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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

An obituary for Professor Daniel C. Dennett which offers a comprehensive overview of his entire philosophical project. It is argued that Dennett, drawing on the results and methods of cognitive sciences and evolutionary biology, attempted a unique reconciliation of the manifest image and the scientific image.

Background and Objectives: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with a highly unfavorable prognosis. Aims: Retrospective statistical analysis of patients with HCC in the field of liver cirrhosis treated at our center from the perspective of demography, and the effects of key changes in diagnostic and therapeutic procedures in the last 10 years on overall survival (OS) and earlier diagnosis. Materials and Methods: This study included 170 cirrhotic patients with HCC (136 men, 80%). Demographic and etiological factors and OS were analyzed based on distribution into three groups according to the period and key changes in diagnostic and therapeutic approaches (BCLC classification staging; standardization of protocol for transarterial chemoembolization (TACE) and the introduction of direct-acting antivirals (DAA) for the treatment of chronic viral hepatitis C (HCV); expansion of systemic oncological therapy). Results: The mean age at the time of diagnosis was 69.3 years (SD = 8.1), and etiology was as follows: non-alcoholic steatohepatitis (NASH) 39%, alcoholic liver disease (ALD) 36%, HCV 18%, cryptogenic liver cirrhosis 3%, chronic hepatitis B infection (HBV) 2%, and other etiology 2%. Distribution of stages according to the BCLC: 0 + A 36%, B 31%, C 22%, and D 11%. However, the distribution in the first studied period was as follows: 0 + A 15%, B 34%, C 36%, and D 15%; and in the last period: 0 + A 45%, B 27%, C 17%, and D 11%, and difference was statistically significant (p < 0.05). The median OS for stages 0 + A, B, C, and D was 58, 19, 6, and 2 months, respectively. During the monitored period, there was a visible increase in the etiology of ALD from 30% to 47% and a decrease in HCV from 22% to 11%. In patients treated with TACE (stage B), the median OS grew from 10 to 24 months (p < 0.0001) between the marginal monitored periods. Conclusions: We described a decreasing number of patients with HCV-related HCC during follow-up possibly linked with the introduction of DAA. In our cohort, an improvement in early-stage diagnosis was found, which we mainly concluded as a result of proper ultrasound surveillance, the institution of a HCV treatment center, and increased experience of our sonographers with an examination of cirrhotic patients. Lastly, we described significantly improved overall survival in patients with intermediate HCC treated by TACE, due to the increased experience of interventional radiologists with the method at our facility and an earlier switch to systemic therapy in case of non-response to TACE.

A review of Denis Dutton’s The Art Instinct: Beauty, Pleasure, and Human Evolution (New York: Bloomsbury Press, 2009, 280 pp. ISBN 978-1-59691-401-8).

The worldwide prevalence of obesity is increasing in the long term. This is closely related to the increase in comorbidities. With obesity and more broadly with metabolic syndrome is associated non-alcoholic fatty liver disease. Bariatric surgery is effective way of treatment of obesity, which is conservatively difficult to treat. The goal of our study was the retrospective evaluation of the presence of nonalcoholic fatty liver disease and liver fibrosis in cohort of patients undergoing sleeve gastrectomy for class III obesity at the Department of Surgery, Military University Hospital Prague and they are followed up at the Department of Internal Medicine, Military University Hospital Prague. Using non-invasive methods, liver steatosis has been reported at the majority of patients, however advanced fibrosis was not detected in our cohort. Obesity is severe health problem. Non-alcoholic fatty liver disease is nearly obvious in these patients and is highly overlooked. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. HCC is often diagnosed late because patients with early-stage cancer have no apparent symptoms. Therefore, it is desirable to find a reliable method for an early diagnosis based on the detection of metabolites - biomarkers, that can be detected in the early stages of the disease. Untargeted metabolomics is often used as a tool to find a suitable biomarker for several diseases. In this work, untargeted metabolomics was performed on blood plasma samples of HCC patients and compared with healthy individuals and patients with liver cirrhosis. A combination of liquid chromatography and high-resolution mass spectrometry was used as an analytical method. More than a thousand peaks were detected in the blood plasma samples, from which mainly amino acids, carboxylic acids, lipids, and their derivatives were evaluated as potential biomarkers. The data obtained were statistically processed using the analysis of variance, correlation analysis, and principal component analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The increasing occurrence of multiple primary cancers (MPC) is a long-term trend, but the prevalence of MPC in patients with hepatocellular carcinoma (HCC) and its impact on overall survival (OS) remains unknown. We retrospectively analyzed 497 patients with HCC treated at two tertiary centers. The cohort was divided into two subgroups - liver transplant (LT, 324 patients) and non-liver transplant (non-LT, 173 patients). We analyzed MPC occurrence, its impact on survival, and identified variables predicting unfavorable outcomes. The MPC were detected in 88 patients (18%). The most common MPC were prostate (17%), skin (15.9%), kidney (12.5%), and lung (10.2%). The median OS of the whole cohort and the LT and non-LT subgroups were 70, 116, and 17 months, respectively (p<0.0001). The median OS in patients with HCC only and HCC with another cancer was 77 (95% CI, 67-96) and 50 months (95% CI, 37-62), respectively (p=0.25). The OS of LT patients was significantly better than that of those in whom LT had been contraindicated owing to concomitant MPC (116 vs. 35 months, p<0.0009). Autoimmune etiology, non-alcoholic steatohepatitis (NASH), HCC as the first diagnosed malignancy, and male sex were identified as factors significantly influencing the patients' outcomes (HR 0.43, 3.2326, 0.70, and 1.43, respectively). The MPC frequency was 18%. The impact of MPC on OS was not significant, except for individuals contraindicated for LT because of MPC. A better prognosis is associated with the autoimmune etiology of cirrhosis, and when HCC is diagnosed as the first malignancy. Male sex and NASH worsened the outcomes.

Aim of the Study: To evaluate the role of hepatic venous pressure gradient (HVPG) measurement in patients with resectable hepatocellular carcinoma (HCC) we describe our experience with the procedure as part of our hospital standard preoperative algorithm. We present our protocol for this situation, the HVPG measurement procedure, and the results of our cohort., Material and Methods: We performed a retrospective statistical analysis of all patients who underwent planned hepatic resection for HCC with HVPG measurement between 1/2016 and 1/2023. The cohort included 35 patients (30 males, mean age 69.5 years) who underwent HVPG measurement before liver resection for HCC., Results: The success rate of measurement was 91.4%, with serious complications in 2.9% of cases. Due to the clinically significant portal hypertension (CSPH) 31.3% of patients were rejected for resection. Seventeen patients with excluded CSPH underwent resection with one case of a postoperative liver event, liver decompensation, representing 5.9% of them. One patient (5.9%) had a complicated postoperative course with fasciitis. None of the patients who underwent resection (88.2%) was readmitted to the hospital due to surgical complications or a liver event during 90 days of follow-up, and no death was reported. The median overall survival (OS) in the resected subgroup was 70 months (95% CI: 52-86), and in patients rejected for surgery (resection and transplantation) 35 months (95% CI: 13-48)., Conclusions: HVPG measurement is the gold standard for the quantification of portal hypertension. Hepatic vein catheterization is invasive, but a safe procedure, with a clear impact on the management of resectable HCC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Clinical and Experimental Hepatology.)

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.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a frequent fatal complication of chronic liver diseases in the stage of liver cirrhosis. HCC develops at a higher rate in patients with type 2 diabetes mellitus (DM2). DM2 is associated with an increased risk of developing malignant tumors. The term multiple primary neoplasia (MPN) is used to describe the occurrence of multiple primary tumors of different organs in the same individual. To the best of the authors knowledge, the topic of the association between HCC and MPN and DM2 has not been addressed in the Czech literature. Here we present the outcomes of retrospective statistical analysis of a cohort of patients with HCC who were dispensed at the Internal Medicine Clinic of the 1st Faculty of Medicine of the Charles University in the period 2011-2021 and the impact of DM2 and MPN on overall survival (OS). MPNs are relatively common in patients with HCC. The occurrence of MPNs in our cohort was associated with DM2 in half of the cases. Median OS in HCC patients was not significantly affected by the coincidence of DM2 and/or MPNs.

Background and Objectives: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with a highly unfavorable prognosis. Aims: Retrospective statistical analysis of patients with HCC in the field of liver cirrhosis treated at our center from the perspective of demography, and the effects of key changes in diagnostic and therapeutic procedures in the last 10 years on overall survival (OS) and earlier diagnosis. Materials and Methods: This study included 170 cirrhotic patients with HCC (136 men, 80%). Demographic and etiological factors and OS were analyzed based on distribution into three groups according to the period and key changes in diagnostic and therapeutic approaches (BCLC classification staging; standardization of protocol for transarterial chemoembolization (TACE) and the introduction of direct-acting antivirals (DAA) for the treatment of chronic viral hepatitis C (HCV); expansion of systemic oncological therapy). Results: The mean age at the time of diagnosis was 69.3 years (SD = 8.1), and etiology was as follows: non-alcoholic steatohepatitis (NASH) 39%, alcoholic liver disease (ALD) 36%, HCV 18%, cryptogenic liver cirrhosis 3%, chronic hepatitis B infection (HBV) 2%, and other etiology 2%. Distribution of stages according to the BCLC: 0 + A 36%, B 31%, C 22%, and D 11%. However, the distribution in the first studied period was as follows: 0 + A 15%, B 34%, C 36%, and D 15%; and in the last period: 0 + A 45%, B 27%, C 17%, and D 11%, and difference was statistically significant (p < 0.05). The median OS for stages 0 + A, B, C, and D was 58, 19, 6, and 2 months, respectively. During the monitored period, there was a visible increase in the etiology of ALD from 30% to 47% and a decrease in HCV from 22% to 11%. In patients treated with TACE (stage B), the median OS grew from 10 to 24 months (p < 0.0001) between the marginal monitored periods. Conclusions: We described a decreasing number of patients with HCV-related HCC during follow-up possibly linked with the introduction of DAA. In our cohort, an improvement in early-stage diagnosis was found, which we mainly concluded as a result of proper ultrasound surveillance, the institution of a HCV treatment center, and increased experience of our sonographers with an examination of cirrhotic patients. Lastly, we described significantly improved overall survival in patients with intermediate HCC treated by TACE, due to the increased experience of interventional radiologists with the method at our facility and an earlier switch to systemic therapy in case of non-response to TACE.

Stable picosecond supercontinuum generated in long crystals is an excellent means of seeding broadband, high-energy CPA systems. The generated output energy and spectrum can be almost three times as stable as the pump for a wide range of input pulse parameters. In this work, we show this is an intrinsic property for crystals longer than the filament and for a range of input energy values. We present a description of the stability mechanism in both the visible and infrared regions together with experimental data that support the theoretical explanation.

Palliative transarterial chemoembolization is indicated for patients with stage B hepatocellular carcinoma (HCC) based on the Barcelona Clinic Liver Cancer classification (BCLC). As this is a very wide and heterogenous group of patients, the ART score was designed to better differentiate these patients and to guide the decision for a second transarterial chemoembolization cycle.The goal of the study is to prove that the ART score is appropriate to define subgroups within the stage BCLC-B HCC group with significantly better or worse overall survival (OS) after repeated transarterial chemoembolization. A combined retrospective and prospective study was performed of the OS of patients with stage BCLC-B HCC that were monitored and treated at the Internal Medicine Clinic of the First Faculty of Medicine, Charles University in Prague and the Central Military Hospital Prague. An analysis of the survival curve using the Kaplan-Meier method was performed using the R software package.The median OS of the entire patient group was 18 months (95% CI 12-33). The median OS of patients with a favorable ART score was 33 months (95% CI 12-33) compared to 12 months (95% CI 6-18) for patients with an unfavorable ART score. The difference in OS in the subgroups differentiated by ART score was statistically significant (p < 0.01). Due to the significant difference in OS of patients differentiated by ART score, the currently recommended guidelines for the treatment of patients with stage BCLC-B hepatocellular carcinoma should be revised.

A simple and compact scheme for synchronization of the pump and signal pulses for short-pulse OPCPA is demonstrated. Relative timing jitter of 17 fs RMS is achieved (1% of the pump pulse duration) and the system remains locked for hours. The scheme uses a balanced optical cross correlator to detect relative delays between the pump and signal pulses and can be operated with just 10's of μJ of pump energy and pJ-level signal energies.

Chromophytes are an important group of microorganisms that contribute significantly to the carbon cycle on Earth. Their photosynthetic capacity depends on efficiency of the light-harvesting system that differs in pigment composition from that of green plants and other groups of algae. Here we employ femtosecond transient absorption spectroscopy to study energy transfer pathways in the main light-harvesting complex of Xanthonema debile, denoted XLH, which contains four carotenoids--diadinoxanthin, heteroxanthin, diatoxanthin, and vaucheriaxanthin--and Chl-a. Overall carotenoid-to-chlorophyll energy transfer efficiency is about 60%, but energy transfer pathways are excitation wavelength dependent. Energy transfer from the carotenoid S(2) state is active after excitation at both 490 nm (maximum of carotenoid absorption) and 510 nm (red edge of carotenoid absorption), but this channel is significantly more efficient after 510 nm excitation. Concerning the energy transfer pathway from the S(1) state, XLH contains two groups of carotenoids: those that have the S(1) route active (~25%) and those having the S(1) pathway silent. For a fraction of carotenoids that transfer energy via the S(1) channel, energy transfer is observed after both excitation wavelengths, though energy transfer times are different, yielding 3.4 ps (490 nm excitation) and 1.5 ps (510 nm excitation). This corresponds to efficiencies of the S(1) channel of ~85% that is rather unusual for a donor-acceptor pair consisting of a noncarbonyl carotenoid and Chl-a. Moreover, major carotenoids in XLH, diadinoxanthin and diatoxanthin, have their S(1) energies in solution lower than the energy of the acceptor state, Q(y) state of Chl-a. Thus, binding of these carotenoids to XLH must tune their S(1) energy to allow for efficient energy transfer. Besides the light-harvesting function, carotenoids in XLH also have photoprotective role; they quench Chl-a triplets via triplet-triplet energy transfer from Chl-a to carotenoid.