BACKGROUND: Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes. CDNs exhibit structural, physical, and biological properties similar to exosomes, containing intracellular protein and genetic components encapsulated by the cell plasma membrane. These characteristics allow CDNs to be used as regenerative medicine and therapeutics on their own, or as a drug delivery system. METHODS: The paper reviews diverse methods for CDN synthesis, current analysis techniques, and presents engineering strategies to improve lesion targeting efficiency and/or therapeutic efficacy. RESULTS: CDNs, with their properties similar to those of exosomes, offer a cost-effective and highly productive alternative due to their non-living biomaterial nature, nano-size, and readiness for use, allowing them to overcome several limitations of conventional cell therapy methods. CONCLUSION Ongoing research and enhancement of CDNs engineering, along with comprehensive safety assessments and stability analysis, exhibit vast potential to advance regenerative medicine by enabling the development of efficient therapeutic interventions.

BACKGROUND/AIMS: Among borderline resectable pancreatic cancer (BRPC), group B BRPC patients have findings that are suggestive but not diagnostic of metastasis. In this study, we attempted to validate whether group B could truly be categorized as a borderline resectable group. METHODS: We placed the BRPC patients into group A or group B. The survival outcomes were compared between the groups. RESULTS: A total of 53 patients with pancreatic adenocarcinoma was classified as either group A or B borderline resectable. In group A, 23 (60.5%) of 38 patients underwent pancreatectomy after concurrent chemoradiotherapy or chemotherapy, but in group B, only five (33.3%) of 15 patients underwent pancreatectomy, mainly because of the progression of suspected distant metastasis. There was a significant difference in overall survival (OS) between group A and B patients (median OS, 21.2 months vs 10.2 months, respectively; p=0.007). Of the patients who underwent pancreatectomy, group B had a higher recurrence rate compared to group A (recurrence rate: 11 of 23 patients [47.8%] vs five of five patients [100%], respectively; p=0.033). CONCLUSIONS: This report is the first to validate the definition of BPRC. Group B had much worse outcomes, and whether group B BRPC can be categorized as BRPC together with group A is questionable.
Adenocarcinoma/classification/mortality/pathology/surgery ; Adult ; Aged ; Aged, 80 and over ; Chemoradiotherapy ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Pancreatectomy ; Pancreatic Neoplasms/*classification/mortality/pathology/*surgery ; Retrospective Studies ; Treatment Outcome

PURPOSE: The purpose of this study was to investigate the value of the alveolar-arterial (A-a) oxygen gradient for patients with community-acquired pneumonia (CAP) in the emergency department (ED). METHODS: A prospective study of patients with CAP in the ED was performed. Patients with clinical and a radiographic diagnosis of CAP were enrolled. Inflammatory biomarkers, such as WBC (white blood cell) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and A-a oxygen gradient were measured. The severity of CAP was assessed by three prediction rules: The Pneumonia Severity Index (PSI), CURB65 (confusion, blood urea nitrogen, respiratory rate, blood pressure and age> or =65 yrs), and the Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) rules. The value of each biomarker (WBC, CRP, ESR) and A-a oxygen gradient for the prediction of mortality and CAP severity were assessed. RESULTS: A total of 126 patients with CAP were included. Sixteen patients, older and in the high-risk group, died within 30 days. Non-survivors had a significantly increased A-a oxygen gradient compared to survivors (91.20 vs. 46.71 mmHg, respectively; p<.01) and a high-sensitivity to C-reactive protein (158.57 vs. 91.28 mg/dL, respectively; p<.01). The median A-a oxygen gradient was significantly higher with severe disease based on the three prediction rules. In regression logistic analyses, the area under the receiver operating characteristic curve of the alveolar-arterial oxygen gradient was 0.807(95% confidence interval, 0.727-0.872). The addition of A-a oxygen gradient to the three prediction rules significantly increased the area under the receiver operating characteristic curve. CONCLUSION: These results suggest that A-a oxygen gradient is useful for the prediction of mortality and disease severity among CAP patients in the ED. The A-a oxygen gradient, as an adjunct to CAP prediction rules, may be worth while for the assessment of prognosis and severity.
Americas ; Biomarkers ; Blood Pressure ; Blood Sedimentation ; Blood Urea Nitrogen ; C-Reactive Protein ; Communicable Diseases ; Diagnosis ; Emergencies ; Humans ; Mortality ; Oxygen* ; Pneumonia* ; Prognosis ; Prospective Studies ; Respiratory Rate ; ROC Curve ; Survivors

PURPOSE: The purpose of this study was to investigate the value of the alveolar-arterial (A-a) oxygen gradient for patients with community-acquired pneumonia (CAP) in the emergency department (ED). METHODS: A prospective study of patients with CAP in the ED was performed. Patients with clinical and a radiographic diagnosis of CAP were enrolled. Inflammatory biomarkers, such as WBC (white blood cell) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and A-a oxygen gradient were measured. The severity of CAP was assessed by three prediction rules: The Pneumonia Severity Index (PSI), CURB65 (confusion, blood urea nitrogen, respiratory rate, blood pressure and age> or =65 yrs), and the Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) rules. The value of each biomarker (WBC, CRP, ESR) and A-a oxygen gradient for the prediction of mortality and CAP severity were assessed. RESULTS: A total of 126 patients with CAP were included. Sixteen patients, older and in the high-risk group, died within 30 days. Non-survivors had a significantly increased A-a oxygen gradient compared to survivors (91.20 vs. 46.71 mmHg, respectively; p<.01) and a high-sensitivity to C-reactive protein (158.57 vs. 91.28 mg/dL, respectively; p<.01). The median A-a oxygen gradient was significantly higher with severe disease based on the three prediction rules. In regression logistic analyses, the area under the receiver operating characteristic curve of the alveolar-arterial oxygen gradient was 0.807(95% confidence interval, 0.727-0.872). The addition of A-a oxygen gradient to the three prediction rules significantly increased the area under the receiver operating characteristic curve. CONCLUSION: These results suggest that A-a oxygen gradient is useful for the prediction of mortality and disease severity among CAP patients in the ED. The A-a oxygen gradient, as an adjunct to CAP prediction rules, may be worth while for the assessment of prognosis and severity.
Americas ; Biomarkers ; Blood Pressure ; Blood Sedimentation ; Blood Urea Nitrogen ; C-Reactive Protein ; Communicable Diseases ; Diagnosis ; Emergencies ; Humans ; Mortality ; Oxygen* ; Pneumonia* ; Prognosis ; Prospective Studies ; Respiratory Rate ; ROC Curve ; Survivors

PURPOSE: Pancreatic neuroendocrine tumors (PNET) are a rare subgroup of tumors. For PNETs, the predictive factors for survival and prognosis are not well known. The purpose of our study was to evaluate the predictive factors for survival and disease progression in PNETs. MATERIALS AND METHODS: We retrospectively analyzed 37 patients who were diagnosed with PNET at Severance Hospital between November 2005 and March 2010. Prognostic factors for survival and disease progression were evaluated using the Kaplan-Meier method. RESULTS: The mean age of the patients was 50.0+/-15.0 years. Eight cases (21.6%) were described as functioning tumors and 29 cases (78.4%) as non-functioning tumors. In univariate analysis of clinical factors, patients with liver metastasis (p=0.002), without resection of primary tumors (p=0.002), or American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage III/IV (p=0.002) were more likely to demonstrate shorter overall survival (OS). Patients with bile duct or pancreatic duct invasion (p=0.031), sized-lesions larger than 20 mm (p=0.036), liver metastasis (p=0.020), distant metastasis (p=0.005), lymph node metastasis (p=0.009) or without resection of primary tumors (p=0.020) were more likely to demonstrate shorter progression-free survival (PFS). In multivariate analysis of clinical factors, bile duct or pancreatic duct invasion [p=0.010, hazard ratio (HR)=95.046] and tumor location (non-head of pancreas) (p=0.036, HR=7.381) were confirmed as independent factors for predicting shorter PFS. CONCLUSION: Patients with liver metastasis or without resection of primary tumors were more likely to demonstrate shorter OS. Patients with bile duct or pancreatic duct invasion or tumors located at body or tail of pancreas were more likely to demonstrate shorter PFS.
Bile Ducts ; Disease Progression ; Disease-Free Survival ; Humans ; Joints ; Liver ; Lymph Nodes ; Methods ; Multivariate Analysis ; Neoplasm Metastasis ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors* ; Pancreas ; Pancreatic Ducts ; Prognosis ; Retrospective Studies ; Tail

Myasthenia gravis (MG) is an autoimmune-mediated disease characterized by weakness and fatigability due to dysfunction of the neuromuscular junction from antibodies directed against the acetylcholine receptor (AchR). The main considerations for the anesthesiologist are the underlying muscle weakness and interactions with various anesthetic drugs. This includes sensitivity to neuromuscular blocking agents and volatile agents, and the risk of postoperative respiratory failure. We report two cases of transsternal thymectomy for MG under general anesthesia with the use of a bispectral index-monitored total intravenous technique using propofol and remifentanil without muscle relaxants.
Acetylcholine ; Anesthesia, General ; Anesthesia, Intravenous ; Anesthetics ; Antibodies ; Humans ; Muscle Weakness ; Muscles ; Myasthenia Gravis ; Neuromuscular Blocking Agents ; Neuromuscular Junction ; Piperidines ; Propofol ; Respiratory Insufficiency ; Thymectomy

PURPOSE: To evaluate the correlation between diabetic retinopathy (DR) and arteriolosclerosis in patients with NIDDM (non-insulin-dependent diabetes mellitus), to investigate the risk factors of DR, and to assess the change of the correlation according to the risk factors. METHODS: The study subjects were selected from consecutive routine clinical visits by random sampling from July 2002 to June 2003. The patients were divided into two groups according to the presence of DR, and the patients' charts, fundus examination and blood test were retrospectively reviewed. ETDRS (Early Treatment DR Study) classification for DR and Scheie classification for arteriolosclerosis were used. Statistical analysis was conducted with SPSS program (version 10.0). The confidence interval was set to 95%, and the level of significance was set at p=0.05. RESULTS: DR had a statistically significant correlation with arteriolosclerosis, especially according to duration of diabetes mellitus (p<0.05). Risk factors including diabetes mellitus duration, HgA1c level, and LDL (low-density lipoprotein) cholesterol level showed statistically significant difference (p<0.05). CONCLUSIONS: From the result of analysis, DR has a statistically significant correlation with arteriolosclerosis, especially according to the duration of diabetes mellitus. To prevent vision-threatening complications of DR, the degree of arteriolosclerosis as well as risk factors such as diabetes mellitus duration, serum HgA1c level, and LDL (low-density lipoprotein) cholesterol level should be carefully considered and monitored in the evaluation, progression, and treatment of DR.
Arteriolosclerosis* ; Cholesterol ; Classification ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Diabetic Retinopathy* ; Hematologic Tests ; Humans ; Retrospective Studies ; Risk Factors

A 46-year-old woman was admitted to emergency room for muscle weakness and repiratory difficulty. She was taking furosemide (4 tablets per day : 160 mg/day) without physician's prescription. Her blood pressure was 90/50 mmHg and her heart rate 74/ min. Her laboratory finding showed a low serum potassium concentration (0.9 mmol/L), CK 368 IU/L, creatine 1.6 mg/dL. The result was rechecked and confirmed. Electrocardiography showed a dip in the ST segment, prolonged QTc, 1st degree AV block and 2 : 1 AV block. Echocardiography was normal. Abdominal CT scan show right lower pole calyceal stones without nephrocalcinosis. Treatment was initiated consisting of intravenous potassium chloride. Hypokalemia was overcome in 3 days. Kidney biopsy showed hypokalemic nephropathy - interstitial nephrosis, vacuolar change of tubule, proliferation of juxtaglomerular apparatus. Paralytic ileus, rebound pleural effusion, glucose intolerance, elevation of CK were associated findings. After correction of hypokalemia, her symptoms and electrocardiographic findings returned to normal.
Atrioventricular Block ; Biopsy ; Blood Pressure ; Creatine ; Echocardiography ; Electrocardiography ; Emergency Service, Hospital ; Female ; Furosemide* ; Glucose Intolerance ; Heart Rate ; Humans ; Hypokalemia* ; Intestinal Pseudo-Obstruction ; Juxtaglomerular Apparatus ; Kidney ; Middle Aged ; Muscle Weakness ; Nephrocalcinosis ; Nephrosis ; Pleural Effusion ; Potassium ; Potassium Chloride ; Prescriptions ; Tablets ; Tomography, X-Ray Computed

OBJECTIVES: This study evaluated the effect of an in-house work-related musculoskeletal disorders (WMSDs) preventive programs in a telephone directory assistance workplace. METHODS: The subjects (N=177) were divided into four groups (nonparticipants, 41; preventive exercise, 31; self-physical therapy, 40; both, 65) by program participation type. The results of WMSDs program were obtained by questionnaire, which consisted of upper extremities'(neck, shoulder, arm, hand) symptom prevalence, self-rating symptom severity, and before-after symptom change between 1995 and 1998 data and workers'satisfaction by program participation. RESULTS: The prevalence of symptoms related WMSDs was only reduced in neck region of nonparticipants, other groups not in significant. The pain scale (5-likert) of each region was significantly decreased in neck, arm and hand of nonparticipants. In other groups, there was no significant change in the prevalence of WMSDs. The change of visual analogue scale was decreased by 21.7% in self-physical therapy group (p=0.043). The subjects mostly were satisfied with this in-house programs. Above all, preventive exercise and both program groups showed content over 80%. CONCLUSIONS: The results of before-after symptoms change was not inconsistent, but subjects were showed high satisfaction about the preventive programs. In attempts to improve the WMSDs related symptoms, the best results will be achieved with ongoing in-house preventive programs practice and periodic outcomes assessments.
Arm ; Hand ; Neck ; Outcome Assessment (Health Care) ; Prevalence ; Shoulder ; Telephone* ; Surveys and Questionnaires

BACKGROUND/AIMS: E-cadherin is involved in intercellular binding and cellular polarity formation. beta-catenin plays a fundamental role in regulation of the E-cadherin cell adhesion complex. The abnormalities of the components of the complex may disrupt this adhesive function. We investigated the expression patterns of E-cadherin and beta-catenin to determine the clinical significance of these proteins in hepatocellular carcinoma. MATERIALS/METHODS: Thirty-six hepaticellular carcinoma tissues and adjacent non-tumor specimens were analyzed. Subcellular distribution of E-cadherin and beta-catenin was examined by immunohistochemistry staining. We evaluated the patterns of the expression, and investigated the relationship with the cause of HCC; level of AFP; TNM stage; tumor size; growth types; metastasis; differentiation grade of HCC; and presence of portal vein thrombosis. RESULTS: Immunohistochemistry showed that all non-tumor tissues had membranous type staining of E-cadherin. All non-tumor tissues showed cytoplasmic type staining of beta-catenin, but no beta-catenin accumulation in nuclei was found. 58% (21/36) of HCC showed positive expression of E-cadherin in cytoplasmic membrane. The cytoplasmic expression of beta-catenin in HCC was 83% (30/36); nuclear expression in 14% (5/36); and no staining in 3% (1/36). Nuclear beta-catenin expression was observed in none (0/4) of the well-differentiated HCC; 17%(3/9) of moderate-differentiated HCC; and 17%(2/6) of poorly-differentiated HCC. There were no relationships between E-cadherin and beta-catenin expression with other clinicopathologic factors. CONCLUSIONS: Loss of cytoplasmic staining of E-cadherin and nuclear accumulation of beta-catenin were observed in HCC. Nuclear accumulation of beta-catenin was not found in well differentiated HCC but was found in poorly differentiated HCC.
Adult ; Aged ; Cadherins/*metabolism ; Carcinoma, Hepatocellular/*metabolism/pathology ; Cytoskeletal Proteins/*metabolism ; English Abstract ; Female ; Human ; Immunohistochemistry ; Liver Neoplasms/*metabolism/pathology ; Male ; Middle Aged ; Trans-Activators/*metabolism