Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis.

Intoduction: Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification. Methods: Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC. Results: In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM. Discussion: These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM.

Health Implications of Lipedema: Analysis of Patient Questionnaires and Population-Based Matched Controls.

We conducted a comparative study involving 39 female patients with lipedema and group-matched controls at a ratio of 1:5. The primary survey tool was the German Health Update (GEDA 2019/2020-EHIS) questionnaire, which was developed by the Robert Koch Institute (RKI), Germany. The secondary survey tool was the German Pain Questionnaire. The prevalence of hypertension (p = 0.041) and high blood lipids (p = 0.024) was lower in the lipedema group compared to the control group. General health and well-being indicators demonstrated lower overall health ratings (p < 0.001) and higher physiotherapy use in patients with lipedema (p = 0.016). Mental health assessment revealed higher depression prevalence and severity (p = 0.001), together with a lower number of close contacts (p = 0.032). Furthermore, patients with lipedema experienced higher levels of pain (p < 0.001) and more significant pain-related disability in daily activities (p < 0.001) than controls. Correlation analysis among patients with lipedema showed a positive correlation between pain severity and depressive symptoms (ρ = 0.612, p < 0.001) and a moderate positive correlation with impaired health-related quality of life (ρ = 0.418, p = 0.010). In summary, our findings highlight significant differences in health and well-being between patients with lipedema and matched controls, especially in overall, metabolic, and mental health, as well as pain perception. The findings emphasize the need for a validated lipedema-specific questionnaire and a multidisciplinary treatment approach with a combination of physical therapies, lifestyle adjustments, and psychological strategies.

Serum Metabolomic Profiling of Patients with Lipedema.

Lipedema is a chronic condition characterized by disproportionate and symmetrical enlargement of adipose tissue, predominantly affecting the lower limbs of women. This study investigated the use of metabolomics in lipedema research, with the objective of identifying complex metabolic disturbances and potential biomarkers for early detection, prognosis, and treatment strategies. The study group (n = 25) comprised women diagnosed with lipedema. The controls were 25 lean women and 25 obese females, both matched for age. In the patients with lipedema, there were notable changes in the metabolite parameters. Specifically, lower levels of histidine and phenylalanine were observed, whereas pyruvic acid was elevated compared with the weight controls. The receiver operating characteristic (ROC) curves for the diagnostic accuracy of histidine, phenylalanine, and pyruvic acid concentrations in distinguishing between patients with lipedema and those with obesity but without lipedema revealed good diagnostic ability for all parameters, with pyruvic acid being the most promising (area under the curve (AUC): 0.9992). Subgroup analysis within matched body mass index (BMI) ranges (30.0 to 39.9 kg/m2) further revealed that differences in pyruvic acid, phenylalanine, and histidine levels are likely linked to lipedema pathology rather than BMI variations. Changes in low-density lipoprotein (LDL)-6 TG levels and significant reductions in various LDL-2-carried lipids of patients with lipedema, compared with the lean controls, were observed. However, these lipids were similar between the lipedema patients and the obese controls, suggesting that these alterations are related to adiposity. Metabolomics is a valuable tool for investigating lipedema, offering a comprehensive view of metabolic changes and insights into lipedema's underlying mechanisms.

Fecal and Urinary Adipokines as Disease Biomarkers.

The use of biomarkers is of great clinical value for the diagnosis and prognosis of disease and the assessment of treatment efficacy. In this context, adipokines secreted from adipose tissue are of interest, as their elevated circulating levels are associated with a range of metabolic dysfunctions, inflammation, renal and hepatic diseases and cancers. In addition to serum, adipokines can also be detected in the urine and feces, and current experimental evidence on the analysis of fecal and urinary adipokine levels points to their potential as disease biomarkers. This includes increased urinary adiponectin, lipocalin-2, leptin and interleukin-6 (IL-6) levels in renal diseases and an association of elevated urinary chemerin as well as urinary and fecal lipocalin-2 levels with active inflammatory bowel diseases. Urinary IL-6 levels are also upregulated in rheumatoid arthritis and may become an early marker for kidney transplant rejection, while fecal IL-6 levels are increased in decompensated liver cirrhosis and acute gastroenteritis. In addition, galectin-3 levels in urine and stool may emerge as a biomarker for several cancers. With the analysis of urine and feces from patients being cost-efficient and non-invasive, the identification and utilization of adipokine levels as urinary and fecal biomarkers could become a great advantage for disease diagnosis and predicting treatment outcomes. This review article highlights data on the abundance of selected adipokines in urine and feces, underscoring their potential to serve as diagnostic and prognostic biomarkers.

Prospective study of computer-aided detection of colorectal adenomas in hospitalized patients.

BACKGROUND: Adenoma detection with polypectomy during total colonoscopy reduces the incidence of colorectal cancer (CRC) and colorectal cancer-associated mortality. The adenoma detection rate (ADR) is an established quality indicator, which is associated with a decreased risk for interval cancer. An increase in ADR could be demonstrated for several artificially intelligent, real-time computer-aided detection (CADe) systems in selected patients. Most studies concentrated on outpatient colonoscopies. This sector often lacks funds for applying costly innovations like CADe. Hospitals are more likely to implement CADe and information about the impact of CADe in the distinct patient cohort of hospitalized patients is scarce. METHODS: In this prospective, randomized-controlled study, we compared colonoscopies performed with or without computer-aided detection (CADe) system (GI Genius, Medtronic) performed at University Medical Center Schleswig-Holstein, Campus Luebeck. The primary endpoint was ADR. RESULTS: Overall, 232 patients were randomized with n = 122 patients in the CADe arm and n = 110 patients in the control arm. Median age was 66 years (interquartile range 51-77). Indication for colonoscopy was most often workup for gastrointestinal symptoms (88.4%) followed by screening, post-polypectomy and post-CRC surveillance (each 3.9%). Withdrawal time was significantly prolonged (11 vs. 10 min, p = 0.039), without clinical relevance. Complication rate was not different between the arms (0.8% vs. 4.5%; p = 0.072). The ADR was significantly increased in the CADe arm compared to the control (33.6% vs. 18.1%, p = 0.008). ADR increase was particularly strong for the detection in elderly patients aged ≥50 years (OR 6.3, 95% CI 1.7 - 23.1, p = 0.006). CONCLUSION: The use of CADe is safe and increases ADR in hospitalized patients.

Factors influencing the time-intensity curve analysis of contrast-enhanced ultrasound in kidney transplanted patients: Toward a standardized contrast-enhanced ultrasound examination.

Background: Time-intensity curve analysis (TIC analysis) based on contrast-enhanced ultrasound (CEUS) provides quantifiable information about the microcirculation of different tissues. TIC analysis of kidney transplantations is still a field of research, and standardized study protocols are missing though being mandatory for the interpretation of TIC parameters in the clinical context. The aim of this study was to evaluate the impact of different sizes and forms of regions of interest (ROIs) on the variance of different TIC parameters and the level of interoperator variance between the different ROI methods in kidney transplantations. Methods: In 25 renal transplanted patients, 33 CEUS of the transplanted kidney were performed, and TIC analysis with ROIs sized 5 mm2 (ROI5), 10 mm2 (ROI10), and ROIs circumscribing the outlines of anatomical regions (ROI Anat ) were analyzed based on CEUS examination. The TIC analysis was repeated by a second independent operator for ROI5 and ROI Anat . Results: Statistical analysis revealed significant differences between TIC parameters of different ROI methods, and overall, the interoperator variance was low. But a greater ROI surface (ROI10) led to higher values of the intensity parameters A and AUC compared with ROI5 (p < 0.05). The difference in the ROI form led to high variation of certain TIC parameters between ROI5 and ROI Anat in the myelon [intraclass correlation coefficient (A, ICC = 0.578 (0.139-0.793); TIC parameter (TTP); and ICC = 0.679 (0.344-0.842) (p < 0.05)]. A mean variation of 1 cm of the depth of ROI5 in the cortex did not show significant differences in the TIC parameters, though there was an impact of depth of ROI Anat on the values of TIC parameters. The interoperator variance in the cortex was low and equal for ROI5 and ROI Anat , but increased in the myelon, especially for ROI Anat . Furthermore, the analysis revealed a strong correlation between the parameter AUC and the time interval applied for the TIC analysis in the cortex and myelon (r = 0.710, 0.674, p < 0.000). Conclusion: Our findings suggest the application of multiple ROIs of 5 mm2 in the cortex and medulla to perform TIC analysis of kidney transplants. For clinical interpretation of AUC, a standardized time interval for TIC analysis should be developed. After the standardization of the TIC analysis, the clinical predictive value could be investigated in further studies.

Hereditary Diffuse Gastric Cancer: Molecular Genetics, Biological Mechanisms and Current Therapeutic Approaches.

Hereditary diffuse gastric cancer is an autosomal dominant syndrome characterized by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is caused by inactivating mutations in the tumor suppressor gene CDH1. Genetic testing technologies have become more efficient over the years, also enabling the discovery of other susceptibility genes for gastric cancer, such as CTNNA1 among the most important genes. The diagnosis of pathogenic variant carriers with an increased risk of developing gastric cancer is a selection process involving a multidisciplinary team. To achieve optimal long-term results, it requires shared decision-making in risk management. In this review, we present a synopsis of the molecular changes and current therapeutic approaches in HDGC based on the current literature.

Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma.

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.