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(1) Background: Liver damage is an important component of acute COVID-19, and the advancement of preexisting liver disease is associated with a worse prognosis; (2) Methods: A nationwide retrospective study including 7444 patients aimed to evaluate levels of selected markers of liver damage and disease advancement and their association with mortality and mechanical ventilation (MV); (3) Results: Elevation of the following markers in multivariate models were associated with increased odds of mortality: Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), fibrosis-4 score (FIB-4), AST-to-platelet ratio index (APRI), and decreased levels of platelet count (PLT). Elevated levels of AST, LDH, APRI, FIB-4, and the AST/ALT ratio and decreased levels of PLT were associated with increased odds of MV in multivariate models. The best predictive accuracy against mortality was achieved with FIB-4 with AUC = 0.733 (95% CI, 0.718-0.749) at the optimal cut-off point of 2.764, while against MV was achieved with LDH with AUC = 0.753 (95% CI, 0.727-0.778) at the optimal cut-off point of 449.5 IU/L. (4) Conclusions: Our study confirms that the advancement of liver damage contributes to a worse prognosis in COVID-19 patients. Markers for liver damage and the advancement of liver disease can provide predictive value in clinical practice among COVID-19 patients.

Background: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs)., Methods: A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015-2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy., Results: Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients., Conclusions: As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients.

Background: The hepatitis B core-related antigen (HBcrAg) correlates with HBV DNA in patients with chronic HBV infection without antiviral treatment. Its utility in monitoring patients during and after the cessation of nucleos(t)ide analog (NA) treatment is unknown., Methods: The levels of HBcrAg were longitudinally determined in two cohorts of chronic HBV-infected patients with (A) newly started NA treatment or (B) after NA cessation during a median follow up (FU) of 60 months or 48 weeks, respectively. The correlation of HBcrAg and HBV DNA and the predictive value for HBeAg seroconversion and HBsAg loss were evaluated., Results: Fifty-six patients with newly-started NA treatment and 22 patients with NA cessation were identified. HBcrAg and HBV DNA strongly correlated before NA treatment (r = 0.77, p < 0.0001) and at virological relapse (0.66, p = 0.0063). At the individual level, the discrepant kinetics of HBcrAg and HBV DNA became evident. During NA treatment, 33% (6/18) and 9% (5/56) of patients showed HBeAg seroconversion or HBsAg loss/HBsAg < 100 IU/mL, respectively. Low levels of HBcrAg were associated with these endpoints., Conclusion: HBcrAg levels before antiviral treatment help to identify patients with chances of HBsAg loss or HBeAg seroconversion. However, its utility in replacing quantitative HBV DNA to evaluate treatment efficacy or virological relapse off-treatment is limited.

This article presents the results of petrophysical analyses of limestones and sandstones used for the construction of the wall structures of a Roman rural settlement located in Podšilo Bay on Rab Island (Croatia). An on-site analysis of the walls indicated the use of different lithotypes, which is an uncommon case in the area. So far, no petrophysical properties of the applied materials have been tested, and their provenance has not been specified. The aim of this research was to determine their usability as construction materials in an attempt to determine the possible reasons behind the usage of multiple lithotypes and their suitability as building materials. The following procedure was used to address these issues: (1) determination of the petrographic characteristics of the rocks, (2) performance of tests to characterise the mechanical properties in a complex stress state of uniaxial tension followed by uniaxial and triaxial compression, and, finally, (3) determination of the internal structure of the rocks using methods based on X-ray imaging. Multi-proxy characteristics of the materials including numerous observations and methods were performed: optical microscopy used to characterise rock petrography and mineralogy, scanning electron microscopy (SEM) coupled with EDS, as well as grinding tests; furthermore, mechanical properties were determined on cylindrical samples in accordance with European standards. X-ray microtomography using the XμCT method enabled microscopic observations and determination of the orientation of discontinuities and the rock structure. The performed analyses allowed us to distinguish three lithological types of sandstone and two types of limestone among the examined stone blocks. Stone blocks of fine- and medium-grained sandstone with carbonate binders, as well as sparitic limestone and mudstone with calcite veins, were used to build the studied structures. The analysed blocks showed traces of partial edge processing. Despite the defects in the material structure identified using XμCT, all the types of rock were characterised by high or very high strength. High values of longitudinal wave velocity confirmed the good quality of the material. These results contribute to a better understanding of the construction process and the related technological choices, and they provide the first dataset which can be used for the reconstruction of the building's original appearance in the future.

The hepatitis B virus (HBV) continues to cause substantial health and economic burdens, and its target of elimination may not be reached in 2030 without further efforts in diagnostics, non-pharmaceutical prevention measures, vaccination, and treatment. Current therapeutic options in chronic HBV, based on interferons and/or nucleos(t)ide analogs, suppress the virus replication but do not eliminate the pathogen and suffer from several constraints. This paper reviews the progress on biotechnological approaches in functional and definitive HBV treatments, including gene-editing tools, i.e., zinc-finger proteins, transcription activator-like effector nucleases, and CRISPR/Cas9, as well as therapeutics based on RNA interference. The advantages and challenges of these approaches are also discussed. Although the safety and efficacy of gene-editing tools in HBV therapies are yet to be demonstrated, they show promise for the revitalization of a much-needed advance in the field and offer viral eradication. Particular hopes are related to CRISPR/Cas9; however, therapeutics employing this system are yet to enter the clinical testing phases. In contrast, a number of candidates based on RNA interference, intending to confer a functional cure, have already been introduced to human studies. However, larger and longer trials are required to assess their efficacy and safety. Considering that prevention is always superior to treatment, it is essential to pursue global efforts in HBV vaccination.

Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness.

The COVID-19 pandemic proceeds in waves, with variable characteristics of the clinical picture resulting from the evolution of the SARS-CoV-2 virus. This study aimed to compare the epidemiological characteristics, symptomatology, and outcomes of the disease in patients hospitalized for COVID-19 during periods of different variants dominance. Comparing the periods of dominance of variants preceding the Delta variant, the Delta period was characterized by a higher share of hospitalized females, less frequent comorbidities among patients, and a different age distribution. The lowest need for oxygen therapy and mechanical ventilation was observed under Omicron dominance. The triad of classic COVID-19 symptoms, cough, fever, dyspnoea, and fatigue, were most prevalent during the Delta period, and significantly less common under the Omicron dominance. During the Omicron period, nearly twice as many patients as in the previous periods could be discharged from the hospital within 7 days; the overall 28-day mortality was significantly lower compared to that of the Delta period. It also did not differ between periods that were dominated by the BA.1 and BA.2 subvariants. The study indicates that the Omicron SARS-CoV-2 variant that dominated between January and June 2022 caused a disease which resembled the common cold, and was caused by seasonal alpha and beta-coronaviruses with a low pathogenicity for humans. However, one should note that this effect may not only have been related to biological features of the Omicron lineage, but may additionally have been driven by the increased levels of immunization through natural infections and vaccinations, for which we could not account for due to a lack of sufficient data.

Background: Sleep is a complex, reversible process that is responsible for the modulation of various physiological mechanisms. COVID-19-related sleep disorders are affecting different populations with a heterogenous prevalence, yet high rates among infected patients are frequently reported. The aim of the study is to assess the prevalence of insomnia in the early post-COVID-19 recovery period and explore the differences in the results acquired by the Athens Insomnia Scale (AIS) by gender and selected infection severity parameters., Methods: The data presented in the paper come from a prospective, observational study on COVID-19 complications (SILCOV-19) consisting of 200 COVID-19 patients. The AIS was used for the quantitative measurement of insomnia symptoms based on ICD-10 criteria., Results: 32% ( n = 64) of all patients in the study group obtained results indicating sleep disturbances (>5 points on the scale), while 21.5% ( n = 43) obtained results indicating insomnia (>10 points on the scale). The analysis of the results obtained by all patients in the AIS showed a significant correlation with the duration of symptoms (Spearman's rank-order: R = 0.18; p < 0.05), but not with the number of days spent in the hospital or age. Women achieved a higher score in overall AIS, as well as in questions assessing total sleep time, well-being the next day, physical and mental fitness the next day, and sleepiness during the day ( p < 0.05)., Conclusions: the prevalence of insomnia in the early post-COVID-19 recovery period is high.

Data on the use of remdesivir, the first antiviral agent against SARS-CoV-2, are limited in oncologic patients. We aimed to analyze contributing factors for mortality in patients with malignancies in the real-world CSOVID-19 study. In total, 222 patients with active oncological disorders were selected from a nationwide COVID-19 study of 4890 subjects. The main endpoint of the current study was the 28-day in-hospital mortality. Approximately half of the patients were male, and the majority had multimorbidity (69.8%), with a median age of 70 years. Baseline SpO2 < 85% was observed in 25%. Overall, 59 (26.6%) patients died before day 28 of hospitalization: 29% due to hematological, and 20% due to other forms of cancers. The only factor increasing the odds of death in the multivariable model was eGFR < 60 mL/min/m2 (4.621, p = 0.02), whereas SpO2 decreased the odds of death at baseline (0.479 per 5%, p = 0.002) and the use of remdesivir (0.425, p = 0.03). This study shows that patients with COVID-19 and malignancy benefit from early remdesivir therapy, resulting in a decrease in early mortality by 80%. The prognosis was worsened by low glomerular filtration rate and low peripheral oxygen saturation at baseline underlying the role of kidney protection and early hospitalization.

Poly-ɛ-caprolactone (PCL) is now widely studied in relation to the engineering of bone, cartilage, tendons, and other tissues. Standard histological protocols can destroy the carefully created trabecular and honeycomb-like architecture of PCL scaffolds, and could lead to scaffold fibers swelling, resulting in the displacement or compression of tissues inside the scaffold. The aim of this study was to modify a standard histopathological protocol for PCL scaffold preparation and evaluate it on porous cylindrical PCL scaffolds in a rat model. In 16 inbred Wag rats, 2 PCL scaffolds were implanted subcutaneously to both inguinal areas. Two months after implantation, harvested scaffolds were first subjected to μCT imaging, and then to histopathological analysis with standard (left inguinal area) and modified histopathological protocols (right inguinal area). To standardize the results, soft tissue percentages (STPs) were calculated on scaffold cross-sections obtained from both histopathological protocols and compared with corresponding µCT cross-sections. The modified protocol enabled the assessment of almost 10× more soft tissues on the scaffold cross-section than the standard procedure. Moreover, STP was only 1.5% lower than in the corresponding µCT cross-sections assessed before the histopathological procedure. The presented modification of the histopathological protocol is cheap, reproducible, and allows for a comprehensive evaluation of PCL scaffolds while maintaining their trabecular, honeycomb-like structure on cross-sections.

The GeniCore Upgraded Field Assisted Sintering Technology U-FAST was applied to the sintering of a commercial Zr-based bulk metallic glass powder AMZ4. The XRD, SEM and DSC analysis of the sintered compacts showed the benefit of the U-FAST method as an enabler for the production of fully amorphous samples with 100% relative density when sintering at 420 °C/480 s (693 K/480 s) and 440 °C/ 60 s (713 K/480 s). The hardness values for fully amorphous samples, over HV1 519, surpass cast materials and 1625 MPa compressive strengths are comparable to commercial cast products. The advantage of the U-FAST technology in this work is attributed to the high heating and cooling rates inherent to ultra-short pulses, which allow to maintain metastable structures and achieve better temperature control during the process. Increasing sintering temperature and time led to the crystallization of the materials. The geometry and material of the dies and punch determine the thermal inertia and pressure distribution inside the compacts, thus affecting the properties of the near net shape NNS compacts made using the U-FAST device.

(1) Background: Treatment of hepatitis C virus (HCV) infections with direct-acting antivirals (DAA) has demonstrated high efficacy and an excellent safety profile. The cured patients showed a sustained virological response and improved liver function, but also a continued risk of hepatocellular carcinoma (HCC) during the 2-3 years of follow-up after treatment; (2) Methods: A total of 192 patients out of 209 of the primary AMBER study were analyzed five years after treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin. Results: We confirmed that HCV clearance after DAA treatment is stable regardless of baseline liver fibrosis. We found that sustained virologic response is associated with a gradual but significant reduction in liver stiffness over 5 years. Liver function improved during the first 2 years of follow-up and remained stable thereafter. The risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful DAA treatment. However, in non-cirrhotic patients, it appears to clear up 3 years after treatment; (3) Conclusions: Monitoring for more than 5 years after curing HCV infection is necessary to assess the long-term risk of possible development of HCC, especially in patients with cirrhosis of the liver.

Tissue engineering (TE) is a field of regenerative medicine that has been experiencing a special boom in recent years. Among various materials used as components of 3D scaffolds, naturally formed chitinous materials seem to be especially attractive because of their abundance, non-toxic and eco-friendly character. In this study, chitinous skeleton isolated from the marine sponge Aplysina fistularis (phylum: Porifera) was used for the first time as a support for the cultivation of murine fibroblasts (Balb/3T3), human dermal fibroblasts (NHDF), human keratinocyte (HaCaT), and human neuronal (SH-SY5Y) cells. Characterization techniques such as ATR FTIR, TGA, and μCT, clearly indicate that an interconnected macro-porous, thermostable, pure α-chitin scaffold was obtained after alkali-acid treatment of air-dried marine sponge. The biocompatibility of the naturally formed chitin scaffolds was confirmed by cell attachment and proliferation determined by various microscopic methods (e.g., SEM, TEM, digital microscopy) and specific staining. Our observations show that fibroblasts and keratinocytes form clusters on scaffolds that resemble a skin structure, including the occurrence of desmosomes in keratinocyte cells. The results obtained here suggest that the chitinous scaffold from the marine sponge A. fistularis is a promising biomaterial for future research about tissues regeneration.

Chitin, as one of nature's most abundant structural polysaccharides, possesses worldwide, high industrial potential and a functionality that is topically pertinent. Nowadays, the metallization of naturally predesigned, 3D chitinous scaffolds originating from marine sponges is drawing focused attention. These invertebrates represent a unique, renewable source of specialized chitin due to their ability to grow under marine farming conditions. In this study, the development of composite material in the form of 3D chitin-based skeletal scaffolds covered with silver nanoparticles (AgNPs) and Ag-bromide is described for the first time. Additionally, the antibacterial properties of the obtained materials and their possible applications as a water filtration system are also investigated.

Background : Minimal hepatic encephalopathy (MHE) refers to a number of neuropsychiatric and neurophysiological disorders in patients with cirrhosis who do not show abnormalities on physical examination or in clinical tests. The aim of this study was to determine the prevalence, risk factors, and predictive value of minimal hepatic encephalopathy and the usefulness of the inhibitory control test (ICT) in the diagnosis. Methods : Seventy patients (mean age 53 years, range 24-77) with liver cirrhosis were enrolled in the study. MHE was diagnosed based on PHES (psychometric hepatic encephalopathy score) and ICT. PHES and ICT were validated in a group of 56 control subjects. Results : Minimal hepatic encephalopathy was diagnosed using PHES in 21 patients (30%). ICT diagnosed MHE in 30 patients (42%), and the test had a sensitivity of 65% and a specificity of 57% compared to PHES. The ICT score (lures/target accuracy rate) correlated with the age of subjects (R = 0.35, p = 0.002) and only slightly with education (education in years R = -0.22, p = 0.06). MHE diagnosed with PHES or ICT was associated with a significantly higher model of end-stage liver disease (MELD) score in the follow-up. MHE diagnosed with ICT was correlated with a significantly higher incidence of symptoms of decompensated cirrhosis ( p = 0.02) in the follow-up. Conclusions : ICT had moderate sensitivity and specificity in diagnosing MHE compared to PHES. Importantly, MHE detected with PHES or ICT was associated with poorer survival and a more severe progression of the disease.

Selective Laser Melting (SLM) is a manufacturing technique that is currently used for the production of functional parts that are difficult to form by the traditional methods such as casting or CNC (Computer Numerical Control) cutting from a wide range of metallic materials. In our study, a mixture of commercially pure titanium (Ti) and 15% at. aluminum nitride (AlN) was Selective Laser Melted to form three-dimensional objects. The obtained 4 mm edge cubes with an energy density that varied from 70 to 140 J/mm 3 were examined in terms of their microstructure, chemical and phase composition, porosity, and Vickers microhardness. Scanning Electron Microscopy (SEM) observations of the etched samples showed inhomogeneities in the form of pores and unmelted and partly melted AlN particles in the fine-grained dendritic matrix, which is typical for titanium nitrides and titanium aluminum nitrides. The AlN particles remained unmelted in samples, but no porosity was observed in the interface area between them and the dendritic matrix. Additionally, samples fabricated with the presintering step had zones with different sizes of dendrites, suggesting a differing chemical composition of the matrix and the possibility of the formation of the phases forming an Ti-Al-N ternary system. The chemical composition in the microareas of the samples was determined using Energy Dispersive X-Ray Spectroscopy (EDS) and revealed differences in the homogeneity of the samples depending on the SLM process parameters and the additional presintering step. The phase composition, examined using X-ray Diffraction analysis (XRD), showed that samples were formed from Ti, TiN, and AlN phases. Porosity tests carried out using a computer microtomography revealed porosities in a range from 7% to 17.5%. The formed material was characterized by a relatively high hardness exceeding 700 HV 0.2 over the entire cross-section, which depended on the manufacturing conditions.

Background and aim : The aim of this study was to assess the diagnostic performance of new morphology-related indices and Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores during hospitalization in predicting the onset of bacterial infection in patients with liver cirrhosis. Material and methods : A total of 171 patients (56.9% males; median age 59 years; total number of hospitalizations 209) with liver cirrhosis were included in this observational study. The diagnosis of cirrhosis was made on the basis of clinical, biochemical, ultrasonic, histological, and endoscopic findings. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), modified aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), Fibrosis-4 index (FIB-4), platelet-to-lymphocyte ratio (PLR), neutrophil-to-monocyte ratio (NMR), and CTP and MELD scores were calculated for the cases of patients with cirrhosis. Results: Bacterial infection was diagnosed in 60 of the 209 (28.7%) hospitalizations of patients with cirrhosis. The most common infections were urinary tract infection (UTI), followed by pneumonia and sepsis. The more severe the liver failure, the greater the bacterial infection prevalence and mortality. Patients with decompensated liver cirrhosis were infected more often than subjects with compensated cirrhosis (50.0% vs. 12.9%, p = 0.003). The calculated MELD score, CTP, NLR, LMR, AAR, monocyte count, and C-reactive protein (CRP) concentration were also related to the bacterial infection prevalence, and mortality areas under the curve (AUC) were 0.629, 0.687, 0.606, 0.715, 0.610, 0.648, and 0.685, respectively. The combined model with two variables (LMR and CTP) had the best AUC of 0.757. The most common bacteria isolated from patients with UTI were Escherichia coli , Enterococcus faecalis , and Klebsiella pneumonia . Gram-negative bacteria were also responsible for spontaneous bacterial peritonitis (SBP), and together with gram-positive streptococci and staphylococci , these microorganisms were isolated from blood cultures of patients with sepsis. Significant differences were found between CTP classification, MELD score, NLR, LMR, AAR, CRP, and PLR in patients with cirrhosis with, or without, bacterial infection. Conclusions: Bacterial infection prevalence is relatively high in patients with liver cirrhosis. Although all analyzed scores, including the LMR, NLR, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), CRP, CTP, and MELD, allowed the prediction of bacterial occurrence, the LMR had the highest clinical utility, according to the area under the curve (AUC) and odds ratio (OR).