CircCOL5A1 inhibits proliferation,migration, invasion,and extracellular matrix production of keloid fibroblasts by regulating the miR-877-5p/EGR1 axis

BackgroundCircular RNA (circRNA) has been proved to mediate the biological functions of fibroblasts to participate in the regulation of keloid formation. However, the role of circCOL5A1 in keloid formation remains to be further confirmed.MethodsPrimary keloid fibroblasts were isolated form keloid tissues. The expression of circCOL5A1, microRNA (miR)? 877–5p, and early growth response 1 (EGR1) were determined by quantitative real-time PCR. Transfection experiments were carried out to explore the effects of circCOL5A1, miR-877–5p, and EGR1 on cell functions. Cell proliferation, migration, invasion and apoptosis were detected using cell counting kit 8 assay, colony formation assay, transwell assay and flow cytometry. The protein levels of apoptosis markers, extracellular matrix (ECM) markers and EGR1 were measured by western blot analysis. The mechanism of circCOL5A1 was confirmed by RNA pull-down assay, dual-luciferase reporter assay and RIP assay.ResultsOur data showed that circCOL5A1 was upregulated in keloid tissues and fibroblasts. Silencing of circCOL5A1 had an inhibition effect on proliferation, migration, invasion and ECM production, while had a promotion effect on apoptosis in keloid fibroblasts. MiR-877–5p could be sponged by circCOL5A1, and its overexpression could repress the biological functions of keloid fibroblasts. The rescue experiments showed that miR-877–5p inhibitor could reverse the suppressive effect of circCOL5A1 knockdown on the biological functions of keloid fibroblasts. In addition, EGR1 was a target of miR-877–5p, and its expression was positively regulated by circCOL5A1. The inhibition effect of miR-877–5p on the biological functions of keloid fibroblasts could be abolished by EGR1 overexpression.ConclusionIn summary, circCOL5A1 facilitates keloid fibroblast proliferation, migration, invasion and ECM production through the miR-877–5p/EGR1 axis, thereby potentially promoting keloid formation.     

LINC01534/miR-135b-5p/PTPRT axis regulates inflammatory response in loosening total hip replacement via modulating NF-κB signaling pathway

Aseptic loosening after total hip replacement brings adverse health outcomes and increased risk for complications. The resorptive activity of inflammatory cells activated by the presence of wear-generated debris plays a critical role in debris-induced osteolysis. Previous studies indicate that the abnormally expressed LINC01534 plays a critical role in inflammatory responses. In this study, we aimed to elucidate the functional role and underlying mechanism of LINC01534 in debris-induced osteolysis. We first confirmed that LINC01534 was highly expressed in hip cartilage tissues from aseptic loosening patients. By using an IL-1β-induced inflammation model mimicking debris-induced osteolysis, we demonstrated that LINC01534 promoted IL-1β-induced inflammatory response in hip chondrocytes. Knockdown of LINC01534 inhibited the expression of inflammatory IL-6, IL-8, and TNF-α in hip chondrocytes. Our results showed that LINC01534 functioned as a competing endogenous RNA (ceRNA) by sponging miR-135b-5p in hip chondrocytes. Moreover, bioinformatics analysis and luciferase reporter assay demonstrated that CCHC-Type Zinc Finger Nucleic Acid Binding Protein (PTPRT) is a downstream target of miR-135b-5p. Knockdown of PTPRT attenuated the IL-1β-induced inflammatory responses in hip chondrocytes. In addition, we revealed that inhibition of miR-135b-5p or overexpression of PTPRT could antagonize the effects of LINC01534 knockdown on inflammation attenuation in hip chondrocytes. Mechanistically, we demonstrated that LINC01534/miR-135b-5p/PTPRT axis regulated the NF-κB signaling pathway in hip chondrocytes. Taken together, our findings suggest that LINC01534/miR-135b-5p/PTPRT axis might be a valuable therapeutic target for the treatment of debris-induced osteolysis.     

3D-printed face protective shield in interventional radiology: Evaluation of an immediate solution in the era of COVID-19 pandemic

PurposeThe purpose of this study was to report the clinical evaluation of a 3D-printed protective face shield designed to protect interventional radiologists from droplet transmission of the SARS-Cov-2.Materials and methodsA protective face shield consisting in a standard transparent polymerizing vinyl chloride (PVC) sheet was built using commercially available 3D printers. The 3D-printed face shield was evaluated in 31 interventional procedures in terms of ability to perform the assigned intervention as usual, quality of visual comfort and tolerance using a Likert scale (from 1, as very good to 5, as extremely poor).ResultsThe mean rating for ability to perform the assigned intervention as usual was 1.7 ± 0.8 (SD) (range: 1–4). The mean visual tolerance rating was 1.6 ± 0.7 (SD) (range: 1–4). The mean tolerability rating was 1.4 ± 0.7 (SD) (range: 1–3).ConclusionThe 3D-printed protective face shield is well accepted in various interventions. It may become an additional option for protection of interventional radiologists.     

Intra-articular injection of culture-expanded adipose tissue-derived stem cells for knee osteoarthritis: Assessments with clinical symptoms and quantitative measurements of articular cartilage volume

BackgroundIntra-articular administration of adipose tissue-derived stem cells (ADSC) is an alternative treatment option for knee osteoarthritis (OA) after conventional treatment fails; however, the clinical results related to the severity of OA grade and changes of cartilage volumes after the administration of ADSC is unknown. This study aimed to determine 1) clinical outcomes after the ADSC administration in knee OA with consideration of radiographic OA grades and 2) changes in cartilage volumes after ADSC administration.MethodsThis observational study included 86 knees from 51 patients who underwent intra-articular administration of cultured ADSC; 47 patients (80 knees) completed follow-up for 6 months (follow-up rate: 93%). The Knee injury and Osteoarthritis Outcome Scores (KOOS) were reported at baseline and 1, 3, and 6 months after the administration. The efficacy rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) was evaluated using the KOOS. Cartilage volume of the knee joint was measured using quantitative 3-dimensional magnetic resonance imaging (3D-MRI) software at baseline and 6 months in 52 knees in 31 patients (follow-up rate: 61%).ResultsAll items on the KOOS except “sports/recreation” improved significantly at 6 months with more significance in knees with a Kellgren–Lawrence (KL) grade 2 or 3 compared with KL grade 4 knees. The OMERACT-OARSI responder at 6 months was significantly greater in knees with KL grade 2 or 3 (64%) than in knees with KL grade 4 (42%, p = 0.045). Cartilage volume changes varied among patients and were not related to the changes in KOOS after ADSC administration.ConclusionsIntra-articular administration of ADSC in knee OA improved KOOS at 6 months. The effects were more significant in knees with KL grade 2 or 3 than with KL grade 4. Changes in KOOS were not related to change in cartilage volumes after ADSC administration.     

Threshold for lateral meniscal body extrusion on MRI in middle-aged and elderly patients with symptomatic knee osteoarthritis

PurposeTo determine the MRI-based threshold of lateral meniscal body extrusion (LMBE) that are associated with meniscal damage, cartilage damage and radiological knee osteoarthritis (OA).Materials and methodsA total of 142 patients (59 men and 83 women) with a mean age of 57.2 ± 7.9 (SD) years (range: 41–77 years) with symptomatic knee OA were included. Radiological assessment was performed using the Kellgren-Lawrence scoring system. Meniscus and cartilage damage were assessed using the whole-organ magnetic resonance imaging score. Meniscal extrusion was quantified on coronal sections of intermediate-weighted MRI sequences. Differences between medial and lateral compartments in meniscal extrusion and incidence of tibiofemoral OA-related structural changes were assessed using Wilcoxon signed rank test and Bowker test. Receiver operating characteristic curves and Youden index were used for determining thresholds for meniscal extrusion.ResultsA total of 142 knees were assessed. Meniscal body extrusion distances between medial and lateral compartments were significantly different in the entire sample, and in subjects with and without radiological knee OA (P < 0.05 for all). The incidence of structural changes between medial and lateral compartments were significantly different (P = 0.003 for meniscal damage; P = 0.001 for femoral cartilage damage). Three mm and 2 mm were determined to be the optimal thresholds for medial and lateral meniscal body extrusion, respectively.ConclusionMedial and lateral meniscal body extrusion were associated with the incidence of OA-related knee structural changes in symptomatic patients with knee OA. A threshold of 2 mm for LMBE with respect to meniscal damage, cartilage damage and radiological knee OA was determined.     

Radiographic evaluation of linear wear of bipolar hemiarthroplasty devices in vivo

BackgroundThe indications for bipolar hemiarthroplasty (BHA) have been narrowing as those for total hip arthroplasty (THA) have been expanding in cases of femoral neck fracture and initial stages of osteonecrosis of femoral head (ONFH). It is difficult to measure wear in vivo after BHA because the equipment used has a dual bearing system with an inner head inside a metal outer cup. The present study aimed to (1) use a roentgenograph to measure linear wear in vivo after BHA with different acetabular conditions around the bipolar cup, and (2) compare the linear wear of polyethylene between integral bipolar cup (IBC) and Centrax prostheses.MethodsFrom among patients who had undergone BHA in our department after 1996, we analyzed 48 joints with osteoarthritis (OA) and without acetabular cartilage, as well as 25 joints with ONFH of stage 3 or less, in which the acetabular cartilage remains. Two types of bipolar cup prostheses were used: the IBC, which was gamma-sterilized in air using 2-Mrad irradiation, and the Centrax, which was gamma-sterilized in nitrogen using 3-Mrad irradiation. To image the inner head in vivo, we used high-pressure X-ray photography; we measured linear wear of the polyethylene with software using Martell Method 1.ResultsComparing mean annual linear wear between the OA and ONFH groups, using IBC prostheses in both groups, there was a significant difference (0.213 mm vs. 0.096 mm, respectively; P = 0.0177). There was a significant difference between the Centrax and IBC prostheses in OA patients in terms of linear wear (0.04 mm vs. 0.213 mm; P = 0.0181).ConclusionThe linear wear of polyethylene in BHA implants can be affected by the material used to manufacture the bipolar cup. Such implants should only be used for appropriate indications.     

Advanced preoperative three-dimensional planning decreases the surgical complications of using large-for-size grafts in pediatric living donor liver transplantation

BackgroundUsing “large-for-size” liver graft, graft-to-recipient weight ratio (GRWR) ≥4%, has been debated in pediatric liver transplantation due to possible graft compartment after abdomen closure. Meticulous preoperative evaluation with three-dimensional (3D) techniques may prevent these problems. This study compared the safety of large-for-size grafts in pediatric living donor liver transplantation (PLDLT) during the eras with or without 3D planning.MethodsWe defined the 3D era was after November 2017 due to our first implication of 3D printing for surgical planning and subsequently developing a 3D simulation implanting model. From November 2004 to July 2021, we enrolled 30 PLDLT patients with body weight (BW) < 10 kg and categorized them into conventional group: GRWR ≥4% before the 3D era (n = 9), 3D group: GRWR ≥4% in the 3D era (n = 8), and control group: GRWR <4% (n = 13). We followed and compared their clinical outcomes.ResultsThe 3D group had the lowest BW and the highest graft volume reduction rate, with all receiving modified left lateral segments (LLS), such as reduced LLS (n = 2), hyperreduced LLS (n = 5), and segment 2 monosegment (n = 1). Overall postoperative complications were similar in conventional and control groups but significantly lower in the 3D group (OR 0.06, 95% CI 0.006?0.70, p = 0.025). However, all groups had similar graft and patient survival at 1, 2, and 4 years.ConclusionAdvanced preoperative 3D planning can decrease post-transplant complications and increase the safety of large-for-size grafts in PLDLT.Level of EvidenceType of study: Retrospective comparative study; Evidence level: Level III     

Making the current non-surgical treatments for knee osteoarthritis more effective: Solutions from a diverse patient group

ObjectiveTo examine patient perceived solutions to barriers to effective non-surgical knee osteoarthritis (OA) treatments in a diverse racial/ethnic group.MethodsNominal groups were conducted with consecutive patients with knee OA at a medical center clinic, oversampling for African Americans with knee OA. Participants discussed potential solutions and rank-ordered their concerns.ResultsThirteen nominal groups with 46 knee OA patients were conducted with mean age, 60.8 years (standard deviation [sd], 10.0) and knee OA duration, 8.1 years (sd, 5.4); 22% were men, and 56% were African American. The following solutions were in the top three ranked solutions in 13 NGTs: (A) more research, effective and/or safer new medications/treatments, and joint cartilage restoration (8 groups; 15% votes [43/276]); (B) early diagnosis (2 groups; 7% votes [20/276]); (C) better and more effective communication (5 groups; 10% votes [29/276]); (D) public and patient education (4 groups; 8% votes [22/276]); (E) motivation and behavioral modification (4 groups; 9% votes [26/276]); (F) team approach (1 group; 1% votes [2/276]); (G) personalized medicine (6 groups; 8% votes [24/276]); (H) cheaper and more affordable medications and treatments (3 groups; 5% votes [15/276]).ConclusionsA diverse group of participants with knee OA identified several solutions to barriers to the effectiveness of current knee OA treatments. This new knowledge can inform the development and implementation of future interventions to improve the outcomes of people with knee OA.     

Characterizing response to a dynamic stability modeled approach for thumb carpometacarpal joint pain: A retrospective study

Study DesignRetrospective case series.IntroductionLiterature trends indicate that thumb dynamic stabilization may benefit clients with thumb carpometacarpal (CMC) joint pain and arthritis. There is minimal research investigating whether client characteristics predict responsiveness to hand therapy for thumb dynamic stabilization.Purpose of the Study1) To investigate how adults with thumb CMC joint pain responded to a hand therapy dynamic stabilization modeled intervention. 2) To determine if various client factors influenced responsiveness and to what extent.MethodsAn electronic medical record search identified adults treated from August 2009 through December 2015 for thumb CMC joint pain. Radiographs were retrospectively staged. Outcome measures were 1) Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) total disability score and 2) Numerical Pain Rating Scale (NPRS). Paired t-tests were performed to compare pre and post treatment measures. Multivariate analyses were used to investigate predictive factors.ResultsA total of 249 charts were analyzed. Large overall significant effects were noted for disability score (QuickDASH P <.001, X = 12.1, Cohen's d = 0.9). The average improvement of 2.1 (SD = 2.6) points exceeded the minimal clinically important difference (MCID) of 1.7 points on the NPRS pain scale. Significant predictors of QuickDASH Scores were radiographic staging, bilateral hand involvement and initial pain ratings. Significant predictors for change in pain scores (meeting or exceeding the minimal clinically important difference for the NPRS) were bilateral thumb involvement and initial “pain at worst” rating.ConclusionAfter completing hand therapy with a dynamic stabilization approach, clients had less pain and disability. Those who had unilateral thumb pain, or those who started with higher pain levels were most likely to have clinically meaningful improvements in pain. Clients in early CMC osteoarthritis (OA) stages responded better than those in later stages, indicating that early referral to therapy is important.     

Steen solution protects pulmonary microvascular endothelial cells and preserves endothelial barrier after lipopolysaccharide-induced injury

ObjectivesAcute respiratory distress syndrome represents the devastating result of acute lung injury, with high mortality. Limited methods are available for rehabilitation of lungs affected by acute respiratory distress syndrome. Our laboratory has demonstrated rehabilitation of sepsis-injured lungs via normothermic ex vivo and in vivo perfusion with Steen solution (Steen). However, mechanisms responsible for the protective effects of Steen remain unclear. This study tests the hypothesis that Steen directly attenuates pulmonary endothelial barrier dysfunction and inflammation induced by lipopolysaccharide.MethodsPrimary pulmonary microvascular endothelial cells were exposed to lipopolysaccharide for 4 hours and then recovered for 8 hours in complete media (Media), Steen, or Steen followed by complete media (Steen/Media). Oxidative stress, chemokines, permeability, interendothelial junction proteins, and toll-like receptor 4-mediated pathways were assessed in pulmonary microvascular endothelial cells using standard methods.ResultsLipopolysaccharide treatment of pulmonary microvascular endothelial cells and recovery in Media significantly induced reactive oxygen species, lipid peroxidation, expression of chemokines (eg, chemokine [C-X-C motif] ligand 1 and C-C motif chemokine ligand 2) and cell adhesion molecules (P-selectin, E-selectin, and vascular cell adhesion molecule 1), permeability, neutrophil transmigration, p38 mitogen-activated protein kinase and nuclear factor kappa B signaling, and decreased expression of tight and adherens junction proteins (zonula occludens-1, zonula occludens-2, and vascular endothelial-cadherin). All of these inflammatory pathways were significantly attenuated after recovery of pulmonary microvascular endothelial cells in Steen or Steen/Media.ConclusionsSteen solution preserves pulmonary endothelial barrier function after lipopolysaccharide exposure by promoting an anti-inflammatory environment via attenuation of oxidative stress, toll-like receptor 4-mediated signaling, and conservation of interendothelial junctions. These protective mechanisms offer insight into the advancement of methods for in vivo lung perfusion with Steen for the treatment of severe acute respiratory distress syndrome.     

Treatment of cT3N1M0/IIIA non–small cell lung cancer and the risk of underuse of surgery

ObjectiveSurgery may be underused for stage IIIA non–small cell lung cancer. Although an argument can be made for definitive chemoradiation for N2/3 mediastinal nodal disease, the role of a nonsurgical strategy is less clear in patients with cT3N1M0 stage IIIA given a lack of randomized data. We sought to determine the outcomes of patients with cT3N1M0 by treatment type from the National Cancer Database.MethodsThe National Cancer Database (2004-2014) was queried for patients with cT3N1M0 non–small cell lung cancer, known treatment modalities, and sequence. Comparisons between groups were performed using Mann–Whitney and chi-square tests. Cox regression was performed to identify predictors of overall survival. Propensity score matching analysis was performed to compare overall survival in surgery versus definitive chemoradiation.ResultsWe identified 1937 patients undergoing surgery (1518 up-front and 419 after neoadjuvant treatment) and 1844 patients undergoing definitive chemoradiation. Among patients undergoing surgery without prior treatment, 19% were overstaged and were found to have pN0, whereas 9.6% had pN2/3. Median overall survival was 33.1 months in the surgery group (± adjuvant/neoadjuvant) versus 18 months in definitive chemoradiation. To compare outcomes in balanced groups, we propensity matched 1081 pairs of patients. Median overall survival was 31.1 months in the surgery group compared with 19.1 months in the definitive chemoradiation group (P < .001). By multivariable analysis, surgery (hazard ratio, 0.65; confidence interval, 0.59-0.73), female sex (hazard ratio, 0.88; confidence interval, 0.79-0.98), age (hazard ratio, 1.02; confidence interval, 1.01-1.03), squamous histology (hazard ratio, 1.22; confidence interval, 1.07-1.38), and Charlson score of 2 (hazard ratio, 1.31; confidence interval, 1.11-1.54) were predictors of survival.ConclusionsIn the National Cancer Database, approximately half of patients with clinical T3N1M0 were treated with definitive chemoradiation rather than surgery. This practice should be avoided in operable patients, because surgical resection is associated with better survival.     

Biportal endoscopic versus microscopic discectomy for lumbar herniated disc: a randomized controlled trial

BACKGROUND CONTEXTBiportal endoscopic discectomy has been frequently performed in recent years and has shown acceptable clinical outcomes. However, evidence regarding its efficacy and safety remains limited.PURPOSEThis study aimed to compare the clinical efficacy and safety of biportal endoscopic with that of open microscopic discectomy in patients with single-level herniated lumbar discs.STUDY DESIGNProspective, randomized, multicenter, open-label, assessor-blind, non-inferiority controlled trial.PATIENT SAMPLESixty-four participants suffering from low back and leg pain with a single-level herniated lumbar disc and required discectomy.OUTCOME MEASURESOutcomes were assessed with the use of patient-reported outcome measures (PROMs), visual analog scale (VAS) pain score for surgical site, low back and lower extremity, Oswestry Disability Index (ODI) for lumbar disabilities, European Quality of Life-5 Dimensions value for quality of life, and painDETECT for neuropathic pain. Surgery-related outcomes such as hospital stay, operation time, and opioid usage were collected. Adverse events occurring during the follow-up period were also noted.METHODSAll participants were randomly assigned in a 1:1 ratio to undergo biportal endoscopic (biportal group) or microscopic discectomy (microscopy group). The primary outcome was the difference in ODI scores at 12-months post surgically based on a modified intention-to-treat strategy, with a non-inferiority margin of 12.8 points. The secondary outcomes included PROMs, surgery-related outcomes, and adverse events.RESULTSThe ODI score at the 12-month follow-up was 11.97 in the microscopy group and 13.89 in the biportal group (mean difference, 1.92; 95% confidence interval [CI], -3.50 to 7.34), showing the non-inferiority of biportal group. The results for the secondary outcomes were similar to those for the primary outcome. Creatinine phosphokinase ratios were low in the biportal group. Early surgical site pain was slightly lower in the biportal group (mean difference of VAS pain score at 48-hr, -0.98; 95% CI, -1.77 to -0.19). Adverse events including reoperation showed no significant difference between the groups.CONCLUSIONBiportal endoscopic discectomy was non-inferior to microscopic discectomy over a 12 month period. Biportal endoscopic discectomy is suggested to be a relatively safe and effective surgical technique with the slight advantage of reduced muscle damage. However, the clinical implications of surgical site pain should be carefully considered.     

Concomitant Patellar Tendon Tear (PTT) with Cruciate and/ Collateral ligament injury (Multi- Ligamentous Knee Injury –MLKI) and new pathoanatomical -Ganga PTT classification aids to strategize treatment options

IntroductionConcomitant patellar tendon (PT) tear with cruciate or multi-ligament knee injuries (MLKI) following high-velocity injury requires a systematic approach.MethodsThe study is a retrospective case series of patients (2008–2019) with concomitant PT ligament injury with cruciate or collateral ligament injury (MLKI), including bony avulsion injuries. Isolated cruciate and MLKI without patellar tendon tears are excluded. N = 32 patients (1 female and 31 male) are divided into two groups, Group 1 (11 patients) with PT tear and ACL tear and group 2 (21 patients) with PT tear and MLKIs. Patients were taken up for a single stage in types 1,2,3 and staged repair with reconstruction for types 4,5 of our new classification. All the patients are followed up regularly, and IKDC and Lyshom's score and objective radiological stress x-rays taken at each follow-upResultsIncidence of PTT combined injuries among all knee ligament injuries is 0.57%. The mean age was 35.09+/-11.96 SD(group1) and 36.55+/-11.89 SD(group2). The average follow-up was 34.45 months +/- 12.86SD (group 1) and 35.3 months +/- 15.75 SD (group2). Mean post-operative Lysholm score and IKDC score of group 1 and group 2 improvement was statistically significant p-value <=0.01. The mean post-operative ROM of the two groups were 132.73 (SD 6.46) (Group 1) and 111.75 (15.75) (Group 2) and was a statistically significant p-value <0.01. Residual lag of 30^° seen in all patients improved by 3rd month in group 1 and 6th month in group 2. Knee stiffness is seen in 2 patients and superficial infection in 2 patients.ConclusionPTT combined injuries are rare and occurs due to direct impact injuries. Single-stage PT repair with ACL reconstruction gives adequate stability, and extensor lag is eminent and needs supervised rehabilitation. PT with MLKI is a challenging scenario that can be performed in single-stage/multiple stages, depending on the injuries, surgical expertise, and institutional facilities. Newer simplified classification aids surgeons in planning a treatment strategy.     

MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model

BackgroundMicroRNA-145 (miR-145) reportedly alters the phenotype of vascular smooth muscle cells (VSMCs) from a proliferative to a contractile state. So far, viral or plasmid vectors have been experimentally used to transduce microRNAs into VSMCs. We hypothesized that a simple ex vivo microRNA delivery system using miR–145-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA NPs) could control the VSMC phenotype and prevent intimal hyperplasia.MethodsJugular vein grafts of male Japanese white rabbits were soaked in phosphate-buffered saline, control microRNA (cont-miR)-loaded PLGA NP solution or miR–145-loaded PLGA NP solution for 30 minutes (n = 8 for each). Vein grafts were implanted in the ipsilateral carotid artery and assessed 2 weeks after the implantation.ResultsQuantitative polymerase chain reaction analysis showed significantly higher miR-145 expression in the miR–145-treated group. The neointimal area was significantly smaller in the miR–145-treated group (phosphate-buffered saline-treated vs cont–miR-treated vs miR–145-treated group; 1.63 ± 0.52 mm² vs 1.67 ± 0.49 mm² vs 0.88 ± 0.34 mm², respectively; P < .01 for the miR–145-treated vs the cont–miR-treated group). In the miR–145-treated group, Ki–67-positive cells were significantly fewer, indicating lower VSMC proliferation. An inflammation-related molecule, CD40 expression was significantly reduced by miR–145-loaded PLGA NP treatment.ConclusionsLocal and sustained release of miR-145 by PLGA NPs attenuated intimal hyperplasia in the rabbit model by maintaining VSMCs in a contractile state. This simple ex vivo miR-145 delivery system would be promising toward broader clinical application.     

Epidemiological features of primary breast lymphoma patients and development of a nomogram to predict survival

BackgroundStudies on the epidemiology and prognosis of primary breast lymphoma (PBL) are lack for low incidence. Therefore, we aimed to investigate the epidemiological characteristics of PBL and develop nomograms to predict patient survival.MethodsData of patients who were diagnosed with PBL from 1975 to 2011 and incidence rate of PBL from 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Time-varying multivariable Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). Nomograms were constructed based on the independent prognostic factors identified in multivariate Cox regression analysis.ResultsA total of 1427 patients diagnosed with PBL were identified with the average age of 67.1 years. The overall incidence of PBL is 1.35/1,000,000 (adjusted to the United States standard population in 2000) from 1975 to 2017, with a significant upward trend by an annual percentage change (APC) of 2.91 (95%CI 2.29–3.94, P < 0.05). Age, sex, race, year of diagnosis, marital status, histological subtype, Ann Arbor Stage, and treatment modality were assessed as independent prognostic factors for OS and DSS by multivariable Cox regression (P < 0.05). Nomograms were constructed to predict the 1-, 3-, 5-, and 10- year OS and DSS. The concordance index (C-index) and calibration plots showed robustness and accuracy of the nomogram.ConclusionThe overall incidence of PBL was steadily increasing over the past four decades. Nomograms constructed can predicting 1-, 3-, 5-, and 10-year OS and identify patients with high-risk PBL.     

Discordance in lumbar bone mineral density measurements by quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women: a prospective comparative study

Background ContextLevel-specific lumbar bone mineral density (BMD) evaluation of a single vertebral body can provide useful surgical planning and osteoporosis management information. Previous comparative studies have primarily focused on detecting spinal osteoporosis but not at specific levels.PurposeTo compare the detection rate of lumbar osteoporosis between quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA); to explore and analyze the distribution models of QCT-derived BMD and DXA T-score at the specific levels; and to evaluate the diagnostic accuracy of level-specific BMD thresholds for the prediction of osteoporotic vertebral compression fracture (OVCF) in postmenopausal women.Study Design/SettingA comparative analysis of prospectively collected data comparing QCT-derived BMD with DXA T-score.Patient SampleA total of 296 postmenopausal women who were referred to the spine service of a single academic institution were enrolled.Outcome MeasuresQCT-derived BMD and DXA T-score at specific levels, with or without osteoporotic vertebral compression fracture.MethodsPostmenopausal women who underwent QCT and DXA within a week of admission from May 2019 to June 2022 were enrolled. The diagnostic criteria for osteoporosis recommended by the World Health Organization and the American College of Radiology were used for lumbar osteoporotic diagnosis. To evaluate differences in lumbar BMD measurements at specific levels, a threshold of T score=-2.5 and QCT-derived BMD = 80 mg/cm³ were used to categorize level-specific lumbar BMD into low and high BMD. Disagreements in BMD categorization between DXA and QCT were classified as a minor or major discordance based on the definition by Woodson. Data between QCT and DXA were visualized in a stacked bar plot and analyzed. Correlations between DXA and QCT at the specific levels were evaluated using Pearson's linear correlation and scatter plots. Curve fitting of BMD distribution, receiver operating characteristic (ROC) and area under the curve (AUC) for each single vertebral level was performed.ResultsOf the 296 patients, QCT diagnosed 61.1% as osteoporosis, 30.4% as osteopenia and 8.4% as normal. For those screened with DXA, 54.1% of the patients had osteoporosis, 29.4% had osteopenia and 16.6% had normal BMD. Diagnoses were concordant for 194 (65.5%) patients. Of the other 102 discordant patients, 5 (1.7%) were major and 97 (32.8%) were minor. Significant correlations in level-specific BMD between DXA and QCT were observed (p<.001), with Pearson's correlation coefficients ranging from 0.662 to 0.728. The correlation strength was in the order of L1 > L2 > L3 > L4. The low BMD detection rate for QCT was significantly higher than that for DXA at the L3 and L4 levels (65% vs. 47.9% and 68.1% vs 43.7, respectively, p<.001). Patients with OVCF showed significantly lower QCT-derived BMD (47.2 mg/cm³ vs. 83.2 mg/cm³, p<.001) and T-score (-3.39 vs. -1.98, p<.001) than those without OVCF. Among these patients, 82.8% (101/122) were diagnosed with osteoporosis by QCT measurement, while only 74.6% (91/122) were diagnosed by DXA. For discrimination between patients with and without OVCF, QCT-derived BMD showed better diagnosed performance (AUC range from 0.769 to 0.801) than DXA T-score (AUC range from 0.696 to 0.753).ConclusionQCT provided a more accurate evaluation of lumbar osteoporosis than DXA. The QCT-derived BMD measurements at a specific lumbar level have a high diagnostic performance for OVCF.     

Trends in surgery and survival for T1-T2 male breast cancer: A study from the National Cancer Database

BackgroundDespite evidence that early-stage male breast cancer (MBC) can be treated the same as in females, we hypothesized that men undergo more extensive surgery.MethodsPatients with clinical T1-2 breast cancer were identified in the National Cancer Database 2004–2016. Trends in surgery type and overall survival were compared between sexes.ResultsOf 9,782 males and 1,078,105 females, most were cN0 with AJCC stage I/II disease. Unilateral mastectomy was most common in men (67.1% vs. 24.1%, p < 0.001) and partial mastectomy in women (64.7% vs. 26.4%, p < 0.001), with no significant change over time. Over 1/3 of men received ALND in 2016. While overall survival was superior in females (HR 0.83, 95% CI 0.73–0.94, p = 0.003), partial mastectomy was associated with a 42% reduction in mortality risk for males (HR 0.58, 95% CI 0.4–0.8, p = 0.003).ConclusionsDe-escalation of surgery could be considered for MBC to improve survival and align with current standards of care.     

Survival outcomes of breast cancer patients with brain metastases: A multicenter retrospective study in Korea (KROG 16–12)

PurposeThis study evaluated the influence of prognostic factors and whole brain radiotherapy (WBRT) on overall survival (OS) of breast cancer (BC) patients with brain metastases (BM).Methods and materialsMedical records of 730 BC patients diagnosed with BM from 2000 to 2014 at 17 institutions were retrospectively reviewed. OS was calculated from BM diagnosis. Median follow-up duration was 11.9 months (range, 0.1–126.2).ResultsMedian OS was 15.0 months (95% CI: 14.0–16.9). Patients with different BC-specific graded prognostic assessment (GPA) scores showed significant differences (p < 0.001) in OS. In multivariate analysis, histologic grade 3 (p = 0.014), presence of extracranial metastasis (p < 0.001), the number of BM (>4; p = 0.002), hormone receptor negativity (p = 0.005), HER2-negativity (p = 0.003), and shorter time interval (<30 months) between BC and BM diagnosis (p = 0.007) were associated with inferior OS. By summing the β-coefficients of variables that were prognostic in multivariate analyses, we developed a prognostic model that stratified patients into low-risk (≤0.673) and high-risk (>0.673) subgroups; the high-risk subgroup had poorer median OS (10.1 months, 95% CI: 7.9–11.9 vs. 21.9 months, 95% CI: 19.5–27.1, p < 0.001). Univariate and multivariate analyses of propensity score-matched patients diagnosed with BM ≥ 30 months after BC diagnosis (n = 389, “late BM”) revealed that WBRT-treated patients showed superior OS compared to non-WBRT-treated patients (p = 0.070 and 0.030, respectively).ConclusionOur prognostic model identified high-risk BC patients with BM who might benefit from increased surveillance; if validated, our model could guide treatment selection for such patients. Patients with late BM might benefit from WBRT as initial local treatment.     

Discriminating between benign and malignant salivary gland tumors using diffusion-weighted imaging and intravoxel incoherent motion at 3 Tesla

PurposeThe purpose of this study was to retrospectively evaluate the diagnostic performances of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) for discriminating between benign and malignant salivary gland tumors (SGTs).Materials and methodsSixty-seven patients with 71 SGTs who underwent MRI examination at 3 Tesla were included. There were 34 men and 37 women with a mean age of 57 ± 17 (SD) years (age range: 20–90 years). SGTs included 21 malignant tumors (MTs) and 50 benign SGTs (33 pleomorphic adenomas [PAs] and 17 Warthin's tumors [WTs]). For each SGT, DWI and IVIM parameters, mean, skewness, and kurtosis of apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion volume fraction (f) were calculated and further compared between SGTs using univariable analysis. Areas under the curves (AUC) of receiver operating characteristic of significant parameters were compared using the Delong test.ResultsSignificant differences in ADC_mean, D_mean and D*_mean were found between SGTs (P < 0.001). The highest AUC values were obtained for ADC_mean (0.949) for identifying PAs and D*_mean (0.985) for identifying WTs and skewness and kurtosis did not outperform mean. To discriminate benign from malignant SGTs with thresholds set to maximize Youden index, IVIM and DWI produced accuracies of 85.9% (61/71; 95% CI: 75.6–93.0) and 77.5% (55/71; 95% CI: 66.0–86.5) but misdiagnosed MTs as benign in 28.6% (6/21) and 61.9% (13/21) of SGTs, respectively. After maximizing specificity to 100% for benign SGTs, the accuracies of IVIM and DWI decreased to 76.1% (54/71; 95% CI: 64.5–85.4) and 64.8% (46/71; 95% CI: 52.5–75.8) but no MTs were misdiagnosed as benign. IVIM and DWI correctly diagnosed 66.0% (33/50) and 50.0% (25/50) of benign SGTs and 46.5% (33/71) and 35.2% (25/71) of all SGTs, respectively.ConclusionIVIM is more accurate than DWI for discriminating between benign and malignant SGTs because of its advantage in detecting WTs. Thresholds set by maximizing specificity for benign SGTs may be advantageous in a clinical setting.