Background Perimembranous ventricular septal defects (pmVSDs) are one of the most common forms of congenital cardiac malformation in children. Results of transcatheter pmVSD closure remain debatable, ...prompting the need for further evaluation with regard to the safety and efficacy of this procedure. The aim of the study was to analyze the safety, efficacy, and long-term follow-up data associated with transcatheter closure of pmVSDs in children using symmetric occluders. Methods From December 2002 to October 2011, 525 children with pmVSDs between 2 and 12 years of age underwent transcatheter closure at three major heart centers in northwest China with symmetric pmVSD occluders. All patients were followed up until October 2011 with electrocardiogram and transthoracic echocardiography. Adverse events were recorded and evaluated. Results There were 252 male and 273 female patients with an average weight of 21.5 kg. The mean age at the time of transcatheter closure was 5.6 years, and the average ratio of pulmonic to systemic blood flow was 2.5. Transcatheter intervention was successfully performed in 502 patients (95.6%). The median device size implanted was 6.5 mm (range, 4 to 18 mm). During a median 45-month follow-up period, no mortality occurred. A total of three major adverse events (0.6%) were reported; two were valve-related. Meanwhile, 104 minor adverse events were detected during the entire follow-up period. All individuals experiencing major adverse events were younger than 3 years of age. The incidence of major adverse events in patients younger than 3 years old was significantly higher than that of patients older than 3 years old (3.75% versus 0.00%; Fisher's exact test p = 0.004). Conclusions Data from the current study suggest that transcatheter pmVSD closure using symmetric occluders displayed an excellent success rate and long-term follow-up results. The transcatheter approach provides a less-invasive alternative to open surgery and displays some promise in the treatment of pmVSDs in certain patient populations.
Abstract Background A history of previous abdominal surgery (PAS) may increase the complexity of laparoscopic colorectal surgery. The aim of this study was to investigate the impact of PAS on the ...outcomes of laparoscopic colorectal resection for colorectal cancer. Methods A total of 378 colorectal cancer patients (group A) with a history of PAS were 1:1 matched to 378 controls (group B) without PAS from our prospective laparoscopic colorectal surgery database. The two groups were matched for age, gender, body mass index, American Society of Anesthesiology score, tumor location, type of surgical procedure, and tumor stage. Results Patients in the two groups were well balanced with respect to baseline demographic and clinical characteristics. Group A was associated with significantly longer median operating time (220 versus 200 min; P = 0.002). Conversion rate in group A (63/378, 16.67%) was almost twice as high as that in group B (36/378, 9.55%; P = 0.004). Conversions caused by adhesion were more common in patients with a history of PAS (55.56% 35/63 versus 27.78% 10/36, P = 0.008). Postoperative recovery time, length of postoperative hospital stay, perioperative mortality and morbidity rate, lymph nodes harvested, circumferential resection margin positive rate, 3-y disease-free survival, and overall survival rate were not significantly different between the two groups. Conclusions Laparoscopic colorectal surgery for colorectal cancer patients with PAS is time consuming, but the incidence of a successfully completed laparoscopic colorectal resection remains high, and the short- and long-term outcomes are not affected by PAS.
Abstract Subtalar arthroereisis has been proved to be an efficient method for correcting flexible adult flatfoot. However, the optimal sinus tarsi implant is still debated and yet to be determined. ...In the present study, we compared the biomechanical effects of type I and II sinus tarsi implants in stage II adult-acquired flatfoot deformity (AAFD). First, a finite element model of stage II AAFD was established in which virtual surgery of subtalar arthroereisis was simulated. The indexes of plantar stress distribution, peak von Mises of the medial and lateral columns, strain of the medial ligaments and plantar fascia, arch height, talo-first metatarsal angle, calcaneus pitch angle, talonavicular coverage angle, and hindfoot valgus angle were all compared and analyzed. The results of the present study have validated the stage II AAFD finite element model by comparing the simulation results with the same parameters measured from weightbearing radiographs in the midstance phase. All the indexes showed that both types of arthroereisis can lower the plantar pressure and the strain of the medial ligaments that support the medial longitudinal arch and can shift the load of the medial column to the lateral column. They can also help to correct the deformity and restore the arch. However, the type II sinus tarsi implant design exhibited a more obvious effect than that of type I.
Genomic alterations in the juxtamembrane exon 14 splice sites in NSCLC lead to increased MET stability and oncogenesis. We present the largest cohort study of MET Exon 14 (METex14) using whole ...transcriptome sequencing.
A total of 21,582 NSCLC tumor samples underwent complete genomic profiling with next-generation sequencing of DNA (592 Gene Panel, NextSeq, whole exome sequencing, NovaSeq) and RNA (NovaSeq, whole transcriptome sequencing). Clinicopathologic information including programmed death-ligand 1 and tumor mutational burden were collected and RNA expression for mutation subtypes and MET amplification were quantified. Immunogenic signatures and potential pathways of invasion were characterized using single-sample gene set enrichment analysis and mRNA gene signatures.
A total of 533tumors (2.47%) with METex14 were identified. The most common alterations were point mutations (49.5%) at donor splice sites. Most alterations translated to increased MET expression, with MET co-amplification resulting in synergistic increase in expression (q < 0.05). Common coalterations were amplifications of MDM2 (19.0% versus 1.8% wild-type WT), HMGA2 (13.2% versus 0.98% WT), and CDK4 (10.0% versus 1.5% WT) (q < 0.05). High programmed death-ligand 1 > 50% (52.5% versus 27.3% WT, q < 0.0001) and lower proportion of high tumor mutational burden (>10 mutations per megabase, 8.3% versus 36.7% WT, p < 0.0001) were associated with METex14, which were also enriched in both immunogenic signatures and immunosuppressive checkpoints. Pathways associated with METex14 included angiogenesis and apical junction pathways (q < 0.05).
METex14 splicing alterations and MET co-amplification translated to higher and synergistic MET expression at the transcriptomic level. High frequencies of MDM2 and CDK4 co-amplifications and association with multiple immunosuppressive checkpoints and angiogenic pathways provide insight into potential actionable targets for combination strategies in METex14 NSCLC.
Abstract Background context Microcirculatory dysfunction of the sub-endplate is considered to reduce nutrient supply to the intervertebral disc (IVD); however, direct interruption or destruction of ...blood vessels in the bone marrow of the vertebrae body adjacent to the endplate has not yet been described, especially with regard to the calcification and ossification of the cartilaginous endplate occurring during IVD degeneration. Purpose The purpose of the study was to evaluate the causal relationship between IVD degeneration and blocking of the main blood supply gateway through the endplate. Study design/setting The study describes a new IVD degeneration model induced by ischemic sub-endplate. Patient sample A total of 40 Sprague-Dawley rats were included in the study group. Outcome measures To assess disc height, a radiograph was taken each month for 4 months. Changes in endplate, nucleus pulposus (NP), and annulus fibrosus (AF) were evaluated by histochemical and immunohistochemical staining to detect IVD degeneration. Methods Injection of 30 μL absolute ethanol into the IVD of rat tail at Co7/Co8 was used to induce injury. Controls were injected with 30 μL of phosphate-buffered saline into the IVD at Co8/Co9. Results In the ethanol-injected group, disc height gradually decreased and bone sclerosis developed in the endplate. In the NP, cell transformation occurred, changing from predominantly vacuolar cells to chondrogenic cells and eventually fibrocartilaginous cells, along with fibrosis of the NP. As degeneration progressed, the AF developed disordered morphology and rough lamellae, and eventually ruptures and fibrosis. The extent of degeneration increased gradually over time, while the wavy tidemark of the growth plate regressed, and eventually disappeared. Initially positive collagen type II staining gradually decreased on the ischemic side of the sub-endplate. Except at the 3-month time point, expression of collagen type II, aggrecan, and Sox-9 in NP decreased gradually as degeneration progressed, compared with the control group. Conclusions This model successfully reproduced IVD degeneration, which could be used for etiological studies on IVD degeneration and investigation of nutrient supply disturbance, and may provide a theoretical foundation for clinical intervention and therapy for IVD degeneration in the future.
To evaluate outcomes relative to treatment using systemic methotrexate (MTX) alone or systemic MTX combined with ultrasound (US)-guided local injection of potassium chloride (KCl) or MTX in women ...with live tubal ectopic pregnancies.
Case-control study (Canadian Task Force classification II-2).
Departments of Obstetrics and Gynecology in 2 hospitals in China.
Eighty-two women with live tubal ectopic pregnancies.
Participants in the study received treatment using either systemic MTX (n = 37; systemic treatment group) or systemic MTX and US-guided local injection of either MTX or KCl (n = 45; combined treatment group).
Patient clinical features and outcomes were compared. There were no significant differences between the patient groups insofar as baseline gestational age, β-human chorionic gonadotropin concentration, or size of conceptus. The success rate in patients who received combined therapy (93.3%) was much higher than in those who received only systemic treatment (73.0%) (p < .05). In the combined treatment group, the success rate was similar between women who received locally injected KCl (95.2%) and those who received locally injected MTX (91.7%).
The significantly higher success rate in patients who received combined US-guided local injection and systemic MTX suggests that this is an efficient nonsurgical option in women with tubal pregnancy, high serum β-human chorionic gonadotropin concentration, and fetal cardiac activity.
Background Osteopontin (OPN) is identified as one of the leading genes that promote the metastasis of malignant tumor through binding to CD44v6 and integrin. The purpose of the current study was to ...assess the prognostic significance of OPN and CD44v6 in patients with non-small cell lung cancer (NSCLC). Methods Tissue microarray was used to detect the expression of OPN and CD44v6 in 159 NSCLC patients undergoing complete pulmonary resection in our hospital between 2003 and 2006. The correlations among OPN, CD44v6, and clinicopathologic data were analyzed using χ2 testing analysis. The prognostic values of OPN and CD44v6 were evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. Results OPN and CD44v6 were both independent predictors for overall survival and disease-free survival. When OPN and CD44v6 were considered together, the predictive range was extended and the sensitivity was improved, especially for those patients with stage I NSCLC. The 6-year overall survival and disease-free survival rates in OPN+ or CD44v6+ patients were 49.1% and 39.6%, respectively, which were significantly lower than those of OPN–/CD44v6– patients (64.4% and 47.7%, respectively), and were higher than those of OPN+/CD44v6+ patients (16.4% and 14.8%, respectively). Stratification into OPN+/CD44v6+, OPN+ or CD44v6+, or OPN–/CD44v6– groups, based on the expression OPN and CD44v6, could efficiently predicted outcomes (p < 0.001) of NSCLC patients. Conclusions The combination of OPN and CD44v6 is a valuable independent predictor of tumor recurrence and survival in NSCLC patients.
Cofilin promotes actin filament turnover by severing and depolymerizing actin filaments. Cofilin is inactivated by phosphorylation on Ser-3 by LIM-kinase1 (LIMK1) and is activated when protein ...phosphatase Slingshot-1L (SSH1L) dephosphorylates this residue. The authors have shown that Ca-induced cofilin dephosphorylation is mediated by calcineurin (Cn)-dependent activation of SSH1L. In this study, Ca/calmodulin-dependent protein kinase II (CaMKII) is shown to negatively regulate SSH1L activity and bind to SSH1L in a complex with 14-3-3. Phosphorylation of LIMK1 by CaMKII and its subsequent activation regulates the subcellular localization of SSH1L. Based on these findings, the authors suggest that CaMKII and Cn provide a switch-like mechanism that controls Ca-dependent LIMK1, SSH1L and cofilin activation, and subsequently actin cytoskeletal reorganization.
Abstract Background Acute heart failure (AHF), a common and growing health-concern worldwide, is associated with high risk of post-discharge rehospitalization and mortality. Existing evidence ...indicates potential therapeutic benefits of serelaxin in Caucasian AHF patients, while corresponding data in Asians remain scarce. RELAX-AHF-ASIA, a multinational, randomized, double-blind, placebo-controlled, phase-III trial, will evaluate the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients, using novel assessments. Methods Patients with AHF, systolic blood pressure ≥125mmHg and mild-to- moderate renal dysfunction will be randomized within 16 hours of presentation to receive 48-hour intravenous infusion of 30µg/kg/day serelaxin or placebo in addition to standard therapy. The composite primary-endpoint includes: (1) treatment success (moderate/marked improvement in patient-reported dyspnea and physician-assessed signs of congestion on Day-2); (2) treatment failure (in-hospital worsening of signs and/or symptoms of heart failure HF requiring intensification of intravenous HF therapy or mechanical ventilation, renal/circulatory support, rehospitalization due to HF/renal-failure, or death through Day-5); and (3) unchanged status. Secondary-endpoints include time to in-hospital worsening HF through Day-5 and all-cause and cardiovascular deaths through Day-180. Conclusion RELAX-AHF-ASIA, the largest randomized clinical trial in Asian AHF patients to-date, has a novel composite primary-endpoint and the potential to become a hallmark of AHF trials.
Abstract Background MicroRNA-223 (miR-223) is a hematopoietic lineage cell-specific microRNA. However, a significant amount of miR-223 has been identified in vascular smooth muscle cells (VSMCs) and ...vascular walls that should not have endogenous miR-223. Objectives This study sought to determine the sources of miR-223 in normal and atherosclerotic arteries and the role of miR-223 in atherogenesis. Methods The levels and sources of miR-223 in blood cells (leukocytes and platelets), serum, blood microparticles, VSMCs, and vascular walls were determined. Both in vivo and in vitro studies were conducted to evaluate miR-223 secretion by blood cells and the ability of miR-223 to enter VSMCs and vascular walls. Subsequent changes in and the effects of miR-223 levels on serum and arteries in atherosclerotic animals and patients were investigated. Results Blood cells were able to secrete miR-223 into serum. MicroRNA-223 from blood cells was the most abundant cell-free miRNA in blood. Blood cell–secreted miR-223 could enter VSMCs and vascular walls, which produced strong biological effects via its target genes. In both atherosclerotic apolipoprotein-E knockout mice and patients with atherosclerosis, miR-223 levels were significantly increased in serum and atherosclerotic vascular walls. The atherosclerotic lesions in apolipoprotein-E knockout mice were exacerbated by miR-223 knockdown. The effect of miR-223 on atherogenesis was verified using miR-223 knockout mice. Conclusions Blood cell–secreted miR-223 enters vascular cells and walls, and appears to play important roles in VSMC function and atherogenesis. As a novel endocrine genetic signal between blood cells and vascular cells, miR-223 may provide a novel mechanism and new therapeutic target for atherosclerosis.
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