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Integrative Analysis of Metabolome and Proteome in the Cerebrospinal Fluid of Patients with Multiple System Atrophy
No full textMultiple system atrophy (MSA) is a progressive neurodegenerative synucleinopathy. Differentiating MSA from other synucleinopathies, especially in the early stages, is challenging because of its overlapping symptoms with other forms of Parkinsonism. Thus, there is a pressing need to clarify the underlying biological mechanisms and identify specific biomarkers for MSA. The metabolic profile of cerebrospinal fluid (CSF) is known to be altered in MSA. To further investigate the biological mechanisms behind the metabolic changes, we created a network of altered CSF metabolites in patients with MSA and analysed these changes using bioinformatic software. Acknowledging the limitations of metabolomics, we incorporated proteomic data to improve the overall comprehensiveness of the study. Our in silico predictions showed elevated ROS, cytoplasmic inclusions, white matter demyelination, ataxia, and neurodegeneration, with ATP concentration, neurotransmitter release, and oligodendrocyte count predicted to be suppressed in MSA CSF samples. Machine learning and dimension reduction are important multi-omics approaches as they handle large amounts of data, identify patterns, and make predictions while reducing variance without information loss and generating easily visualised plots that help identify clusters, patterns, or outliers. Thus, integrated multiomics and machine learning approaches are essential for elucidating neurodegenerative mechanisms and identifying potential diagnostic biomarkers of MSA
18F-FDOPA PET/CT in Oncology: Procedural Guideline by the Korean Society of Nuclear Medicine
No full textThis guideline outlines the use of 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanine positron emission tomography / computed tomography for the diagnosis and management of neuroendocrine tumors, brain tumors, and other tumorous conditions. It provides detailed recommendations on patient preparation, imaging procedures, and result interpretation. Based on international standards and adapted to local clinical practices, the guideline emphasizes safety, quality control, and the effective application of 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanine positron emission tomography / computed tomography for various tumors such as insulinomas, pheochromocytomas, and medullary thyroid carcinoma. It also addresses the use of premedication with carbidopa, fasting protocols, and optimal imaging techniques. The aim is to assist nuclear medicine professionals in delivering precise diagnoses, improving patient outcomes, and accommodating evolving medical knowledge and technology. This comprehensive document serves as a practical resource to enhance the accuracy, quality, and safety of 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanine positron emission tomography / computed tomography in oncology
Genome Sequencing of Rare Disease Patients Through the Korean Regional Rare Disease Diagnostic Support Program
No full textAffecting fewer than 20,000 people as defined in South Korea, rare diseases pose significant diagnostic challenges due to their diverse manifestations and genetic heterogeneity. Genome sequencing (GS) offers a promising solution by enabling simultaneous screening for thousands of rare genetic disorders. This study explores the diagnostic utility and necessity of GS within the government-funded Korean Regional Rare Disease Diagnostic Support Program (KR-RDSP), a collaborative initiative involving 11 regional rare disease centers across Korea. The program was launched as a proof-of-concept study in 2023 to equip the genetic clinics with a diagnostic tool to expedite the diagnoses for rare disease patients who reside outside the urban Seoul region where diagnostic resources are limited. The study leveraged GS to diagnose a cohort of 400 patients exhibiting a wide spectrum of symptoms. The overall diagnostic yield was 36.3% (145/400), with 4.8% (7/145) of the diagnosed patients being reported with variants that could not have been identified by chromosomal microarray or exome sequencing (ES), highlighting the added value of comprehensive genomic analysis. The implementation of a centralized GS analysis system streamlined the diagnostic process, enabling timely reporting within a reasonable turnaround time of ≤ 35 days. Segregation analysis by Sanger sequencing played a crucial role in confirming or reclassifying variant pathogenicity by elucidating inheritance patterns. Here, we summarize diagnostic statistics from the 400 GS dataset gathered from June 2023 to December 2023 and show interesting and informative case examples that illustrate the diagnostic efficacy of GS, highlighting its ability to uncover elusive genetic etiologies and provide personalized treatment insights. The study also highlights the successful implementation of the program for the 11 regional rare disease centers across Korea with a practical workflow, comprehensive testing, comparable diagnostic yield to previous reports, and, most importantly, reasonable turnaround time
Sarcopenia: how to determine and manage
No full textBACKGROUND: Understanding sarcopenia is becoming increasingly important as society ages. This comprehensive review covers the definition, epidemiology, causes, pathogenesis, diagnosis, prevention, management, and future directions for the management of sarcopenia, and the major issues related to sarcopenia in the knee joint. MAIN TEXT: Sarcopenia, a condition related to aging, is characterized by decreased muscle mass and strength, which significantly affects physical function. Its prevalence may vary by region and age, with reports of up to 50% prevalence in the elderly population. The potential causes of sarcopenia include neurodegeneration, poor nutrition, changes in hormonal effects, elevated levels of proinflammatory cytokines, and reduced activation of muscle satellite cells. Various pathogeneses, such as apoptosis, proteolysis, and inhibition of the signaling for increasing muscle mass, contribute to the development of sarcopenia. Generally, the diagnostic criteria for sarcopenia are based on reduced muscle mass, reduced muscle strength, and decreased physical performance, and can be assessed using various equipment and clinical tests. A healthy lifestyle consisting of a balanced diet, sufficient protein intake, and regular exercise is recommended to prevent sarcopenia. The management of sarcopenia involves resistance exercise, proper nutrition, and deprescribing from polypharmacy. In the future, pharmacological treatment and personalized nutrition may become alternative management options for sarcopenia. Finally, since sarcopenia can be associated with knee osteoarthritis and poor outcomes after total knee arthroplasty, appropriate management of sarcopenia is important for physicians treating knee-related conditions. CONCLUSIONS: Sarcopenia is a significant pathological condition that needs to be recognized, especially in the older population. Although sarcopenia is common as aging occurs, it can be prevented by a healthy lifestyle. Currently, there are no approved drugs for sarcopenia; however, resistance exercise and proper nutritional supplementation are essential methods for managing sarcopenic conditions. Given its diverse causes, a personalized approach may be necessary to effectively manage sarcopenia. Finally, appropriate management of sarcopenia can contribute to the prevention and effective treatment of knee osteoarthritis
A Longitudinal Increase in Serum Gamma-Glutamyl Transferase Levels, but Not in Alanine Aminotransferase Levels, Improves the Prediction of Risk of Impaired Fasting Glucose in Male
No full textBACKGROUND: Impaired fasting glucose (IFG), being a pre-diabetic condition, can increase the risk of overt diabetes; thus early detection and prediction of IFG are important to reduce the incidence of overt diabetes. Some predictive factors, including serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), have been reported in several studies, but none of the studies have investigated the effect of longitudinal changes in individual serum ALT and GGT levels on the risk of IFG. METHODS: We aimed to investigate the association between changes in the serum ALT and GGT levels and the risk of IFG using a checkup database between 1999 and 2014. RESULTS: A total of 3,598 males and 3,275 females were enrolled in the study. We performed a follow-up test of serum ALT or GGT in each individual, and classified the cases in which the serum ALT or GGT level was increased or decreased during the follow-up test compared to the baseline. According to the multivariate Cox proportional hazards model, the hazard ratio was 1.76 (95% confidence interval, 1.45-2.12; P < 0.001) in male subjects with an increased serum GGT level compared to male subjects with a decrease in the serum GGT level at follow-up compared to the baseline. However, the relationship between the serum ALT level and incidence of new-onset IFG was not statistically significant in both sexes; and in females, the relationship between the serum GGT level and incidence of new-onset IFG was also not statistically significant. CONCLUSION: We revealed that a longitudinal increase in serum GGT levels was related to an increased risk of IFG in males. Therefore, monitoring the changes in serum GGT levels is important for predicting new-onset IFG, and it can be used as an early indicator of onset of overt diabetes in males
Fluid resuscitation in trauma: What you need to know
No full textThere have been numerous changes in resuscitation strategies for severely injured patients over the last several decades. Certain strategies, such as aggressive crystalloid resuscitation, have largely been abandoned because of the high incidence of complications and worsening of trauma-induced coagulopathy. Significant emphasis has been placed on restoring a normal coagulation profile with plasma or whole blood transfusion. In addition, the importance of the lethal consequences of trauma-induced coagulopathy, such as hyperfibrinolysis, has been easily recognized by the use of viscoelastic testing, and its treatment with tranexamic acid has been extensively studied. Furthermore, the critical role of early intravenous calcium administration, even before blood transfusion administration, has been emphasized. Other adjuncts, such as fibrinogen supplementation with fibrinogen concentrate or cryoprecipitate and prothrombin complex concentrate, are being studied and incorporated in some of the institutional massive transfusion protocols. Finally, balanced blood component transfusion (1:1:1 or 1:1:2) and whole blood have become commonplace in trauma centers in North America. This review provides a description of recent developments in resuscitation and a discussion of recent innovations and areas for future investigation
Short-term Outcomes of Linear vs. Circular Stapling for Esophagojejunostomy in Gastric Cancer: an Inverse Probability of Treatment Weighting Analysis
No full textPURPOSE: Minimally invasive surgery for gastric cancer has become popular owing to its proven technical feasibility and oncological safety compared with conventional open gastrectomy. Although intracorporeal (IC) esophagojejunostomy (EJ) is commonly performed, a standardized method remains undetermined. This study compared short-term outcomes of IC EJ using circular versus linear stapling techniques. MATERIALS AND METHODS: We retrospectively assessed 586 patients with gastric cancer who underwent minimally invasive proximal or total gastrectomy between 2010 and 2021. Finally, 158 and 392 patients who underwent IC EJ anastomosis with circular and linear stapling, respectively, were included in this study. Surgical outcomes and complication rates were compared between the 2 groups after adjusting for confounding variables using inverse probability of treatment weighting. RESULTS: The total number of complications did not differ between the 2 groups (P=0.138). However, major complications occurred more frequently in the circular stapling group than in the linear stapling group (15.2% vs. 7.4%, P=0.041). There was no significant intergroup difference in EJ-related anastomotic leakage (1.9% vs. 2.1%, P=0.916). The incidence of anastomotic stenosis was lower in the linear stapling group than in the circular stapling group (10.8% vs. 0.5%, P<0.001). Additionally, the pain score on postoperative day 1 was lower in the linear stapling group (3.48 vs. 3.09, P<0.001). CONCLUSIONS: Both linear and circular stapling can be used in IC EJ. However, linear stapling is a more suitable option because it has several advantages, including a reduced incidence of EJ-related stenosis and less postoperative pain attributable to differences in the length of the incision
2025 clinical practice guidelines for diabetes management in korea: Recommendation of the korean diabetes association
No full textSputum immunoglobulin E levels correlate with eosinophilic airway regardless of atopy
No full textImmunoglobulin E (IgE) is a key molecule that induces mast cell activation in allergic inflammation and contributes to type 2/eosinophilic inflammation in asthmatic airways. This cross-sectional study investigated the role of local IgE in asthmatic airways according to atopy, asthma control, and eosinophilic inflammation. A total of 31 adult patients with moderate-to-severe asthma were enrolled. The study subjects were classified into (1) atopic/non-atopic, (2) controlled/partly controlled/uncontrolled asthma and (3) eosinophilic/non-eosinophilic asthma. Serum/sputum IgE and serum/urine eosinophil-derived neurotoxin (EDN) were measured. Serum IgE levels were higher in atopic asthmatics than in non-atopic asthmatics, whereas no differences were noted in sputum IgE levels. Sputum IgE levels were significantly higher in uncontrolled asthmatics than in partly controlled or controlled asthmatics, and in eosinophilic asthmatics than in non-eosinophilic asthmatics, whereas no differences were noted in serum IgE levels. Significant correlations were observed between serum EDN and serum/sputum IgE levels. The production of local IgE in asthmatic airways could contribute to type 2/eosinophilic inflammation, irrespective of atopy, resulting in poor asthma control. Strategies targeting IgE may be effective in the management of non-atopic and atopic asthma
Vasopressin-Sensitive Aqp2 Regulation Mediated by the TAZ-NR4A1 Axis in Renal Collecting Duct Cells
No full textRegulation of aquaporin-2 (Aqp2) gene is essential for body water homeostasis. This study investigated how TAZ (a transcriptional coactivator with PDZ-binding motif, Wwtr1) controls vasopressin-driven AQP2 expression. AQP2 expression was studied using collecting duct-specific TAZ-knockout (TAZ(f/f); HoxB7Cre) mice and siRNA-mediated knockdown of TAZ in vasopressin-responsive mpkCCDc11 cells. Downstream factors of TAZ were identified using transcriptomics and bioinformatics. The TAZ(f/f); HoxB7Cre mice demonstrated polyuria and a significant decrease in AQP2 abundance in the kidney cortex and the outer medulla. dDAVP treatment (10(-9) M, 24 h) on mpkCCDc11 cells significantly increased AQP2 mRNA and protein levels. However, siRNA-mediated TAZ knockdown (TAZ-KD) markedly attenuated these effects without affecting cAMP levels. Immunocytochemical analysis revealed a substantial decrease in AQP2 immunolabeling intensity in TAZ-KD cells following dDAVP stimulation. RNA sequencing analysis identified 1370 and 1985 differentially expressed genes in TAZ-KD cells under basal conditions and after dDAVP treatment, respectively. Among 17 previously identified transcription factor (TF) candidates, seven (Nr4a1, Cebpb, Mef2d, Elf3, Klf5, Junb, Stat3) were significantly upregulated by dDAVP in either control or TAZ-KD conditions. Among them, RT-qPCR analysis identified Nr4a1 as a TAZ-dependent TF, and immunoblotting revealed reduced NR4A1 protein levels in TAZ-KD cells upon dDAVP stimulation. This finding suggests its role as a TAZ-regulated target in dDAVP response pathway. Accordingly, Nr4a1-KD reduced the dDAVP-induced upregulation of Aqp2 mRNA and protein. KEGG pathway enrichment analysis revealed that HIF-1 signaling and glycolysis as central pathways affected by TAZ. TAZ-NR4A1 axis acts as a novel transcriptional regulatory mechanism in controlling vasopressin-mediated AQP2 expression