Insulin resistance and central obesity determine hepatic steatosis and explain cardiovascular risk in steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed to replace non-alcoholic fatty liver disease and focus on patients with progressive disease due to the presence of metabolic dysfunction. However, it is unclear whether the new definition actually identifies patients with hepatic steatosis at increased cardiovascular risk. Methods: A total of 4,286 asymptomatic subjects from the SAKKOPI study aged 45-80 years undergoing screening colonoscopy were analyzed. Steatosis was diagnosed by abdominal ultrasound. MASLD was diagnosed according to the recent expert consensus. Insulin resistance was assessed by homeostasis model assessment-insulin resistance score (HOMA-IR) (cutoff: ≥2.5), subclinical inflammation was estimated by ferritin/CRP/uric acid, and cardiovascular risk was assessed using SCORE2/ASCVD. Results: Mean age was 59.4 ± 8.5 years, 51.6% were male; mean BMI was 27.0 ± 4.5 kg/m², 9.2% had type 2 diabetes mellitus. In total, 1,903 (44.4%) were diagnosed with hepatic steatosis and were characterized by more severe metabolic dysfunction including insulin resistance (47.1% vs. 12.2%, p < 0.001) and central obesity (waist circumference ≥102/88 cm, 71.8% vs. 37.1%, p < 0.001). This translated into higher (subclinical) inflammation (ferritin 153 vs. 95 mg/dL, p < 0.001, uric acid 6.3 mg/dL vs. 5.2 mg/dL, p < 0.001) and 10-year cardiovascular risk (SCORE2 7.8 points vs. 5.1 points, p < 0.001, ASCVD 17.9 points vs. 10.8 points, p < 0.001). 99.0% of subjects with steatosis met the MASLD definition, 95.4% met the MAFLD definition, and 53.6% met the definition of metabolic syndrome, while 95.4% of subjects without steatosis also met the MASLD criteria for metabolic dysfunction compared to 69.0% and 17.4% who met the MAFLD and metabolic syndrome criteria, respectively. Forward stepwise regression indicated that waist circumference, HOMA-IR, and triglycerides were most relevant in explaining the presence of hepatic steatosis across all subgroups of increasing metabolic dysfunction. At the same time, hepatic steatosis was not associated with cardiovascular risk in the overall cohort (SCORE2: B = 0.060, 95% CI: -0.193-0.314, and p = 0.642) and in patients with metabolic dysfunction after adjusting for age, sex, and these three metabolic dysfunction components. Conclusion: Although hepatic steatosis is associated with increased central obesity and insulin resistance, metabolic dysfunction per se rather than hepatic steatosis explains cardiovascular risk in these patients.

[Update and Trends in Breast Reconstruction After Mastectomy]. / Update und Trends bei der plastisch-chirurgischen Brustrekonstruktion nach Mastektomie.

Due to refinements in operating techniques, autologous breast reconstruction has become part of standard care. It has become more difficult to advise patients due to the expansion of oncologic options for mastectomy, radiation therapy and the variety of reconstructive techniques. The goal of reconstruction is to achieve oncologically clear margins and a long-term aesthetically satisfactory result with a high quality of life. Immediate reconstruction preserves the skin of the breast and its natural form and prevents the psychological trauma associated with mastectomy. However, secondary reconstructions often have a higher satisfaction, since here no restitutio ad integrum is assumed. Alloplastic, i. e., implant-based, breast reconstruction and autologous breast reconstruction are complementary techniques. This article provides an overview of current options for breast reconstruction including patients' satisfaction and quality of life following breast reconstruction. Although immediate reconstruction is still the preferred choice of most patients and surgeons, delayed reconstruction does not appear to compromise clinical or patient-reported outcomes. Recent refinements in surgical techniques and autologous breast reconstruction include stacked-flaps, as well as microsurgical nerve coaptation to restore sensitivity, which lead to improved outcomes and quality of life. Nowadays Skin-sparing and nipple-sparing mastectomy, accompanied by improved implant quality, allows immediate prosthetic breast reconstruction as well as reemergence of the prepectoral implantation. The choice of breast reconstruction depends on the type of mastectomy, necessary radiation, individual risk factors, as well as the patient's habitus and wishes. Overall, recent developments in breast reconstruction led to an increase in patient satisfaction, quality of life and aesthetic outcome with oncological safety.

Insights into the material properties of dragline spider silk affecting Schwann cell migration.

Dragline silk of Trichonephila spiders has attracted attention in various applications. One of the most fascinating uses of dragline silk is in nerve regeneration as a luminal filling for nerve guidance conduits. In fact, conduits filled with spider silk can measure up to autologous nerve transplantation, but the reasons behind the success of silk fibers are not yet understood. In this study dragline fibers of Trichonephila edulis were sterilized with ethanol, UV radiation, and autoclaving and the resulting material properties were characterized with regard to the silk's suitability for nerve regeneration. Rat Schwann cells (rSCs) were seeded on these silks in vitro and their migration and proliferation were investigated as an indication for the fiber's ability to support the growth of nerves. It was found that rSCs migrate faster on ethanol treated fibers. To elucidate the reasons behind this behavior, the fiber's morphology, surface chemistry, secondary protein structure, crystallinity, and mechanical properties were studied. The results demonstrate that the synergy of dragline silk's stiffness and its composition has a crucial effect on the migration of rSCs. These findings pave the way towards understanding the response of SCs to silk fibers as well as the targeted production of synthetic alternatives for regenerative medicine applications.

Systematic Comparison of Commercial Hydrogels Revealed That a Synergy of Laminin and Strain-Stiffening Promotes Directed Migration of Neural Cells.

Hydrogels have shown potential in replacing damaged nerve tissue, but the ideal hydrogel is yet to be found. In this study, various commercially available hydrogels were compared. Schwann cells, fibroblasts, and dorsal root ganglia neurons were seeded on the hydrogels, and their morphology, viability, proliferation, and migration were examined. Additionally, detailed analyses of the gels' rheological properties and topography were conducted. Our results demonstrate vast differences on cell elongation and directed migration on the hydrogels. Laminin was identified as the driver behind cell elongation and in combination with a porous, fibrous, and strain-stiffening matrix structure responsible for oriented cell motility. This study improves our understanding of cell-matrix interactions and thereby facilitates tailored fabrication of hydrogels in the future.

Silk-in-Silk Nerve Guidance Conduits Enhance Regeneration in a Rat Sciatic Nerve Injury Model.

Advanced nerve guidance conduits can provide an off-the-shelf alternative to autografts for the rehabilitation of segmental peripheral nerve injuries. In this study, the excellent processing ability of silk fibroin and the outstanding cell adhesion quality of spider dragline silk are combined to generate a silk-in-silk conduit for nerve repair. Fibroin-based silk conduits (SC) are characterized, and Schwann cells are seeded on the conduits and spider silk. Rat sciatic nerve (10 mm) defects are treated with an autograft (A), an empty SC, or a SC filled with longitudinally aligned spider silk fibers (SSC) for 14 weeks. Functional recovery, axonal re-growth, and re-myelination are assessed. The material characterizations determine a porous nature of the conduit. Schwann cells accept the conduit and spider silk as growth substrate. The in vivo results show a significantly faster functional regeneration of the A and SSC group compared to the SC group. In line with the functional results, the histomorphometrical analysis determines a comparable axon density of the A and SSC groups, which is significantly higher than the SC group. These findings demonstrate that the here introduced silk-in-silk nerve conduit achieves a similar regenerative performance as autografts largely due to the favorable guiding properties of spider dragline silk.

Non-alcoholic fatty liver disease is not independently associated with Helicobacter pylori in a central European screening cohort.

BACKGROUND: The association between Helicobacter pylori (Hp) infection and non-alcoholic fatty liver disease (NAFLD) is subject of a contentious debate. Data mainly stem from Asian cohorts whereas European data are scarce. We, therefore, investigated an Austrian colorectal cancer screening cohort for an association between Hp and NAFLD. METHODS: In total, 5338 consecutive participants undergoing screening colonoscopy at a single center in Austria were evaluated in this cross-sectional study. The primary risk factor was being Hp negative or positive. The primary endpoint was the presence of NAFLD defined by ultrasound (NAFLD; primary endpoint). Uni- and multivariable logistic regression models were fitted to obtain odds ratios (OR) and 95% confidence intervals (95%CI). Finally, this association was analyzed in a subgroup of 1128 patients in whom NAFLD was diagnosed by transient elastography (TE, secondary endpoint). RESULTS: NAFLD prevalence defined by ultrasound did not differ between Hp positive (48%) and negative patients (45%, P=0.097). Accordingly, in uni- (OR 1.12 95% CI 0.98-1.29; P=0.098) and multivariable analysis adjusting for different risk factors (aOR 0.96 95%CI 0.82-1.13; P=0.601) no independent association was found. On subgroup analysis, NAFLD diagnosed by TE was more prevalent in the Hp positive compared to the Hp negative group (49% vs. 38%, P=0.004) and these patients also had higher steatosis grades. However, after adjustment for risk factors, no independent association between Hp positivity and NAFLD diagnosed by TE (aOR 1.26 95%CI 0.89-1.78; P=0.194) was confirmed. CONCLUSIONS: In this Central European cohort, Hp-positivity was not associated with the diagnosis of NAFLD. Although Hp positive patients seem to be more likely to have a concomitant NAFLD diagnosis, this association might rather relate to a cardiometabolic risk phenotype than causality.

How miRNAs Regulate Schwann Cells during Peripheral Nerve Regeneration-A Systemic Review.

A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.

Nuclear Magnetic Resonance Treatment Accelerates the Regeneration of Dorsal Root Ganglion Neurons in vitro.

Functional recovery from peripheral nerve injuries depends on a multitude of factors. Schwann cells (SCs) are key players in the regenerative process as they develop repair-specific functions to promote axon regrowth. However, chronically denervated SCs lose their repair phenotype, which is considered as a main reason for regeneration failure. Previous studies reported a modulatory effect of low nuclear magnetic resonance therapy (NMRT) on cell proliferation and gene expression. To provide first insight into a possible effect of NMRT on cells involved in peripheral nerve regeneration, this study investigated whether NMRT is able to influence the cellular behavior of primary SC and dorsal root ganglion (DRG) neuron cultures in vitro. The effect of NMRT on rat SCs was evaluated by comparing the morphology, purity, proliferation rate, and expression levels of (repair) SC associated genes between NMRT treated and untreated SC cultures. In addition, the influence of (1) NMRT and (2) medium obtained from NMRT treated SC cultures on rat DRG neuron regeneration was examined by analyzing neurite outgrowth and the neuronal differentiation status. Our results showed that NMRT stimulated the proliferation of SCs without changing their morphology, purity, or expression of (repair) SC associated markers. Furthermore, NMRT promoted DRG neuron regeneration shown by an increased cell survival, enhanced neurite network formation, and progressed neuronal differentiation status. Furthermore, the medium of NMRT treated SC cultures was sufficient to support DRG neuron survival and neurite outgrowth. These findings demonstrate a beneficial impact of NMRT on DRG neuron survival and neurite formation, which is primarily mediated via SC stimulation. Our data suggest that NMRT could be suitable as a non-invasive auxiliary treatment option for peripheral nerve injuries and encourage future studies that investigate the effect of NMRT in a physiological context.

Machine Learning Models Cannot Replace Screening Colonoscopy for the Prediction of Advanced Colorectal Adenoma.

Screening for colorectal cancer (CRC) continues to rely on colonoscopy and/or fecal occult blood testing since other (non-invasive) risk-stratification systems have not yet been implemented into European guidelines. In this study, we evaluate the potential of machine learning (ML) methods to predict advanced adenomas (AAs) in 5862 individuals participating in a screening program for colorectal cancer. Adenomas were diagnosed histologically with an AA being ≥ 1 cm in size or with high-grade dysplasia/villous features being present. Logistic regression (LR) and extreme gradient boosting (XGBoost) algorithms were evaluated for AA prediction. The mean age was 58.7 ± 9.7 years with 2811 males (48.0%), 1404 (24.0%) of whom suffered from obesity (BMI ≥ 30 kg/m²), 871 (14.9%) from diabetes, and 2095 (39.1%) from metabolic syndrome. An adenoma was detected in 1884 (32.1%), as well as AAs in 437 (7.5%). Modelling 36 laboratory parameters, eight clinical parameters, and data on eight food types/dietary patterns, moderate accuracy in predicting AAs with XGBoost and LR (AUC-ROC of 0.65-0.68) could be achieved. Limiting variables to established risk factors for AAs did not significantly improve performance. Moreover, subgroup analyses in subjects without genetic predispositions, in individuals aged 45-80 years, or in gender-specific analyses showed similar results. In conclusion, ML based on point-prevalence laboratory and clinical information does not accurately predict AAs.

Defining the regenerative effects of native spider silk fibers on primary Schwann cells, sensory neurons, and nerve-associated fibroblasts.

The search for a suitable material to promote regeneration after long-distance peripheral nerve defects turned the spotlight on spider silk. Nerve conduits enriched with native spider silk fibers as internal guiding structures previously demonstrated a regenerative outcome similar to autologous nerve grafts in animal studies. Nevertheless, spider silk is a natural material with associated limitations for clinical use. A promising alternative is the production of recombinant silk fibers that should mimic the outstanding properties of their native counterpart. However, in vitro data on the regenerative features that native silk fibers provide for cells involved in nerve regeneration are scarce. Thus, there is a lack of reference parameters to evaluate whether recombinant silk fiber candidates will be eligible for nerve repair in vivo. To gain insight into the regenerative effect of native spider silk, our study aims to define the behavioral response of primary Schwann cells (SCs), nerve-associated fibroblasts (FBs), and dorsal root ganglion (DRG) neurons cultured on native dragline silk from the genus Nephila and on laminin coated dishes. The established multi-color immunostaining panels together with confocal microscopy and live cell imaging enabled the analysis of cell identity, morphology, proliferation, and migration on both substrates in detail. Our findings demonstrated that native spider silk rivals laminin coating as it allowed attachment and proliferation and supported the characteristic behavior of all tested cell types. Axonal out-growth of DRG neurons occurred along longitudinally aligned SCs that formed sustained bundled structures resembling Bungner bands present in regenerating nerves. The migration of SCs along the silk fibers achieved the reported distance of regenerating axons of about 1 mm per day, but lacked directionality. Furthermore, rFBs significantly reduced the velocity of rSCs in co-cultures on silk fibers. In summary, this study (a) reveals features recombinant silk must possess and what modifications or combinations could be useful for enhanced nerve repair and (b) provides assays to evaluate the regenerative performance of silk fibers in vitro before being applied as internal guiding structure in nerve conduits in vivo.

Correlating the secondary protein structure of natural spider silk with its guiding properties for Schwann cells.

The successful reconstruction of supercritical peripheral nerve injuries remains a major challenge in modern medicine. Progress in tissue engineering has enabled the development of nerve guidance conduits as an alternative to autologous nerve transplantation and the enrichment of conduits with fibrous materials or hydrogels has shown great potential in bridging nerve defects. The application of the dragline silk of spider genus Nephila as a filament for nerve guidance conduits has led to promising results. However, the use of spider silk has been phenomenological so far and the reasons for its success are still not identified. This renders a targeted tuning of synthetic fibrous luminal fillings such as recombinant silk out of reach. In this work the existing research was extended and in addition to dragline, the cocoon silk of Nephila edulis, as well as the connecting and attaching silk of Avicularia avicularia were investigated. Scanning electron microscopy revealed a difference in size and morphology of the spider silks. However, in vitro experiments indicated that Schwann cells adhere to the four fibers, independent of these two attributes. Raman spectroscopy in native state and aqueous environment demonstrated similar secondary protein structures for dragline, cocoon, and connecting silk. In contrast, the attaching silk showed a significant lower conformation of ß-sheets, crucial for the stiffness of the silk. This was in line with the in vitro experiments, where the flexible attaching silk fibers adhered to each other when placed in liquid. This resulted in their inability to guide Schwann cells, leading to the generation of cell agglomerations. This direct comparison demonstrated the crucial role of ß-sheets conformation for the guidance properties of natural spider silk, providing essential insights into the necessary material properties for the integration of fibrous luminal fillings in nerve guidance conduits.

Automated image analysis of stained cytospins to quantify Schwann cell purity and proliferation.

In response to injury, adult Schwann cells (SCs) re-enter the cell cycle, change their expression profile, and exert repair functions important for wound healing and the re-growth of axons. While this phenotypical instability of SCs is essential for nerve regeneration, it has also been implicated in cancer progression and de-myelinating neuropathies. Thus, SCs became an important research tool to study the molecular mechanisms involved in repair and disease and to identify targets for therapeutic intervention. A high purity of isolated SC cultures used for experimentation must be demonstrated to exclude that novel findings are derived from a contaminating fibroblasts population. In addition, information about the SC proliferation status is an important parameter to be determined in response to different treatments. The evaluation of SC purity and proliferation, however, usually depends on the time consuming, manual assessment of immunofluorescence stainings or comes with the sacrifice of a large amount of SCs for flow cytometry analysis. We here show that rat SC culture derived cytospins stained for SC marker SOX10, proliferation marker EdU, intermediate filament vimentin and DAPI allowed the determination of SC identity and proliferation by requiring only a small number of cells. Furthermore, the CellProfiler software was used to develop an automated image analysis pipeline that quantified SCs and proliferating SCs from the obtained immunofluorescence images. By comparing the results of total cell count, SC purity and SC proliferation rate between manual counting and the CellProfiler output, we demonstrated applicability and reliability of the established pipeline. In conclusion, we here combined the cytospin technique, a multi-colour immunofluorescence staining panel, and an automated image analysis pipeline to enable the quantification of SC purity and SC proliferation from small cell aliquots. This procedure represents a solid read-out to simplify and standardize the quantification of primary SC culture purity and proliferation.

Ineffective Esophageal Motility in Patients with GERD is no Contraindication for Nissen Fundoplication.

BACKGROUND: Patients with preoperative ineffective esophageal motility (IEM) are thought to be at increased risk for postoperative dysphagia leading to the recommendations for tailoring or avoiding anti-reflux surgery in these patients. The aim of this study was to evaluate if IEM has an influence on postoperative outcome after laparoscopic Nissen fundoplication (LNF). METHODS: Seventy-two consecutive patients with IEM underwent LNF and were case-matched with 72 patients without IEM based on sex, age, BMI, HH size, total pH percentage time, total number of reflux episodes and the presence of BE. Standardized interview assessing postoperative gastrointestinal symptoms, proton pump inhibitor intake, GERD-health-related-quality-of-life (GERD-HRQL), alimentary satisfaction and patients' overall satisfaction was evaluated. RESULTS: Although a higher rate of preoperative dysphagia was observed in patients with IEM (29% IEM vs. 11% no IEM, p = 0.007), there was no significant difference in rates of dysphagia postoperatively (2 IEM vs. 1 no IEM, p = 0.559). Furthermore, no distinction was found in the postoperative outcome regarding symptom relief, quality of life, gas bloating syndrome, ability to belch and/or vomit or revision surgery between the two groups. CONCLUSION: Although preoperative IEM has an influence on GERD presentation, it has no effect on postoperative outcome after LNF. IEM should not be a cause for avoiding LNF, as is has been shown as the most effective and safe anti-reflux treatment.

Tailored modern GERD therapy - steps towards the development of an aid to guide personalized anti-reflux surgery.

As the incidence of gastroesophageal reflux disease (GERD) is rising, surgical treatment is continuously advancing in an effort to minimize side effects, whilst maintaining efficacy. From a database of patients that underwent anti-reflux surgery at our institution between 2015 and 2018, the last 25 consecutive patients that underwent electrical stimulation (ES), magnetic sphincter augmentation (MSA) and Nissen fundoplication (NF), following a personalized treatment decision aid, were included in a comparative analysis. After preoperative evaluation each patient was referred for an ES, MSA or NF based on esophageal motility, hiatal hernia (HH) size and the patients' preferences. Postoperative gastrointestinal symptoms and GERD-Health-related-Quality-of-Life were assessed. Preoperatively the median DCI (299 ES vs. 1523.5 MSA vs. 1132 NF, p = 0.001), HH size (0.5 cm ES vs. 1 cm MSA vs. 2 cm NF, p = 0.001) and presence of GERD-related symptoms differed significantly between the groups. The highest rate of postoperative dysphagia was seen after MSA (24%, p = 0.04), while the median GERD HRQL total score was equally distributed between the groups. The positive short-term postoperative outcome and patient satisfaction indicate that such an aid in treatment indication, based on esophageal motility, HH size and patient preference, represents a feasible tool for an ideal choice of operation and an individualized therapy approach.

Persistent dysphagia is a rare problem after laparoscopic Nissen fundoplication.

BACKGROUND: Although around 30% of patients with gastroesophageal reflux disease (GERD) are insufficiently treated with medical therapy, only 1% opt for surgical therapy. One of the reasons behind this multifactorial phenomenon is the described adverse effect of long-term dysphagia or gastric bloating syndrome after surgical treatment. Aim of this study was to evaluate the most common side effects associated with anti-reflux surgery, as well as long-term outcomes in a large cohort of highly surgically standardized patients after laparoscopic Nissen fundoplication (LNF). METHODS: Out of a prospective patients' database including all patients that underwent anti-reflux surgery between 01/2003 and 01/2017 at our institution, 350 consecutive patients after highly standardized LNF were included in this study. A standardized interview was performed by one physician assessing postoperative gastrointestinal symptoms, proton pump inhibitor intake (PPI), GERD-Health-Related-Quality-of-Life (GERD-HRQL), Alimentary Satisfaction (AS), and patients' overall satisfaction. RESULTS: After a median follow-up of 4 years, persistent dysphagia (PD) after LNF was observed in 8 (2%) patients, while postoperative gas-bloat syndrome in 45 (12.7%) cases. Endoscopic dilatation was needed in 7 (2%) patients due to dysphagia, and 19 (5%) patients underwent revision surgery due to recurrence of GERD. The postoperative GERD-HRQL total score was significantly reduced (2 (IQR 0-4.3) vs. 19 (IQR 17-32); p < 0.000) and the median AS was 9/10. Heartburn relief was achieved in 83% of patients. Eighty-three percent of patients were free of PPI intake after follow-up, whereas 13% and 4% of the patients reported daily and irregular PPI use, respectively. CONCLUSION: LNF is a safe and effective surgical procedure with low postoperative morbidity rates and efficient GERD-related symptom relief. PD does not represent a relevant clinical issue when LNF is performed in a surgical standardized way. These results should be the benchmark to which long-term outcomes of new surgical anti-reflux procedures are compared.

Correction: Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers.

[This corrects the article DOI: 10.1371/journal.pone.0189641.].

Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers.

BACKGROUND: Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in average risk patients but has not been investigated until now in female BRCA mutation carriers. METHODS: Using a multiplex, bead-based, immunoassay system, we analyzed the concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, CA125 and human epididymis antigen 4 in 26 healthy wild type women, 26 healthy BRCA1 mutation carriers, 28 wildtype OC patients and 26 OC patients with BRCA1 mutation. RESULTS: Using the ROC analysis, we found a high overall sensitivity of 94.3% in differentiating healthy controls from OC patients with comparable results in the wildtype subgroup (sensitivity 92.8%, AUC = 0.988; p = 5.2e-14) as well as in BRCA1 mutation carriers (sensitivity 95.2%, AUC = 0.978; p = 1.7e-15) at an overall specificity of 92.3%. The used algorithm also allowed to identify healthy BRCA1 mutation carriers when compared to healthy wildtype women (sensitivity 88.4%, specificity 80.7%, AUC = 0.895; p = 6e-08), while this was less pronounced in patients with OC (sensitivity 66.7%, specificity 67.8%, AUC = 0.724; p = 0.00065). CONCLUSION: We have developed an algorithm, which can differentiate between healthy women and OC patients and have for the first time shown, that such an algorithm can also be used in BRCA mutation carriers. To clarify a suggested benefit to the existing early detection program, large prospective trials with mainly early stage OC cases are warranted.