis relies on histopathologic examination. The importance in recognizing the lesions is to differentiate from other more aggressive tumors.

[Correlation of VISTA and PD-L1 expression with the clinicopathological features and prognosis in triple-negative breast cancer].

Objective: To investigate the expression of VISTA and PD-L1 in triple-negative breast cancer (TNBC) and to explore its relationship with clinicopathologic features and prognosis. Methods: Ninety TNBC patients who underwent surgical resections between 2016 to 2018 in Jiangsu Province Hospital were selected. The expression of VISTA and PD-L1 in both tumor cells and immune cells was evaluated by immunohistochemistry, and the relationship with clinicopathologic parameters and prognosis was analyzed. Results: VISTA was expressed in 17.8% (16/90) of the tumors. The expression of VISTA in tumor cells was related to a higher Ki-67 proliferation index (P=0.02) and higher number of tumor-infiltrating lymphocytes (TIL, P<0.01). VISTA was expressed in 71.1% (64/90) of the immune cells and the expression correlated with smaller tumor size (P=0.02), lower T stage (P=0.04), higher number of TIL (P<0.01), higher number of CD8+T cells (P=0.03) and higher Ki-67 proliferation index (P=0.02). PD-L1 was expressed in 17.8% (16/90) of the immune cells and the expression correlated with higher histologic grade (P=0.04), higher Ki-67 proliferation index (P=0.02) and higher number of TIL (P<0.01). VISTA expression was higher in immune cells within TNBC patients than PD-L1 (P<0.01). Among 90 TNBC patients, complete follow-up was obtained in 85 patients, 8 of whom had recurrences or metastasis after surgery, and two patients cases died of recurrences or metastasis. Conclusions: The expression rate of VISTA is higher than that of PD-L1 in TNBC. The expression of VISTA in immune cells predicts a lower T stage. VISTA may act as an effective immunotherapy target.

[CIC-rearranged sarcoma with rhabdoid features: a clinicopathological analysis].

Objective: To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of CIC-rearranged sarcoma (CRS) with rhabdoid features. Methods: The clinical and pathologic data of two cases of CRS diagnosed between 2019 and 2021 at the Department of Pathology, Jiangsu Province Hospital were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The relevant literature was reviewed. Results: Both patients were female, one was 58 years old, with tumor located in left thigh; the other was 43 years old, with tumor located in left pelvic cavity. Microscopically, both tumors were composed of small to medium-sized round, oval cells, arranged in nodules or sheets. The tumor cells showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Both cases showed rhabdoid phenotype with myxoid stromal changes. Immunohistochemically, both cases were positive for CD99 and c-myc. High WT1 reactivity was seen in classic area, with low reactivity in rhabdoid area. There was no INI1 lost in both cases. Both were negative for NKX2.2 and NKX3.1. By FISH both cases demonstrated convincing break-apart signals of CIC gene. One patient died of disease after 1 month, and the other died of disease after 3 months. Conclusions: CRS is a small round cell undifferentiated sarcoma of the bone and soft tissue defined by molecular genetic characteristics, and may show atypical morphologic and immunophenotypic characteristics such as rhabdoid features. A correct understanding of its rare morphologic and immunophenotypic characteristics, combined with molecular pathologic detection, is conducive to correct diagnosis.

[Preliminary evaluation on the efficacy of emergency transcatheter aortic valve replacement: a multicenter study].

Objectives: To explore the efficacy and safety of emergency transcatheter aortic valve replacement (TAVR). Methods: Data of patients who underwent emergency TAVR in eight centers, namely Fuwai Hospital, Wuhan Asia Heart Hospital, Xijing Hospital, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Zhengzhou University, the Second Xiangya Hospital of Central South University, between May 2017 and December 2020 were retrospectively analyzed. The use of mechanical circulatory support system (MCS) and the results of laboratory tests (N-terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography (mean aortic valve cross valve pressure difference and left ventricular ejection fraction) before and after operation were collected. The primary endpoint was all-cause death, and the secondary endpoints were stroke, major bleeding, major vascular complications, myocardial infarction, permanent pacemaker implantation, and acute renal injury. Device success was caculated, which refered to absence of procedural mortality and correct positioning of a single prosthetic heart valve into the proper anatomical location and intended performance of the prosthetic heart valve (mean aortic valve gradient<20 mmHg(1 mmHg=0.133 kPa) or peak velocity<3 m/s, with no moderate or severe prosthetic valve regurgitation). Kaplan-Meier survival curve was used to estimate the survival rate of patients during follow-up. Results: This study included 48 patients. The age was (72.5±8.1) years, and 34 patients were males (70.8%). Device success rate was 91.7% (44/48). The mean aortic valve transvalvular pressure was significantly decreased after operation ((12.3±6.4)mmHg vs. (60.2±23.8)mmHg, P<0.000 1). Left ventricular ejection fraction was significantly increased ((41.5±11.7)% vs. (31.0±11.3)%, P<0.000 1). NT-proBNP significantly decreased (3 492.0 (1 638.8, 7 165.5) ng/L vs. 12 418.5 (6 693.8, 35 000.0) ng/L, P<0.000 1). In-hospital all-cause mortality was 8.3% (4/48). During hospitalization, the rate of stroke was 2.1% (1/48), major bleeding was 6.3% (3/48), major vascular complications was 10.4% (5/48), myocardial infarction was 4.2% (2/48), permanent pacemaker implantation was 6.3% (3/48), and the rate of acute renal injury was 12.5% (6/48). MCS was used in 20 patients (41.7%). The median follow-up time was 196 days. During the follow-up, one patient died (due to systemic metastasis of pancreatic cancer), two cases suffered new myocardial infarction and one case received permanent pacemaker implantation. The survival rate of 30 days, 1 year and 2 years after the operation were 91.7% (44/48), 89.6% (43/48), 89.6% (43/48), respectively. Conclusion: Emergency TAVR may be a safe and effective treatment for patients with severe decompensated aortic valve stenosis.

[Single center experience of transcatheter aortic valve replacement with a simplified operative protocol].

Objective: To summarize the single center experience of transcatheter aortic valve replacement (TAVR) with a simplified operative protocol. Methods: Consecutive patients who underwent transfemoral TAVR (TF-TAVR) from July 2020 to December 2020 in Fuwai Hospital were retrospectively analyzed. We compared the baseline characteristic, procedure information, 30-day follow-up outcomes of the patients who underwent TF-TAVR without the simplified operative protocol (routine group) or with the simplified operative protocol (simplified protocol group). Results: 93 patients were collected, 42 patients belonging to routine group, 51 patients belonging to simplified protocol group. In simplified protocol group, there were 51 patients planned to use ultrasound-guided femoral access puncture, procedure was successful in all 51 patients (100%). There were 49 patients planned to use the radial artery as the secondary access, procedure was successful in 45 patients (92%). There were 48 patients planned to use the strategy of avoidance of urinary catheter, this strategy was achieved in 35 patients (73%). There were 12 patients planned to use the left ventricular guidewire to pace, procedure was successful in 11 patients (92%). There were no differences in baseline characteristics, major clinical endpoints and 30-day follow-up outcomes between the two groups. Meanwhile, the procedure time ((62.5±17.9)min vs. (78.3±16.7)min, P<0.001), operation room time ((133.7±25.1)min vs. (159.2±42.6)min, P<0.001), X-ray exposure time ((17.2±6.5)min vs. (20.2±7.7)min, P=0.027) were significantly shorten in simplified protocol group compared with the routine group. Conclusion: Our study results indicate that the simplified operative protocol of TF-TAVR is as effective and safe as the routine operative protocol, meanwhile using the simplified operative protocol can significantly increase the operative efficiency of TF-TAVR.

[Initial clinical experience of left bundle branch pacing after transcatheter aortic valve implantation].

Objective: To investigate the efficacy and safety of left bundle branch pacing(LBBP) in patients after transcatheter aortic valve implantation (TAVI). Methods: This is a retrospective study. A total of 35 patients underwent TAVI and received pacemaker implantation from January 2018 to December 2020 in Beijing Fuwai Hospital were enrolled. Patients were divided into LBBP group (n=12) and right ventricular apex pacing (RVAP) group (n=23) according to the pacing position. The success rate of operation in LBBP group was calculated, and the occurrence of complications were observed, and the parameters of pacemaker were measured on the 3rd day and 1, 3 and 6 months after operation. The N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiographic and ECG indexes were compared between the two groups on the 3rd day and 1, 3, and 6 months after pacemaker implantation. Result: A total of 35 patients were included, The age was (76.4±7.7) years, including 19 males (54.3%). The procedure time ((86.58±17.10)min vs. (68.74±9.18)min, P<0.001) and fluoroscopy duration ((20.08±4.44)min vs. (17.00±2.26)min, P<0.001) were significantly longer in LBBP group compared with RVAP group. The operation success rate of LBBP group was 11/12. There was no serious operation related complications such as pneumothorax, hemothorax, electrode dislocation, infection, and lower limb bleeding. The patients were followed up for 7.43 (5.21, 9.84) months. The programmed parameters of pacemaker were in the ideal range and stable during follow-up. At 3 and 6 months after operation, the left ventricular ejection fraction in LBBP group was higher than that in RVAP Group (at 3 months: (60.75±2.89)% vs. (57.35±3.33)%, P=0.004; at 6 months: (63.17±3.33)% vs. (56.17±3.97)%, P<0.001), NT-proBNP values was lower in LBBP group than that in RVAP Group (at 3 months: 822 (607, 1 150)ng/L vs. 1 052 (902, 1 536)ng/L, P=0.006; at 6 months: 440 (330,679)ng/L vs. 783 (588, 1 023)ng/L, P=0.001). At 1, 3 and 6 months after operation, the QRS duration was shorter in LBBP group than that in RVAP group (1 month: 99 (97, 107)ms vs. 126(124, 130)ms, P<0.001; 3 months: 98(96, 105)ms vs. 129(128, 133)ms, P<0.001; 6 months: 96(94, 104)ms vs. 130(128, 132)ms, P<0.001). Conclusions: For patients with permanent pacemaker indications after TAVI, LBBP is feasible, safe and reliable. It could improve the cardiac function in the short term, the long-term effect of LBBP needs to be further observed.

Anifrolumab for the treatment of active systemic lupus erythematosus: a meta-analysis of randomized controlled trials.

We surveyed randomized controlled trials (RCTs) examining the efficacy and safety of anifrolumab 300 mg in patients with active systemic lupus erythematosus (SLE) despite receiving standard therapy, using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis performed to determine treatment efficacy and safety outcomes of three RCTs (459 patients and 468 controls) revealed that the BICLA responses were significantly higher in the anifrolumab group than in the placebo group (OR = 2.071, 95%CI 1.575-2.725, p < 0.001). Steroid reduction and CLASI reduction were also significantly higher in the anifrolumab group than in the placebo group (OR = 1.811, 95%CI = 1.308-2.506, p < 0.001; OR = 2.245, 95%CI = 1.437-3.506, p < 0.001). Compared with placebo, anifrolumab significantly increased the SRI7 and SRI8 responses in SLE patients (OR = 1.866, 95%CI = 1.372-2.536, p < 0.001; OR = 1.925, 95%CI = 1.387-2.672, p < 0.001). The SRI4, 5, and 6 responses also tended to be higher in the anifrolumab group than in the placebo group. Adverse event incidence was significantly higher in the anifrolumab group than in the placebo group (OR = 1.815, 95%CI = 1.262-2.611, p = 0.001); serious adverse events were significantly lower in the anifrolumab group than in the placebo group (OR = 0.679, 95%CI = 0.468-0.986, p = 0.042). Herpes zoster infection was significantly higher in the anifrolumab group than in the placebo group (OR = 4.089, 95%CI = 1.750-9.522, p = 0.001). Anifrolumab is effective for treating active SLE. However, anifrolumab increased the incidence of herpes zoster infection compared with placebo.

Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs.

OBJECTIVE: The relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib were assessed in patients with rheumatoid arthritis (RA) with inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in RA patients with inadequate responses to bDMARDs. RESULTS: Four RCTs comprising 1399 patients met the inclusion criteria. Tofacitinib, baricitinib, upadacitinib, and filgotinib achieved significant American College of Rheumatology 20% (ACR20) responses versus placebo. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by filgotinib 200 mg, baricitinib 4 mg, filgotinib 100 mg, tofacitinib 5 mg, and placebo. The ranking in SUCRA based on the ACR50 response rate indicated that baricitinib 4 mg had the highest probability of achieving the ACR50 response rate, followed by filgotinib 200 mg, tofacitinib 5 mg, upadacitinib 15 mg, filgotinib 100 mg, and placebo. Tofacitinib 5 mg showed a significantly higher ACR70 response rate than filgotinib 100 mg and upadacitinib 15 mg. Tofacitinib 5 mg, filgotinib 200 mg, and placebo showed a significantly lower serious adverse event rate than upadacitinib 15 mg. CONCLUSION: Tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for RA patients with an inadequate response to bDMARDs but with different efficacy and safety profiles.

Circulating interleukin-23 levels in ankylosing spondylitis and their correlation with disease activity : A meta-analysis.

OBJECTIVE: To systematically investigate the relationship between circulating interleukin-23 (IL­23) levels and ankylosing spondylitis (AS) and establish a correlation between these hematological indices and AS activity/severity. METHODS: We searched the Medline, Embase, and Cochrane databases; performed a meta-analysis comparing serum/plasma IL­23 levels in patients with AS to those of controls; and examined the correlation coefficients between serum/plasma IL­23 levels and AS activity. RESULTS: Ten studies including 1724 patients with AS and 1589 controls were included in this meta-analysis. This meta-analysis showed that circulating IL­23 levels were significantly higher in the AS than in the control group (standardized mean difference [SMD] 1.479; 95% confidence interval [CI] 0.308-2.650; p = 0.013). Stratification by ethnicity showed a significantly increased IL­23 level in the AS group in an Asian population (SMD 1.551; 95% CI 0.543-2.558; p = 0.003). Stratification by adjustment for age and sex revealed significantly higher IL­23 levels in the AS adjustment group. Subgroup analysis of sample size showed a significantly higher IL­23 level for a small (n < 150) sample number in the AS group. Meta-analysis of correlation coefficients revealed that the IL­23 level was positively associated with the Bath Ankylosing Spondylitis Metrology Index (BASMI; correlation coefficient 0.464; 95% CI 0.027-0.752; p = 0.038), erythrocyte sedimentation rate (ESR; correlation coefficient 0.258; 95% CI 0.076-0.422; p = 0.006), and C­reactive protein (CRP; correlation coefficient 0.291; 95% CI 0.053-0.498; p = 0.017). CONCLUSION: This meta-analysis demonstrated that the circulating IL­23 level is significantly higher in patients with AS, and a significant positive correlation exists between the circulating IL­23 level and BASMI, ESR, and CRP.

Comparative efficacy and safety of mycophenolate mofetil versus cyclophosphamide in patients with active antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of randomized trials.

OBJECTIVE: This study aimed to assess the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) in patients with active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We performed a meta-analysis of four randomized clinical trials (RCTs; 300 patients) to examine the relative efficacy and safety of MMF compared to CYC in patients with active AAV. RESULTS: There was no significant difference in remission at 6 months between MMF and CYC (odds ratio [OR] 1.311, 95% confidence interval [CI] 0.570-3.017, P = 0.524). Additionally, the relapse rate did not differ between the MMF and CYC groups (OR 1.331, 95% CI 0.497-3.568, P = 0.570). There was no significant difference in serious adverse event (SAE; OR 1.232, 95% CI 0.754-2.014, P = 0.404) and infection rates (OR 0.958, 95% CI 0.561-1.634, P = 0.873) between the MMF and CYC groups. Some heterogeneity was found in the meta-analysis of remission and relapse rates (I2 = 57.4%, 63.4%), but no between-study heterogeneity was found during the meta-analysis of SAE and infection rate. Egger's regression test showed no evidence of publication bias (Egger's regression test P-values >0.1). CONCLUSION: MMF was an equally effective alternative treatment to CYC and MMF was comparable to CYC in patients with active AAV in terms of safety, suggesting that MMF can be used as an alternative to CYC for remission induction in AAV.

Comparative efficacy and safety of secukinumab and ixekizumab in patients with active ankylosing spondylitis.

OBJECTIVE: Evaluation of the effectiveness and safety of secukinumab and ixekizumab in active ankylosing spondylitis (AS) patients. METHODS: A Bayesian network meta-analysis was conducted using direct and indirect data from five randomized controlled trials that examined the efficacy and safety of secukinumab 150 mg every 4 weeks and ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) in active AS patients. RESULTS: Data from 1433 patients were analyzed. The Assessment of Spondyloarthritis International Society evaluation 20% response rates (ASAS20) were significantly higher with secukinumab 150 mg, IXEQ2W, IXEQ2W, and adalimumab 40 mg (odds ratio [OR] 2.75, 95% Bayesian credible interval [CrI] 2.04-3.69; OR 2.59, 95% CrI 1.69-3.98; OR 2.45, 95% CrI 1.60-3.75; and OR 1.94, 95% CrI 1.13-3.37, respectively) compared to the placebo group. Efficacies of secukinumab and ixekizumab were numerically higher compared to adalimumab 40 mg, although there was no significant difference in the ASAS20 response rates. The ASAS40 response rate showed a pattern of distribution similar to the ASAS20 response rate, with the exception of the ixekizumab group, which was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ASAS40 response rate. Based on the SUCRA rating, secukinumab 150 mg had the highest probability of being the best ASAS20 response rate therapy, followed by IXEQ2W, IXEQ4W, adalimumab 40 mg, and placebo. There was no significant difference between the treatments regarding the number of serious adverse events (SAEs). CONCLUSION: Secukinumab and ixekizumab were effective in active AS treatment, without the risk of SAEs.