Aneurysmal 99m Tc-HMPAO Uptake in Brain Death.

ABSTRACT: A 41-year-old man was admitted to hospital due to sudden loss of consciousness. A regional brain perfusion SPECT/low-dose CT showed abnormal 99m Tc-HMPAO uptake in the right hemisphere frontotemporally without any other supratentorial or infratentorial radiotracer uptake. A neuropathological examination disclosed a middle cerebral artery aneurysm. Presumably, vessel wall fibrosis prevented collapse. Multiple transmural dissections of the fibrotic aneurysmal wall were the source of the subarachnoid hemorrhage. This interesting image shows that radiotracer accumulation in cerebral artery aneurysms can be a diagnostic pitfall in brain death scintigraphy assessment.

Photon-counting CT using multi-material decomposition algorithm enables fat quantification in the presence of iron deposits.

PURPOSE: A new generation of CT detectors were recently developed with the ability to measure individual photon's energy and thus provide spectral information. The aim of this work was to assess the performance of simultaneous fat and iron quantification using a clinical photon-counting CT (PCCT) and its comparison to dual-energy CT (DECT), MRS and MRI at 3 T. METHODS: Two 3D printed cylindrical phantoms with 32 samples (n = 12 fat fractions between 0 % and 100 %, n = 20 with mixtures of fat and iron) were scanned with PCCT and DECT scanners for comparison. A three-material decomposition approach was used to estimate the volume fractions of fat (FF), iron and soft tissue. The same phantoms were examined by MRI (6-echo DIXON, a.k.a. Q-DIXON) and MRS (multi-echo STEAM, a.k.a. HISTO) at 3 T for comparison. RESULTS: PCCT, DECT, MRI and MRS computed FFs showed correlation with reference fat fraction values in samples with no iron (r > 0.98). PCCT decomposition showed slightly weaker correlation with FFref in samples with added iron (r = 0.586) compared to MRI (r = 0.673) and MRS (r = 0.716) methods. On the other hand, it showed no systematic over- or underestimation. Surprisingly, DECT decomposition-derived FF showed strongest correlation (r = 0.758) in these samples, however systematic overestimation was observed. FF values computed by three-material PCCT decomposition, DECT decomposition, MRI and MRS were unaffected by iron concentration. CONCLUSIONS: This in-vitro study shows for the first time that photon-counting computed tomography may be used for quantification of fat content in the presence of iron deposits.

Proteinase-activated Receptor 2: Springboard of Tumors.

Proteinase-activated receptors (PARs) were discovered more than 25 years ago and since then, their role in cancer has been under investigation. Research has primarily focused on the receptors located on the membrane of cancer cells and their impact on metabolism, intracellular signalling, and proliferation. Regarding the host response to cancer, studies have predominantly examined the relationship of thrombin receptors (PAR-1, PAR-3, and PAR-4) with blood clotting in distant metastatic spread. However, limited studies have examined the role of PARs, especially PAR-2, in the host anti-tumor immunity. This review article provides insights into the role of PAR-2 on cancer cells and immune competent cells involved in cancer development and progression. It also discussed the current knowledge of the importance of PAR-2 activation at various stages of cancer progression and its association with cancer-related pain.

The way to data: opinions and recommendations for the provision of health data for secondary use.

Healthcare data held by state-run organisations is a valuable intangible asset for society. Its use should be a priority for its administrators and the state. A completely paternalistic approach by administrators and the state is undesirable, however much it aims to protect the privacy rights of persons registered in databases. In line with European policies and the global trend, these measures should not outweigh the social benefit that arises from the analysis of these data if the technical possibilities exist to sufficiently protect the privacy rights of individuals. Czech society is having an intense discussion on the topic, but according to the authors, it is insufficiently based on facts and lacks clearly articulated opinions of the expert public. The aim of this article is to fill these gaps. Data anonymization techniques provide a solution to protect individuals' privacy rights while preserving the scientific value of the data. The risk of identifying individuals in anonymised data sets is scalable and can be minimised depending on the type and content of the data and its use by the specific applicant. Finding the optimal form and scope of deidentified data requires competence and knowledge on the part of both the applicant and the administrator. It is in the interest of the applicant, the administrator, as well as the protected persons in the databases that both parties show willingness and have the ability and expertise to communicate during the application and its processing.

Advances in Liposome-Encapsulated Phthalocyanines for Photodynamic Therapy.

This updated review aims to describe the current status in the development of liposome-based systems for the targeted delivery of phthalocyanines for photodynamic therapy (PDT). Although a number of other drug delivery systems (DDS) can be found in the literature and have been studied for phthalocyanines or similar photosensitizers (PSs), liposomes are by far the closest to clinical practice. PDT itself finds application not only in the selective destruction of tumour tissues or the treatment of microbial infections, but above all in aesthetic medicine. From the point of view of administration, some PSs can advantageously be delivered through the skin, but for phthalocyanines, systemic administration is more suitable. However, systemic administration places higher demands on advanced DDS, active tissue targeting and reduction of side effects. This review focuses on the already described liposomal DDS for phthalocyanines, but also describes examples of DDS used for structurally related PSs, which can be assumed to be applicable to phthalocyanines as well.

Perishing rich, expanding poor: Demography and population genetic patterns in two congeneric butterflies.

In human-altered landscapes, specialist butterflies typically form spatially restricted populations, genetically differentiated due to dispersal restrictions. Generalists, in contrast, display minimum differentiation but high genetic diversity. While local-level actions suffice to conserve specialists and landscape-level actions are necessary for generalists, minimum information exists regarding conservation of species with intermediate features. We targeted two congeneric butterflies, the recently re-expanding Argynnis adippe and the strongly declining A. niobe, co-occurring in the pastoral landscape of the Carpathian Mountains, Czech Republic. We integrated species distribution models, mark-recapture and microsatellite analysis to compare their habitat requirements, adult demography, dispersal and genetic patterns, and expanded the genetic analysis across the Carpathian Arc and beyond to delimit spatial conservation units. In two mountain valleys, both species formed interconnected populations numbering thousands of individuals. Mobility patterns suggested the populations' interconnection across the Czech Carpathians. Genetic diversity was extremely poor in the nonthreatened A. adippe and moderate in the declining A. niobe. No population differentiation was detected within the Czech Carpathians (~1500 km2 ). Low genetic diversity and no differentiation was preserved in A. adippe across East Central Europe, whereas in A. niobe, populations from Serbia were differentiated from the Carpathian Arc + Alps. The high adult mobility linked to low differentiation probably reflects the distribution of larval resources, historically widespread but sparse and currently declining for A. niobe (grazing-disturbed grounds), while currently increasing for A. adippe (abandonment scrub, disturbed woodlands). Units as large as entire mountain systems define population boundaries, and hence conservation management units, for both species.

SARS-CoV-2 Specific Humoral Immune Responses after BNT162b2 Vaccination in Hospital Healthcare Workers.

BACKGROUND: COVID-19 pandemic has led to a loss of human life in millions and devastating socio-economic consequences worldwide. So far, vaccination is the most effective long-term strategy to control and prevent severe COVID-19 disease. The aim of the current study was to evaluate the humoral immune responses raised against the BNT162b2 vaccine in hospital healthcare workers. METHODS: Total number of 173 healthcare workers enrolled in the study. Their blood samples were collected in three different time intervals after the second SARS-CoV-2 vaccination and evaluated by the ELISA method to detect anti-spike protein IgM and IgG antibodies. The baseline characteristics of all participants were collected using questionnaires and were evaluated for finding any significant data. RESULTS: Our results demonstrated that the levels of antibodies were higher in the young group (21-30 years old) and also among male participants. Moreover, the highest levels of antibodies were detected from the group that received the third shot vaccination. CONCLUSIONS: Our results indicate that age, gender and third-dose vaccination can affect the levels of humoral immune responses against the BNT162b2 vaccine in healthcare workers.

Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers.

Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.

Epithelioid sarcoma with retained INI1 expression as a cause of a chronic leg ulcer.

Epithelioid sarcoma is a rare soft-tissue sarcoma typically presenting itself as a subcutaneous or deep dermal mass in distal portions of the extremities of adolescents and young adults. They are frequently mistaken for ulcers, abscesses, or infected warts resistant to standard medical treatment. Patients often develop multiple local recurrences with subsequent metastases. We report a case of a 66-year-old patient with chronic leg ulcer who died of generalization of an epithelioid sarcoma.

[Role of chloramphenicol in current clinical practice].

INTRODUCTION: Chloramphenicol is an antibiotic with a broad spectrum of action and excellent tissue penetration. It had been widely used in clinical practice until the 1970s, but due to its potential myelotoxicity, it was gradually replaced by newly introduced antibiotics in the following years. The aim of the study was to find out to what extent and with what experience it is currently used in the Czech Republic. METHODS: A questionnaire survey was conducted in July and August 2022. The heads of all inpatient infectious diseases departments, hospital infectious diseases specialists and consulting microbiologists from antibiotic centers in large teaching hospitals without an infectious diseases department were asked to fill out the questionnaire. RESULTS: Thirty-five out of 39 hospitals contacted took part in the study, a response rate of 90 %. Chloramphenicol is used in 37 % of participating hospitals, with a frequency of up to 10 patients treated per year. The most common indications are brain abscesses, purulent meningitis, intra-abdominal, pelvic and lung abscesses, and polymicrobial infections with anaerobes. Chloramphenicol is almost always administered as an alternative antibiotic because of polyvalent allergy, bacterial resistance, and failure of previous treatment. Sixty-six percent of respondents described the effect as reliable or partially reliable, 34 % did not rate the effect. Fifty-two percent of respondents considered a dose of 8-9 g to be the maximum dose for an adult patient. In practice, 60 % of respondents did not encounter or could not assess the myelotoxic effects of chloramphenicol, 37 % observed reversible bone marrow suppression at least once, and only one respondent encountered aplastic anemia once. CONCLUSION: Unfortunately, chloramphenicol is currently used in less than half of hospitals in the Czech Republic. Because of its unique properties, it still has a place in today's anti-infective treatment. When properly indicated and after weighing the benefits and risks, it can be a suitable and sometimes life-saving alternative.

[Updated Czech guidelines for the treatment of patients with colitis due to Clostridioides difficile].

The updated Czech guidelines differ in some aspects from the 2021 guidelines issued by the ESCMID Study Group for Clostridium difficile. The key points of these Czech recommendations may be summarized as follows: • The drug of choice for hospitalized patients is orally administered fidaxomicin or vancomycin. In outpatients with a mild first episode of C. difficile infection, metronidazole can also be used. • If the patient's response to treatment is good and there are no complications, the duration of antibiotic treatment can be reduced (e.g. to 5 days in case of fidaxomicin or to 6-7 days in case of vancomycin). • If oral therapy is impossible, the drug of choice is tigecycline, 100 mg i.v., b.i.d., with initial shortening of the interval between the first and second doses for faster saturation. If the severity of the disease progresses during this antibiotic treatment, it is necessary to access the ileum or cecum, i.e. to perform double ileostomy or percutaneous endoscopic cecostomy, and to instill vancomycin or fidaxomicin lavages. • Fulminant C. difficile colitis should be treated with oral fidaxomicin ± tigecycline i.v. If peristalsis ceases, fidaxomicin should be administered into the ileum or cecum as described above. If sepsis develops, a broad-spectrum beta-lactam antibiotic (piperacillin/tazobactam, carbapenem) i.v. is added to topically administered fidaxomicin instead of tigecycline i.v.; at the same time, colectomy should be considered as the last resort. • To treat first recurrence, fidaxomicin or vancomycin is administered with a subsequent fecal microbiota transplant (FMT) from a healthy donor. For second or subsequent recurrence, administration of fidaxomicin is of little benefit; the therapy of choice is oral vancomycin and subsequent FMT. Prolonged vancomycin or fidaxomicin taper and pulse treatment is appropriate only when FMT cannot be performed.

Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers.

Iron and copper are essential micronutrients needed for the proper function of every cell. However, in excessive amounts, these elements are toxic, as they may cause oxidative stress, resulting in damage to the liver and other organs. This may happen due to poisoning, as a side effect of thalassemia infusion therapy or due to hereditary diseases hemochromatosis or Wilson's disease. The current golden standard of therapy of iron and copper overload is the use of low-molecular-weight chelators of these elements. However, these agents suffer from severe side effects, are often expensive and possess unfavorable pharmacokinetics, thus limiting the usability of such therapy. The emerging concepts are polymer-supported iron- and copper-chelating therapeutics, either for parenteral or oral use, which shows vivid potential to keep the therapeutic efficacy of low-molecular-weight agents, while avoiding their drawbacks, especially their side effects. Critical evaluation of this new perspective polymer approach is the purpose of this review article.

[COVID-19: diagnosis and treatment].

The guidelines provide evidence-based recommendations for the management of COVID-19. The clinical manifestations of the disease are described and indication criteria for hospital admission of patients with COVID-19 are listed. Polymerase chain reaction and antigen testing are used in direct diagnostics. Indirect detection of infection by antibodies is currently of limited value. There are a number of hematological and biochemical laboratory test used to diagnose COVID-19. Pathological values of some laboratory parameters are associated with severity of COVID-19. Of the imaging studies, chest X-ray, chest computer tomography and lung ultrasound are used. COVID-19 therapy includes symptomatic and specific therapy (antivirals, immunotherapeutics and anticoagulants) and intensive care in the severe and critical forms of the disease. Remdesivir and favipiravir are available as antiviral agents. Immunotherapeutics include monoclonal antibodies (casirivimab/imdevimab, bamlanivimab/etesevimab), dexamethas one, baricitinib and tocilizumab. Low-molecular-weight heparin is a dominant form of anticoagulant therapy. The guidelines provide specific therapeutic recommendations for each stage of the disease. Antibiotics are recommended only if bacterial superinfection is suspected or demonstrated, which is not common in the early stages of the disease.

Restoring a butterfly hot spot by large ungulates refaunation: the case of the Milovice military training range, Czech Republic.

BACKGROUND: Refaunation/rewilding by large ungulates represents a cost-efficient approach to managing natural biotopes and may be particularly useful for areas whose biodiversity depends on disturbance dynamics and is imperilled by successional changes. To study impacts of refaunation on invertebrates, we focused on butterflies inhabiting the former military training range Milovice, Czech Republic, refaunated since 2015 by a combination of Exmoor pony ("wild" horse), Tauros cattle ("aurochs"), and European wisent. METHODS: We analysed butterfly presence-absence patterns immediately after the military use termination (early 1990s), prior to the refaunation (2009), and after it (2016-19); and current abundance data gained by monitoring butterflies at refaunated and neglected plots. We used correspondence analysis for the presence-absence comparison and canonical correspondence analysis for the current monitoring, and related results of both ordination methods to the life history and climatic traits, and conservation-related attributes, of recorded butterflies. RESULTS: Following the termination of military use, several poorly mobile species inclining towards oceanic climates were lost. Newly gained are mobile species preferring warmer continental conditions. The refaunated plots hosted higher butterfly species richness and abundances. Larger-bodied butterflies developing on coarse grasses and shrubs inclined towards neglected plots, whereas refaunated plots supported smaller species developing on small forbs. CONCLUSION: The changes in species composition following the cessation of military use were attributable to successional change, coupled with changes in species pool operating at larger scales. By blocking succession, large ungulates support butterflies depending on competitively poor plants. Restoring large ungulates populations represents a great hope for conserving specialised insects, provided that settings of the projects, and locally adapted ungulate densities, do not deplete resources for species with often contrasting requirements.

COVID-19 severe pneumonia: Prospective multicentre study on demands on intensive care capacities.

OBJECTIVES: The aim of the study was to obtain data on demands on the intensive care capacities to treat COVID-19 patients, and to identify predictors for in-hospital mortality. METHODS: The prospective observational multicentre study carried out from 1 March till 30 June 2020 included adult patients with confirmed SARS-CoV-2 infection with respiratory failure requiring ventilatory support or high-flow nasal oxygen therapy (HFNO). RESULTS: Seventy-four patients, 46 males and 28 females, median age 67.5 (Q1-Q3: 56-75) years, were included. Sixty-four patients (86.5%) had comorbidity. Sixty-six patients (89.2%) were mechanically ventilated, four of them received extracorporeal membrane oxygenation therapy. Eight patients (10.8%) were treated with non-invasive ventilation and HFNO only. The median of intensive care unit (ICU) stay was 22.5 days. Eighteen patients (24.3%) needed continuous renal replacement therapy. Thirty patients (40.5%) died. Age and acute kidney injury were identified as independent predictors of in-hospital death, and chronic kidney disease showed trend towards statistical significance for poor outcome. CONCLUSIONS: Sufficient number of intensive care beds, organ support equipment and well-trained staff is a decisive factor in managing the COVID-19 epidemic. The study focused on the needs of intensive care in the COVID-19 patients. Advanced age and acute kidney injury were identified as independent predictors for in-hospital mortality. When compared to clinical course and ICU management of patients with severe community-acquired pneumonia caused by other pathogens, we observed prolonged need for ventilatory support, high rate of progression to acute respiratory distress syndrome and significant mortality in studied population.

Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection - An observational cohort study.

PURPOSE: We aimed to evaluate the efficacy of different antibiotic regimens for the treatment of Clostridioides difficile infection (CDI) with regard to the CDI episode number and disease severity. METHODS: An observation cohort study included 271 CDI patients hospitalised between 2013-2016. Univariate logistic regression was used to evaluate the association between patients' clinical outcome (sustained clinical cure or recurrence) in a 60-day follow-up and the antibiotic regimen used (oral metronidazole, oral vancomycin, combination of oral vancomycin and metronidazole, oral fidaxomicin). Subgroup analyses, based on CDI episode number and severity, were performed. RESULTS: In the overall population, fidaxomicin was superior to metronidazole, vancomycin or their combination, for a sustained clinical response and in the prevention of recurrent CDI (rCDI). In the subgroup analyses, fidaxomicin was superior to vancomycin or metronidazole for a sustained clinical response and in the prevention of rCDI in the initial episode, first recurrence and non-severe cases. In the oral treatment of severe CDI, fidaxomicin had a similar treatment outcome to vancomycin and none of the antibiotic treatments were superior in the prevention of rCDI. Fidaxomicin, vancomycin, or a combination of metronidazole and vancomycin, had similar outcomes for sustained clinical response and prevention of rCDI in patients with multiple rCDI. CONCLUSION: Fidaxomicin was superior to metronidazole or vancomycin for the treatment of the initial episode, first recurrence, and non-severe CDI.

Biophysical Characterization and Anticancer Activities of Photosensitive Phytoanthraquinones Represented by Hypericin and Its Model Compounds.

Photosensitive compounds found in herbs have been reported in recent years as having a variety of interesting medicinal and biological activities. In this review, we focus on photosensitizers such as hypericin and its model compounds emodin, quinizarin, and danthron, which have antiviral, antifungal, antineoplastic, and antitumor effects. They can be utilized as potential agents in photodynamic therapy, especially in photodynamic therapy (PDT) for cancer. We aimed to give a comprehensive summary of the physical and chemical properties of these interesting molecules, emphasizing their mechanism of action in relation to their different interactions with biomacromolecules, specifically with DNA.

Disseminated Pelvic Actinomycosis Caused by Actinomyces Naeslundii.

Actinomycosis is a chronic bacterial infection characterized by continuous local spread, irrespective of anatomical barriers, and granulomatous suppurative inflammation. Due to its expansive local growth, it can simulate a malignant tumour. Subsequent hematogenous dissemination to distant organs can mimic metastases and further increase suspicion for malignancy. A case of severe disseminated pelvic actinomycosis associated with intrauterine device is described here. The patient presented with a pelvic mass mimicking a tumour, bilateral ureteral obstruction, ascites, multinodular involvement of the liver, lungs and spleen, inferior vena cava thrombosis and extreme cachexia. Actinomycosis was diagnosed by liver biopsy and confirmed by culture of Actinomyces naeslundii from extracted intrauterine contraceptive device (IUD). Prolonged treatment with aminopenicillin and surgery resulted in recovery with moderate sequelae.

Chelating Polymers for Hereditary Hemochromatosis Treatment.

Hemochromatosis (iron overload) encompasses a group of diseases that are characterized by a toxic hyperaccumulation of iron in parenchymal organs. Currently, only few treatments for this disease have been approved; however, all these treatments possess severe side effects. In this study, a paradigm for hemochromatosis maintenance/preventive therapy is investigated: polymers with negligible systemic biological availability form stable complexes with iron ions in the gastrointestinal tract, which reduces the biological availability of iron. Macroporous polymer beads are synthesized with three different iron-chelating moieties (benzene-1,2-diol, benzene-1,2,3-triol, and 1,10-phenanthroline). The polymers rapidly chelate iron ions from aqueous solutions in vitro in the course of minutes, and are noncytotoxic and nonprooxidant. Moreover, the in vivo biodistribution and pharmacokinetics show a negligible uptake from the gastrointestinal tract (using 125 I-labeled polymer and single photon emission computed tomography/computed tomography), which generally prevents them from having systemic side effects. The therapeutic efficacy of the prepared polymers is successfully tested in vivo, and exhibits a significant inhibition of iron uptake from the gastrointestinal tract without any noticeable signs of toxicity. Furthermore, an in silico method is developed for the prediction of chelator selectivity. Therefore, this paradigm can be applied to the next-generation maintenance/preventive treatment for hemochromatosis and/or other diseases of similar pathophysiology.