Comparing the efficacy and safety of high-voltage and standard-voltage pulsed radiofrequency for the treatment of postherpetic neuralgia: A pooled analysis from randomized controlled trials.

Postherpetic neuralgia (PHN) is one of the most common and serious complications of herpes zoster infection. Pulsed radiofrequency (PRF) therapy has emerged to be a neuromodulation technique for the treatment of PHN. Two therapeutic options are available for PRF, including high-voltage and standard-voltage PRF. Some studies suggested that the former one had better clinical efficacy than the latter one. For the first time, this pooled analysis compared the efficacy and safety of these two surgeries for the treatment of PHN. Five commonly used databases were applied to identify the eligible studies. This study was registered on the PROSPERO (ID: CRD42023460236), which provided more relevant information. Finally, four randomized controlled trials (RCTs) with 285 participants were included. The combined odds ratios (OR) showed that high-voltage PRF exhibited a significantly higher treatment efficiency than the standard PRF (OR = 1.4, 95%CI: 1.16 to 1.69, P < 0.001). Additionally, the visual analogue scale (VAS) in the high-voltage PRF group was significantly lower than that of the standard PRF group at one week (SMD = -0.776, 95%CI: -1.408 to -0.145, P = 0.016), one month (SMD = -0.544, 95%CI: -0.907 to -0.180, P = 0.003), and three months (SMD = -1.096, 95%CI: -1.504 to -0.687, P < 0.001) after treatment, particularly at the three months after surgery. However, the VAS was comparable between the two groups (SMD = -0.94, 95%CI: -1.985 to 0.104, P = 0.077). Patients who underwent high-voltage PRF did not have a significantly higher incidence of adverse events than those with standard PRF (OR = 1.56, 95%CI: 0.78 to 3.13, P = 0.208). In summary, the current study revealed that high-voltage PRF is superior to standard-voltage PRF in improving analgesic efficacy in patients with PHN. Additionally, it does not increase the incidence of treatment-related adverse effects. Further studies are still warranted to determine the optimal voltage and duration of PRF treatment for patients with PHN.

Knockdown of ZEB1 Inhibits Hypertrophic Scarring through Suppressing the Wnt/ß-catenin Signaling Pathway in a Mouse Model.

BACKGROUND: Hypertrophic scars (HS) cause functional impairment and cosmetic deformities following surgeries or burns (30% to 94%). There is no target therapy yet because the pathogenesis of HS progression is not well-known. In tissue fibrosis, Zinc finger E-box binding homeobox 1 (ZEB1) abnormal upregulation is an important cause for extracellular matrix (ECM) overexpression, which is the main molecular change in HS. Therefore, we hypothesized that ZEB1-knockdown inhibits HS formation. METHODS: ZEB1 expression in human HS and TGF-ß1-induced fibroblasts were identified by PCR and western blotting. ZEB1 was knockdown by siRNA in HS fibroblasts (HSFs) and mouse HS model (C57/BL6, male, 8-12 weeks). After 8-hour-transfection, HSFs were subjected to PCR, western blotting and CCK-8, apoptosis, migration and contraction assays. Mice HS were analyzed by HE staining, PCR and western blotting after 56 days. RESULTS: ZEB1 was upregulated in HS tissue (2.0-fold; p < 0.001). ZEB1 knockdown inhibited HSFs activity (0.6 to 0.7-fold; p < 0.001), the expression of fibrotic markers (0.4 to 0.6-fold; p < 0.001) and ß-catenin, cyclinD1 and c-Myc expression (0.5-fold; p < 0.001). In mouse HS models, HS skin thickness was thinner (1.60 ± 0.40 mm vs. 4.04 ± 0.36 mm; p < 0.001) after ZEB1 knockdown. CONCLUSIONS: Knockdown of ZEB1 inhibits HS formation both in vitro and in vivo. However, this is an in vitro/mouse model and more validation is needed. CLINICAL RELEVANCE STATEMENT: The discovery of ZEB1 as a mediator of HS formation might be a potential therapeutic target in HS treatment.

Assessment of atherectomy treatment for Thromboangiitis Obliterans: A single center experience.

BACKGROUND AND AIMS: Endovascular recanalizaiton (ER) has been proven to be a feasible method for Thromboangiitis Obliterans (TAO). The aims of this study were to evaluate the effectiveness and safety of atherectomy for TAO compared to nonatherectomy ER in our center. METHODS: Patients diagnosed as TAO were reviewed from January 2016 to June 2021 in our center. Basic characteristics of patients before ER and perioperative data were collected and compared between the atherectomy and nonatherectomy groups. The vascular event-free survival and limb salvage were calculated to evaluate the prognosis of TAO patients after ERs. Logistic Regression and Cox Regression were used to identify the risk factors for technical failure and prognosis, respectively. RESULTS: Seventy-two TAO patients with 79 lower limbs who met the criteria were included in this report. Compared with the nonatherectomy group, no significant improvement was identified in ER technical success, vascular event-free survival, or limb salvage in the atherectomy group. The total technical success rate was 91.1% (atherectomy group, 95.2%; nonatherectomy group, 89.7%), and the multiple limb involvement (p = 0.005; odds ratio [OR], 28.16; confidence interval [CI], 3.28-241.55) was the independent risk factor for technical failure. The total vascular event-free survival proportion was 66.05% and 58.40% at 1 and 3 years, respectively. Technical failure (OR, 5.61; 95% CI, 1.57-20.04; p = 0.008), and runoff grade 0 (OR, 3.28; 95% CI, 1.09-9.85; p = 0.034) were independent risk factors for vascular events. The total limb salvage proportion at 1 and 3 years was 95.84% and 92.53%, respectively. Technical failure (OR, 8.54; 95% CI, 1.71-40.73; p = 0.02) was identified as an independent risk factor for above ankle amputation. CONCLUSIONS: No significant difference in prognosis was found between the atherectomy group and the nonatherectomy group during a midterm follow-up. The technical success of ER was crucial for TAO prognosis.

Internal iliac artery preservation during endovascular aortic repair using in situ laser fenestration.

OBJECTIVE: The purpose of the present study was to evaluate the technical and short-term clinical outcomes of internal iliac artery (IIA) reconstruction during endovascular aortic repair (EVAR) with in situ laser-assisted fenestration in cases of abdominal aortic aneurysm (AAA) in which the iliac artery is unfit for an internal branched device (IBD). METHODS: In the present single-institution retrospective study, we analyzed patients with AAAs who had undergone EVAR with in situ laser-assisted fenestration for IIA reconstruction between January 2018 and April 2021. The study included patients with iliac artery anatomy unfit for the use of commercial IBDs. The primary safety end point was freedom from major adverse events and unplanned reinterventions within 30 days. The primary efficacy end point was freedom from IIA restenosis, reintervention, and symptoms due to pelvic ischemia at 1 year after the procedure. RESULTS: A total of 20 patients requiring IIA reconstruction but with anatomy unfit for IBD placement were treated with in situ laser-assisted fenestration during EVAR for aortoiliac aneurysms during the study period. The mean age of our patients was 72 years, and 90% were men. The technical success rate was 100%. No patient had died within 30 days after the procedure. A suspicious IIA perforation had occurred in one patient, which was treated with an additional covered stent, for a primary safety end point of 95.0%. After a mean follow-up of 11 months, all except for one of the reconstructed IIAs were patent. Three patients reported symptoms of buttock claudication on the IIA occluded side at their 3-month follow-up after the procedure. However, these symptoms had subsided in two of these patients at 6 months. Type II endoleaks without sac expansion had occurred in two patients owing to retrograde blood flow from the inferior mesenteric artery and lumbar artery. Both patients were kept under close surveillance. The rate of freedom from major adverse events and unplanned reinterventions within 30 days (primary efficacy end point) was 86.3% at 1 year after procedure. CONCLUSIONS: In situ laser-assisted fenestration was found to be a safe and effective alternative method for IIA reconstruction during EVAR for aortoiliac aneurysms in patients with anatomy unfit for IBD.

σ2R/TMEM97 in retinal ganglion cell degeneration.

The sigma 2 receptor (σ2R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ2R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ2R/TMEM97 in neurodegenerative processes. To understand the function of σ2R/TMEM97 in neurodegeneration pathways, we characterized ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97-/- mice and found that RGCs in TMEM97-/- mice are resistant to degeneration. In addition, intravitreal injection of a selective σ2R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that σ2R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of σ2R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ2R/TMEM97 in RGCs and likely in other σ2R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting σ2R/TMEM97.

Development of a Model for Predicting the Effectiveness of Pulsed Radiofrequency on Zoster-Associated Pain.

INTRODUCTION: Zoster-associated pain (ZAP), which may cause anxiety, depression, and sleep disorders and reduce quality of life, is often refractory to current standard treatments. Studies have shown that pulsed radiofrequency (PRF) can alleviate ZAP and reduce the incidence of postherpetic neuralgia (PHN). This study aimed to explore the clinical characteristics associated with PRF responsiveness, develop a model for identifying risk factors of inadequate PRF management, and help clinicians make better decisions. METHODS: Patients who underwent PRF for ZAP between January 2017 and October 2020 in our hospital were included in this study. Patients were evaluated using the numerical rating scale (NRS), Insomnia Severity Index, Patient Health Questionnaire-9, and 36-Item Short Form Health Survey (SF-36) before and 3 months after the procedure. Patient demographic data and blood test results were also collected. We defined the effectiveness of PRF for ZAP as relief of > 50% in NRS scores compared to pre-PRF. Least absolute shrinkage and selection operator (LASSO) regression analyses were subsequently performed to identify factors related to the therapeutic effect of PRF in patients with ZAP. The performance of the prediction model was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: The effectiveness of PRF in patients with ZAP was 69.6% (total 313 patients) after 3 months. LASSO regression analysis extracted the seven most powerful features in the developed prediction model: sex, stage of herpes zoster (HZ), pregabalin dose, bodily pain indicators of SF-36, lymphocyte count, and low-density lipoprotein cholesterol (LDLC) and complement C4 in peripheral blood. Model = 1.586 + 0.148 × lymphocyte + (-0.001) × bodily pain indicators of SF-36 + (-0.001) × pregabalin dose + 0.028 × LDLC + 0.001 × C4 + (-0.508) × sex + (-0.128) × stage of HZ. We generated the ROC curve for the prediction model, and the final AUC was 0.701. The sensitivity, specificity, and overall accuracy of the model were 90%, 33%, and 73%, respectively. CONCLUSIONS: Seven factors were significantly associated with poor PRF outcome: male sex, advanced stage of HZ, higher pregabalin dose, higher bodily pain indicators of SF-36, and lower lymphocyte count, LDLC, and complement C4 in the peripheral blood. PRF should be applied to patients with ZAP as early as possible to achieve satisfactory outcomes.

Exosomes from Adipose Mesenchymal Stem Cells Overexpressing Stanniocalcin-1 Promote Reendothelialization After Carotid Endarterium Mechanical Injury.

OBJECTIVE: Stanniocalcin-1 (STC-1) is a secreted glycoprotein that participates in the regulation of inflammation, apoptosis, and necrosis. We investigated the reendothelialization effect of exosomes from adipose stem cells (ADSC) overexpressing STC-1 on injured carotid endarterium. METHODS: ADSCs were transfected with lentivirus vectors containing pre-STC-1. PHK-26 as molecular probe was used to track the exosomes engulfed by mice arterial endothelial cells (MAEC). The role of STC-1-ADSC-Exosome (S-ADSC-Exo) in MAECs was verified through scratch test and tube forming. Expressions of STC-1 and NLRP3 inflammasome were detected by western blot and quantitative reverse transcription polymerase chain reaction. Reendothelialization effect was inhibited by the antagonist of siRNA targeting STC-1. Carotid endarterium mechanical injury was induced by insertion with a guidewire into the common carotid artery lumen. Carotid arteries were harvested for histological examination, immunofluorescence staining, and Evan's blue staining. RESULTS: Transfection of STC-1 significantly enhanced STC-1 levels in ADSCs, their exosomes, and MAECs. Compared with the control group and the ADSC-Exo group, STC-1 enriched exosomes markedly inhibited the expressions of NLRP3, Caspase-1, and IL-1ß in MAECs, exhibited good lateral migration capacity, and promoted angiogenesis. Administration of siRNA targeting STC-1 completely abolished down-regulation of NLRP3, Caspase-1, and IL-1ß by STC-1 and inhibited effects of S-ADSC-Exo on lateral migration and angiogenesis. In vivo administration of S-ADSC-Exo had reendothelialization effect on post-injury carotid endarterium as evidenced by thinner arterial wall, low-expressed NLRP3 inflammasome, and more living endothelial cells. CONCLUSIONS: The reendothelialization effect of exosomes from ADSCs on post-injury carotid endarterium could be enhanced by genetic modification of the exosomes to contain elevated STC-1, possibly through suppression of NLRP3 inflammasome-mediated inflammation.

Efficacy and safety of treating chronic nonspecific low back pain with radial extracorporeal shock wave therapy (rESWT), rESWT combined with celecoxib and eperisone (C + E) or C + E alone: a prospective, randomized trial.

BACKGROUND: To investigate whether respectively radial extracoporeal shock wave therapy (rESWT) or a combination of rESWT, celecoxib and eperisone (rESWT + C + E) are superior in reducing pain in patients with chronic nonspecific low back pain (cnsLBP) compared to C + E alone (a standard treatment of this condition in China). METHODS: 140 patients with cnsLBP were randomly allocated to rESWT (n = 47), rESWT + C + E (n = 45) or C + E alone (n = 48) for four weeks between November 2017 and March 2019. Outcome was evaluated using the Pain Self-Efficacy Questionnaire (PSEQ), Numerical Rating Scale (NRS), Oswestry Low Back Pain Disability Questionnaire and Patient Health Questionnaire 9, collected at baseline as well as one week (W1), W2, W3, W4 and W12 after baseline. RESULTS: All scores showed a statistically significant improvement over time. The PSEQ and NRS scores showed a significant Time × Treatment effect. Patients treated with rESWT had significantly lower mean NRS values than patients treated with rESWT + C + E at W1 and W3, as well as than patients treated with C + E alone at W3 and W4. No severe adverse events were observed. CONCLUSIONS: rESWT may not be inferior to respectively rESWT + C + E or C + E alone in reducing pain in patients with cnsLBP. LEVEL OF EVIDENCE: Level I, prospective, randomized, active-controlled trial. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03337607. Registered November 09, 2017, https://www.clinicaltrials.gov/ct2/show/NCT03337607 . LEVEL OF EVIDENCE: Level I; prospective, randomized, controlled trial.

Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia.

BACKGROUND: Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics. METHODS: ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted from ADSCs (G-ADSC-Exos) were isolated and characterized to coculture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high-glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson's staining, immunofluorescence, and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored. RESULTS: The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high-glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel's density than the ADSC-Exo and control groups by Masson's staining and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1ß, as well as the increased secretion of VEGF, IGF-1, and FGF. CONCLUSION: Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.

Outcomes of endovenous laser ablation with additional iliac vein stenting of nonthrombotic lesions in patients presenting with active venous ulcers.

OBJECTIVE: We evaluated the clinical outcomes of superficial and perforator ablation and the effects on wound healing by adding iliac vein stenting of nonthrombotic iliac vein lesions (NIVLs) in patients presenting with active venous ulcers. METHODS: A retrospective analysis was performed of patients who had presented with venous ulcers and had a diagnosis of NIVLs from January 2017 to December 2019. Patients with a >50% diameter reduction in the iliac vein as determined by computed tomography venography had undergone transfemoral venography for further confirmation. Patients were divided into the endovenous laser ablation (EVLA) group and EVLA with stenting (EVLAS) group. The EVLA group had undergone endovascular laser treatment of superficial venous reflux, and the EVLAS group had undergone EVLA and stenting for NIVLs. The clinical outcomes were compared between the two groups. The primary end point was cumulative ulcer healing at 12 months. The secondary end points included complications, venous clinical severity score improvements, and pain scores during the follow-up period. Univariable and multivariable regression models were used to determine the refractory ulcer predictors. RESULTS: A total of 157 patients were included, 93 in the EVLAS group and 64 in the EVLA group. Of the 93 patients in the EVLAS group and patients in the EVLA group, 30 (32.26%) and 17 (26.56%) had presented with iliac venous occlusion, respectively (P = .48). The mean percentage of stenosis was 78.0% ± 13.6% in EVLAS group and 77.0% ± 14.0% in the EVLA group (P = .36). No significant differences in the general preoperative data were observed between the two groups. Cumulative ulcer healing at 1 year was 86.8% and 65.6% in the EVLAS and EVLA groups, respectively (P = .001). After a mean follow-up of 22 months (median, 24 months), the EVLAS group had a significantly improved venous clinical severity score compared with the EVLA group (EVLAS group, 8.3; EVLA group, 11.7; P = .01). Multivariable analysis of the entire cohort showed that obesity and employment that requires standing were predictive of refractory ulcers and that iliac venous stent placement was a protective factor for ulcer healing. CONCLUSIONS: The results of the present study have suggested an association between improvement in the overall success of venous leg ulcer healing when including treatment of NIVLs with stents into a treatment plan that already includes saphenous and perforator vein ablation.

Outcomes of Drug-Coated Balloon Angioplasty for Isolated Chronic Occlusion of the Popliteal Artery: A Retrospective Single-Institution Study.

PURPOSE: To assess the 12-month safety and effectiveness of paclitaxel drug-coated balloon (DCB) for the treatment of patients with isolated chronic occlusions in popliteal arteries and evaluate the risk factors of lesion reocclusion. MATERIALS AND METHODS: From January 2018 to December 2019, DCB angioplasty was performed in 54 limbs with isolated chronic popliteal artery occlusion of 48 patients (32 men) with a mean age of 71.5 ± 12.1 (range, 50-97) years, mean occlusive length of 6.3 ± 3.0 (range, 1-15) cm, and mean preoperative ankle-brachial index (ABI) of 0.42 ± 0.12 (range, 0.19-0.58). A total of 18.5% (10/54) of lesions were long-segment occlusions involving the entire popliteal artery from P1 to P3. Twenty seven of 54 limbs presented with critical limb ischemia (CLI) with a mean ABI of 0.33 ± 0.10 (range, 0.19-0.51). The primary endpoint was primary patency rate at 12 months. The secondary endpoints included technical success rate, 1-year secondary patency rate, limb salvage rate, and improvement in clinical symptoms. Univariate Cox regression analysis was used to determine the predictors of lesion reocclusion. RESULTS: The technical success rate was 85.2% (46/54), and bailout stenting was performed in 14.8% (8/54) of lesions. The 12-month primary and secondary patency rates by the Kaplan-Meier estimate were 72.6% and 88.3%, respectively. Two thirds of the reocclusions occurred within 6 months after intervention. No 30-day mortality was observed. The limb salvage rate was 100% during a mean follow-up period of 13 months, and all minor amputations occurred in the limbs presented with CLI. The mean ABI increased from 0.42 before the procedure to 0.73 after the procedure. Patients younger than 60 years and the lesions exhibiting long-segment occlusions present as trending risk factors for lesion reocclusion. CONCLUSIONS: Paclitaxel DCB angioplasty is safe and effective in managing isolated chronic occlusion of popliteal arteries. Younger patients and long-segment occlusions of the popliteal artery are associated with a relatively higher reocclusion rate after the procedure.

Altered spontaneous brain activity patterns in patients with neovascular glaucoma using amplitude of low-frequency fluctuations: A functional magnetic resonance imaging study.

BACKGROUND: Neovascular glaucoma (NVG) can cause irreversible visual impairment and abnormal spontaneous changes in brain's visual system and other systems. There is little research on this aspect at present. However, amplitude of low-frequency fluctuations (ALFFs) can be used as an rs-fMRI analysis technique for testing changes in spontaneous brain activity patterns. PURPOSE: The aim of this study was to probe the local characteristics of spontaneous brain activity in NVG patients and analyze their correlation with clinical behaviors. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were obtained from eighteen patients with NVG (8 males, 10 females) and eighteen healthy controls (HCs; 8 males and 10 females) who were matched in age, gender, and education level. We evaluated spontaneous brain activity with the ALFF method. A receiver operating characteristic (ROC) curve was used to compare the average ALFF values for altered brain regions of NVG patients with those of HCs. RESULTS: Compared with HCs, NVG patients had lower ALFF values in the right cuneus, right middle occipital gyrus, left cingulate gyrus, right precuneus, and left medial frontal gyrus (p < 0.001). Higher ALFF values were observed in the right superior frontal gyrus and left middle frontal gyrus (p < 0.001). Analysis of the ROC curves of the brain regions showed that the specificity and accuracy of ALFF values between NVG and HCs in the area under the curve were acceptable (p < 0.001). CONCLUSION: The patients with NVG exhibited anomalous spontaneous activity in different brain regions; these finding should establish the foundation for a more comprehensive understanding of the pathological mechanisms of NVG. Furthermore, these abnormal variations in specific brain regions can be considered possible clinical indices of NVG.

Comparing Safety and Efficacy of Rivaroxaban with Warfarin for Patients after Successful Stent Placement for Chronic Iliofemoral Occlusion: A Retrospective Single Institution Study.

OBJECTIVE: The aim was to compare the safety and effectiveness of rivaroxaban and warfarin as anticoagulants for treating patients with post-thrombotic syndrome (PTS) with chronic iliofemoral venous occlusion undergoing iliofemoral venous stenting. METHODS: This single institution retrospective study analysed patients with PTS with chronic iliofemoral venous occlusion who were prescribed rivaroxaban or warfarin for one year after successfully undergoing iliofemoral venous stenting. The primary safety and efficacy endpoints were bleeding complication rate and primary patency rate at one year. Secondary outcomes included Villalta score, symptom recurrence rate, ulcer healing rate, and clinically driven target lesion revascularisation (CD-TLR) rate during follow up. RESULTS: From January 2016 to December 2017, 154 legs from 154 patients were included in this study (69 in rivaroxaban group and 85 in warfarin group). The groups were well matched for patient demographics, clinical characteristics, and procedural details. There was no significant difference between the rivaroxaban group and warfarin group in bleeding complication rate (10% vs. 16%, p = .23, hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.25 - 1.37) at one year, as well as major bleeding complication rate (0% vs. 2%, p = .20, HR 0.16, 95% CI 0.01 - 2.61) and minor bleeding complication rate (10% vs. 14%, p = .40, HR 0.67, 95% CI 0.27 - 1.66). The primary patency rate was higher in the rivaroxaban group at one year (84% vs. 71%, p = .049, HR 0.50, 95% CI 0.26 - 0.96) and at two years (79% vs. 63%, p = .037, HR 0.52, 95% CI 0.29 - 0.93). At a mean follow up of 24 months (range 1 - 42 months), the rivaroxaban group had a significantly lower post-operative Villalta score (4.87 ± 3.51 vs. 6.88 ± 5.85, p = .010, t = 2.64, 95% CI 0.50 - 3.52), lower rate of symptom recurrence (4% vs. 32%, p < .001), lower CD-TLR rates (3% vs. 13%, p = .039), and higher ulcer healing rate (90% vs. 59%, p = .004) than the warfarin group. CONCLUSION: For PTS patients with chronic iliofemoral venous occlusion undergoing iliofemoral venous stenting, rivaroxaban probably exhibited similar safety but superior efficacy to warfarin. However, further prospective control studies with large sample size are necessary to confirm the results.

WeChat app-based reinforced education improves the quality of opioid titration treatment of cancer-related pain in outpatients: a randomized control study.

BACKGROUND: As inadequate pain communication contributes to difficulties in optimizing outcomes of outpatients, we investigated the effect of reinforced education using WeChat App to the opioid titration treatment of cancer-related pain in the outpatient setting. METHODS: We conducted a prospective study to compare reinforced education using Wechat with care as usual from February to December 2019. Patients in the reinforced education group received reinforced education via Wechat, while those in the control group received care as usual. Effect measurements for both groups are carried out with questionnaires at the baseline and 3 days later. Questionnaires include pain intensity (NRS), treatment-related adverse events, cancer-related quality of life (QOL), sleep (PSQI), satisfaction, anxiety (GAD-7) and depression (PHQ-9). Number of patients whose NRS reduced to less than three points in 24 h was the primary outcomes. Secondary outcomes included treatment-related adverse events, cancer-related quality of life, sleep, satisfaction, anxiety and depression. RESULTS: Although there was no significant difference regarding pain intensity (NRS) between the two groups at 72 h, the rate of NRS that reduced to less than three points in 24 h was significantly higher in the Wechat group than in the control group. Patients' satisfaction was significantly higher in the Wechat group than in the control group. There was no significant difference between the two groups regarding the other findings at 72 h, including pain intensity (NRS), cancer-related quality of life (QOL), anxiety (GAD-7), depression (PHQ-9), and sleep (PSQI). However, no significant difference was found between the two groups for constipation, nausea, vomiting, dizziness, somnolence, pruritus, loss of consciousness, and death. CONCLUSIONS: Our results indicated that receiving instructions delivered by Wechat resulted an increased number of patients with good pain control and better satisfaction. The study provided insight into the effectiveness of the reinforced education using a Wechat app delivered by a doctor to outpatients in the titration treatment of cancer-related pain. TRIAL REGISTRATION: This study was registered at chictr.org (Registration number: ChiCTR1900021150 , Date of Registration: January 30, 2019).

Allogeneic adipose-derived stem cells promote ischemic muscle repair by inducing M2 macrophage polarization via the HIF-1α/IL-10 pathway.

Adipose-derived mesenchymal stem cells (ASCs) are multipotent stromal cells that possess considerable therapeutic potential for tissue remodeling. However, their protective mechanism in critical limb ischemia has not been fully defined. After the occlusion of blood vessels, hypoxia becomes a prominent feature of the ischemic limb. This study investigated the immunomodulatory effect of ASCs on ischemic muscle repair and explored the specific mechanism. We found that the ability of RAW264.7 cells to migrate was impaired in hypoxia, whereas coculturing with ASCs could enhance the migration capacity. In addition, under hypoxic conditions, the paracrine effect of ASCs was enhanced and ASCs could induce RAW264.7 macrophages toward the anti-inflammatory M2 phenotype. We further demonstrated that ASCs-derived interleukin 10 (IL-10), mediated by hypoxia inducible factor-1α (HIF-1α), played a crucial role in the induction of M2 macrophages by activating the signal transducer and activator of transcription 3 (STAT3)/Arginase (Arg-1) pathway. Our in vivo experiments revealed that transplanted ASCs exhibited an immunomodulatory effect by recruiting macrophages to ischemic muscle and increasing the density of M2 macrophages. The transplantation of ASCs into ischemic limbs induced increased blood flow reperfusion and limb salvage rate, whereas the depletion of tissue macrophages or transplanting HIF-1α-silenced ASCs inhibited the therapeutic effect. These findings elucidated the critical role of macrophages in ASCs-mediated ischemic muscle repair and proved that allogeneic ASCs could exert the protective effect by enhancing the recruitment of macrophages and inducing macrophages toward M2 phenotype through HIF-1α/IL-10 pathway.

A meta-analysis of combined proximal stent grafting with or without adjunctive distal bare stent for the management of aortic dissection.

BACKGROUND: The efficacy and safety of placement of a proximal covered stent graft combined with a distal bare stent are controversial because of the lack of evidence. This systematic review and meta-analysis compared the outcomes of combined proximal covered stent grafting with distal bare stenting (BS group) and proximal covered stent grafting without distal bare stenting (non-BS group). METHODS: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and key references were searched up to January 26, 2019. Predefined outcomes of interest were mortality, morbidity, and postoperative assessment of aortic remodeling. We pooled risk ratios (RRs) of the outcomes of interest using fixed effects model or random effects model. RESULTS: Overall, eight observational studies involving 914 patients were included. There were no significant differences in overall aorta-related mortality (RR, 0.54; confidence interval [CI], 0.24-1.24; P = .15), complete thoracic false lumen (FL) thrombosis rate (RR, 1.23; CI, 0.83-1.81; P = .30), or complete abdominal FL thrombosis rate (RR, 1.96; CI, 0.68-5.69; P = .21) between the BS group and the non-BS group. The BS group had a lower rate of partial thoracic FL thrombosis (RR, 0.40; CI, 0.25-0.65; P = .0002), a lower stent graft-induced new entry rate (RR, 0.08; CI, 0.02-0.41; P = .003), and a lower reintervention rate (RR, 0.42; CI, 0.26-0.69; P = .0005). CONCLUSIONS: Combined proximal covered stent grafting with distal adjunctive bare stenting had the potential to reduce the partial thoracic FL thrombosis rate and the rates of stent graft-induced new entry and reintervention but was not associated with lower aorta-related mortality or the complete FL thrombosis rate. Further research with a stricter methodology is needed.

VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund's Adjuvant.

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, it remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in inflammatory pain mediated by Cdk5 in the inflammatory pain model induced by complete Freund's adjuvant (CFA). Our results showed that the coexpression of Cdk5/VGLUT2 in small- and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.

Treatment of lateral epicondylitis with acupuncture and glucocorticoid: A retrospective cohort study.

Lateral epicondylitis (LE) is a common musculoskeletal disorder for which an effective treatment strategy remains unknown. The goal of this study is to examine whether acupuncture is more effective than injection of glucocorticoid in adults with LE.Adults with LE received either acupuncture or injection of glucocorticoid were followed-up for 6 months. All patients assessed before treatment, 0, 3 months, and 6 months after the therapy. Outcome measures consisted of visual analog scores (VAS) and the Mayo elbow performance score (MEPS).The acupuncture group and the corticosteroid group did not differ on demographic or clinical characteristics (P < .05). VAS and MEPS score was not significantly different between 2 groups at 0 and 3 months. MEPS scores were significantly lower in the corticosteroid group at 6 months, compared with those in the acupuncture group (P < .05). However, the VAS score was not significantly different (P > .05). There were no complications related to the use of acupuncture or corticosteroid injection.We found that both methods were effective for external humeral epicondylitis. However, after 6 months of treatment, patients with chronic LE with acupuncture achieved pain relief and function improve significantly, exceeding the effect of corticosteroid injection.

Effects of ghrelin on pGSK-3ß and ß-catenin expression when protects against neuropathic pain behavior in rats challenged with chronic constriction injury.

Ghrelin has been shown to alleviate neuropathic pain by inhibiting the release of proinflammatory cytokines. The purpose of this study was to investigate the role of GSK-3ß/ß-catenin signaling in mediating the effect of ghrelin on neuropathic pain and to understand the associated mechanisms. Chronic constriction injury (CCI) of the sciatic nerve was used to establish a rat model of neuropathic pain. Hyperalgesia and allodynia were evaluated by observing the mechanical withdrawal threshold and the thermal withdrawal latency. Wnt3a and ß-catenin protein expression and GSK-3ß phosphorylation were detected by western blotting analysis. The levels of tumor necrosis factor-α and IL-1ß were determined using an enzyme-linked immunosorbent assay. In addition, we used immunohistochemical analysis to determine the levels of GSK-3ß phosphorylation in the dorsal horn of the spinal cord. Intrathecal delivery of ghrelin effectively ameliorated CCI-induced mechanical allodynia and thermal hyperalgesia at 7 and 14 days and reduced the levels of tumor necrosis factor-α. Ghrelin inhibited CCI-induced GSK-3ß activation and ß-catenin overexpression in the spinal dorsal horn. Moreover, intrathecal injection of ghrelin suppressed the activation of GSK-3ß in the spinal dorsal horn of CCI rats, as assessed by immunohistochemical analysis. Our data indicated that ghrelin could markedly alleviate neuropathic pain by inhibiting the expression of ß-catenin, via the suppression of GSK-3ß activation, in the spinal cord of CCI rats.

Intrathecal morphine combined with ropivacaine induces spinal myoclonus in cancer patients with an implanted intrathecal drug delivery system: Three case reports.

RATIONALE: Although intrathecal opioid infusion has been used for decades for the treatment of severe pain, myoclonus as one of the complications of this therapeutic modality is now beginning to be recognized more. PATIENTS CONCERNS: Here, we report three patients who developed myoclonus after dose adjustment in intrathecal drug delivery system for the treatment of refractory cancer pain. DIAGNOSIS: Spinal myoclonus is a sudden, brief, shock-like muscle contractions originating from the central nervous system. In our cases, it occurred after opioid administration via intrathecal delivery system with no abnormality found in laboratory or imaging examinations. INTERVENTIONS: Spinal myoclonus can be treated effectively by reducing the dose or infusion rate as described in case 1, or changing from an intrathecal to systemic administration in case 2, or correcting infusion and bolus parameters mistakes in case 3. OUTCOMES: All patients recovered quickly after stopping or decreasing the intrathecal drug infusion. LESSONS: Prevention is more important than treatment as for spinal myoclonus. Pain management teams should be aware of this distressing complication. Dose of intrathecal drugs should not exceed the recommended maximal daily doses by guidelines and patient education is important for successful intrathecal analgesic therapy.