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Background/Objectives: The Omicron variant of SARS-CoV-2 is undergoing constant mutation. New strains vary in neuropathogenicity and the neurological spectrum of disease. The aim of this study was to assess the frequency and clinical characteristics of neurological manifestations during the Omicron dominance among hospitalized patients, including the differences between three subsequent periods. Methods: This retrospective single-center study included 426 hospitalized adults with confirmed COVID-19 divided into three periods (O1, O2, and O3) dependent on the dominance of Omicron subvariants in Poland. Demographic and clinical data, in particular neurological manifestations, were collected and compared. Results: The median age of the group was 74, older in subsequent (later) periods. The number of patients with a history of previous SARS-CoV-2 infection or vaccination increased with the duration of the pandemic. The severity of COVID-19 became lower in successive periods. Neurological manifestations were observed in 55.4% of patients, and the most frequent were delirium, headache, myalgia, dizziness, cerebrovascular diseases, and encephalopathy. In subsequent periods of Omicron dominance, a higher frequency of neurological manifestations such as delirium, transient ischemic attack (TIA), and encephalopathy was observed. Headache or myalgia was related to a shorter hospitalization while delirium, cerebrovascular diseases, and ischemic stroke were linked with an increased risk of death. Conclusions: The Omicron variant of SARS-CoV-2 presents a wide spectrum of neurological manifestations. Although there is an improvement in the survival rate of patients with COVID-19, the frequency of neurological manifestations increases. The occurrence of delirium, cerebrovascular diseases, and ischemic stroke results in higher mortality.

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Abstract The outbreak of the SARS-CoV-2 pandemic has put healthcare systems worldwide to their limits, resulting in increased waiting time for diagnosis and required medical assistance. With chest radiographs (CXR) being one of the most common COVID-19 diagnosis methods, many artificial intelligence tools for image-based COVID-19 detection have been developed, often trained on a small number of images from COVID-19-positive patients. Thus, the need for high-quality and well-annotated CXR image databases increased. This paper introduces POLCOVID dataset, containing chest X-ray (CXR) images of patients with COVID-19 or other-type pneumonia, and healthy individuals gathered from 15 Polish hospitals. The original radiographs are accompanied by the preprocessed images limited to the lung area and the corresponding lung masks obtained with the segmentation model. Moreover, the manually created lung masks are provided for a part of POLCOVID dataset and the other four publicly available CXR image collections. POLCOVID dataset can help in pneumonia or COVID-19 diagnosis, while the set of matched images and lung masks may serve for the development of lung segmentation solutions.

Celem artykułu jest wskazanie, w jaki sposób pandemia SARS-CoV-2 może determinować kluczowe kierunki polityki przestrzennej miast w Polsce. Przeanalizowano: wytyczne związane z medycznym punktem widzenia (w zakresie priorytetów polityki zdrowotnej) oraz główne tezy międzynarodowej dyskusji naukowej na temat zmian miejskich polityk przestrzennych. Na podstawie powyższej analizy, a także wskazanych aktualnych rozwiązań planistycznych w Polsce zostały opracowane rekomendacje dotyczące kierunkowych zagadnień polityki przestrzennej miast. W artykule określono, w jakim zakresie w polskich realiach jest możliwa realizacja poszczególnych postulatów. Opracowane w taki sposób rekomendacje zachowają wymiar uniwersalny - możliwy do odniesienia do większości dokumentów rozwojowych i przestrzennych polskich miast (w szczególności strategii rozwoju oraz studiów uwarunkowań i kierunków zagospodarowania przestrzennego). Istotnym wkładem autorów artykułu będzie również próba interdyscyplinarnego ujęcia perspektywy medycznej i urbanistycznej oraz przełożenie jej na konkretne postulaty.

Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major health burden worldwide due to high mortality rates and hospital bed shortages. SARS-CoV-2 infection is associated with several laboratory abnormalities. We aimed to develop and validate a risk score based on simple demographic and laboratory data that could be used on admission in patients with SARS-CoV-2 infection to predict in-hospital mortality. Methods Three cohorts of patients from different hospitals were studied consecutively (developing, validation, and prospective cohorts). The following demographic and laboratory data were obtained from medical records: sex, age, hemoglobin, mean corpuscular volume (MCV), platelets, leukocytes, sodium, potassium, creatinine, and C-reactive protein (CRP). For each variable, classification and regression tree analysis were used to establish the cut-off point(s) associated with in-hospital mortality outcome based on data from developing cohort and before they were used for analysis in the validation and prospective cohort. The covid-19 score was calculated as a sum of cut-off points associated with mortality outcome. Results The developing, validation, and prospective cohorts included 129, 239, and 497 patients, respectively (median age, 71, 67, and 70 years, respectively). The following cut of points associated with in-hospital mortality: age > 56 years, male sex, hemoglobin 92.9 fL, leukocyte count > 9.635 or 315.5 103/µL, CRP > 51.14 mg/dL, creatinine > 1.115 mg/dL, sodium 145.4 mEq/L, and potassium 6.255 mEq/L. The AUC of the covid-19 score for predicting in-hospital mortality was 0.89 (0.84–0.95), 0.850 (0.75–0.88), and 0.773 (0.731–0.816) in the developing, validation, and prospective cohorts, respectively (P

In a retrospective analysis of 477 fatal COVID-19 cases hospitalised at a single medical centre during the period from 6 March 2020 to 30 June 2022, several factors defining those patients at admission were assessed, as well as the course of the hospitalisation and factors contributing to death. There was a predominance of men (59.3% (283)) burdened by comorbidities, with increased inflammation at admission. Patients aged ≥ 81 years were significantly more likely to be admitted to and die in infectious diseases units (IDU) due to respiratory failure, their hospital stays were shorter, and they were most likely not to receive specialist treatment. The most common COVID-19 complications included acute kidney injury in 31.2% (149) patients and thromboembolic complications in 23.5% (112). The course of hospitalisation was complicated by healthcare-associated infections (HAI) in 33.3% (159) of cases, more often in those treated with baricitinib (p < 0.001). The initial use of an antibiotic, although common (94.8% (452)), was unwarranted in almost half of the cases (47.6% (215)). Complications of hospitalisation (46.1% (220)) and adverse events involving staff (49.7% (237)) were found in almost half of the patients. In 88.7% (423) of the cases, death was due to respiratory failure in the course of SARS-CoV-2 infection. Adverse events during hospitalisation should be considered as an additional factor that, in addition to the infection itself, may have influenced the death of patients.

BackgroundThe COVID-19 pandemic has sped up the implementation of telehealth solutions in medicine. A few symptom checkers dedicated for COVID-19 have been described, but it remains unclear whether and how they can affect patients and health systems. ObjectiveThis paper demonstrates our experiences with the COVID-19 risk assessment (CRA) tool. We tried to determine who the user of the web-based COVID-19 triage app is and compare this group with patients in the infectious diseases ward’s admission room to evaluate who could benefit from implementing the COVID-19 online symptom checker as a remote triage solution. MethodsWe analyzed the answers of 248,862 people interacting with an online World Health Organization–based triage tool for assessing the probability of SARS-CoV-2 infection. These users filled in an online questionnaire between April 7 and August 6, 2020. Based on the presented symptoms, risk factors, and demographics, the tool assessed whether the user’s answers were suggestive of COVID-19 and recommended appropriate action. Subsequently, we compared the sociodemographic and clinical characteristics of tool users with patients admitted to the Infectious Diseases Admission Room of J. Gromkowski Hospital in Wrocław. ResultsThe CRA tool tended to be used by asymptomatic or oligosymptomatic individuals (171,226 [68.80%] of all users). Most users were young (162,432 [65.27%] were below 40 years of age) and without comorbidities. Only 77,645 (31.20%) of the self-assessment app users were suspected of COVID-19 based on their reported symptoms. On the contrary, most admission room patients were symptomatic—symptoms such as fever, cough, and dyspnea were prevalent in both COVID-19-positive and COVID-19-negative patients. COVID-19-suspected patients in the CRA tool group presented similar COVID-19 symptoms as those who presented to the admission room. These were cough (25,062/40,007 [62.64%] in the CRA tool group vs 138/232 [59.48%] in the admission room group), fever (23,123/40,007 [57.80%] in the CRA tool group vs 146/232 [62.93%] in the admission room group), and shortness of breath (15,157/40,007 [37.89%] in the CRA tool group vs 87/232 [37.50%] in the admission room group). ConclusionsThe comparison between the symptomatology of the users interacting with the CRA tool and those visiting the admission room revealed 2 major patient groups who could have benefited from the implementation of the self-assessment app in preclinical triage settings. The primary users of the CRA tool were young, oligosymptomatic individuals looking for screening for COVID-19 and reassurance early in the COVID-19 pandemic. The other group were users presenting the typical symptoms suggestive of COVID-19 at that time. The CRA tool recognized these individuals as potentially COVID-19 positive and directed them to the proper level of care. These use cases fulfil the idea of preclinical triage; however, the accuracy and influence on health care must be examined in the clinical setting.

The role of immune dysregulation in the course and prognosis of COVID-19 is not clearly established. In particular, immune status in specific populations such as haematological patients, who have an impaired immunological system, has not been described so far. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subsets in 27 SARS-CoV-2-infected patients, including 16 patients with haematological malignancies. We identified T cell subpopulations, B cells, NK cells and TCR α/ß and ɣ/ƍ-expressing T cells during COVID-19 infection, with significant changes observed in immune profiles during the course of disease, especially in haematological patients. We observed an increase in activated T lymphocytes (CD3+HLA-DR+ and CD3+CD8+HLA-DR+) in the early stages of SARS-CoV-2 infection with a concomitant decrease in the CD4/CD8 ratio in haematological patients compared to non-haematological patients affected by COVID-19. We also found a decrease in ɣ/ƍ T cells in both studied groups of patients, with lower numbers of CD25+ T cells and CD16+CD56+ NK cells in haematological patients compared to non-haematological patients with COVID-19. Our findings demonstrate, for the first time, impaired adaptive immunity in patients with haematological malignancies infected with COVID-19, resulting in impaired cellular immune responses to SARS-CoV-2. This warrants further investigation of this disease group in COVID-19 patient cohorts

IntroductionQuantitative computed tomography (QCT) is used to objectively assess the degree of parenchymal impairment in COVID-19 pneumonia.Materials and methodsRetrospective study on 61 COVID-19 patients (severe and non-severe; 33 men, age 63+/-15 years) who underwent a CT scan due to tachypnea, dyspnoea or desaturation. QCT was performed using VCAR software. Patients' clinical data was collected, including laboratory results and oxygenation support. The optimal cut-off point for CT parameters for predicting death and respiratory support was performed by maximizing the Youden Index in a receiver operating characteristic (ROC) curve analysis.ResultsThe analysis revealed significantly greater progression of changes: ground-glass opacities (GGO) (31,42% v 13,89%, pConclusionQCT is a good diagnostic tool which facilitates decision-making regarding intensification of oxygen support and transfer to an intensive care unit in patients severely ill with COVID-19 pneumonia. QCT can make an independent and simple screening tool to assess the risk of death, regardless of clinical symptoms. Usefulness of QCT to predict the risk of death is higher than to assess the indications for respiratory support.

The emergence of a highly transmissible and a more pathogenic B.1.617.2 (delta) variant of SARS-CoV-2 has brought concern over COVID-19 vaccine efficacy and the increased risk of severe breakthrough infections. The objective of this study was to assess the frequency and the clinical characteristics of severe breakthrough COVID-19 cases recorded in 10 Polish healthcare units between 1 June and 31 December 2021, a period during which a rapid surge in the share of B.1.617.2 infections was seen, while a significant number of populations were already fully vaccinated. Overall, 723 individuals who completed the initial vaccination regime (fully vaccinated group) and an additional 18 who received a booster dose were identified—together, they represented 20.8% of all the COVID-19 patients hospitalized during the same period in the same healthcare institutions (0.5% in the case of a group that received a booster dose). Although laboratory and clinical parameters did not differ between both groups, patients who received a booster tended to have lower CRP, IL-6, PCT, and d-dimer levels and they required oxygen therapy less frequently. The most common early COVID-19 symptoms in the studied group were fatigue, cough, fever (>38 °C), and dyspnea. Individuals with no detectable anti-spike IgG antibodies constituted 13%; the odds of being a humoral non-responder to the vaccine were increased in patients aged >70 years. Fully vaccinated patients hospitalized after more than 180 days from the last vaccine dose were significantly older and they were predominantly represented by individuals over 70 years and with comorbidities, particularly cardiovascular disease. Contrary to mRNA vaccines, most patients vaccinated with adenoviral vector vaccines were infected within six months. A total of 102 fatal cases (14% of all deaths among vaccinated individuals; 0.7% in the case of a group that received a booster dose) were recorded, representing 17.6% of all the COVID-19 fatalities recorded in June–December 2021 in the considered healthcare units. The odds of death were significantly increased in men, individuals aged >70 years, patients with comorbidities, and those identified as humoral non-responders to vaccination; in fully vaccinated patients the odds were also increased when the second vaccine dose was given >180 days before the first COVID-19 symptoms. The mortality rate in immunocompromised subjects was 19%. The results indicate that compared to vaccinated individuals, severe COVID-19 and deaths in the unvaccinated group were significantly more prevalent during the B.1.617.2-dominated wave in Poland; and, it highlight the protective role of a booster dose, particularly for more vulnerable individuals.

Background and Objectives: Patients living with HIV (PLWH), especially those diagnosed too late or not receiving treatment with antiretroviral drugs in the stage of advanced immunodeficiency AIDS for various reasons, develop additional opportunistic infections or AIDS-defining diseases that may contribute directly to the death of these patients. Material and Methods: In this work, we focused on disorders of the central nervous system (CNS) by retrospectively analyzing the symptoms, clinical and autopsy diagnoses of patients diagnosed with HIV infection who died in the provincial specialist hospital in the Lower Silesia region in Poland. Results: The autopsy was performed in 27.4% cases. The cause of death was determined to be HIV-related/AIDS-associated in 78% patients. The most common AIDS-defining CNS diseases in our cohort were toxoplasmosis and cryptococcosis. Conslusions: The presented results of the most common causes of changes in the central nervous system among deceased HIV-infected patients are comparable to the results of studies by other scientists cited in the publication.

Abstract Background According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs. ledipasvir/sofosbuvir±RBV (LSR) in PI-experienced patients in real-life setting. Methods Our analysis included patients registered in the nationwide, investigators initiated, multicentre EpiTer-2 database. Among 4530 patients registered, 335 with genotype 1 (93% 1b) were previously treated with IFN-based regimens with PIs: 127 with boceprevir (BOC), 208 with telaprevir (TVR). Patients with advanced fibrosis (F3/F4) were significantly predominant (BOC 28.4%/61.4%, TVR 18.8%/64.4%, respectively). Subjects were assigned to IFN-free retreatment as follows: BOC - 64 (50.4%) PrODR and 63 (49.6%) LSR; TVR- 103 (49.5%) PrODR and 105 (50.5%) LSR. Results SVR rates were comparable for particular groups: BOC → PrODR- 100%; BOC → LSR - 98%; TVR → PrODR - 97%; TVR → LSR - 96% (intent-to treat analysis-ITT) and BOC → PrODR→100%; BOC → LSR - 99%; TVR → PrODR - 99%; TVR → LSR - 98% (modified intent-to treat analysis-mITT). Both treatment regimens had a favourable safety profile. Adverse events (AEs) were generally mild or moderate in severity. Three deaths were reported. The treatment was stopped due to AEs in five patients (three treated with PrODR and two with LSR). Conclusion Efficacy and safety of treatment with PrODR and LSR is comparable in BOC or TVR-experienced patients.

Hepatocellular carcinoma (HCC) is the most common liver cancer, accountable for 90% cases. Visfatin and vaspin are adipocytokines with various suggested functions and proven significant correlations between BMI and percentage of body fat. The aim was to assess visfatin and vaspin serum levels in HCC patients and controls, compare their levels in patients with different cancer etiology and grade assessed according to the Barcelona-Clinic Liver Cancer (BCLC) staging system. The additional aim was to analyze relationship between analyzed adipokines and metabolic abnormalities and liver disfunction severity. The study was performed on 69 cirrhotic patients (54 males/15 females) with HCC, aged 59.0 ± 12.1 years, and with BMI 29.0 ± 4.5 kg/m2 compared to 20 healthy volunteers. Serum visfatin and vaspin concentrations were significantly increased in HCC patients compared to controls (p = 0.01 and p = 0.02, respectively). Serum vaspin was significantly higher in HCC patients with viral compared to those with non-viral etiology (p = 0.02), with more evident increase in chronic hepatitis C patients (CHC). Serum visfatin levels were significantly higher in patients with higher insulin resistance (p = 0.04) and with platelets count > 100 000/mm3 (p30 kg/m2 had markedly up-regulated vaspin levels (p = 0.04). There was no difference in vaspin and visfatin serum levels with respect to liver dysfunction and BCLC classification. In conclusion, our study revealed serum vaspin and visfatin to be significantly increased in HCC patients independently of cancer etiology compared to controls. Additionally, serum vaspin was elevated in viral disease, especially in CHC. Vaspin up-regulation can be a compensatory mechanism against IR in HCC patients. Serum visfatin and vaspin, although up-regulated, seem not to be associated with cancer grade and cirrhosis severity.

The clinical trials of the COVID-19 vaccines that are authorized in the European Union have revealed high efficacy in preventing symptomatic infections. However, during vaccination campaigns, some vaccine recipients, including those partially and fully vaccinated, will experience severe COVID-19, requiring hospitalization. This may particularly concern patients with a diminished immune response to the vaccine, as well as non-responders. This work has retrospectively analyzed the 92 cases of patients who were hospitalized between 27 December 2020 and 31 May 2021 in four Polish healthcare units due to COVID-19, and who have previously received the COVID-19 vaccine (54.3% ≤ 14 days after the first dose, 26.1% > 14 days after the first dose, 7.6% ≤ 14 days after the second dose, and 12% > 14 days after the second dose). These patients represented a minute fraction (1.2%) of all the COVID-19 patients who were hospitalized during the same period in the same healthcare institutions. No significant differences in white blood count, absolute lymphocyte count nadir, C-reactive protein, interleukin-6, procalcitonin, oxygen saturation, lung involvement, and fever frequency were found between the recipients of the first and second vaccine dose. A total of 15 deaths were noted (1.1% of all fatal COVID-19 cases in the considered period and healthcare units), including six in patients who received the second dose (five > 14 days after the second dose)—three of these subjects were using immunosuppressive medicines, and two were confirmed to be vaccine non-responders. The study reassures that severe COVID-19 and deaths are not common in vaccinated individuals, highlights that the clinical course in such patients may not reveal any distinctive features, and advocates for close monitoring of those at a higher risk of vaccine failure.

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/β and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/β and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.

The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes. Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies. We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48–72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy. Overall survival in those who received convalescent plasma was significantly higher than in the historical group (p = 0.03460). The plasma–treated group also showed a significantly milder course of infection (p = 0.03807), characterized by less severe symptoms and faster recovery (p = 0.00001). In conclusion, we have demonstrated that convalescent plasma is an effective treatment and its early administration leads to clinical improvement, increased viral clearance and longer overall survival in patients with hematological malignancies and COVID-19. To our knowledge, this is the first report to analyze the efficacy of convalescent plasma in a cohort of patients with hematological malignancies.

COVID-19 vaccinations are about to begin in various countries or are already ongoing. This is an unprecedented operation that is also met with a loud response from anti-vaccine communities—currently using all available channels to manipulate public opinion. At the same time, the strategy to educate on vaccinations, explain their mechanism of action, and build trust in science is subdued in different world parts. Such actions should go much beyond campaigns promoting the COVID-19 vaccines solely on the information provided by the health institutions and national authorities. In this paper, actions provided by independent expert groups needed to counteract the anti-vaccine propaganda and provide scientific-based information to the general public are offered. These actions encompass organizing groups continuously communicating science on COVID-19 vaccines to the general public; tracking and tackling emerging and circulating fake news; and equipping celebrities and politicians with scientific information to ensure the quality of messages they communicate, as well as public letters, and statements of support for vaccination by healthcare workers, recognized scientists, VIPs, and scientific societies; and no tolerance to false and manipulated claims on vaccination spread via traditional and social media as well as by health professionals, scientists, and academics. These activities should be promptly implemented worldwide, regardless of the current status and availability of the COVID-19 vaccine in a particular region. If we are about to control the pandemic for the sake of public benefit, it is high time to collectively speak out as academic and medical societies with support from decision-makers. Otherwise, the battle will be lost to those who stand against scientific evidence while offering no feasible solution to the problem.

Background and Aim. The development of interferon- (IFN-) free regimens substantially improved efficacy of treatment for HCV, but despite excellent effectiveness the failures still occur. The aim of our study was to evaluate the efficacy of retreatment with genotype specific direct acting antivirals- (DAA-) based regimens in nonresponders to previous IFN-free therapy. Materials and Methods. Analysed population consisted of 31 nonresponders to IFN-free regimen, which received second IFN-free rescue therapy, selected from 6228 patients included in a national database EpiTer-2. Results. Age and gender distribution were similar, whereas proportion of genotype 1b was slightly higher and genotype 4 lower in the whole population compared to studied one. Patients included in the study demonstrated much more advanced fibrosis. Primary therapy was discontinued in 12 patients, which were recognized as failures due to nonvirologic reason, whereas virologic reason of therapeutic failure was recognized in 19 patients which completed therapy. Overall sustained virologic response (SVR) rate was 81% and 86% in intent-to-treat (ITT) and modified ITT analysis, respectively (74% and 78% in virologic failures, 92% and 100% in nonvirologic failures). Resistance-associated substitutions (RAS) testing was carried out in 8 patients from the group of completed primary therapy and three of them had potential risk for failure of rescue therapy due to NS5A association, while two of them achieved SVR. Conclusions. We demonstrated moderate effectiveness of genotype specific rescue therapy in failures due to virologic reason and high in those who discontinued primary therapy. Therefore rescue therapy with genotype specific regimens should be considered always if more potent regimens are not available.

Contemporary post-mortem diagnostics of sepsis makes it possible to obtain multiple evidence verifying the cause of death which is valuable for forensic medicine. There are a number of reports indicating the usefulness of tests of inflammatory markers (chiefly C-reactive protein and procalcitonin) that are employed in clinical medicine. During medico-legal autopsy, it becomes necessary to perform a careful search of pathological symptoms and inflammatory foci – both during external and internal examinations. Although sepsis lacks pathognomonic lesions that can be identified by histopathological examination, it represents an intrinsic element of post-mortem diagnostics. In order to be able to interpret the findings and establish the cause of death, the evaluation must concurrently take into account the circumstances of death, clinical symptoms, results of microbiological and biochemical tests, autopsy findings and histopathological examination results.

Clinical practice has an effective methodology of diagnostic procedures to be followed in cases of sepsis. However, there are as yet no corresponding standards of action in post-mortem diagnostics. The scope of examinations is limited to an autopsy and histopathological tests. This situation may lead to errors in medico-legal opinions on the cause of death and in the assessment of appropriateness of medical procedures. In cases of suspected sepsis, medico-legal investigations require obtaining detailed information about the circumstances of death (including symptoms and results of intravital examinations) before autopsy is performed, as well as sterile collection of specimens for microbiological tests and interpretation of their results on the basis of knowledge of epidemiology, pathophysiology and clinical progression of sepsis.

Hepatocellular carcinoma is the fifth most common malignancy and the third leading mortality cause worldwide. It typically develops secondarily to liver cirrhosis, due to hepatitis B or C infection, alcohol abuse, metabolic disease, and so forth. According to the American Association for the Study of Liver Diseases (AASLD) guidelines, which constitute diagnostic standards, the diagnosis of primary hepatocellular carcinoma (HCC) should be based on contrast-enhanced imaging. Lesion hyperenhancement should be observed throughout the arterial phase, followed by the washout during the venous phase. The diagnosis can also be based on the histopathological evaluation of liver biopsy specimen. Although the standards are clear, we often see patients with advanced HCC in clinical practice, who cannot be offered any effective treatment. Patients with chronic liver disease, presenting with inconclusive and changeable test results, constitute a separate problem. In such cases the diagnostic process is typically long-term and delayed. In this paper we present three case reports where the diagnosis could not be made promptly and the patients died as a result of a delayed diagnostic process.

Macrophage activation seems to be a feature of chronic liver diseases. Picolinic acid (PA) as a macrophage secondary signal causes the activation of interferon-gamma- (IFN-γ-) prime macrophage and triggers cytokine-driven inflammatory reactions. The rationale for seeking increased PA formation in chronic viral hepatitis is based on the involvement of activated macrophages in chronic viral hepatitis-associated inflammation. The aim of this study was to determine serum PA levels in patients with chronic hepatitis C infection, taking into account the presence of diabetes. We assessed PA and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation in 51 patients with chronic hepatitis C infection (CHC), both with and without diabetes and 40 controls. Compared with the controls, the patients with CHC showed a significant increase in plasma concentrations of PA and hsCRP (P