Ultrasound-Guided peripheral nerve blocks for major amputation in critically ill patients with peripheral artery disease.

OBJECTIVE: The aim of this study was to assess the safety and efficacy of major amputation under ultrasound-guided peripheral nerve blocks in critical peripheral artery disease (PAD) patients. METHODS: We reviewed the medical records of consecutive patients who underwent major amputation at our center between December 2012 and December 2020. The patients' baseline demographics and comorbidities were collected. The primary outcomes were 30-day and 12-month mortality. The secondary outcomes were intraoperative events, complications and intensive care unit (ICU) admission. RESULTS: Fifteen patients classified as American Society of Anesthesiologist (ASA) III and 13 ASA IV (mean age: 76.07 ± 11.78 years) were included in the study. These patients were critically ill and had many comorbidities, such as coronary artery disease. All amputations were successfully performed under ultrasound-guided PNB without conversion to GA, but intravenous analgesia was given in 7 patients during the operation. The majority of the patients had stable hemodynamics except for 2 patients who had hypoxia, so none of the patients were transferred to the ICU postoperatively. None of the patients suffered from acute cardio-cerebral events. However, 5 patients had wound infections, and 4 of 5 patients had to receive reamputation. None of the patients died within 48 h after amputation. However, the 30-day mortality was 3.57%, and the 12-month mortality was up to 35.71%. CONCLUSION: This study demonstrates that major amputation could be safely and effectively performed under ultrasound-guided peripheral nerve blocks for critically ill patients, and ultrasound-guided peripheral nerve blocks could be an alternative for patients at high risk of general anesthesia or spinal anesthesia.

Percutaneous Mechanical Thrombectomy for Acute Symptomatic Iliofemoral Deep Venous Thrombosis Patients With Recent Aneurysmal Subarachnoid Hemorrhage.

PURPOSE: To investigate the efficacy, safety, and mid-term outcomes of percutaneous mechanical thrombectomy (PMT) for acute symptomatic iliofemoral deep venous thrombosis (DVT) patients with recent (within 4 weeks) aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: From January 2016 to February 2020, 11 acute symptomatic iliofemoral DVT patients with a recent history of aSAH were enrolled in this study. All patients had a history of aneurysm ligation or clipping previously, computed tomography (CT) scans revealed ventricular hemorrhage had been absorbed obviously and no residual aneurysm. The mean time of DVT onset after aSAH ictus was 19.2±4.5 days, and the mean Glasgow score was 6.8 ± 0.7 (range, 6-8). These patients underwent PMT with an 8 French Aspirex®S device (Straub Medical AG, Wangs, Switzerland), subsequent stenting was performed to relieve the underlying stenosis, followed by anticoagulation alone. The procedure-related complications were assessed after intervention. The follow-ups were conducted up to 1 year, the patency was evaluated via duplex ultrasonography, and the incidence of post-thrombotic syndrome (PTS) was evaluated using the Villalta scale. RESULTS: Grade III (>90%) clearance was achieved in all 11 patients. Stenting was performed in 7 patients (63.6%). There were no cerebral rebleeding events or other severe complications except 1 puncture site bleeding during treatment. A total of 90.9% (10 of 11) of patients were alive at the 12 month follow-up, and 7 patients achieved a good functional outcome. At the 1 year follow-up, there was 1 patient (10%) with mild PTS. The ultrasound showed that the patency of the iliofemoral veins was 100%, and femoral valvular incompetence was observed in 1 patient. CONCLUSION: Percutaneous mechanical thrombectomy seems to be a feasible and safe treatment for acute iliofemoral DVT in selected patients with recent aSAH, and it shows promising results in restoring patency and reducing the risk of PTS.

The incidence, risk factors, characteristics, and prognosis of recurrent deep venous thrombosis in the contralateral lower extremity.

BACKGROUND: Recurrent events after a first symptomatic deep venous thrombosis (DVT) are relatively frequent, but little is known about contralateral recurrent DVT (RDVT). METHODS: We retrospectively reviewed the medical records of patients with a first symptomatic lower extremity DVT between January 2017 and April 2021. The incidence, demographics, risk factors, and prognosis of RDVT were analyzed, with differences compared between patients with contralateral RDVT and those with ipsilateral RDVT. RESULTS: In 570 consecutive patients with DVT, 28 patients (4.91%) developed contralateral RDVT, and 49 patients (8.60%) developed ipsilateral RDVT during a mean follow-up of 27.62 ± 14.84 months. Contralateral RDVT was more frequently found in the right lower extremity, whereas ipsilateral RDVT had more left lower extremity involvement. The median follow-up was 12 months until ipsilateral RDVT and 26.5 months until contralateral RDVT. In multivariate Cox analysis, inherited thrombophilia, stent extension with 50% to 100% coverage, autoimmune disease and anticoagulation noncompliance were identified as risk factors for contralateral RDVT. During follow-up, 5 patients (17.86%) with contralateral RDVT and 10 patients (20.41%) with ipsilateral RDVT died (P > .05), with 12 of 15 dying of an underlying malignancy. CONCLUSIONS: The incidence of contralateral RDVT after a first symptomatic DVT is relatively low, and contralateral DVT is strongly associated with stent extension with 50% to 100% coverage, autoimmune disease, anticoagulation noncompliance, and inherited thrombophilia. Compared with ipsilateral RDVT, contralateral RDVT occurs later and is more often in the right lower extremity. Survival following contralateral RDVT is similar to survival following ipsilateral RDVT, with underlying malignancy being the leading cause of death.

Pure proton therapy for skull base chordomas and chondrosarcomas: A systematic review of clinical experience.

Background: Skull base chordoma and chondrosarcoma are exceptionally rare bone tumors with high propensity for local recurrence. Different postoperative radiation modalities are often used to improve the clinical efficacy. Proton therapy (PT) might be among the most promising ones because of the unique ballistic characteristics of high-energy particles. However, previous meta-analysis often included studies with combined radiation techniques. No systematic review to date has directly analyzed the survival and toxicity of pure PT for these two types of malignancies. Methods: By following the PRISMA guidelines, a systematic search of three databases was conducted. Articles were screened and data were extracted according to a prespecified scheme. R 4.2.0 software was used to conduct the meta-analysis. Normal distribution test was used for the incidence rate of each subgroup. Results: A total of seven studies involving 478 patients were included in this analysis. The quality of included articles ranged from moderate to high quality. All patients were histopathologically diagnosed with chordoma or chondrosarcoma, and the follow-up time of the cohort ranged from 21 to 61.7 months. For PT planning, the median target volume ranged from 15 cc to 40 cc, and the administered median dose varied from 63 to 78.4 GyRBE at 1.8-2.0 GyRBE per fraction. The 1-, 2-, 3-, 5-, and 7-year local control and overall survival rates were 100%, 93%, 87%, 78%, and 68%, and 100%, 99%, 89%, 85%, and 68%, respectively. The late grade 3 or higher toxicities were reported in only two involved articles. Conclusions: Until now, medical centers worldwide have exerted PT to improve outcomes of skull base chordomas and chondrosarcomas. PT not combined with other radiation modalities showed favorable local control and survival with a low incidence of severe radiation-induced toxicities, which manifests promising clinical benefits. However, high-quality evidence is still limited, requiring future clinical trials and prospective studies in selected patients.

SDCBP-AS1 destabilizes ß-catenin by regulating ubiquitination and SUMOylation of hnRNP K to suppress gastric tumorigenicity and metastasis.

BACKGROUND: Gastric cancer (GC) is among the most malignant tumors, yet the pathogenesis is not fully understood, especially the lack of detailed information about the mechanisms underlying long non-coding RNA (lncRNA)-mediated post-translational modifications. Here, the molecular mechanisms and clinical significance of the novel lncRNA syndecan-binding protein 2-antisense RNA 1 (SDCBP2-AS1) in the tumorigenesis and progression of GC were investigated. METHODS: The expression levels of SDCBP2-AS1 in 132 pairs of GC and adjacent normal tissues were compared, and the biological functions were assessed in vitro and in vivo. RNA pull-down and immunoprecipitation assays were conducted to clarify the interactions of SDCBP2-AS1 and heterogeneous nuclear ribonucleoprotein (hnRNP) K. RNA-sequencing, immunoprecipitation, immunofluorescence, and luciferase analyses were performed to investigate the functions of SDCBP2-AS1. RESULTS: SDCBP2-AS1 was significantly downregulated in GC tissues and predictive of poor patient prognosis. Silencing of SDCBP2-AS1 promoted the proliferation and migration of GC cells both in vitro and in vivo. Mechanically, SDCBP2-AS1 physically bound to hnRNP K to repress SUMOylation of hnRNP K and facilitated ubiquitination of hnRNP K and ß-catenin, thereby promoting the degradation of ß-catenin in the cytoplasm. Silencing of SDCBP2-AS1 caused SUMOylation of hnRNP K and stabilized ß-catenin activity, which altered transcription of downstream genes, resulting in tumorigenesis and metastasis of GC. Moreover, the knockdown of hnRNP K partially abrogated the effects of SDCBP2-AS1. CONCLUSIONS: SDCBP2-AS1 interacts with hnRNP K to suppress tumorigenesis and metastasis of GC and regulates post-transcriptional modifications of hnRNP K to destabilize ß-catenin. These findings suggest SDCBP2-AS1 as a potential target for the treatment of GC.

Safety and Efficacy of Rivaroxaban for Inferior Vena Cava Thrombosis after Successful Catheter-Directed Thrombolysis.

Rivaroxaban use for inferior vena cava (IVC) thrombosis after successful catheter-directed thrombolysis (CDT) is rarely reported. This study aimed at investigating the safety and efficacy of rivaroxaban for IVC thrombosis after CDT. The clinical data on 38 consecutive patients with IVC thrombosis (68% male; mean age, 51.5 ± 16.5), who received rivaroxaban after CDT between July 2017 and January 2020, were retrospectively analyzed in this study. Safety and efficacy of rivaroxaban (bleedings and recurrent venous thromboembolism), cumulative prevalence of post-thrombotic syndrome (PTS), primary patency, clinically driven target lesion revascularization rate, and other adverse events including all-cause mortality and vascular events (systemic embolism, acute coronary syndrome, ischemic stroke, and transient ischemic attack) were retrospectively analyzed. Of the 38 patients who received rivaroxaban for IVC thrombosis after CDT, 27 (71%) had an anticoagulant duration of 6 months and 11 patients (29%) of more than 6 months. Four patients (10%) suffered recurrent thrombosis. No patient suffered major bleeding, while clinically relevant nonmajor bleeding occurred in two (5%) patients. The cumulative prevalence of PTS was 18% (7/38) during the 12 months follow-up period. Primary patency at 1, 3, 6, and 12 months was 97, 92, 90, and 90%, respectively. According to follow-up data, the clinically driven target lesion revascularization of this study was 10%. Cardiovascular events and mortality did not occur in any patient during the study period. Rivaroxaban for IVC thrombosis after successful CDT can be safe and effective.

5,10-methylenetetrahydrofolate reductase C677T gene polymorphism and peripheral arterial disease: A meta-analysis.

INTRODUCTION: Peripheral arterial disease is one common vascular disease most caused by atherosclerosis. As with stroke and coronary heart disease, peripheral arterial disease is one clinical type of atherosclerotic cardiovascular disease with many unmeasured environmental and genetic components. MTHFR C677T polymorphism is associated with the increased risk of ischemic stroke and coronary heart disease. MTHFR C677T polymorphism is associated with decreasing enzyme activity and increasing homocysteine levels. Meta-analysis of studies had demonstrated an association between elevated plasma homocysteine levels and peripheral arterial disease. Elevated plasma homocysteine level is closely related to MTHFR C677T polymorphism. Recent studies had clarified the relationship of MTHFR C677T polymorphism and peripheral arterial disease. So we performed a meta-analysis to investigate the association between MTHFR C677T polymorphism and peripheral arterial disease. MATERIALS AND METHODS: We searched the database PubMed, Embase, and Cochrane Library for all English-language articles related to peripheral arterial disease and MTHFR C677T through 30 June 2020. Analysis results were shown by forest plot. Publication bias was estimated using funnel plot. RESULTS: A total of 15 studies comprising 1929 patients with peripheral arterial disease and 2952 healthy controls were included in the meta-analysis. Significant associations between MTHFR C677T genetic polymorphism and peripheral arterial disease were found (OR = 1.31, 95% CI: 1.09-1.58, P <0.01). But there was no significant association (poor OR = 1.11, 95% CI: 0.98-1.26, P =0.11) between the T allele carrier and peripheral arterial disease. CONCLUSION: Our meta-analysis suggested that MTHFR C677T genetic polymorphism TT genotype may be associated with increased peripheral arterial disease risk. But further studies with large sample sizes are needed to confirm our findings.

Outcomes of Aspirex®S thrombectomy system combined with catheter-directed thrombolysis for treating bilateral lower extremity deep venous thrombosis.

BACKGROUND: Pharmacomechanical catheter-directed thrombolysis (PCDT) is rarely reported in treating bilateral lower extremity deep venous thrombosis (LEDVT). This study was aimed to investigate the safety, patency, and mid-term outcomes of the Aspirex®S thrombectomy system combined with catheter-directed thrombolysis (CDT) in treating symptomatic bilateral LEDVT. PATIENTS AND METHODS: The clinical data of 45 consecutive patients with acute or subacute bilateral LEDVT (60.00% male; mean age, 53.8 ± 16.5 years) who received endovascular treatment with PCDT between January 2015 and June 2019 were retrospectively analyzed in this study. The clinical efficacy of thrombolysis (≥50% thrombolysis), complications, primary patency, valvular function, and cumulative prevalence of post-thrombotic syndrome (PTS) were retrospectively analyzed. RESULTS: PCDT was performed in all 45 patients successfully. No serious procedure-related complication or death was observed. The average urokinase dosage was 4.1 ± 1.5 million IU, and the average thrombolysis time was 5.3 ± 1.3 days. The mean length of hospital stay was 9.9 ± 2.5 days. The primary patency was 100% after lysis. The clinical efficacy of thrombolysis was 86.7% (39/45). Deep venous thrombosis recurrence was observed in six (13.3%) patients within 12 months after discharge. The primary patency at 1-, 3-, 6-, 9-, and 12-month follow-up was 97.8%, 93.3%, 88.9%, 82.2%, and 73.3%, respectively. The cumulative prevalence of PTS was 24.4% (11/45) throughout the follow-up period, whereas the prevalence of moderate and severe PTS was only 6.7% (3/45). CONCLUSIONS: PCDT for treating bilateral LEDVT is feasible, effective, and safe.

The novel lncRNA p4516 acts as a prognostic biomarker promoting gastric cancer cell proliferation and metastasis.

Purpose: Emerging evidence has shown that long noncoding RNAs (lncRNAs) participate in oncogenesis and tumor progression. We previously found a novel lncRNA p4516 which was closely associated with prognosis by preliminary study of lncRNA expression profile from paired tumors and nontumor tissues in 198 gastric cancer (GC) patients. However, the exact biological functions and the underlying molecular mechanisms of p4516 in gastric tumorigenesis still remain unclear. Materials and methods: The RNA fluorescence in situ hybridization (RNA-FISH) analysis, cytoplasmic and nuclear RNA isolation and qRT-PCR were applied to determine the subcellular localization of p4516. Expression levels of p4516 were assessed using qRT-PCR in both GC cell lines and in 142 primary GC tissues. Correlations between p4516 expression and GC patients' clinicopathological parameters were analyzed. Gain- and loss-of-function experiments were employed to investigate the role of p4516 in proliferation, migration and invasion both in vitro and in vivo. In addition, Western blotting and immunohistochemical staining were used to examine the protein expression levels. Results: LncRNA p4516 was mainly localized in the nucleus of GC cells and p4516 tended to have higher expression levels in GC cells compared to the normal gastric mucosa-derived cells GES-1. Furthermore, higher expression levels of p4516 correlated with worse clinical outcomes in GC patients and acted as an independent prognostic biomarker. Functional analysis revealed that p4516 participated in the regulation of GC cell proliferation, invasion and migration both in vivo and in vitro. Moreover, p4516 was involved in epithelial-mesenchymal transition (EMT) in GC cells. Conclusion: Our study demonstrated the oncogenic role of novel lncRNA p4516 in the gastric carcinogenesis for the first time. High expression of p4516 may act as prognostic marker in patient with gastric cancer.

ISL1 predicts poor outcomes for patients with gastric cancer and drives tumor progression through binding to the ZEB1 promoter together with SETD7.

ISL1, a LIM-homeodomain transcription factor, serves as a biomarker of metastasis in multiple tumors. However, the function and underlying mechanisms of ISL1 in gastric cancer (GC) have not been fully elucidated. Here we found that ISL1 was frequently overexpressed in GC FFPE samples (104/196, 53.06%), and associated with worse clinical outcomes. Furthermore, the overexpression of ISL1 and loss-of-function of ISL1 influenced cell proliferation, invasion and migration in vitro and in vivo, including GC patient-derived xenograft models. We used ChIP-seq and RNA-seq to identify that ISL1 influenced the regulation of H3K4 methylation and bound to ZEB1, a key regulator of the epithelial-mesenchymal transition (EMT). Meanwhile, we validated ISL1 as activating ZEB1 promoter through influencing H3K4me3. We confirmed that a complex between ISL1 and SETD7 (a histone H3K4-specific methyltransferase) can directly bind to the ZEB1 promoter to activate its expression in GC cells by immunoprecipitation, mass spectrometry, and ChIP-re-ChIP. Moreover, ZEB1 expression was significantly positively correlated with ISL1 and was positively associated with a worse outcome in primary GC specimens. Our paper uncovers a molecular mechanism of ISL1 promoting metastasis of GC through binding to the ZEB1 promoter together with co-factor SETD7. ISL1 might be a potential prognostic biomarker of GC.