The "blownknee" patient's stress fracture of distal tibial component after unilateral TKA: A case report.

RATIONALE: Periprosthetic fractures (PPF) are rare complications of total knee arthroplasty (TKA). The most common PPF after TKA is supracondylar femoral fracture, which is a relatively rare complication that is usually associated with high-energy trauma, with a reported incidence ranging from 0.4 to 1.7% according to the AOANJRR. However, in TKA patients, it is rarer that the stress fracture around the tibial prosthesis occurs due to changes in the lower limb force line, increasing weight-bearing, and changes in walking gait. PATIENT CONCERNS: A 68-year-old woman visited our hospital with "both knees had aggravated pain and deformity for 8 years." TKA was performed first on the left knee and the patient was discharged within 1 week. Three months later, the patient complained of pain in the upper middle 1/3 part of the medial tibia for 2 weeks, which gradually worsened and affected weight-bearing. DIAGNOSES: Physical examination showed that the left knee joint presented varus deformity, and the right valgus deformity, which diagnosed as osteoarthritis of both knees and was so-called "blownknee". The disease was initially diagnosed as osteoarthritis of both knees on first admission and PPF of the tibia in second. INTERVENTIONS: Three operations were performed on this patient. The first was TKA of the left knee, the second was open reduction and internal fixation of the PPF of the tibia 3 months after the first operation, and the third was TKA of the right knee. OUTCOMES: Until now, the patient has had no recurrent PPF, and the fracture is healing from the last X-ray. LESSONS: Clinicians should be aware of the possibility of PPF after TKA, especially in such patients, the most preferred surgical treatment method was open reduction and internal fixation of fractures using locking plates, and if the PPF with loosened implants, Revision TKA, or megaprosthesis was the better choice.

A five-year follow-up clinical study of the B cell maturation antigen chimeric antigen receptor-T cell therapy HDS269B in patients with relapsed or refractory multiple myeloma.

PURPOSE: This study aimed to report the five-year clinical outcomes of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in relapsed/refractory multiple myeloma (RRMM) patients, including those with poor performance status (Eastern Cooperative Oncology Group [ECOG] 3-4), and to identify factors influencing long-term outcomes. METHODS: Forty-nine RRMM patients enrolled from 2016 to 2020 received HDS269B (9×106 cells/kg) after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics. RESULTS: With a median follow-up of 59.0 months, the overall response rate was 77.55%. The median progression-free survival (PFS) and overall survival (OS) were 9.5 months (95% confidence interval [CI], 5.01-13.99) and 20.0 months (95% CI, 11.26-28.74), respectively. The 5-year PFS and OS rates were 21.3% (95% CI, 12.3%-36.7%) and 34.1% (95% CI, 22.7%-51.3%), respectively. Patients with ECOG 0-2 had marked longer survival, with a median PFS of 11.0 months and median OS of 41.8 months. Early minimal residual disease negativity, and higher and persistent CAR-T cell expansion and absence of extramedullary disease were associated with better survival outcomes. No new CAR-T cell therapy associated toxicities were observed. Importantly, ECOG 0-2, prior therapy lines <4, and CAR-T cell persistence at ≥6 months were independently associated with longer OS. CONCLUSIONS: HDS269B is effective and safe, especially for patients with ECOG 0-2. Early CAR-T cell intervention may improve prognosis in patients with RRMM.

Correlation between computed tomography-based body composition parameters and hepatic venous pressure gradient in patients with cirrhosis: a systematic review and meta-analysis.

PURPOSE: Computed tomography (CT)-based body composition parameters and the hepatic venous pressure gradient (HVPG) are key characteristics in patients with liver cirrhosis. The present study aims to explore the correlation between CT-based body composition parameters and HVPG, as well as the difference in HVPG between patients with and patients without sarcopenia. METHODS: A literature search for studies reporting the correlation between HVPG and CT-based body composition parameters published in English up to August 2023 in four databases, Embase, MEDLINE (via PubMed), Web of Science, and Cochrane Library, was conducted. The correlation coefficient between HVPG and CT-based body composition parameters was the primary outcome, and the difference in the HVPG value between the sarcopenia and non-sarcopenia groups was the secondary outcome. A meta-analysis was conducted using a random-effects models. The methodologic quality was assessed using the Quality Assessment of Diagnostic Studies instrument. RESULTS: A total of 652 articles were identified, of which nine studies (n = 1,569) met the eligibility criteria. Among them, seven studies reported the primary outcome via the muscle index, five via the skeletal muscle index (SMI), two via the psoas-muscle-related index (PRI), and three via two adipose tissue indexes. A total of five studies reported the secondary outcome: four via SMI and one via PRI. No evidence of a significant correlation was determined between the various body composition parameters and the HVPG value, either in the muscle index or the adipose tissue index. Higher HVPG values were observed in patients with sarcopenia than in patients without sarcopenia [pooled standardized mean difference (SMD): 0.628 (-0.350, 1.606), P < 0.001; I2 = 92.8%; P < 0.001] when an Asian sarcopenia definition was adopted. In contrast, when a Western cut-off value was applied, the HVPG value was higher in patients without sarcopenia than in patients with sarcopenia [pooled SMD: -0.201 (-0.366, -0.037), P = 0.016; I2 = 0.00%; P = 0.785]. CONCLUSION: No sufficient evidence regarding a correlation between the CT-based body composition and HVPG value was discovered. The difference in the HVPG value between the sarcopenia and non-sarcopenia groups was likely dependent on the sarcopenic cut-off value.

The predictive value of four traumatic hemorrhage scores for early massive blood transfusion in trauma patients in the pre-hospital setting.

OBJECTIVES: We aimed to explore the predictive value of four traumatic hemorrhage scores for early massive blood transfusion in trauma patients in the pre-hospital setting. METHODS: Trauma patients admitted to Shenzhen University General Hospital from July 2018 to December 2022 were included in this study. They were divided into the massive transfusion group and the non-massive transfusion group according to the blood transfusion volume within 24 h. Basic information about patients was collected. Glasgow Coma Scale (GCS), focused assessment with sonography for trauma (FAST), and injury severity score (ISS) were performed. The receiving operating characteristic (ROC) curve was used to compare the predictive value of four trauma transfusion scores for early massive blood transfusion in the pre-hospital setting. RESULTS: A total of 475 patients were enrolled, 43 received massive blood transfusions and 29 died within 24 h. The sensitivity and specificity of the four trauma hemorrhage scores in predicting the need for massive blood transfusions in trauma patients at their recommended cutoff points were all high. Among the four scores, the area under the ROC curve was larger for the assessment of blood consumption (ABC) score (0.864) and smaller for the trauma-induced coagulopathy clinical score (TICCS) score (0.795, p > 0.05). CONCLUSIONS: All four pre-hospital trauma hemorrhage scores have a high predictive value in assessing massive blood transfusion in trauma patients.

Unmanned aerial vehicle based intelligent triage system in mass-casualty incidents using 5G and artificial intelligence.

BACKGROUND: Rapid on-site triage is critical after mass-casualty incidents (MCIs) and other mass injury events. Unmanned aerial vehicles (UAVs) have been used in MCIs to search and rescue wounded individuals, but they mainly depend on the UAV operator's experience. We used UAVs and artificial intelligence (AI) to provide a new technique for the triage of MCIs and more efficient solutions for emergency rescue. METHODS: This was a preliminary experimental study. We developed an intelligent triage system based on two AI algorithms, namely OpenPose and YOLO. Volunteers were recruited to simulate the MCI scene and triage, combined with UAV and Fifth Generation (5G) Mobile Communication Technology real-time transmission technique, to achieve triage in the simulated MCI scene. RESULTS: Seven postures were designed and recognized to achieve brief but meaningful triage in MCIs. Eight volunteers participated in the MCI simulation scenario. The results of simulation scenarios showed that the proposed method was feasible in tasks of triage for MCIs. CONCLUSION: The proposed technique may provide an alternative technique for the triage of MCIs and is an innovative method in emergency rescue.

Paclitaxel inhibits hepatocellular carcinoma tumorigenesis by regulating the circ_0005785/miR-640/GSK3ß.

Paclitaxel (PTX) is an effective chemotherapeutic agent for cancer patients. It has been reported that circular RNA (circRNA) circ_0005785is involved in the progression of hepatocellular carcinoma (HCC). The purpose of this study is to explore the role and mechanism of circ_0005785 in the PTX resistance of HCC. Cell viability, proliferation, invasion, migration, apoptosis, and angiogenesis were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, transwell, wound-healing, flow cytometry, and tube formation assay. Circ_0005785, microRNA-640 (miR-640), and Glycogen synthase kinase-3 beta (GSK3ß) levels were detected using real-time quantitative polymerase chain reaction. Protein levels of Proliferating cell nuclear antigen (PCNA), Bcl-2, and GSK3ß were measured using western blot assay. After being predicted using Circular RNA interactome or TargetScan, binding between miR-640 and circ_0005785 or GSK3ß was verified using dual-luciferase reporter and RNA Immunoprecipitation assay. PTX treatment could repress HCC cell viability, decrease circ_0005785 and GSK3ß expression, and increase the miR-640 level in HCC cell lines. Furthermore, circ_0005785 and GSK3ß were increased, and miR-640 was decreased in HCC tissues and cell lines. Moreover, circ_0005785 knockdown hindered proliferation, migration, invasion, angiogenesis, and boosted apoptosis in PTX-treated HCC cells in vitro. In addition, circ_0005785 silencing improved the PTX sensitivity of HCC in vivo. Mechanistically, circ_0005785 acted as a sponge of miR-640 to regulate GSK3ß expression. PTX restrained HCC tumorigenesis partly via regulating the circ_0005785/miR-640/GSK3ß axis, hinting at a promising therapeutic target for the HCC treatment.

The association between iron metabolism with the change of blood pressure and risk of hypertension: A large cross-sectional study.

BACKGROUND: The relationship between iron metabolism and variations in blood pressure and hypertension risk is still not clear. This study aimed to determine whether iron metabolism is associated with changes in blood pressure and hypertension prevalence in the general United States population. METHODS: The National Health and Nutrition Examination Survey (NAHNES) database contains data on 116876 Americans from 1999 to 2020 years. Data from the NHANES database were used to examine the relationships between iron metabolism (serum iron [SI], serum ferritin [SF], and soluble transferrin receptor [sTfR]) and changes in blood pressure and hypertension prevalence. Generalized linear models and restricted cubic spline (RCS) plot curves were used to estimate the relationship between iron metabolism and hypertension. Further, generalized additive models with smooth functions were used to identify the relationship between iron metabolism and blood pressure. Finally, a stratified subgroup analysis was performed. RESULTS: A total of 6710 participants were included in our analysis. The RCS plot showed a linear relationship between SI, as well as sTfR, and hypertension prevalence. SF and hypertension prevalence were associated in a J-shape. In addition, the relationship between SI and systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased initially and then increased. A correlation between SF, SBP, and DBP first decreased, then increased, and finally decreased. A positive linear correlation existed between sTfR and SBP, but it increased and then decreased with DBP. CONCLUSION: The correlation between SF and hypertension prevalence displayed a J-curve. In contrast, the correlation between SI, as well as sTfR, and hypertension risk was negative and positive, respectively.

Safety and efficacy of transcatheter arterial embolization for management of refractory hematuria of prostatic origin.

Objective: To estimate the safety and efficacy of transcatheter arterial embolization (TAE) in the treatment of refractory hematuria of prostatic origin (RHPO). Methods: This retrospective study included 23 patients who underwent TAE for RHPO between May 2013 and August 2021. Technical and clinical success rates were calculated, and arteriogram findings and complications were detected. Results: Embolization was performed 24 times in 23 patients. Technical success was achieved in 24/24 (100%) embolization procedures. Contrast agent extravasation was detected during 2 of the 24 angiographic procedures. Bilateral embolization was performed in 23 (95.8%) of the 24 procedures. The clinical success rate was 21/23 (91.3%), and hematuria stopped 1-4 days after TAE. No serious complications were observed. Conclusion: TAE is a safe and effective minimally invasive technique for treating patients with RHPO.

Long-term outcomes of transarterial embolization with lipiodol-bleomycin emulsion plus polyvinyl alcohol particles versus the particles alone for large symptomatic focal nodular hyperplasia: a propensity score-matched analysis.

OBJECTIVES: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH). METHODS: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ2 test. RESULTS: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019). CONCLUSION: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms. KEY POINTS: • Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). • No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups.

CAR-T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status.

In this open-label, single-arm, phase I/II clinical trial, we evaluated the efficacy of anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in 49 relapsed/refractory multiple myeloma (RRMM) patients, including 20 with Eastern Cooperative Oncology Group (ECOG) grade 3-4. After HDS269B infusion (9 × 106 CAR+ cells/kg), 17 patients (34.69%, 11 ECOG 0-2, 6 ECOG 3-4) developed cytokine release syndrome [grade 1-2: 14 patients (28.57%); grade 3: 3 patients (6.12%)]. The objective response rate (ORR) was 77%, with a complete response (CR) achieved in 47%. Ongoing response >12 months occurred in 15 patients, and was extended beyond 38 months in one patient. The median progression-free survival (PFS) and overall survival (OS) were 10 months (95% CI 5.3-14.7) and 29 months (95% CI 10.0-48.0), respectively. The PFS (12 months) and OS (18 months) rates were 41.64% and 62.76%, respectively. In patients with ECOG 0-2 and 3-4, ORR was 79.31% (23/29) and 75.0% (15/20) and PFS were 15 months (95% CI 5.4-24.6) and 4 months (95% CI 0-11.7), respectively. OS was not reached in ECOG 0-2 patients, but was 10.5 months (95% CI 0-22) in ECOG 3-4 patients. Single-cell sequencing indicated that treatment efficacy might be related to mTORC1 signaling. Thus, HDS269B therapy is safe and effective for RRMM patients, even those with ECOG 3-4.

Long noncoding RNA SNHG1 silencing accelerates hepatocyte-like cell differentiation of bone marrow-derived mesenchymal stem cells to alleviate cirrhosis via the microRNA-15a/SMURF1/UVRAG axis.

Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to attenuate cirrhosis. Long noncoding RNA (lncRNA) SNHG1 has been demonstrated to orchestrate BMSC differentiation, whereas its role in cirrhosis remains elusive. Therefore, this study was performed to figure out whether lncRNA SNHG1 was involved in cirrhosis by affecting HLC differentiation of BMSCs. Mouse BMSCs were isolated, and the BMSC differentiation into HLCs was induced by hepatocyte growth factor (HGF). A cirrhotic mouse model was established using carbon tetrachloride and phenobarbital, followed by intravenous injection of BMSCs with manipulated expression of lncRNA SNHG1, microRNA (miR)-15a, and SMURF1. Subsequent to HGF induction, expression of hepatocyte-related genes, albumin secretion, and glycogen accumulation was increased in BMSCs, suggesting the differentiation of BMSCs into HLCs. Mechanistically, lncRNA SNHG1 bound to miR-15a that targeted SMURF1, and SMURF1 diminished ATG5 and Wnt5a expression by enhancing the ubiquitination of UVRAG. LncRNA SNHG1 or SMURF1 silencing or miR-15a overexpression promoted differentiation of BMSCs into HLCs and repressed cirrhosis of mice by upregulating ATG5 and Wnt5a via UVRAG. Conclusively, lncRNA SNHG1 silencing might facilitate HLC differentiation from mouse BMSCs and alleviate cirrhosis via the miR-15a/SMURF1/UVRAG/ATG5/Wnt5a axis.

Comparison of long-term outcomes of balloon angioplasty with or without stent placement for hepatic vein type Budd-Chiari syndrome.

PURPOSE: To compare percutaneous transluminal balloon angioplasty (PTBA) alone with PTBA plus stent placement for Budd-Chiari syndrome (BCS) patients with short-segmental obstruction of hepatic vein. METHODS: Between May 2001 and December 2010, 91 hepatic vein type BCS patients (mean age, 32.8 ± 10.8; M:F ratio 50:41) were included and divided into two groups (PTBA alone, as group A, n = 48; PTBA plus stent, as group B, n = 43). The incidence of restenosis, long-term patency, and survival were evaluated. RESULTS: All 91 patients were successfully treated with hepatic vein recanalization. During follow-up period (median 161 months, range: 84-234), group B had a significantly higher proportion of hepatic vein restenosis (56%, 24/43) than group A (33%, 16/48; P < 0.05). Cumulative primary patency rates at 1, 5, 10, 15 years were 96%, 81%, 69%, 65% and 91%, 60%, 47%, 47% in group A and group B, respectively (log-rank P < 0.05). Secondary technical success rates of target hepatic vein were 93% and 57% in group A and group B, respectively (P < 0.05). Clinical complete response rates were 94% and 86% in group A and group B, respectively (P > 0.05). The 15-year cumulative survival rates were 98% and 95% in group A and group B, respectively (P > 0.05). Major procedure-related complications occurred in 3 (3%) patients (1 in group A, 2 in group B). CONCLUSIONS: Hepatic vein recanalization is safe and efficient for hepatic vein type BCS patients with hepatic vein short segmental obstruction. Restenosis after hepatic vein stenting is more common and difficult to manage than that after hepatic vein balloon angioplasty alone.

Long-term outcomes of individualized interventional treatment for primary Budd-Chiari syndrome complicated by inferior vena cava thrombosis.

BACKGROUND: Various endovascular treatments were used for Budd-Chiari syndrome (BCS) patients complicated by inferior vena cava (IVC) thrombosis. The best treatment for this disease remains unknown. To evaluate safety and efficacy of individualized interventional treatment for primary BCS with IVC thrombosis. METHODS: Forty-seven consecutive patients with IVC involvement BCS complicated by IVC thrombosis between June 2002 and August 2020 were analyzed retrospectively. They were treated with individualized interventional treatment based on thrombus type and size. Agitation thrombolysis, transcatheter thrombus aspiration, and catheter-directed thrombolysis were initially used for fresh and mixed thrombus (n = 20), then stent implantation for compressing thrombus and IVC recanalization were performed according to the size of the residual thrombus. Direct balloon angioplasty was used for old thrombus (n = 27). RESULTS: Median follow-up duration was 109 (5-223) months (average 114 ± 60 months). IVC recanalization were attempted in forty patients and failed in one. The technical successful rate of IVC recanalization was 97.5%. Thrombus was completely lysed in eight patients with fresh thrombus (40%, 8/20), partially lysed in 11 patients with mixed thrombus (55%, 11/20), and no response in one patient with mixed thrombus (5%, 1/20). Thrombolytic-related complications occurred in one patient (5%, 1/20). No symptomatic pulmonary embolism occurred. Among the 11 patients with thrombus partially lysed, five patients underwent stent implantation for compressing thrombus, six patients received conservative treatment. Old thrombus was completely lysed in 15 patients (55.6%, 15/27) during follow-up. Restenosis occurred in six patients (15.4%, 6/39). Primary patency rates at 1, 5, 10 and 15 years were 92, 92, 86 and 80%, respectively. Hepatocellular carcinoma (HCC) occurred in four patients (8.5%, 4/47). One patient died of HCC. The survival rate was 97.9%. CONCLUSIONS: The individualized interventional treatment based on thrombus type and size for primary BCS complicated by IVC thrombosis patients is safe and effective with long-term patency and survival.

Restenosis after Balloon Dilatation with versus without Stent Placement for Hepatic Vein Involvement Budd-Chiari Syndrome.

Balloon angioplasty with or without stent placement has become the mainstream treatment of Budd-Chiari syndrome (BCS). Restenosis of hepatic vein (HV) is a tough problem. The aim of this study was to perform a meta-analysis to compare the restenosis in HV involvement type BCS patients treated by balloon dilatation with versus without stent. Meta-analysis was used to calculate the combined effect size and their 95% confidence intervals (CI), based on random effect; and calculate the risk ratio (RR) and its 95% CI based on fixed effect. The publication bias was assessed by funnel plot and Begg's test. Sixteen studies were selected for meta-analysis. One thousand and eighty-two patients (1,019 from Asian, 63 from non-Asian countries) were included. Seven hundred and five of 1,019 (69%) Asian patients received HV balloon dilatation alone. RR value (RR=0.85, 95% CI 0.68-1.08) of the two groups was obtained through meta-analysis, which meant that the risk of restenosis in balloon dilatation alone group was 15% lower than that in combined with stent placement group; although there was no significant statistical difference between two groups (p=0.178). The current meta-analysis indicated that balloon dilatation alone is first preferred approach in Asian BCS patients compared to the non-Asian patients. Balloon dilatation combined with stent placement does not reduce restenosis risk over balloon dilation alone in the treatment of BCS with HV occlusion. It is suggested that stent should be used cautiously for such patients. Key Words: Balloon dilatation, Budd-Chiari syndrome, Stent, Restenosis, Meta-analysis.

The outcomes of interventional treatment for Budd-Chiari Syndrome complicated by inferior vena cava thrombosis: Systematic review and meta-analysis.

PURPOSE: The aim of this study was to perform a systematic review and meta-analysis to assess the safety and efficacy of interventional treatment for Budd-Chiari syndrome (BCS) complicated by Inferior Vena Cava thrombosis (IVCT) patients. METHODS: We evaluated the published studies on interventional treatment for BCS complicated by IVCT. Meta-analysis was used to calculate the combined effect size and their 95% confidence intervals (CI) based on random effect. The publication bias was assessed by Begg's test. RESULTS: Sixteen studies on interventional treatment for BCS complicated by IVCT patient were selected for meta-analysis, a total of 767 BCS complicated by IVCT patients were included. The combined effect size (95% CI) were 99% (98-100%) for the total successful rate of IVC recanalization, 15% (11-21%) for the rate of IVC restenosis after initial operation, 92.0% (86-97%) for the rate of clinical improvement, 76% (68-84%) for the rate of thrombus clearance and 0.00% (0-1%) for the incidence of pulmonary embolism (PE). Through subgroup meta-analysis about the rate of thrombus clearance, we got the pooled results (95% CI) of individualized treatment strategy (ITS) group and non-individualized treatment strategy (non-ITS) group, were 81% (71-92%) and 73% (63-83%), respectively. CONCLUSIONS: The interventional treatment for BCS complicated by IVCT patients is safe and effective with low incidence of PE, high thrombus clearance rate, high technically successful rate, good patency, and high clinical improvement rate. Moreover, subgroup analysis indicated that management based on the type and extent of the thrombus is proposed.

Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: Lung cancer is a major cause of death among patients, and non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers in many countries. AIM: To evaluate the clinical benefit (CB) of COX-2 inhibitors in patients with advanced NSCLC using systematic review. METHODS: We searched the six electronic databases up until December 9, 2019 for studies that examined the efficacy and safety of the addition of COX-2 inhibitors to chemotherapy for NSCLC. Overall survival (OS), progression free survival (PFS), 1-year survival rate (SR), overall response rate (ORR), CB, complete response (CR), partial response (PR), stable disease (SD), and toxicities were measured with more than one outcome as their endpoints. Fixed and random effects models were used to calculate risk estimates in a meta-analysis. Potential publication bias was calculated using Egger's linear regression test. Data analysis was performed using R software. RESULTS: The COX-2 inhibitors combined with chemotherapy were not found to be more effective than chemotherapy alone in OS, progression free survival, 1-year SR, CB, CR, and SD. However, there was a difference in overall response rate for patients with advanced NSCLC. In a subgroup analysis, significantly increased ORR results were found for celecoxib, rofecoxib, first-line treatment, and PR. For adverse events, the increase in COX-2 inhibitor was positively correlated with the increase in grade 3 and 4 toxicity of leukopenia, thrombocytopenia, and cardiovascular events. CONCLUSION: COX-2 inhibitor combined with chemotherapy increased the total effective rate of advanced NSCLC with the possible increased risk of blood toxicity and cardiovascular events and had no effect on survival index.