Multi-biomarker panel prediction model for diagnosis of pancreatic cancer.

BACKGROUND/PURPOSE: The current study aimed to develop a prediction model using a multi-marker panel as a diagnostic screening tool for pancreatic ductal adenocarcinoma. METHODS: Multi-center cohort of 1991 blood samples were collected from January 2011 to September 2019, of which 609 were normal, 145 were other cancer (colorectal, thyroid, and breast cancer), 314 were pancreatic benign disease, and 923 were pancreatic ductal adenocarcinoma. The automated multi-biomarker Enzyme-Linked Immunosorbent Assay kit was developed using three potential biomarkers: LRG1, TTR, and CA 19-9. Using a logistic regression model on a training data set, the predicted values for pancreatic ductal adenocarcinoma were obtained, and the result was classification into one of the three risk groups: low, intermediate, and high. The five covariates used to create the model were sex, age, and three biomarkers. RESULTS: Participants were categorized into four groups as normal (n = 609), other cancer (n = 145), pancreatic benign disease (n = 314), and pancreatic ductal adenocarcinoma (n = 923). The normal, other cancer, and pancreatic benign disease groups were clubbed into the non-pancreatic ductal adenocarcinoma group (n = 1068). The positive and negative predictive value, sensitivity, and specificity were 94.12, 90.40, 93.81, and 90.86, respectively. CONCLUSIONS: This study demonstrates a significant diagnostic performance of the multi-marker panel in distinguishing pancreatic ductal adenocarcinoma from normal and benign pancreatic disease states, as well as patients with other cancers.

CORRIGENDUM: Addition of data source: Diagnostic model for pancreatic cancer using a multi-biomarker panel.

[This corrects the article on p. 144 in vol. 100, PMID: 33748028.].

Analysis of Fracture Patterns and Characteristics in Sacral Insufficiency Fracture: Do Sacral Fractures Occur in Patients Who Had Previous Lumbosacral Fusion Insufficiency Fractures or Stress Fractures?

STUDY DESIGN: This study is a retrospective analysis of a case. PURPOSE: The purpose of this study is to investigate the fracture patterns and risk factors of sacral insufficiency fractures (SIFs) to improve their diagnosis in clinical practice. OVERVIEW OF LITERATURE: SIFs occur when normal stresses are applied to a bone with decreased density, most often due to osteoporosis. Individuals who receive lumbosacral fusion procedures may also suffer from increased incidents of SIFs because of decreased bone density related to aging. METHODS: In total, 55 patients with SIFs were retrospectively investigated in this study. The study population was divided into lumbosacral fusion (n=20) and non-fusion (n=35) groups. Subsequently, the patients' demographic characteristics, comorbidities, medication history, results of diagnostic imaging studies, and bone mineral density were assessed. The fracture patterns were classified either according to the five typical types (H-pattern bilateral vertical plus horizontal component, unilateral vertical only, bilateral vertical only, unilateral vertical plus horizontal component, and horizontal only fracture) or atypical types. RESULTS: In total, 44 of 55 patients (80%) suffered from more than one senile disease and received corresponding medications that caused secondary osteoporosis. A total of 12 patients had S1 lumbosacral fixation. Moreover, three of these 12 patients who developed a SIF immediately after a lumbosacral fracture had an unstable sacral U fracture. The remaining nine patients showed fracture patterns similar to the non-fusion patients. Single-photon emission computed tomography (SPECT)/computed tomography (CT) can identify fracture recurrence in previously healed fractures. In total, 24 patients (43.6%) had fractures of the pelvis, femur, and thoracolumbar spine. CONCLUSIONS: SIF develops in elderly patients with multiple adult diseases that can induce secondary osteoporosis. Such fractures may occur in the patients with instrumented lumbosacral fusion. Importantly, some patients showed stress fractures after multilevel instrumented lumbosacral fusion, whereas others showed insufficiency fractures. The different fracture patterns correspond to different grades of SIF, and SPECT/CT can easily identify the fracture status.

Diagnostic model for pancreatic cancer using a multi-biomarker panel.

PURPOSE: Diagnostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) have been used for early detection to reduce its dismal survival rate. However, clinically feasible biomarkers are still rare. Therefore, in this study, we developed an automated multi-marker enzyme-linked immunosorbent assay (ELISA) kit using 3 biomarkers (leucine-rich alpha-2-glycoprotein [LRG1], transthyretin [TTR], and CA 19-9) that were previously discovered and proposed a diagnostic model for PDAC based on this kit for clinical usage. METHODS: Individual LRG1, TTR, and CA 19-9 panels were combined into a single automated ELISA panel and tested on 728 plasma samples, including PDAC (n = 381) and normal samples (n = 347). The consistency between individual panels of 3 biomarkers and the automated multi-panel ELISA kit were accessed by correlation. The diagnostic model was developed using logistic regression according to the automated ELISA kit to predict the risk of pancreatic cancer (high-, intermediate-, and low-risk groups). RESULTS: The Pearson correlation coefficient of predicted values between the triple-marker automated ELISA panel and the former individual ELISA was 0.865. The proposed model provided reliable prediction results with a positive predictive value of 92.05%, negative predictive value of 90.69%, specificity of 90.69%, and sensitivity of 92.05%, which all simultaneously exceed 90% cutoff value. CONCLUSION: This diagnostic model based on the triple ELISA kit showed better diagnostic performance than previous markers for PDAC. In the future, it needs external validation to be used in the clinic.

Poor Dietary Protein Intake in Elderly Population with Sarcopenia and Osteosarcopenia: A Nationwide Population-Based Study.

BACKGROUND: Our purpose in this study was to evaluate any deficiency of protein intake for different types of sarcopenia, including osteosarcopenia and sarcopenic obesity and to establish a cut-off value for the relationship between malnutrition, sarcopenia, and osteosarcopenia. METHODS: The cross-sectional study was performed using data from the Korea National Health and Nutrition Examination Survey. A total of 4,020 participants (men, 1,698 and women, 2,322) were analyzed in the present study. Sarcopenia is defined according to the criteria for the Asia Working Group for Sarcopenia. To evaluate the adequacy of protein intake, the value obtained by dividing the amount of protein consumed through food by the daily recommended protein amount (50 g/day) of Korean males was defined as the nutrient intake ratio. RESULTS: Total protein (P<0.001 in men, P<0.001 in women) and low dietary intake protein (P<0.001 in men, P=0.046 in women) were significantly lower in the sarcopenia group than in the normal group, and were significantly lower in the osteosarcopenia group than in the normal group for both men and women. The cut-off value of the adjusted weight of protein intake for sarcopenia was 0.58 g/kg/day in men and 0.98 g/kg/day in women. The cut-off value for adjusted weight of protein intake for osteo-sarcopenia was 0.8 g/kg/day in men and 0.5 g/kg/day in women. CONCLUSIONS: A comprehensive dietary assessment to detect nutritional deficits that predispose one to or aggravate muscle atrophy is important for establishing a treatment plan for patients with malnutrition.

Facile Preparation and Characterization of Carbon Fibers with Core-Shell Structure from Graphene-Dispersed Isotropic Pitch Compounds.

In this study, isotropic pitch-based carbon fibers were prepared from a mixture of petroleum residue and graphene nanoplatelets with different contents. The softening point and synthetic yield of synthesized isotropic pitches were analyzed and compared to characterize the nature of the pitches. The surface and thermal characteristics of the fibers were observed using scanning electron microscopy and thermogravimetric analysis (TGA), respectively. From the results, it was observed that the prepared carbon fibers had an interesting core-shell structure. In the TGA analysis with air, the carbon fiber having 0.1 wt.% of graphene showed a higher residue yield than that of the sample having 1.0 wt.% of graphene. This result can be explained due to the graphene being placed on the surface region of the carbon fibers and directly helping to increase the surface area of the carbon fibers, resulting in rapid oxidation due to the enhanced contact area with oxygen.

Correction: Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel.

[This corrects the article DOI: 10.18632/oncotarget.21861.].

Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel.

Due to its high mortality rate and asymptomatic nature, early detection rates of pancreatic ductal adenocarcinoma (PDAC) remain poor. We measured 1000 biomarker candidates in 134 clinical plasma samples by multiple reaction monitoring-mass spectrometry (MRM-MS). Differentially abundant proteins were assembled into a multimarker panel from a training set (n=684) and validated in independent set (n=318) from five centers. The level of panel proteins was also confirmed by immunoassays. The panel including leucine-rich alpha-2 glycoprotein (LRG1), transthyretin (TTR), and CA19-9 had a sensitivity of 82.5% and a specificity of 92.1%. The triple-marker panel exceeded the diagnostic performance of CA19-9 by more than 10% (AUCCA19-9 = 0.826, AUCpanel= 0.931, P < 0.01) in all PDAC samples and by more than 30% (AUCCA19-9 = 0.520, AUCpanel = 0.830, P < 0.001) in patients with normal range of CA19-9 (<37U/mL). Further, it differentiated PDAC from benign pancreatic disease (AUCCA19-9 = 0.812, AUCpanel = 0.892, P < 0.01) and other cancers (AUCCA19-9 = 0.796, AUCpanel = 0.899, P < 0.001). Overall, the multimarker panel that we have developed and validated in large-scale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.

Development of SPR biosensor for the detection of human hepatitis B virus using plasma-treated parylene-N film.

A plasma-treated parylene-N film was presented for the immobilization of proteins through physical adsorption. The changes in surface properties of the parylene-N film after plasma-treatment were analyzed using contact angle microscopy and AFM. To demonstrate the high protein-immobilization efficiency of the plasma-treated parylene-N film, the immobilization efficiencies of differently modified surfaces were compared using model proteins with different surface charges, such as streptavidin (pI=5, negatively charged at pH 7), horseradish peroxidase (pI=6.6, nearly neutral at pH 7), and avidin (pI=10, positively charged at pH 7). The application of the plasma-treated parylene-N film as an SPR biosensor was also tested by immobilizing model proteins. An SPR biosensor based on the plasma-treated parylene-N film was developed for the detection of the human hepatitis virus surface antigen (HBsAg), and the plasma-treated parylene-N film was estimated to improve the sensitivity of SPR biosensor as much as 1000-fold by enhancing immobilization of receptor antibodies.

Capacitive immunoaffinity biosensor based on vertically paired ring-electrodes.

A capacitive biosensor was developed by using a vertically paired ring-electrode for the non-labeled immunoassay. The vertically paired ring-electrode was prepared by sequential deposition and etching processes. Two electrodes were layered on glass substrate by sputtering of gold layers with thicknesses of 50 nm and 100 nm, and a parylene-C film with a thickness of 550 nm was positioned between the electrode layers as a dielectric material by thermal deposition. The top layer was made by spin coating of SU-8. And then, the ring-electrodes were exposed at the wall of the layered structure by sequential etching processes. The fabricated electrodes were characterized by cyclic voltammetry of a well-known redox couple of 3,3',5,5'-tetramethylbenzidine. The non-labeled detection of antigen-antibody interaction was demonstrated by using anti-horseradish peroxidase (HRP) antibodies and C-reactive protein (CRP) as model analytes. When the model analytes were bound to the vertically paired ring-electrode, the impedance change was measured during the immunoassay steps, and the measured impedance was analyzed by using a model circuit of the ring-electrode, and the capacitance was estimated to be dependent on the adsorption of analytes between the ring-electrodes.

Development of SCAR marker for simultaneous identification of Miscanthus sacchariflorus, M. sinensis and M. x giganteus.

The sequence-characterized amplified region (SCAR) marker for simultaneous identification of Miscanthus sacchariflorus, Miscanthus sinensis, and Miscanthus x giganteus was developed. In this study, it was attempted for the first time to develop the SCAR marker for detecting the molecular phenotypes among Miscanthus species. Randomly amplified polymorphic DNA technique was applied for this study and one fragment which is unique to M. sacchariflorus was identified and then sequenced. Based on the specific fragment, one SCAR primer pair designated as MS62-5F and MS62-5R was designed to amplify an approximately 1,000 bp DNA fragment within the sequenced region. Diagnostic PCR was performed using the primer pair. Using this SCAR marker, approximately 1,000 bp and 1,200 bp DNA fragments were obtained in M. sacchariflorus and M. sinensis, respectively. Moreover, M. x giganteus was obtained both bands at the same time. The result showed that this SCAR marker can clearly distinguish the M. sacchariflorus, M. sinensis, and M. x giganteus, respectively.

OASIS: online application for the survival analysis of lifespan assays performed in aging research.

BACKGROUND: Aging is a fundamental biological process. Characterization of genetic and environmental factors that influence lifespan is a crucial step toward understanding the mechanisms of aging at the organism level. To capture the different effects of genetic and environmental factors on lifespan, appropriate statistical analyses are needed. METHODOLOGY/PRINCIPAL FINDINGS: We developed an online application for survival analysis (OASIS) that helps conduct various novel statistical tasks involved in analyzing survival data in a user-friendly manner. OASIS provides standard survival analysis results including Kaplan-Meier estimates and mean/median survival time by taking censored survival data. OASIS also provides various statistical tests including comparison of mean survival time, overall survival curve, and survival rate at specific time point. To visualize survival data, OASIS generates survival and log cumulative hazard plots that enable researchers to easily interpret their experimental results. Furthermore, we provide statistical methods that can analyze variances among survival datasets. In addition, users can analyze proportional effects of risk factors on survival. CONCLUSIONS/SIGNIFICANCE: OASIS provides a platform that is essential to facilitate efficient statistical analyses of survival data in the field of aging research. Web application and a detailed description of algorithms are accessible from http://sbi.postech.ac.kr/oasis.

Evolutionary conservation in multiple faces of protein interaction.

Protein interfaces are believed to be evolutionarily more conserved than the rest of the protein surface, but this has not been properly verified using a large protein structural set. Furthermore, recent systematic protein interaction analyses have proved that proteins interacting with many partners have multiple interfaces to connect protein interaction networks, which have never taken into account for conservation analysis of protein interface. Here, we studied the evolutionary conservation of protein interfaces using a large-scale dataset of 2646 protein interfaces with the classification of homodimeric/heterodimeric and obligatory/transient interactions, considering all their known multiple interfaces. We found that protein interfaces were indeed more conserved than noninterface surfaces, and the conservation level of protein interfaces increased when multiple interfaces were properly considered. These findings suggest that conservation analysis should be a good descriptor for protein interface identification and protein-protein interaction predictions. We applied this evolutionary feature to filter docking decoys and found that protein interface conservation worked remarkably well in selecting the near-native structures from the large number of generated docking complexes. Moreover, we discovered that a strong correlation exist between protein interface size and protein interface conservation, which could be a useful filter for the prediction of protein-protein interactions.

Clinical aspects of rifampicin-associated pseudomembranous colitis.

Pseudomembranous colitis (PMC) is known to develop after antibiotic administration, but antituberculosis agents are rarely associated with this disorder. We report 6 cases of PMC after rifampicin administration; the clinical manifestations, laboratory findings, imaging findings, and clinical course are described. The median age of patients was 68 years (range, 54 to 82 y). All patients were diagnosed with active pulmonary tuberculosis by sputum smear and culture, and 2 suffered from type 2 diabetes mellitus. The average interval between initiation of antituberculosis therapy and the onset of diarrhea was 19.8 days. The anatomic distribution of PMC included the rectum and sigmoid colon in 5 cases and up to the hepatic flexure in 1 case. All patients were cured with medical treatment, which include discontinuation of rifampicin and oral metronidazole and vancomycin. PMC recurred in 1 patient after retreatment with rifampicin. Our findings suggest that patients who are treated with antituberculosis agents, who develop acute diarrhea during or after therapy, should be evaluated for PMC.

Solid-pseudopapillary tumor of the pancreas.

BACKGROUND: Solid-pseudopapillary tumor (SPT) of the pancreas is a low-grade malignancy, which has been infrequently observed in adolescent and young adult females since first report by Frantz in 1959. In this article, we describe our experience of 8 cases of SPT with the clinical features, diagnosis, treatments, and outcomes. METHODS: We retrospectively reviewed the medical records and images of 8 patients who underwent surgery for SPT between January 1995 and December 2004. RESULTS: Seven females and 1 male with the mean age of 29 years (range, 10 to 64) at presentation were identified. Three patients presented palpable abdominal mass, 2 with abdominal pain, and the remainder with no specific symptom. The mean diameter of the tumors was 7.9 cm (range, 4.0 to 10.0). Four were located in the tail, 3 in the body, and 1 in the head. Surgical procedure included distal pancreatectomy with/without splenectomy in 7 patients and Whipple operation in 1 with no surgical morbidity and mortality. All were alive without evidence of recurrence after mean follow-up of 26.4 months (range, 1 to 66). CONCLUSIONS: SPT of the pancreas is an unusual neoplasm and typically occurs in young females presenting well-demarcated pancreatic masses, which are amenable to cure by complete surgical resection.

[The factors related to the prognosis of solitary hepatocellular carcinoma after radiofrequency ablation].

BACKGROUND/AIMS: Several risk factors, such as size and location, are related to local recurrence after radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC). The objectives of this study were to clarify factors related to prognosis. METHODS: From October 1999 to December 2002, we performed RFA for 107 consecutive patients with solitary HCC. We evaluated spiral computed tomography and serum alpha-fetoprotein level every 3 months after RFA. Seven possible factors for prognosis were analyzed using the Cox proportional hazards regression model: tumor size, tumor location, age, sex, etiology, platelet count, and Child-Pugh classification. Overall survival and disease free survival rate were estimated using the Kaplan-Meier method, and differences between two groups were compared using the log rank test. RESULTS: The Kaplan-Meier estimates of overall survival after radiofrequency ablation were 90.5% at 12 months, 67.4% at 24 months and 46.4% at 36 months and disease free survival were 71.4%, 46.7% and 20.9%, respectively. Using the Cox proportional hazards regression model, it was shown that with regard to overall survival and disease free survival, Child-Pugh classification (P=0.001, P=0.026) and platelet count (P<0.001, P=0.002) were statistically significant factors. The other factors did not have a statistically significant relationship to overall survival and disease free survival. CONCLUSIONS: The size and location known as local recurrence factors were not statistically significant with regard to survival and disease free survival. The Child-Pugh classification and platelet count, that reflect the liver function at the time of RFA, were significant factors for prognosis.

[The comparative results of radiofrequency ablation versus surgical resection for the treatment of hepatocellular carcinoma].

BACKGROUND/AIMS: Although surgical resection remains the gold standard of therapy for hepatocellular carcinoma (HCC), only selected patients can undergo resection because of the severity of the underlying cirrhosis or due to the diffuse distribution of the tumor. Radiofrequency ablation (RFA) has recently shown comparable results to surgical resection for the treatment of HCC. We compared the results of RF ablation and surgical resection for the treatment of HCC. METHODS: From January 2000 to December 2002, one hundred-sixty patients who had undergone surgical resection or RFA were analyzed retrospectively. The patients with a tumor size less than 5 cm in diameter, with less than 3 tumors in number, with tumor having a Child-Pugh class A classification and no evidence of extrahepatic metastasis were enrolled in the study. The recurrence pattern was classified into local and distant recurrence. We compared the recurrence patterns, the survival rates, the recurrence rates and the complications between the two groups. RESULTS: 1) The local recurrence rate was 9.8% for surgical resection and 18.2% for RFA and the distant recurrence rate were 32.8% and 28.3%, respectively. 2) The 1-, 2- and 3-year overall cumulative survival rates after RFA and surgery were 95.8%, 86.8%, 80.0%, 98.3%, 87.0% and 77.4%, respectively. 3) The incidence of complication was similar between the two groups. CONCLUSIONS: Radiofrequency ablation shows comparable results to surgical resection for the treatment of HCC. Therefore, RFA should be considered as the treatment of choice those patients who are not candidates for resection. However, intrahepatic recurrence of tumor after RFA was as frequent as that seen after surgical resection. Further investigation is warranted to clarify whether the current RFA technology could offer improved long-term results.

A human case of Echinostoma hortense (Trematoda: Echinostomatidae) infection diagnosed by gastroduodenal endoscopy in Korea.

A human Echinostoma hortense infection was diagnosed by gastroduodenoscopy. An 81-year-old Korean male, living in Yeongcheon-shi, Gyeongsangbuk-do and with epigastric discomfort of several days duration, was subjected to upper gastrointestinal endoscopy. He was in the habit of eating fresh water fish. Two live worms were found in the duodenal bulb area and were removed using an endoscopic forceps. Based on their morphological characteristics, the worms were identified as E. hortense. The patient was treated with praziquantel 10 mg/kg as a single dose. The source of the infection in this case remains unclear, but the fresh water fish consumed, including the loach, may have been the source. This is the second case of E. hortense infection diagnosed by endoscopy in Korea.

Endoscopic incision of a septum in a case of spontaneous intramural dissection of the esophagus.

Intramural dissection of the esophagus is a rare esophageal disorder that is characterized by a long laceration between the esophageal mucosa and submucosa but without perforation. It reveals characteristic radiologic and endoscopic features. The etiology of intramural dissection of the esophagus remains uncertain. The most common presenting symptoms are sudden retrosternal pain, hematemesis, odynophagia, dysphagia, and back pain. Conservative management is usually thought to be adequate. We report a case of spontaneous intramural esophageal dissection, in which the symptom of dysphagia did not improve with the conservative management, and an endoscopic incision of the septum between true and false lumens using a needle-type diathermy knife was done safely and effectively.