Video-Assisted Thoracic Surgery Core Needle Biopsy for Pulmonary Nodules in Patients with Impaired Lung Function: Is It Feasible and Safe?

Background: The number of patients with incidentally identified pulmonary nodules is increasing. This study attempted to confirm the usefulness and safety of video-assisted thoracic surgery (VATS) core needle biopsy of pulmonary nodules. Methods: Data from 18 patients diagnosed with pulmonary nodules who underwent VATS core need biopsy were retrospectively reviewed. Results: Of the 18 patients, 15 had malignancies (primary lung cancer, n=14; metastatic lung cancer, n=1), and 3 had benign nodules. Mortality and pleural metastasis did not occur during the follow-up period. Conclusion: In patients with solitary pulmonary nodules that require tissue confirmation, computed tomography-guided percutaneous cutting needle biopsy or diagnostic pulmonary resection sometimes may not be feasible choices due to the location of the solitary pulmonary nodule or the patient's impaired pulmonary function, VATS core needle biopsy may be performed in these patients as an alternative method.

Prognostic Factors Leading to Good or Poor Outcomes Based on Functional and Radiological Findings After a Rotator Cuff Retear.

BACKGROUND: A retear after rotator cuff repair is a common problem; however, there is little information related to the prognosis after a retear. In addition, some patients with retears have satisfactory outcomes, which raises the question of whether a retear leads to a poor prognosis. PURPOSE: To identify radiological factors that influence the prognosis after a retear. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 51 patients with retears confirmed by magnetic resonance imaging at 1 year after arthroscopic rotator cuff repair with a minimum follow-up of 24 months were enrolled in this study. Patients were divided into 2 groups according to whether they achieved the minimal clinically important difference for clinical outcome measures. Range of motion and radiological variables, including preoperative and postoperative anteroposterior (AP) and mediolateral (ML) tear sizes, sagittal extent of the retear, acromiohumeral distance (AHD), and degree of fatty degeneration, were analyzed using magnetic resonance imaging. RESULTS: Overall, 36 patients were allocated to the good prognosis (GP) group and 15 to the poor prognosis (PP) group. The 2 groups had no significant differences in baseline demographics and preoperative radiological parameters. Postoperative range of motion was decreased in the PP group at the last follow-up. The AP and ML retear sizes decreased in both groups after arthroscopic rotator cuff repair, but the retear size was significantly larger in the PP group (both P < .05). The AHD increased in the GP group (P < .001) but decreased in the PP group (P = .230) postoperatively. Logistic regression analysis revealed that postoperative AHD (P = .003), fatty degeneration of the infraspinatus tendon (P = .001), posterior (P = .007) and anterior (P = .025) sagittal extent of the retear, and change in the AP tear size (P = .017) were related to poor outcomes after a retear. However, change in the ML tear size (P = .105) and middle sagittal extent of the retear (P = .878) were not related to a poor prognosis. Also, further analysis showed that posterior (P = .006) and anterior (P = .003) sagittal extent of the retear were related to rotator cable involvement. CONCLUSION: An increased AP retear size and decreased AHD were radiological parameters that were associated with poor clinical outcomes after a retear. In particular, patients who had posterior and anterior sagittal extent of the retear, possibly with rotator cable involvement and more severe fatty degeneration of the infraspinatus tendon, showed worse outcomes.

Factors affecting contralateral wrist surgery after one carpal tunnel release in bilateral carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) can be bilateral, with varying incidence. Carpal tunnel release (CTR) in one wrist may relieve the symptoms of the contralateral wrist, avoiding the need for second surgery; conversely, the symptoms may persist or worsen, requiring contralateral surgery in some cases. The present study investigated whether surgical treatment was finally required for the non-operated CTS wrist, and in what cases non-operative treatment was possible. We compared baseline characteristics, risk factors and electrodiagnostic data between CTS patients who underwent only unilateral CTR and those who subsequently underwent bilateral surgery at various time intervals. This single-center retrospective study included 188 patients with bilateral CTS managed between 2010 and 2020; 137 patients (group 1, 73%) underwent only unilateral CTR, and 51 (group 2, 27%) subsequently underwent contralateral CTR. In group 1, contralateral CTS symptoms were assessed in 4 categories and compared to the presenting symptoms in the index wrist. There were no significant differences in age, gender, preoperative symptom duration, body status, addictive behavior, electrodiagnostic study or comorbidities, other than a higher rate of dialysis in group 2. The contralateral wrist showed partial or complete symptom relief in 57% of patients undergoing unilateral CTR. High BMI and history of diabetes were risk factors for persistent severe CTS or subsequent contralateral CTR.

Therapeutic Effect of Pericytes for Diabetic Wound Healing.

Objective: Numerous attempts have been made to devise treatments for ischemic foot ulcer (IFU), which is one of the most severe and fatal consequences of diabetes mellitus (DM). Pericytes, which are perivascular multipotent cells, are of interest as a treatment option for IFU because they play a critical role in forming and repairing various tissues. In this study, we want to clarify the angiogenic potential of pericytes in DM-induced wounds. Methods: We evaluated pericyte stimulation capability for tube formation, angiogenesis, and wound healing (cell migration) in human umbilical vein endothelial cells (HUVECs) with in-vivo and in-vitro models of high glucose conditions. Results: When HUVECs were co-cultured with pericytes, their tube-forming capacity and cell migration were enhanced. Our diabetic mouse model showed that pericytes promote wound healing via increased vascularization. Conclusion: The findings of this study indicate that pericytes may enhance wound healing in high glucose conditions, consequently making pericyte transplantation suitable for treating IFUs.

Epidemiology of pediatric fractures before versus during the coronavirus disease 2019 pandemic.

Several studies have reported changes in the prevalence of childhood fractures between the prepandemic and coronavirus disease 2019 pandemic periods considering the overall decrease in activity during the latter. This review aimed to organize and summarize the global trends in pediatric fracture incidence. Our findings should help predict fracture patterns in the postpandemic period by identifying changes in the past and present, thus aiding patient management.

Patch augmentation does not provide better clinical outcomes than arthroscopic rotator cuff repair for large to massive rotator cuff tears.

PURPOSE: Patch augmentation for large and massive rotator cuff tears (LMRCTs) has been suggested as a repair strategy that can mechanically reinforce tendons and biologically enhance healing potential. The purpose of this study was to determine whether patients who underwent patch augmentation would have lower rates of retears and superior functional outcomes. METHODS: Patients who underwent arthroscopic rotator cuff repair (ARCR) with patch augmentation (group A) were matched by age, sex, degree of retraction, and supraspinatus muscle occupation ratio to those treated with ARCR without using a patch (group B) with a minimum follow-up of 24 months. The retear (Sugaya IV or V) rates were evaluated by magnetic resonance imaging at 3 and 12 months post-surgery. The Constant- Murley Score (CMS), Korean Shoulder Score (KSS), and University of California-Los Angeles Shoulder Rating Scale (UCLA) score were retrospectively analyzed. RESULTS: This study included 34 patients (group A, n = 17; group B, n = 17). The mean follow-up period was 46.5 ± 17.4 months. At postoperative 1-year follow-up, group B (6 patients, 35.3%) showed higher rates of retears than group A (1 patient, 5.9%), which was statistically significant (P = 0.034). However, the postoperative CMS, KSS, and UCLA scores did not differ between the two groups at 3 months, 12 months, and the final follow-up. Additionally, the clinical outcomes of patients with retear were not significantly different from those of the healed patients in both groups. CONCLUSION: The use of an allodermal patch for LMRCT is effective in preventing retears without complications. However, the clinical outcomes of ARCR using allodermal patch augmentation were not superior to those of only ARCR. LEVEL OF EVIDENCE: III.

Therapeutic Potential of Human Fetal Mesenchymal Stem Cells in Musculoskeletal Disorders: A Narrative Review.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for diverse diseases and injuries. The biological and clinical advantages of human fetal MSCs (hfMSCs) have recently been reported. In terms of promising therapeutic approaches for diverse diseases and injuries, hfMSCs have gained prominence as healing tools for clinical therapies. Therefore, this review assesses not the only biological advantages of hfMSCs for healing human diseases and regeneration, but also the research evidence for the engraftment and immunomodulation of hfMSCs based on their sources and biological components. Of particular clinical relevance, the present review also suggests the potential therapeutic feasibilities of hfMSCs for musculoskeletal disorders, including osteoporosis, osteoarthritis, and osteogenesis imperfecta.

Carpal tunnel release can be a risk factor for trigger finger: National Health Insurance data analysis.

PURPOSE: We aimed to compare trigger finger (TF) development between patients with carpal tunnel syndrome (CTS) treated with carpal tunnel release (CTR) and those treated conservatively, using the National Health Insurance Services data of Korea. We also aimed to investigate risk factors for post-CTR TF development. METHODS: We selected CTS patients with or without CTR (3543 patients in each group) between 2002 and 2015. Sex, age, follow-up duration after CTS diagnosis, and comorbidities associated with TF-development were matched using propensity score. We compared the rates of TF diagnosis and subsequent TF operations between groups. Thereafter, we selected patients with CTS undergoing CTR, for whom minimum follow-up exceeded five years. We compared sex, age, height, weight, and comorbidities associated with TF risk factors between the TF-occurrence and non-TF-occurrence groups. RESULTS: On comparing CTR-treated patients with those treated conservatively for CTS, CTR-treated patients presented with significantly higher rates of TF diagnosis (12.2%) and TF operations (4.7%) than patients without CTR (6.2% and 1.2%, respectively). Among 433 TF-diagnosed patients and 166 TF-operated patients after CTR, most were identified < 5 years after CTR, with 379 diagnosed (87.5%) and 147 operated (88.5%) patients. A total of 240 patients presented with newly developed TF over a five year period. Patients with subsequent TF exhibited a higher female sex rate and shorter height. None of the variables was significant risk factors for TF development in logistic regression analysis. CONCLUSION: We confirmed high incidences of post-CTR TF diagnosis and operations. TF develops most frequently in the first postoperative year.

Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways.

Sea hare-derived compounds induce macrophage activation and reduce asthmatic parameters in mouse models of allergic asthma. These findings led us to study the role of sea hare hydrolysates (SHH) in cancer pathophysiology. SHH treatment-induced M1 macrophage activation in RAW264.7 cells, peritoneal macrophages, and THP-1 cells, as did lipopolysaccharide (LPS) (+ INF-γ), whereas SHH reduced interleukin (IL)-4 (+IL-13)-induced M2 macrophage polarization. In addition, SHH treatment inhibited the actions of M1 and M2 macrophages, which have anticancer and pro-cancer effects, respectively, in non-small cell lung cancer cells (A549 and HCC-366) and tumor-associated macrophages (TAMs). Furthermore, SHH induced G2/M phase arrest and cell death in A549 cells. SHH also downregulated STAT3 activation in macrophages and A549 cells, and the down-regulation was recovered by colivelin, a STAT3 activator. SHH-induced reduction of M2 polarization and tumor growth was blocked by colivelin treatment. SHH-induced cell death did not occur in the manner of apoptotic signaling pathways, while the death pattern was mediated through pyroptosis/necroptosis, which causes membrane rupture, formation of vacuoles and bleb, activation of caspase-1, and secretion of IL-1ß in SHH-treated A549 cells. However, a combination of SHH and colivelin blocked caspase-1 activation. Z-YVAD-FMK and necrostatin-1, pyrotosis and necroptosis inhibitors, attenuated SHH's effect on the cell viability of A549 cells. Taken together, SHH showed anticancer effects through a cytotoxic effect on A549 cells and a regulatory effect on macrophages in A549 cells. In addition, the SHH-induced anticancer effects were mediated by non-apoptotic regulated cell death pathways under STAT3 inhibition. These results suggest that SHH may be offered as a potential remedy for cancer immunotherapy.

Micropatterned conductive hydrogels as multifunctional muscle-mimicking biomaterials: Graphene-incorporated hydrogels directly patterned with femtosecond laser ablation.

Multifunctional biomaterials that can provide physical, electrical, and structural cues to cells and tissues are highly desirable to mimic the important characteristics of native tissues and efficiently modulate cellular behaviors. Especially, electrically conductive biomaterials can efficiently deliver electrical signals to living systems; however, the production of conductive biomaterials presenting multiple cell interactive cues is still a great challenge. In this study, we fabricafed an electrically conductive, mechanically soft, and topographically active hydrogel by micropatterning a graphene oxide (GO)-incorporated polyacrylamide hydrogel (GO/PAAm) with femtosecond laser ablation (FLA) and subsequent chemical reduction. FLA parameters were optimized to efficiently produce distinct line patterns on GO/PAAm hydrogels to induce myoblast alignment and maturation. The line patterns distances (PD) were varied to have different topographies (20-80 µm PD). In vitro studies with C2C12 myoblasts revealed that the micopatterned hydrogels are superior to the unpatterned substrates in inducing myogenesis and myotube alignment. Reduced GO/PAAm with 50 µm PD, i.e., PD50/r(GO/PAAm), showed the best results among the various features for differentiation and myotube alignment. Electrical stimulation of myoblasts on the micropatterned conductive hydrogels further promoted the differentiation of myoblasts. In vivo implantation studies indicated good tissue compatibility of PD50/r(GO/PAAm) samples. Altogether, we successfully demonstrated that the micropatterned r(GO/PAAm) may offer multiple properties capable of positively affecting myoblast responses. This hydrogel may serve as an effective multifunctional biomaterial, which possesses the topography for cell alignment/maturation, mechanical properties of the native skeletal muscle tissue, and desirable electrical conductivity for delivering electrical signals to cells, for various biomedical applications such as muscle tissue scaffolds. STATEMENT OF SIGNIFICANCE: Micropatterned conductive hydrogels were created by polymerization of a graphene oxide-incorporated polyacrylamide hydrogel, micropatterning with femtosecond laser ablation, and chemical reduction, which can mimic important characteristics of native skeletal muscle tissues. The micropatterned conductive hydro-gels promoted myogenesis/alignment, enabled electrical stimulation of myoblasts, and displayed good tissue compatibility, which can therefore serve as a multifunctional biomaterial that is topographically active, mechanically soft, and electrically conductive for delivering multiple cell stimulating signals for potential skeletal muscle tissue engineering applications.

Prognostic impact of CD8 and programmed death-ligand 1 expression in patients with resectable non-small cell lung cancer.

BACKGROUND: The prognostic impact of the expression of CD8 and programmed death-ligand 1 (PD-L1) has not been established in patients with resectable non-small cell lung cancer (NSCLC). METHODS: Surgical tissue specimens were obtained from 136 patients with NSCLC who underwent surgical resection. The expression levels of CD8 and PD-L1 were assessed using tissue microarrays and immunohistochemistry. RESULTS: The CD8-positive group showed significant increases in overall survival (OS) (median, not reached [NR] vs. 28.452 months) and relapse-free survival (RFS) (median, NR vs. 14.916 months) compared with the CD8-negative group. In contrast to CD8, the PD-L1-negative group demonstrated significant increases in OS (median, NR vs. 29.405 months) and RFS (median, 63.573 vs. 17.577 months) compared with the PD-L1-positive group. Two prognostic groups were stratified according to CD8/PD-L1 expression: group 1 (CD8-positive/PD-L1-negative) vs. group 2 (CD8/PD-L1: positive/positive, negative/negative, negative/positive). Group 1 had better OS (median, NR vs. 29.405 months) and RFS (median, NR vs. 17.577 months) than group 2. Multivariate analysis indicated that group 1 constituted an independent favourable prognostic factor for OS (hazard ratio [HR], 0.329, p = 0.001) and RFS (HR, 0.293; p < 0.001). CONCLUSIONS: Positive CD8 and negative PD-L1 expression together may be favourable prognostic markers in resectable NSCLC.

Quantitative severity of pulmonary emphysema as a prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer.

BACKGROUND: Pulmonary emphysema is a major component of chronic obstructive pulmonary disease and lung cancer. However the prognostic significance of quantitative emphysema severity in patients with lung cancer is unclear. We analyzed whether numerical emphysema value is a prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer. METHODS: We quantified emphysema severity of the whole lung and regional lobes in 45 patients (mean age 68.0 years) using an automated chest computed tomography-based program. Predictive factors for recurrence were investigated using a Cox proportional hazards model. Recurrence-free and overall survival was compared after dichotomization of patients according to whole lung emphysema severity. RESULTS: The mean percentage emphysema ratio of the whole lung was 1.21 ± 2.04. Regional lobar emphysema severity was highest in the right middle lobe (1.93 ± 0.36), followed by right upper (1.35 ± 2.50), left upper (1.34 ± 2.12), left lower (1.05 ± 2.52), and right lower (0.78 ± 2.28) lobes. The low severity group showed significantly longer overall survival compared to the high severity group (log-rank test, P = 0.018). Quantitative emphysema severity of the whole lung (hazard ratio 1.36; 95% confidence interval 1.0-1.73) and stage III (hazard ratio 6.17; 95% confidence interval 1.52-25.0) were independent predictors of recurrence after adjusting for age, gender, smoking status, and forced expiratory volume in one second. CONCLUSION: The severity of whole lung emphysema was independently associated with recurrence. Patients with non-small cell lung cancer and marginal pulmonary emphysema at lower severity survive longer after curative-intent surgery.

Comparison of stereotactic body radiotherapy versus metastasectomy outcomes in patients with pulmonary metastases.

BACKGROUND: We compared the treatment outcomes of stereotactic body radiotherapy (SBRT) and metastasectomy in patients with pulmonary metastases. METHODS: Twenty-one patients received SBRT (total radiation doses 60 Gy in 3 fractions or 48 Gy in 4 fractions) and 30 underwent metastasectomy, most (93.3%) with wedge resection. The patients were followed for a median of 13.7 months. The tumor size in the SBRT group was larger than in the metastasectomy group (median 2.5 vs. 1.25 cm; P = 0.015). Patients with synchronous metastases were more likely to be treated with SBRT than with metastasectomy (P = 0.006). RESULTS: There was no significant difference in the local control rates of the treatment groups (P = 0.163). Progression-free survival (PFS) was longer in the metastasectomy than in the SBRT group (P = 0.02), with one and two-year PFS rates of 51.1% and 46% versus 23.8% and 11.9%, respectively. The one and two-year overall survival (OS) rates were 95% and 81.8% in the metastasectomy group and 79.5% and 68.2%, in the SBRT group, respectively. In multivariate analysis, synchronous metastasis was related to poor PFS, and tumor size was the most significant factor affecting OS. There were no significant differences in PFS and OS between treatment groups after dividing patients according to the presence or absence of synchronous metastases. CONCLUSIONS: SBRT is considered a suitable local modality against pulmonary metastases; however, patients with synchronous metastases are only likely to obtain a small benefit from local treatment with either SBRT or surgery.

Optical design of dental light using a remote phosphor light-emitting diode package for improving illumination uniformity.

The projection-type dental lighting based on the remote phosphor light-emitting diode (LED) package is designed to enhance uniformity of illuminance and correlated color temperature (CCT) on a target plane and to remove glare in the eyes of the patient. This dental lighting enables dentists to illuminate effectively the patient's mouth by increasing the inner area (50 mm×25 mm) described in ISO 9680. The optical module comprised of the LED package and optical lens is modeled to satisfy the inner area wider than 100 mm×50 mm and illuminance over 5,000 lx per the designed optical module. The fabricated prototype dental lighting contains four optical modules, and the maximum illuminance is 22,786 lx. The measured inner area is 105 mm×74 mm, and the ratio of inner area to outer area is about 76%. Also, the CCT variation is below 450 K in total illuminance pattern.

Thymoma and Synchronous Primary Mediastinal Seminomas with Florid Follicular Lymphoid Hyperplasia in the Anterior Mediastinum: A Case Report and Review of the Literature.

Thymoma is the most common neoplasm of the anterior mediastinum and has malignant potential. Germ cell tumors (GCTs) found in the anterior mediastinum are usually benign, and malignant GCTs, such as seminomas, are rare. Histologically, mediastinal seminoma is indistinguishable from testicular seminoma except for site-associated morphological features such as lymphoid follicular hyperplasia. Therefore, excluding metastasis is very important. Recently, we treated a young adult patient with multiple thymic masses that occurred simultaneously. The patient underwent a thymectomy for the removal of the mediastinal masses, one of which was diagnosed as type B2 invasive thymoma, and two of which were diagnosed as primary mediastinal seminomas with massive follicular hyperplasia. The patient received adjuvant chemotherapy after surgical resection. To our knowledge, this is the first description of a thymoma and a mediastinal seminoma occurring simultaneously in the thymus. We present this case along with a literature review.

Establishing the heparin therapeutic range using aPTT and anti-Xa measurements for monitoring unfractionated heparin therapy.

BACKGROUND: Unfractionated heparin (UFH) has unstable pharmacokinetics and requires close monitoring. The activated partial thromboplastin time (aPTT) test has been used to monitor UFH therapy for decades in Korea, but its results can be affected by numerous variables. We established an aPTT heparin therapeutic range (HTR) corresponding to therapeutic anti-Xa levels for continuous intravenous UFH administration, and used appropriate monitoring to determine if an adequate dose of UFH was applied. METHODS: A total of 134 ex vivo samples were obtained from 71 patients with a variety of thromboembolisms. All patients received intravenous UFH therapy and were enrolled from June to September 2015 at Gyeongsang National University Hospital. All laboratory protocols were in accordance with the Clinical and Laboratory Standards Institute guidelines and the College of American Pathologist requirements for aPTT HTR. RESULTS: An aPTT range of 87.1 sec to 128.7 sec corresponded to anti-Xa levels of 0.3 IU/mL to 0.7 IU/mL for HTR under our laboratory conditions. Based on their anti-Xa levels, blood specimen distribution were as follows: less than 0.3 IU/mL, 65.7%; 0.3-0.7 IU/mL (therapeutic range), 33.6%; and more than 0.7 IU/mL, 0.7%. No evidence of recurring thromboembolism was observed. CONCLUSION: Using the conventional aPTT target range may lead to inappropriate dosing of UFH. Transitioning from the aPTT test to the anti-Xa assay is required to avoid the laborious validation of the aPTT HTR test, even though the anti-Xa assay is more expensive.

Comparing the clinical outcomes in stereotactic body radiotherapy for lung tumors between Ray-Tracing and Monte-Carlo algorithms.

PURPOSE: The purpose of this study was to compare the clinical outcomes between the groups using Ray-Tracing (RAT) and Monte-Carlo (MC) calculation algorithms for stereotactic body radiotherapy (SBRT) of lung tumors. MATERIALS AND METHODS: Thirty-five patients received SBRT with CyberKnife for 47 primary or metastatic lung tumors. RAT was used for 22 targets in 12 patients, and MC for 25 targets in 23 patients. Total dose of 48 to 60 Gy was prescribed in 3 to 5 fractions on median 80% isodose line. The response rate, local control rate, and toxicities were compared between RAT and MC groups. RESULTS: The response rate was lower in the RAT group (77.3%) compared to the MC group (100%) (p = 0.008). The response rates showed an association with the mean dose to the gross tumor volume, which the doses were re-calculated with MC algorithm in both groups. However, the local control rate and toxicities did not differ between the groups. CONCLUSIONS: The clinical outcome and toxicity of lung SBRT between the RAT and MC groups were similar except for the response rate when the same apparent doses were prescribed. The lower response rate in the RAT group, however, did not compromise the local control rates. As such, reducing the prescription dose for MC algorithm may be performed but done with caution.

A Novel Mediastinal Drainage Tube for Mediastinitis.

Mediastinitis is a life-threatening disease, and effective drainage is needed to treat mediastinitis with abscess formation. We recommend an alternative drainage method using chest tube binding with a Silastic Penrose drainage tube. The use of a Silastic Penrose drainage tube may help to manage mediastinitis with abscess formation. This method facilitates effective draining and prevents tissue adhesion.

Neuroprotective Effects of Human Serum Albumin Nanoparticles Loaded With Brimonidine on Retinal Ganglion Cells in Optic Nerve Crush Model.

PURPOSE: We investigated the neuroprotective effect of human serum albumin nanoparticles (HSA-NPs) and their conjugation with brimonidine (HSA-Br-NPs) on retinal ganglion cells (RGCs) in optic nerve crush (ONC) model. METHODS: We fabricated HSA-Br-NPs by ethanol precipitation, including 0.18% brimonidine (Br) and 3.5% human serum albumin (HSA) in HSA-Br-NP solution. We performed ONC and intravitreal injection in Sprague-Dawley rats, which were divided into (1) Normal, (2) balanced salt solution (BSS)-injected ONC, (3) HSA-NP-injected ONC, (4) Br-injected ONC, and (5) HSA-Br-NP-injected ONC groups. Survival of RGC was compared 5 and 14 days after procedures. A cell viability assay evaluated the amyloid-ß (Aß)-associated neuroprotective mechanism of HSA-NP. RESULTS: The HSA-Br-NPs showed a narrow size distribution (152.8 ± 51.1 nm) and a negatively charged surface (-29.7 ± 7.5 mV), releasing Br for 5 days. The percentages of RGC survival in the HSA-NP (52.6 ± 3.3%), Br (58.0 ± 4.2%), and HSA-Br-NP (63.5 ± 7.1%) groups relative to Normal (100%) were significantly higher than in the BSS group (29.2 ± 3.3%) 5 days after ONC (P < 0.001). However, the HSA-Br-NP (38.1 ± 3.6%) group showed significantly higher RGC density than the BSS (10.3 ± 5.6%, P < 0.001) or Br (18.6 ± 3.9%, P = 0.006) group at 14 days. The HSA-NP injection reduced Aß deposition in the RGC layer of ONC model, and a cell viability test showed that HSA-NP can inhibit Aß-induced RGC death. CONCLUSIONS: Human serum albumin nanoparticles showed neuroprotective potential by inhibiting Aß deposition, and exerted a sustained therapeutic effect with the combined neuroprotective agent. Our results suggest the potential of HSA-Br-NP as a promising neuroprotective agent.

High-level expression of Hsp90ß is associated with poor survival in resectable non-small-cell lung cancer patients.

AIMS: The aim of this study was to investigate the expression of Hsp90ß and GRP94, and elucidate the clinical significance of their expression, in patients with resectable non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: Surgical tissue specimens were obtained from 208 patients with NSCLC who underwent surgical resection. The expression levels of Hsp90ß and GRP94 were assessed with tissue microarrays and immunohistochemistry. No correlations were observed between Hsp90ß or GRP94 expression and several clinicopathological factors. The high-Hsp90ß group [median overall survival (OS) 20.4 months; 95% confidence interval (CI) 0.000-40.864] showed a significant decrease in OS as compared with the low-Hsp90ß group (median OS not reached; P = 0.003). In contrast to the Hsp90ß analysis, the GRP94 analysis did not show a difference in OS. Moreover, in subgroup analyses of patients with squamous cell carcinoma histology, OS (P = 0.012) and relapse-free survival (P = 0.044) were significantly worse in the high-Hsp90ß group than in the low-Hsp90ß group. Multivariate analysis suggested that old age [hazard ratio (HR) 1.568; 95% CI 1.019-2.412; P = 0.041], advanced disease (HR 2.066; 95% CI 1.218-3.502; P = 0.007) and high Hsp90ß expression (HR 1.802; 95% CI 1.061-3.060; P = 0.029) were independent poor prognostic factors for OS. CONCLUSIONS: Hsp90ß expression might be a useful marker of poor OS, although further large prospective studies are warranted to validate our findings.