Adjuvant Osimertinib in Patients With Stage IB to IIIA EGFR Mutation-Positive NSCLC After Complete Tumor Resection: ADAURA China Subgroup Analysis.

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People's Republic of China from ADAURA. Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. Results: Of 682 patients enrolled globally, 159 patients in the People's Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13-0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17-0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21-1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

Ferroptosis is Involved in the Pharmacological Effect of Ginsenoside.

Ginsenoside is the principal active ingredient in ginseng. Several investigations have found that ginsenosides have anti-inflammatory, antioxidant, anti-apoptotic, anti-cancer, and antiallergic activities. Ferroptosis is an iron-dependent, non-apoptotic form of cell-regulated death caused by lipid peroxidation. Iron, lipid, and amino acid metabolism orchestrate the complex ferroptosis response through direct or indirect regulation of iron accumulation or lipid peroxidation. More and more research has demonstrated that ginsenoside impacts illnesses via ferroptosis, implying that ferroptosis might be employed as a novel target of ginsenoside for disease therapy. This article examines the molecular mechanism of ferroptosis as well as the current advancement of ginsenoside in influencing disorders via ferroptosis.

Prevotella histicola Prevented Particle-Induced Osteolysis via Gut Microbiota-Dependent Modulation of Inflammation in Ti-Treated Mice.

Wear particles generated from total joint replacements induce chronic osteolysis mediated by inflammatory upregulation, which leads to implant failure. Recent studies have suggested an important role of the gut microbiota in modulating the host's metabolism and immune system, leading to alterations in bone mass. Following gavage with P. histicola, micro-CT and HE staining revealed that osteolysis was significantly reduced in titanium (Ti)-treated mice. Immunofluorescence analysis revealed an increased macrophage (M)1/M2 ratio in the guts of Ti-treated mice, which decreased when P. histicola was added. P. histicola was also found to upregulate the tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the gut, reduce the levels of inflammatory factors IL-1ß, IL-6, IL-8, and TNF-α, primarily in the ileum and colon, and decrease the expression of IL-1ß and TNF-α and increase the level of IL-10 in the serum and cranium. Furthermore, P. histicola treatment resulted in a significant downregulation of CTX-1, RANKL, and RANKL/OPG. These findings demonstrate that P. histicola significantly mitigates osteolysis in Ti-treated mice by improving intestinal microbiota that repairs intestinal leakage and reduces systemic and local inflammation which in turn inhibits RANKL expression for bone resorption. P. histicola treatment may thus be therapeutically beneficial for particle-induced osteolysis.

Analysis of Flavonoid Metabolism during the Process of Petal Discoloration in Three Malus Crabapple Cultivars.

Malus crabapple has high ornamental and ecological value. Here, the flavonoids in the petals of three pink Malus crabapple cultivars, Malus 'Strawberry Parfait' (GD), M. 'Pink Spire' (FY), and M. 'Hongyi' (HY), at the bud stage (flower buds are swollen, and the pistils and stamens are about to appear; L), full bloom stage (the flowers are fully open, and the stigma and anthers have recently appeared; S), and end bloom stage (the stigma and anthers are dry; M) were identified, and their abundances were determined. First, Kodak Color Control Patches were used to describe the colors of petals, and a colorimeter was used to determine the phenotypic values of flower colors. Flavonoids were determined using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In all three crabapple cultivars, the red and yellow hues of the petals gradually disappeared, the color of the flowers changed from bright to dull, and the petals gradually faded. The extent of fading of the red hue of the petals was highest in GD, followed by FY and HY. A total of 302 metabolites were detected in the three cultivars. The content of total flavonoids in the three cultivars significantly differed, but there were no significant differences among species. The total flavonoid content of the three crabapple varieties was highest in HY, followed by FY and GD. The content of the anthocyanins delphinidin-3-O-sophoricoside-5-O-glucoside, pelargonidin-3-O-(6″-O-malonyl)glucoside, pelargonidin-3-O-glucoside, peonidin-3-O-glucoside, and cyanidin-3-O-arabinoside decreased significantly, which resulted in the discoloration of GD petals from L to M. The flavonoids and flavonols in FY might interact with anthocyanins in metabolic pathways. The content of these five anthocyanins decreased slowly, which resulted in the weaker discoloration of FY and HY compared with GD. The content of the five anthocyanins in HY did not decrease significantly, but the content of chalcone increased significantly, which might facilitate the production of anthocyanin auxiliary pigments and result in less pronounced fading of the petals. Cyanidin-3-O-arabinoside and pelargonidin-3-O-glucoside were the key flavonoids of the three crabapple cultivars. The total content and changes in anthocyanins were the key factors affecting petal color development and fading. Nonanthocyanin polyphenols, such as flavonoids, flavonols, and chalcone, are auxiliary pigments that affect petal fading. Overall, the results of this study provide new insights into the mechanism underlying the fading of the color of Malus crabapple flowers, and these new insights could aid the breeding of cultivars with different flower colors.

Comparison Between Periarticular Analgesia Versus Intraarticular Injection for Effectiveness and Safety After Total Knee Arthroplasty.

PURPOSE: In most studies, local infiltration analgesia (LIA) can provide better analgesic effect in the early postoperative period, but the optimal technique is unknown. Our study was designed to evaluated the early clinical efficacy and safety of periarticular analgesia versus intraarticular injection in Total knee arthroplasty (TKA). DESIGN: A prospective study was conducted on 100 patients admitted for TKA. Subjects were divided into two groups: 50 in group A, 50 in Group B. METHODS: Patients in group A received periarticular analgesia with ropivacaine 300 mg and morphine 5 mg (the drugs were diluted with saline to 50 ml) in the periosteal borders, posterior capsule and extensor apparatus and subcutaneous tissues during surgery. After stitching of joint capsule, tranexamic acid (TXA) 2 g (20 ml) was injected into the articular cavity. Group B patients had all of the 70 mL mixture (ropivacaine 300 mg, morphine 5 mg and TXA 2 g) injected intraarticularly after stitching of the joint capsule. We assessed postoperative length of stay (LOS), knee functional outcome, pain, and complications after surgery. FINDINGS: There was no statistical difference in visual analog scale (VAS) scores for knee pain between the two groups on postoperative day (POD)1, 3, or 30 (P > .05). Mean postoperative LOS was 7.40 ± 1.98 days in Group A, compared to 8.02 ± 2.09 days in Group B (P > .05). No significant differences between groups were seen in the mean swelling ratio (P > .05), and no significant differences were found in the Hospital for Special Surgery (HSS) knee score and range of motion (ROM) at 30 days follow-up (P > .05). There was also no statistical difference in the incidence of complications (such as superficial wound infection, deep vein thrombosis (DVT) and nausea and vomiting) between the Group A and the Group B. CONCLUSIONS: In conclusion, it seems that intraarticular injection had a similar analgesic effect compared with periarticular injection when adopting a multi-modal analgesia regimen. Our results suggest that there is no obvious advantage with the use of periarticular injections compared to intraarticular injection. The authors believe that intraarticular injection may be a better technique compared with periarticular injections in the absence of a drainage tube because intraarticular injection can reduce the number of surgical steps and have similar postoperative outcomes.

A combined diagnostic approach based on serum biomarkers for sarcopenia in older patients with hip fracture.

OBJECTIVE: To develop prediction models for sarcopenia in older patients with hip fracture based on a specific set of serum biomarkers aimed at estimating appendicular skeletal muscle mass and diagnosing sarcopenia. METHODS: Older patients with hip fracture admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2020 to June 2021 were recruited, screened for sarcopenia and tested for peripheral blood levels of specific serum biomarkers preoperatively. Participants were randomly divided into a training set and test set. Common factors were extracted from selected biomarkers through factor analysis, and regression models were established in the training set and verified in the test set. RESULTS: A total of 212 patients were enrolled, and the prevalence of sarcopenia was 22.8% in men and 19.5% in women. Significant differences in cystatin C, estimated glomerular filtration rate based on cystatin C, sarcopenia index, new sarcopenia index, haemoglobin and albumin were observed between patients with and without sarcopenia. Two regression models were developed in the training set. The validation of the test set confirmed that the linear regression model showed good consistency in predicting appendicular skeletal muscle mass index, while the logistic regression model showed high accuracy in predicting sarcopenia. CONCLUSIONS: Both prediction models exhibited potential clinical application value for estimating appendicular skeletal muscle mass and predicting sarcopenia in older patients with hip fracture, providing new insights into the serological diagnosis of sarcopenia.

Characteristics and clinical outcomes in patients with prior chest radiation undergoing TAVR: Observations from PARTNER-2.

OBJECTIVES: The purpose of this study is to investigate the viability of transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS) in patients with prior chest radiation therapy (cXRT). BACKGROUND: Since patients with prior cXRT perform poorly with surgical aortic valve replacement, TAVR can be a viable alternative. However, clinical outcomes after TAVR in this patient population have not been well studied. METHODS: From the pooled registry of the placement of aortic transcatheter valves II trial, we identified patients with and without prior cXRT who underwent TAVR (n = 64 and 3923, respectively). The primary outcome was a composite of all-cause death and any stroke at 2 years. Time to event analyses were shown as Kaplan-Meier event rates and compared by log-rank testing. Hazard ratios (HRs) were estimated and compared by Cox proportional hazards regression model. RESULTS: There was no significant difference in the primary outcome between the patients with and without prior cXRT (30.7% vs. 27.0%; p = 0.75; HR, 1.08; 95% confidence interval, 0.66-1.77). Rates of myocardial infarction, vascular complications, acute kidney injury, or new pacemaker implant after TAVR were not statistically different between the two groups. The rate of immediate reintervention with a second valve for aortic regurgitation after TAVR was higher among the patients with prior cXRT. However, no further difference was observed during 2 years follow-up after discharge from the index-procedure hospitalization. CONCLUSIONS: TAVR is a viable alternative for severe symptomatic AS in patients who had cXRT in the past.

Total hip revision with custom-made spacer and prosthesis: A case report.

BACKGROUND: Both periprosthetic joint infections (PJIs) and severe femoral segmental defects are catastrophic complications of total hip arthroplasty (THA), and both present a significant challenge in revisional surgery. There are limited data available to guide clinical decision making when both occur concurrently. CASE SUMMARY: A 61-year-old woman presented with a 6-mo history of a sinus tract at the site of her original THA incision. Radiological imaging revealed a total hip joint implant with an ipsilateral segmental femoral defect. Based on histological, radiological, laboratory, and clinical features, a diagnosis of concurrent chronic PJI and segmental femoral defect (Type IIIB, Paprosky classification) was made. After multidisciplinary team discussion, three-dimensional (3D)-printed, custom-made antibiotic spacers were created that could be used to mold antibiotic-loaded cement spacer. These were placed following PJI debridement in the first stage of revision surgery. After the PJI was eliminated, a 3D-printed, custom-made, femoral prosthesis was created to repair the considerable femoral defect. After 20-mo follow-up, the patient had excellent functional outcomes with a near-normal range of hip movement. So far, neither evidence of recurrent infection nor loosening of the prosthesis has been observed. CONCLUSION: We describe a case of "two-stage, custom-made" total hip revision to treat PJI with a concurrent segmental femoral defect. Use of a personalized, 3D-printed spacer and proximal femoral prosthesis led to satisfactory hip function and no early postoperative complications. Use of a customized implant provides surgeons with an alternative option for patients where no suitable spacer or implant is available. However, the long-term function, longevity, and cost-effectiveness of the use of custom-made prostheses have yet to be fully explored.

An emerging role of Prevotella histicola on estrogen deficiency-induced bone loss through the gut microbiota-bone axis in postmenopausal women and in ovariectomized mice.

BACKGROUND: The gut microbiota (GM)-bone axis has emerged as a crucial mediator of bone homeostasis. Estrogen deficiency-induced bone loss is closely associated with an altered GM. However, the underlying mechanisms remain unclear. OBJECTIVES: We sought to explore the putative effects of GM on estrogen deficiency-induced bone loss and determine a potential mechanism. METHODS: Fecal samples collected from postmenopausal women with osteoporosis (PMO) and with normal bone mass (PMN) were examined by 16S ribosomal RNA (rRNA) gene sequencing and analysis. Prevotella histicola, a typical species of Prevotella, was orally given to female C57BL6/J mice after ovariectomy [ovariectomized (OVX)]. The primary outcomes were changes in bone microstructures as measured by micro-computed tomography scanning and bone histomorphometry analysis. Secondary outcomes included changes in osteoclast activity, the expression of osteoclastogenic cytokines, and gut permeability, which were measured by ELISA, qRT-PCR, western blot, and immunofluorescence. RESULTS: As demonstrated through 16S rRNA gene sequencing and analysis, the GM in the PMO group featured a significantly decreased proportion of the genus Prevotella in comparison with that in the PMN group (∼60%, P < 0.05). In animal experiments, P. histicola-treated OVX mice maintained a relatively higher bone volume than OVX controls. Mechanistically, the protective effects of P. histicola on bone mass were found to be associated with its modulation of gut permeability as well as its inhibitory effects on osteoclast activity which function by attenuating osteoclastogenic cytokine expression. CONCLUSIONS: The GM diversity and composition between the PMN and PMO groups were significantly different. In particular, the proportion of the genus Prevotella was notably higher in the PMN group, demonstrating its potential bone-protective effects on osteoporosis. Further animal study using osteoporotic mice showed P. histicola could prevent estrogen deficiency-induced bone loss through the GM-bone axis. Thus, P. histicola may serve as a therapeutic agent or target for osteoporosis treatment.

Left coronary artery calcification patterns after coronary bypass graft surgery: An in-vivo optical coherence tomography study.

OBJECTIVES: We sought to evaluate the severity and patterns of calcifications in the left main coronary artery (LMCA) and proximal segments of left anterior descending coronary artery (LAD) and left circumflex artery (LCX) using optical coherence tomography (OCT) in patients with and without prior coronary artery bypass grafting (CABG). BACKGROUND: CABG may accelerate upstream calcium development. METHODS: OCT images (n = 76) of the LMCA bifurcation from either the LAD or LCX in 76 patients with at least one patent left coronary graft, on average 7.0 ± 5.6 years post-CABG, were compared with 148 OCT images in propensity-score-matched non-CABG controls. RESULTS: Minimum lumen areas in the LMCA, LAD, and LCX in post-CABG patients were smaller than non-CABG controls. Maximum calcium arc and thickness as well as calcium length were greater in the LMCA and LCX, but not in the LAD in post-CABG patients versus non-CABG controls. Calcium located at the carina of a bifurcation, calcified nodules (CN), thin intimal calcium, and lobulated calcium were more prevalent in post-CABG patients. After adjusting for multiple covariates, prior CABG was an independent predictor of calcification at the carina of a bifurcation (odds ratio [OR] 5.77 [95% confidence interval, CI: 1.5-21.6]), thin intimal calcium (4.7 [1.5-14.4]), and the presence of a CN (15.60 [3.2-76.2]). CONCLUSIONS: Prior CABG is associated with greater amount of calcium in the LMCA and the proximal LCX, as well as higher prevalence of atypical calcium patterns, including CN, thin or lobulated calcium, and calcifications located at the carina of a bifurcation, compared with non-CABG controls.

Ipsilateral femoral neck and intertrochanteric fractures with posterior dislocation of the hip: A report of two cases.

Traumatic hip dislocation usually occurs in young patients, with the increasing number of high-energy injuries, and 62-93% of reported adult traumatic hip dislocations were caused by high-speed motor vehicle crashes. However, ipsilateral femoral neck fractures and intertrochanteric fractures with posterior dislocation of the hip are extremely rare, and this injury poses a challenge to orthopaedic surgeons. Here, we report two cases of simultaneous ipsilateral femoral neck fracture, intertrochanteric fracture and posterior dislocation of the hip joint in young patients who were treated with proximal femoral locking compression plate (PFLCP). The long-term follow-up (one patient was followed up for 3 years and the other for 7 years) showed that these patients had excellent functional outcomes with near-normal ranges of hip movement. The authors believe that using smaller plates with the lateral PFLCP is an acceptable method to treat this injury in young patients.

Mortality After Repeat Revascularization Following PCI or CABG for Left Main Disease: The EXCEL Trial.

OBJECTIVES: The aim of this study was to investigate the incidence and impact on mortality of repeat revascularization after index percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD). BACKGROUND: The impact on mortality of the need of repeat revascularization following PCI or CABG in patients with unprotected LMCAD is unknown. METHODS: All patients with LMCAD and site-assessed low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores randomized to PCI (n = 948) or CABG (n = 957) in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial were included. Repeat revascularization events were adjudicated by an independent clinical events committee. The effect of repeat revascularization on mortality through 3-year follow-up was examined in time-varying Cox regression models. RESULTS: During 3-year follow-up, there were 346 repeat revascularization procedures among 185 patients. PCI was associated with higher rates of any repeat revascularization (12.9% vs. 7.6%; hazard ratio: 1.73; 95% confidence interval: 1.28 to 2.33; p = 0.0003). Need for repeat revascularization was independently associated with increased risk for 3-year all-cause mortality (adjusted hazard ratio: 2.05; 95% confidence interval: 1.13 to 3.70; p = 0.02) and cardiovascular mortality (adjusted hazard ratio: 4.22; 95% confidence interval: 2.10 to 8.48; p < 0.0001) consistently after both PCI and CABG (pint = 0.85 for both endpoints). Although target vessel revascularization and target lesion revascularization were both associated with an increased risk for mortality, target vessel non-target lesion revascularization and non-target vessel revascularization were not. CONCLUSIONS: In the EXCEL trial, repeat revascularization during follow-up was performed less frequently after CABG than PCI and was associated with increased mortality after both procedures. Reducing the need for repeat revascularization may further improve long-term survival after percutaneous or surgical treatment of LMCAD. (EXCEL Clinical Trial; NCT01205776).

Impact of Smoking on Platelet Reactivity and Clinical Outcomes After Percutaneous Coronary Intervention: Findings From the ADAPT-DES Study.

BACKGROUND: Smoking is a potent risk factor for coronary artery disease; however, prior studies describe increased platelet inhibition with clopidogrel among smokers, and some studies report improved outcomes among smokers, a finding described as the smoker's paradox. This study assessed the relationship between platelet reactivity and clinical outcomes after percutaneous coronary interventions among current smokers and nonsmokers. METHODS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. Platelet reactivity was assessed by the VerifyNow point-of-care assay; high on-treatment platelet reactivity (HPR) was defined as P2Y12 reaction units >208. A propensity-adjusted multivariable analysis was performed to determine the relationship between current smoking, platelet reactivity, and subsequent adverse events. RESULTS: Among 8582 patients, 22.6% were active smokers at the time of their percutaneous coronary intervention procedure. Current smokers were younger and had fewer comorbidities compared with nonsmokers. Current smokers had lower mean P2Y12 reaction units and lower rates of HPR compared with nonsmokers. Current smokers had similar rates of adverse events compared with nonsmokers. HPR was associated with higher rates of adverse events for both smokers and nonsmokers; however, there was evidence of interaction between smoking status and the effect of HPR. Smokers with HPR had significantly higher rates of stent thrombosis. Adverse event rates were highest among current smokers with HPR. CONCLUSIONS: Current smoking was associated with lower P2Y12 reaction units and lower rates of HPR on average; however, the combination of current smoking and HPR was associated with high rates of stent thrombosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Effects of Polypropylene Fibre and Strain Rate on Dynamic Compressive Behaviour of Concrete.

This paper presents an experimental study on the dynamic compressive behaviour of polypropylene (PP) fibre reinforced concrete under various strain rates using split Hopkinson pressure bar (SHPB) equipment. The effects of PP fibre content and strain rate on the dynamic compressive stress-strain relationship and failure patterns were estimated. The results indicated that the addition of PP fibre enhanced the dynamic compressive properties of concrete mixtures although it resulted in a significant reduction in workability and a slight decrease in static compressive strength. Considering the workability, static compressive strength and dynamic compressive behaviour, the optimal PP fibre content was found to be 0.9 kg/m3 as the mixture exhibited the highest increase in dynamic compressive strength of 5.6%, 40.3% in fracture energy absorption and 11.1% in total energy absorption; further, it showed the least reduction (only 5.8%) in static compressive strength among all mixtures compared to the reference mixture without fibre. For all mixtures, the dynamic compressive properties, energy absorption capacity, strain at peak stress, ultimate strain and dynamic increase factor (DIF) were significantly influenced by strain rate, i.e., strain rate effect. When the strain rate was relatively low, PP fibres were effective in controlling the cracking, and the dynamic compressive properties of PP fibre reinforced mixtures were improved accordingly.

Impact of chronic obstructive pulmonary disease on prognosis after percutaneous coronary intervention and bypass surgery for left main coronary artery disease: an analysis from the EXCEL trial.

OBJECTIVES: Percutaneous coronary intervention (PCI) is often favoured over coronary artery bypass grafting (CABG) surgery for revascularization in patients with chronic obstructive pulmonary disease (COPD). We studied whether COPD affected clinical outcomes according to revascularization in the Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial, in which PCI with everolimus-eluting stents was non-inferior to CABG for the treatment of patients with left main coronary artery disease and low or intermediate SYNTAX scores. METHODS: Patients with a history of COPD were propensity score matched to those without COPD. Outcomes at 30 days and 3 years in both groups were compared in patients randomized to PCI versus CABG. RESULTS: COPD status was available for 1901 of 1905 randomized patients (99.8%), 148 of whom had COPD (7.8%). Propensity score matching yielded 135 patients with COPD and 675 patients without COPD. Patients with COPD had higher 3-year rates of the primary composite end point of death, myocardial infarction or stroke (31.7% vs 14.5%, P < 0.0001), death (17.1% vs 7.5%, P = 0.0005) and myocardial infarction (18.3% vs 7.3%, P < 0.0001), but not stroke (3.3% vs 2.9%, P = 0.84). There were no statistically significant interactions in the relative risks of PCI versus CABG for the primary composite end point in patients with and without COPD at 30 days [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.12-1.21 vs HR 0.55, 95% CI 0.29-1.06; Pinteraction = 0.61] or at 3 years (HR 0.85, 95% CI 0.46-1.56 vs HR 1.28, 95% CI 0.84-1.94; Pinteraction = 0.27). CONCLUSIONS: In the EXCEL trial, COPD was independently associated with poor prognosis after left main coronary artery disease revascularization. The relative risks of PCI versus CABG at 30 days and 3 years were consistent in patients with and without COPD. CLINICAL TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov; NCT01205776.

Outcomes of patients with and without baseline lipid-lowering therapy undergoing revascularization for left main coronary artery disease: analysis from the EXCEL trial.

OBJECTIVES: There is a paucity of data on the effect of baseline lipid-lowering therapy (LLT) in patients undergoing revascularization for left main (LM) coronary artery disease (CAD). We compared outcomes for patients with LMCAD randomized to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) according to the presence of baseline LLT in the EXCEL trial. PATIENTS AND METHODS: The EXCEL trial randomized 1905 patients with LMCAD and SYNTAX scores up to 32 to PCI with everolimus-eluting stents versus CABG. Patients were categorized according to whether they were medically treated with LLT at baseline, and their outcomes were examined using multivariable Cox proportional hazards regression. The primary endpoint was a composite of death, stroke, or myocardial infarction at 3 years. RESULTS: Among 1901 patients with known baseline LLT status, 1331 (70.0%) were medically treated with LLT at baseline. There were no significant differences between the PCI and CABG groups in the 3-year rates of the primary endpoint in patients with versus without baseline LLT (Pinteraction=0.62). Among patients with baseline LLT, the 3-year rate of ischemia-driven revascularization was higher after PCI compared with CABG (13.7 vs. 5.3%; adjusted hazard ratio=2.97; 95% confidence interval: 1.95-4.55; P<0.0001), in contrast to patients without baseline LLT (9.8 vs. 12.1%; adjusted hazard ratio=0.79; 95% confidence interval: 0.47-1.33; P=0.39) (Pinteraction=0.0003). CONCLUSION: In the EXCEL trial, 3-year major adverse event rates after PCI versus CABG for LMCAD were similar and consistent in patients with and without LLT at baseline; however, revascularization during follow-up was more common after PCI compared with CABG in patients with baseline LLT, but not in those without baseline LLT.

Decellularized Periosteum-Covered Chitosan Globule Composite for Bone Regeneration in Rabbit Femur Condyle Bone Defects.

Critical-sized bone defects are incapable of self-healing and are commonly seen in clinical practice. The authors explore a new treatment for this, decellularized periosteum is applied to chitosan globules (chitosan-DP globules) as a hybrid material. The efficacy of chitosan-DP globules on rabbit femoral condyle bone defects is assessed with biocompatibility, biomechanics, and osteogenic efficiency measurements, and compared with the results of chitosan globules and empty control. No difference in cytotoxicity is observed among chitosan-DP globules, chitosan globules, and the empty control. Chitosan-DP globules possesse a better surface for cell adhesion than did chitosan globules. Chitosan-DP globules demonstrate superior efficiency for osteogenesis in the defect area compared to chitosan globules as per microcomputed tomography examination and push-out testing, with relatively minor histological differences. Both chitosan globule groups show more satisfactory results than those for the empty control. The results implicate chitosan-DP globules as a promising solution for bone defects.

Evaluation of left ventricular reverse remodeling in patients with severe aortic regurgitation undergoing aortic valve replacement: Comparison between diameters and volumes.

BACKGROUND: In patients with severe aortic regurgitation (AR), the left ventricular ejection fraction (LVEF) and left ventricle (LV) size are crucial for determining clinical prognosis and timing of valve intervention. In clinical practice, LV internal diameters obtained at end-diastole are used to assess the degree of LV dilatation. Whether quantification of LV volumes would provide more robust information as compared to LV linear dimensions is unknown. METHODS: We retrospectively analyzed preoperative and postoperative transthoracic echocardiograms of patients who underwent aortic valve replacement (AVR) for severe AR. Indexed linear LV end-diastolic and end-systolic diameters along with indexed LV end-diastolic and end-systolic volumes were obtained as per current guidelines. Post-AVR LV reverse remodeling, defined as ≥10% reduction in measures of LV volumes (Teichholz and Simpson's methods), was determined. Positive and negative agreement was calculated between the volume- and diameter-based LV reverse remodeling. RESULTS: Sixty-two consecutive patients were included. Nine patients (17%) without LV reverse remodeling based on Teichholz were reclassified as having LV reverse remodeling based on Simpson (positive agreement 0.846 [95% CI 0.772, 0.921], negative agreement 0.200 [95% CI -0.350, 0.435]). Left ventricle (LV) reverse remodeling assessed by the Teichholz method was underestimated by a mean of 31 mL/m2 (ß = -0.65 [95% CI -1.06 to -0.24], P = .003) compared to Simpson method. CONCLUSION: Compared to the volume-based method, diameter-based LV measurement incorrectly identified LV reverse remodeling post-AVR in 17% of patients with severe AR. Left ventricle (LV) volume may be a better measure to assess LV remodeling post-AVR than LV diameter-based measurements.