Efficacy of blood plasma spectroscopy for early liver cancer diagnostics in obese patients.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide. A considerable proportion of HCC is caused by cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH). Due to the increasing prevalence of metabolic syndrome, it is estimated that MASH-related HCC will become the most prevalent etiology of HCC. Currently, HCC screening is based on liver ultrasonography; however, the sensitivity of ultrasonography for early HCC stages in obese patients only reaches 23 %. To date, no studied biomarker shows sufficient efficacy for screening purposes. Nevertheless, the usage of spectroscopic methods offers a new perspective, as its potential use would provide cheap, fast analysis of samples such as blood plasma. MATERIAL AND METHODS: We employed a combination of conventional and chiroptical spectroscopic methods to study differences between the blood plasma of obese cirrhotic patients with and without HCC. We included 20 subjects with HCC and 17 without evidence of liver cancer, all of them with body mass index ≥ 30. RESULTS: Sensitivities and specificities reached values as follows: 0.780 and 0.905 for infrared spectroscopy, 0.700 and 0.767 for Raman spectroscopy, 0.840 and 0.743 for electronic circular dichroism, and 0.805 and 0.923 for Raman optical activity. The final combined classification model based on all spectroscopic methods reached a sensitivity of 0.810 and a specificity of 0.857, with the highest area under the receiver operating characteristic curve among all models (0.961). CONCLUSIONS: We suggest that this approach can be used effectively as a diagnostic tool in patients who are not examinable by liver ultrasonography. CLINICAL TRIAL REGISTRATION: NCT04221347.

Vibrational and chiroptical analysis of blood plasma for hepatocellular carcinoma diagnostics.

More than one fifth of the world's population suffers from liver cirrhosis or other chronic liver diseases. Unfortunately, some of them will inevitably develop hepatocellular carcinoma (HCC), due to the vast majority of HCC cases arising against the background of liver cirrhosis. Despite this clearly identified high-risk group, the lack of early diagnostic options causes HCC mortality to approach its incidence. As opposed to many types of cancer, the incidence of HCC is expected to grow in the coming decades, which makes the search for an effective early diagnostic option a pressing necessity. This study presents evidence that blood plasma analysis employing a combination of chiroptical and vibrational spectroscopic methods might be the key to the improvement of the current status. One hundred samples of patients with HCC and controls with cirrhosis were classified using principal component analysis together with a random forest algorithm. Differentiation of the specific spectral patterns of the studied groups was successful in more than 80%, indicating the prospect of including spectroscopy in the screening of high-risk groups, such as patients with cirrhosis.

Comprehensive spectroscopic, metabolomic, and proteomic liquid biopsy in the diagnostics of hepatocellular carcinoma.

Liquid biopsy is a very topical issue in clinical diagnostics research nowadays. In this study, we explored and compared various analytical approaches to blood plasma analysis. Finally, we proposed a comprehensive procedure, which, thanks to the utilization of multiple analytical techniques, allowed the targeting of various biomolecules in blood plasma reflecting diverse biological processes underlying disease development. The potential of such an approach, combining proteomics, metabolomics, and vibrational spectroscopy along with preceding blood plasma fractionation, was demonstrated on blood plasma samples of patients suffering from hepatocellular carcinoma in cirrhotic terrain (n = 20) and control subjects with liver cirrhosis (n = 20) as well as healthy subjects (n = 20). Most of the applied methods allowed the classification of the samples with an accuracy exceeding 80.0 % and therefore have the potential to be used as a stand-alone method in clinical diagnostics. Moreover, a final panel of 48 variables obtained by a combination of the utilized analytical methods enabled the discrimination of the hepatocellular carcinoma samples from cirrhosis with 94.3 % cross-validated accuracy. Thus, this study, although limited by the cohort size, clearly demonstrated the benefit of the multimethod approach in clinical diagnosis.

Effects of a 12-Week Interventional Exercise Programme on Muscle Strength, Mobility and Fitness in Patients With Diabetic Foot in Remission: Results From BIONEDIAN Randomised Controlled Trial.

Objectives: Diabetic foot syndrome (DFS) is a serious late diabetic complication characterised by limited joint mobility and other biomechanical and muscle abnormalities. Aim: To evaluate the effect of an interventional exercise programme on anthropometric parameters, muscle strength, mobility and fitness in patients with diabetic foot in remission. Data Sources and Study Selection: Thirty-eight patients with type 2 diabetes and DFS without active lesions (mean age 65 ± 6.9 years, BMI 32 ± 4.7 kg.m-2, waist-hip ratio (WHR)1.02 ± 0.06) were enrolled in our randomised controlled trial. All subjects were randomised into two groups: an intervention group (I; n=19) and a control group (C; n=19). The 12-week exercise intervention focused on ankle and small-joint mobility in the foot, strengthening and stretching of the lower extremity muscles, and improvements in fitness. Changes (Δ=final minus initial results) in physical activity were assessed using the International Physical Activity Questionnaire (IPAQ), with joint mobility detected by goniometry, muscle strength by dynamometry, and fitness using the Senior Fitness Test (SFT). Data extraction: Due to reulceration, 15.8% of patients from group I (3/19) and 15.8% of patients from group C were excluded. Based on the IPAQ, group I was more active when it came to heavy (p=0.03) and moderate physical activity (p=0.06) after intervention compared to group C. Group I improved significantly in larger-joint flexibility (p=0.012) compared to controls. In group I, dynamometric parameters increased significantly in both lower limbs (left leg; p=0.013, right leg; p=0.043) compared to group C. We observed a positive trend in the improvement of fitness in group I compared to group C. We also confirmed positive correlations between heavy physical activity and selected parameters of flexibility (r=0.47; p=0.007), SFT (r=0.453; p=0.011) and dynamometry (r=0.58; p<0.0025). Anthropometric parameters, such as BMI and WHR, were not significantly influenced by the intervention programme. Conclusion: Our 12-week interventional exercise programme proved relatively safe, resulting in improved body flexibility and increased muscle strength in DF patients in remission.