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    Comparison of CAD modelling approaches for developing individual dental abutments

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    U današnjoj dentalnoj protetici, primjena CAD (engl. Computer-Aided Design) tehnologije postala je ključna za postizanje visoke preciznosti i učinkovitosti u izradi dentalnih nadogradnji. Individualna dentalna nadogradnja je komponenta dentalnog implantološkog sklopa, čija je uloga da poveže implantat s protetskim nadomjeskom (dentalnom krunicom, mostom). Ona se konstruira posebno za svakog pacijenta, uzimajući u obzir specifične anatomske karakteristike, kao što su kut i dubina ugradnje implantata, promjer otvora na tkivu oko ugrađenog implantata, oblik desni te položaj susjednih zuba. Za konstruiranje individualne dentalne nadogradnje i njihove prilagodbe, uobičajeno se koriste specijalizirani dentalni CAD alati (npr. Exocad ili 3Shape) čije su mogućnosti i sučelje optimirani za potrebe dentalnih tehničara. Međutim, zbog njihove specifične namjene, ovi alati imaju određena ograničenja u pogledu fleksibilnosti i mogućnosti modeliranja složenih 3D geometrija. U kontekstu konstruiranja takvih nadogradnji, nameću se mogućnosti korištenja tradicionalnih inženjerskih CAD alata (npr. PTC Creo, SolidWorks) te alata namijenjenih za modeliranje NURBS krivuljama (npr. Rhinoceros 3D). U suradnji s tvrtkom Neo Dens, u okviru ovog rada uspoređuje se CAD modeliranje navedenih triju grupa alata te su definirane smjernice za njihovu upotrebu u kontekstu konstruiranja i prilagodbi individualnih dentalnih nadogradnji.In modern dental prosthetics, the use of CAD (Computer-Aided Design) technology has become essential for achieving high precision and efficiency in the creation of dental restorations. An individual dental abutment is a component of the dental implant system, designed to connect the implant to the prosthetic replacement (dental crown or bridge). It is specifically constructed for each patient, considering unique anatomical characteristics, such as the angle and depth of implant placement, the diameter of the opening in the tissue around the implanted implant, the shape of the gums, and the position of adjacent teeth. Specialized dental CAD tools (e.g., Exocad or 3Shape) are commonly used for designing and adjusting individual dental abutments, as their features and interface are optimized for the needs of dental technicians. However, due to their specific purpose, these tools have certain limitations in terms of flexibility and the ability to model complex 3D geometries. In the context of designing such abutments, the potential use of traditional engineering CAD tools (e.g., PTC Creo, SolidWorks) and tools for modeling NURBS curves (e.g., Rhinoceros 3D) comes into play. In collaboration with Neo Dens, this paper compares the approaches to CAD modeling using these three types of tools and provides guidelines for their use in the design and adjustment of individual dental abutments

    Optimization of specimen geometry for uniaxial and biaxial tensile testing

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    Statički vlačni pokus standardna je metoda za određivanje mehaničkih svojstava materijala, bez obzira na to radi li se o elastičnim, viskoelastičnim ili elastoplastičnim materijalima. Za homogene izotropne materijale, poput metala, najčešće se koriste jednoosni vlačni testovi, dok se za anizotropne materijale zahtijeva dvoosno vlačno ispitivanje. Za vlačna ispitivanja koriste se epruvete čiji je oblik propisan normama ovisno o ispitivanom materijalu. Laboratorijskim ispitivanjima pokazano je da epruvete propisane normom pucaju izvan ispitnog područja, a razlog tomu je što se maksimalno naprezanje ne nalazi u homogenom području unutar ispitnog dijela. Posljedica toga su krivi rezultati vlačnog ispitivanja. Stoga je svrha ovog rada konstruirati ispitni uzorak za jednoosna i dvoosna vlačna ispitivanja, pri čemu geometrija uzorka osigurava da maksimalno naprezanje tijekom ispitivanja bude ravnomjerno raspoređeno u što većem homogenom području ispitnog dijela epruvete. Kako bi se odredila odgovarajuća geometrija ispitnih uzoraka, korištene su metode strukturne optimizacije, uključujući topološku optimizaciju i optimizaciju oblika, implementirane u programskom paketu Abaqus. Uvodnim dijelom rada prikazane su osnove jednooosnog i dvoosnog vlačnog ispitivanja, rezultati iz literature te problemi vezani za geometrije epruveta. U nastavku je opisan pojam strukturne optimizacije uključujući njenu matematičku osnovu. Također su pobliže opisane optimizacija oblika i topološka optimizacija kao vrste strukturne optimizacije korištene za optimizaciju epruveta. Nakon toga, provedena je validacija topološke optimizacije na primjeru iz literature s poznatim rješenjima kako bi se potvrdila točnost i pouzdanost zadanih simulacijskih parametara. Posljednja dva poglavlja prikazuju postupke optimizacije različitih geometrija jednoosnih i dvoosnih epruveta, čiji su rezultati korišteni kao smjernice za konstruiranje optimalnih geometrija ispitnih uzoraka namijenjenih vlačnom ispitivanju.The static tensile test is a standard method for determining the mechanical properties of materials, regardless of whether they are elastic, viscoelastic, or elastoplastic. For homogeneous isotropic materials, such as metals, uniaxial tensile tests are commonly used, whereas biaxial tensile testing is required for anisotropic materials. Tensile tests are performed using specimens whose shapes are defined by standards depending on the material being tested. Laboratory testing has shown that standardized specimens often fail outside the testing area, primarily because the maximum stress is not located in the homogeneous region of the testing section. This results in inaccurate tensile test outcomes. The objective of this paper is to design a test specimen for uniaxial and biaxial tensile testing with a geometry that ensures that the maximum stress during testing is evenly distributed over as large a homogeneous area as possible within the testing section. To determine the appropriate specimen geometry, structural optimization methods, including topology optimization and shape optimization, implemented in the Abaqus software, were employed. The introductory part of the paper presents the basics of uniaxial and biaxial tensile testing, literature results, and issues related to specimen geometries. The concept of structural optimization is then described, including its mathematical foundation. Shape optimization and topology optimization, as types of structural optimization used for specimen design optimization, are also elaborated. Following this, the validation of topology optimization was conducted using a literature example with known solutions to confirm the accuracy and reliability of the specified simulation parameters. The final two chapters present the optimization processes for various geometries of uniaxial and biaxial specimens. The results of these processes served as guidelines for designing optimal geometries of test specimens intended for tensile testing

    New Chinese herbal drugs (rhizoma et radice) in the eleventh edition of the European pharmacopoeia

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    Fitoterapija predstavlja glavni oblik prevencije i liječenja bolesti u sustavu tradicionalne kineske medicine koja se primjenjuje u Kini već stotinama godina, a u novije vrijeme joj i zapadna medicina pridaje na važnosti. Sa ciljem proširenja znanja u području fitofarmacije, teorijski je istraženo pet biljnih droga dobivenih od korijenja i podanaka kineskih ljekovitih biljaka: Belamcandae chinensis rhizoma, Cyathulae radix, Rehmanniae radix, Sanguisorbae radix i Scrophulariae radix. Pregledom stručne i znanstvene literature, za navedene biljne droge u radu je dan pregled dosadašnjih spoznaja o biljnim izvorima, tradicionalnoj primjeni, fitokemijskom sastavu te pretklinički i klinički dokazanim učincima kao i hrvatski prijevod pripadajućih monografija u aktualnom, 11. izdanju Europske farmakopeje.Phytotherapy is the main form of prevention and treatment of diseases in the system of traditional Chinese medicine, which has been applied in China for hundreds of years, and in recent times Western medicine has also given importance to it. With the aim of expanding the knowledge in the field of phytopharmacy, five herbal drugs obtained from the roots and rhizomes of Chinese medicinal plants were theoretically investigated: Belamcandae chinensis rhizoma, Cyathulae radix, Rehmanniae radix, Sanguisorbae radix and Scrophulariae radix. Through a review of professional and scientific literature, an overview of current knowledge on plant sources, traditional use, phytochemical composition, and preclinical and clinically proven effects, together with the Croatian translation of the corresponding monographs in the actual, 11th edition of the European Pharmacopoeia, is given for the aforementioned herbal drug in this thesis

    Optimization of fragmentation conditions for alpelisib and deuterated abemaciclib in a triple quadrupole mass spectrometer

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    Rak dojke je najčešća zloćudna novotvorina u žena, a njegova prevalencija širom svijeta raste. Personalizirani pristup je bitan dio liječenja, stoga je važno razviti specifične analitičke metode za istraživanje lijekova. Alpelisib i abemaciklib su se pokazali učinkovitim lijekovima u liječenju hormonski ovisnog raka dojke. Oba djeluju na signalne puteve koji su važni za stanični rast i proliferaciju te posljedično, rast tumora. Cilj ovog istraživanja je bio optimizirati uvjete fragmentacije alpelisiba i deuteriranog abemacikliba u trostrukim kvadrupolima dva različita spektrometra masa, Agilent Ultivo i Agilent 6470. Određene su optimalne vrijednosti fragmentorskih napona i kolizijskih energija, te je provedena identifikacija i kvantifikacija ključnih fragmenata specifičnih za ove spojeve. U Agilent Ultivo spektrometru masa uz pozitivnu ionizaciju elektroraspršenjem, alpelisib daje molekulski ion m/z vrijednosti 442,1 uz fragmetorski napon od 120 V. Nastaju fragmentni ioni m/z vrijednosti 328,0, 114,7, 288,0 i 273,1 uz kolizijske energije od 25, 15 45 i 60 eV. Deuterirani abemaciklib daje molekulski ion m/z vrijednosti 515,2 uz fragmentorski napon od 120 V. Nastaju fragmentni ioni m/z vrijednosti 176,8, 393,0 i 351,3 uz kolizijske energije od 105, 25 i 70 eV. U Agilent 6470 spektrometru masa uz pozitivnu ionizaciju elektroraspršenjem, alpelisib daje molekulski ion m/z vrijednosti 442,2, uz fragmentorski napon od 140 V. Nastaju fragmentni ioni m/z vrijednosti 328,1 115,0, 288,1, 273,0 i 129,0 uz kolizijske energije od 25, 15, 50, 60 i 105 eV. Deuterirani abemaciklib daje molekulski ion m/z vrijednosti 515,3 uz fragmentorski napon od 120 eV. Nastaju fragmentni ioni od 177,0, 393,1 i 244,9 uz kolizijske energije od 105, 25 i 75 eV. Provedena je analiza i uz negativnu ionizaciju elektroraspršenjem, gdje se ova metoda pokazala manje osjetljivom.Breast cancer is the most common malignant tumor in women, and its prevalence is increasing worldwide. A personalized approach is a crucial part of treatment, making it important to develop specific analytical methods for drug research. Alpelisib and abemaciclib have proven to be effective drugs in the treatment of hormone-dependent breast cancer. Both act on signaling pathways important for cell growth and proliferation, and consequently, tumor growth.The aim of this study was to optimize the fragmentation conditions for alpelisib and deuterated abemaciclib in triple quadrupoles of two different mass spectrometers, the Agilent Ultivo and Agilent 6470. Optimal values for fragmentor voltages and collision energies were determined, and identification and quantification of key fragments specific to these compounds were conducted.In the Agilent Ultivo mass spectrometer with positive electrospray ionization, alpelisib produces a molecular ion with an m/z value of 442,1 at a fragmentor voltage of 120 V. Fragment ions with m/z values of 328,0, 114,7, 288,0, and 273,1 are formed with collision energies of 25, 15, 45, and 60 eV, respectively. Deuterated abemaciclib produces a molecular ion with an m/z value of 515.2 at a fragmentor voltage of 120 V. Fragment ions with m/z values of 176,8, 393,0, and 351,3 are formed with collision energies of 105, 25, and 70 eV, respectively.In the Agilent 6470 mass spectrometer with positive electrospray ionization, alpelisib produces a molecular ion with an m/z value of 442,2 at a fragmentor voltage of 140 V. Fragment ions with m/z values of 328,1, 115,0, 288,1, 273,0 and 129,0 are formed with collision energies of 25, 15, 50, and 105 eV, respectively. Deuterated abemaciclib produces a molecular ion with an m/z value of 515,3 at a fragmentor voltage of 120 V. Fragment ions with m/z values of 177,0, 393,1, and 244,9 are formed with collision energies of 105, 25, and 75 eV, respectively. Analysis was also conducted using negative electrospray ionization, where this method proved to be less sensitive

    Bridge carrier for telescopic winch crane

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    U ovom radu bit će prikazan proračun, konstrukcijska izvedba i odabir komponenti mosnog granika. Mosni granik će se koristit za rukovanje, pregled i održavanje komoraza ispitivanje te će bit konstruiran u skladu s zahtjevima. Glavni nosač će bit izveden pomoću kutijastih profila, dok će pomoćni nosač biti izveden pomoću HEB profila. U ovome radu će još biti i prikazan proračun pomoćnog vitla.In this paper calculation, design and selection of bridge crane components will be presented. The bridge crane will be used for handling, inspection and maintenance of the test chamber and will be constructed in accordance with the requirements. The main bridge will be constructed using box profiles while the auxiliary bridge will be constructed using HEB profile. Calculation of the auxiliary winch will also be presented in this paper

    Masticatory and gustatory stimuli in burning mouth syndrome diagnosis and treatment

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    Sindrom pekućih usta (SPU) je idiopatski orofacijalni bolni poremećaj nejasne etiologije kojemu se danas pripisuje neuropatska geneza. Kako se dosadašnji pristupi liječenju SPU-a nisu pokazali uspješnijima od placeba, svrha ove studije je istražiti jedan poseban fenomen SPU-a koji do danas nije prihvaćen ni uključen u bilo koju od postojećih definicija, a to je da se u ovih bolesnika simptom žarenja privremeno smanjuje/povlači tijekom obroka. U istraživanje su uključena 52 ispitanika koji dolaze na pregled zbog spontanog žarenja usne šupljine sa zdravom oralnom sluznicom na mjestima prijave simptoma. Vrijednosti intenziteta simptoma zabilježene su numeričkom skalom za ocjenjivanje boli 0-10. Početak ublažavanja i povlačenja simptoma mjerio se zapornim satom nakon početka žvakanja komadića parafina te otapanja bombona u ustima. Po postizanju potpunog (ili maksimalnog) poboljšanja, mjerilo se vrijeme do povratka simptoma. Kod svih osim jednog ispitanika (98,1%) tijekom eksperimenta je došlo do poboljšanja dok je kod njih 44 (84,6%) postignuta privremena potpuna remisija na barem jedan od podražaja. Poboljšanje započinje unutar prve minute, dok se maksimalni učinak postiže tijekom tri minute. Povratak simptoma nakon završetka stimulacije započinje oko prve minute te se vraća na početnu razinu prije početka stimulacije unutar tri minute i 20 sekundi. Zaključno, ovaj fenomen jednostavno i pouzdano osigurava brzu i točnu dijagnozu SPU-a dok privremeno upravlja simptomima sa zasigurno najvišim postotkom učinkovitosti. Iz tog razloga, naši rezultati traže uključivanje istog u definiciju SPU-a.Burning mouth syndrome (BMS) is an idiopathic orofacial pain disorder of unclear etiology, now attributed to neuropathic genesis. Since previous approaches to treating BMS have not proven to be more successful than placebo, the study aimed to investigate a special phenomenon of BMS, not accepted or included in any of the existing definitions, that in these patients the burning symptom temporarily reduces/disappears during meals. The study included 52 subjects examined for spontaneous burning pain of the oral cavity with healthy oral mucosa at sites where symptoms were reported. Symptom intensity was recorded using a numerical pain rating scale of 0-10. The beginning of alleviation and withdrawal of symptoms was measured with a stopwatch after the beginning of chewing a piece of paraffin and dissolving a candy in their mouth. After achieving complete (or maximum) improvement, the time until the symptoms returned was measured. All but one subject (98,1%) improved during the experiment, while 44 of them (84,6%) achieved a temporary complete remission by at least one stimulus. The improvement starts within the first minute, while the maximum effect is achieved within three minutes. The return of symptoms after the end of stimulation begins around the first minute and returns to the initial level within three minutes and 20 seconds. In conclusion, this phenomenon provides a quick and accurate diagnosis of BMS simply and reliably, while temporarily managing the symptoms with certainly the highest percentage of effectiveness. For this reason, our results call for its inclusion in the definition of BMS

    Biological activities of the plant species Globularia alypum L.

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    Među vrstama roda Globularia L. najviše istražena je vrsta Globularia alypum L. zbog svoje široke primjene u tradicionalnoj medicini za liječenje mnogih bolesti. S obzirom na sve veći broj istraživanja o ovoj biljnoj vrsti, u ovom diplomskom radu okupljeni su svi originalni znanstveni radovi objavljeni u periodu od 2017. do 2023. godine koji su ispitivali biološka djelovanja njezinih ekstrakata. Pretraživanjem 12 baza podataka ukupno je pronađeno 38 radova. Među svim zabilježenim djelovanjima (77), najčešće istraživana bila su antioksidacijsko (34 %), antibakterijsko (14 %) i protuupalno djelovanje (9 %). Brojni ekstrakti pokazali su značajno antioksidacijsko djelovanje (neki snažnije od standardnih antioksidansa). Metanolni ekstrakt pokazao je najširi spektar antibakterijskog djelovanja, dok je za različite ekstrakte zabilježeno antifungalno i antibiofilm djelovanje. Protuupalno djelovanje ekstrakata, popraćeno analgetskim djelovanjem, potvrđeno je inhibicijom proupalnih markera i citokina. Ekstrakti su također pokazali antipiretsko, citotoksično, antidijabetsko, antihiperlipidemijsko, nefroprotektivno, antihemolitičko, antikoagulacijsko, laksativno i antiartritičko djelovanje, a osim toga metanolni ekstrakt utjecao je na zacjeljivanje kože što ide u prilog njegovoj upotrebi u kozmetičkim pripravcima za topikalnu primjenu. Dobiveni rezultati ukazuju na to da biljna vrsta G. alypum može poslužiti kao izvor prirodnih antioksidansa, antibakterijskih i protuupalnih spojeva. S obzirom na zabilježena djelovanja njezinih ekstrakata, navedena vrsta pokazuje značajan terapijski potencijal, ali daljnja istraživanja potrebna su kako bi se bolje razumjeli mehanizmi djelovanja i optimalne doze ekstrakata.Among the species of the Globularia L. genus, Globularia alypum L. has been the most extensively studied due to its widespread use in traditional medicine for treating various diseases. Given the increasing number of studies on this plant, this diploma thesis compiles all original scientific articles that were published from 2017 to 2023 that have investigated biological activities of its extracts. Through searching 12 databases, a total of 38 studies were found. Among all documented activities (77), the most researched were antioxidant (34%), antibacterial (14%), and anti-inflammatory activity (9%). Numerous extracts showed significant antioxidant activity (some stronger than standard antioxidants). The methanolic extract exhibited the broadest spectrum of antibacterial activity, while various extracts showed antifungal and antibiofilm activities. The anti-inflammatory activity of extracts, accompanied by analgesic activity, was confirmed by the inhibition of inflammatory markers and cytokines. Extracts also demonstrated antipyretic, cytotoxic, antidiabetic, anti-hyperlipidemic, nephroprotective, anti-hemolytic, anticoagulant, laxative, and antiarthritic effects. Furthermore, the methanolic extract has been shown to promote skin healing, which goes in favor of its use in cosmetic products for topical application. The results obtained indicate that G. alypum plant species could serve as a source of natural antioxidants, antibacterial, and anti-inflammatory compounds. Considering the documented activities of its extracts, this species shows significant therapeutic potential, but further research is needed to better understand the mechanisms of action and optimal dosages of extracts

    New Chinese herbal drugs (fructus et semina) in the eleventh edition of the European pharmacopoeia

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    Tradicionalna kineska medicina drevni je medicinski sustav koji pridonosi ljudskom zdravlju već tisućama godina na području Azije, a u novije vrijeme sve je više prihvaćaju i koriste pacijenti u zapadnim zemljama. Sustavnim pretraživanjem i proučavanjem relevantne stručne i znanstvene literature, ovime je radom dani sistematični pregled biljnih izvora, tradicionalne primjene, kao i dosadašnjih znanstvenih spoznaje o fitokemijskom sastavu, pretkliničkom i kliničkom djelovanju za četiri odabrane kineske biljne droge s dugom primjenom u sustavu tradicionalne kineske medicine: Chaenomeles fructus, Forsythiae fructus, Armeniacae semen amarum i Persicae semen. Odabrane su biljne droge dobivene od plodova i sjemenki kineskih biljaka za koje su utvrđene norme kakvoće u obliku monografija u aktualnom 11. izdanju Europske farmakopeje te su sastavni dio rada i hrvatski prijevodi tih monografija.Traditional Chinese medicine is an ancient medical system that has contributed to human health for thousands of years in Asia, and in recent times it has been increasingly accepted and used by patients in Western countries. Through a systematic search and study of the relevant professional and scientific literature, this paper aims to provide a systematic overview of herbal sources, traditional application, as well as current scientific knowledge about the phytochemical composition, preclinical and clinical studies for four selected Chinese herbal drugs with a long history of use in the system of traditional Chinese medicine: Chaenomeles fructus, Forsythiae fructus, Armeniacae semen amarum and Persicae semen. Herbal drugs obtained from the fruits and seeds of Chinese plants were selected, for which quality standards have been established in the form of monographs in the current 11th edition of the European Pharmacopoeia, so the Croatian translations of these monographs are an integral part of this thesis

    Mercury in dietary supplements for the treatment of inflammatory bowel diseases

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    Dodaci prehrani namijenjeni za pomoćno liječenje upalnih bolesti crijeva mogu imati značajnu ulogu u liječenju tih bolesti zbog prisustva raznih biološki aktivnih. Također sve se češće koriste za povećanje unosa esencijalnih vitamina i minerala, no zbog manje restriktivnih zakonskih zahtjeva i nedovoljne kontrole, postoji rizik od kontaminacije i nuspojava. Cilj ovoga rada bio je procijeniti kvalitetu dodataka prehrani mjerenjem koncentracije žive u tim pripravcima. Živa i njezini spojevi spadaju među najtoksičnije okolišne kontaminante. Izloženost čak i malim količinama žive može izazvati ozbiljne zdravstvene probleme, uključujući mutagene i teratogene učinke, oksidativni stres, disfunkciju mitohondrija, te toksičnost za središnji i periferni živčani sustav, kao i bubrege. Upravo zbog ovih razloga potrebno je odrediti moguće kontaminacije živom. Koncentracija žive u ispitanim dodacima prehrani određena je atomskom apsorpcijskom spektrometrijom uz pomoć analizatora žive. Ova metoda je korištena zbog njezine brzine i jednostavnosti. Rezultati istraživanja uspoređeni su sa maksimalnom dopuštenom razinom žive u dodacima prehrani koja je postavljena od strane različitih regulatornih tijela. Svi analizirani dodaci prehrani zadovoljavaju zahtjeve to jest razina žive je ispod maksimalne dopuštene razine, osim u dva uzorka justicije. Odnosno, analizom rezultata utvrđeno je da izračunate vrijednosti hipotetskog unosa žive u slučaju tjedne uporabe testiranih pripravaka ne prelaze PTWI vrijednost (privremeni podnošljivi tjedni unos), ali primjenom dva uzorka utvrđene su PDE vrijednosti iznad dozvoljenih. U zaključku ovog rada istaknuta je važnost stalne kontrole sadržaja žive u tržišno dostupnim dodacima prehrani.Dietary supplements intended for adjunct treatment of inflammatory bowel diseases can play a significant role in treating these conditions due to the presence of various biologically active substances. They are also increasingly used to boost the intake of essential vitamins and minerals. Still, due to less stringent regulatory requirements and insufficient control, there is a risk of contamination and side effects. This study aimed to assess the quality of dietary supplements by measuring the mercury concentration in these products. Mercury and its compounds are among the most toxic environmental contaminants. Exposure to even small amounts of mercury can cause serious health problems, including mutagenic and teratogenic effects, oxidative stress, mitochondrial dysfunction, and toxicity to the central and peripheral nervous systems, as well as the kidneys. For these reasons, it is necessary to determine potential mercury contamination. The mercury concentration in the tested dietary supplements was determined using atomic absorption spectrometry with a mercury analyzer. This method was chosen for its speed and simplicity. The research results were compared with the maximum allowable mercury level in dietary supplements set by various regulatory bodies. All analyzed dietary supplements meet the requirements, meaning the mercury levels are below the maximum permissible level, except in two justice samples. The analysis of the results also showed that the calculated values of hypothetical mercury intake in the case of weekly use of the tested products do not exceed the PTWI (provisional tolerable weekly intake). Still, after orally administering two samples, the PDE values were determined to be above the permitted ones. In the conclusion of this work, the importance of constant control of the mercury content in commercially available food supplements is emphasized

    Estimated plasma volume status in COVID-19 patients and its relation to comorbidities and clinical outcomes

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    Blood plasma is a large reservoir of circulating mediators of inflammation and its expansion has been associated with unfavorable outcomes in patients with inflammatory and cardiovascular diseases. The aim of this study was to determine clinical and prognostic value of estimated plasma volume status (ePVS) in hospitalized patients with COVID-19. We retrospectively investigated 5871 consecutive COVID-19 patient hospitalized in our tertiary-level institution in period 3/2020-6/2021. ePVS was determined using the Strauss-derived Duarte formula and was correlated with clinical characteristics and unwanted outcomes. Median ePVS was 4.77 dl/g with interquartile range 4.11-5.74. Higher ePVS was significantly associated with older age, female sex, higher comorbidity burden, worse functional status, less severe COVID-19 clinical presentation with lower severity and longer duration of symptoms, but more pronounced inflammatory profile with higher C-reactive protein, interleukin-6 and D-dimer levels (P < 0.05 for all analyses). In the multivariate regression analysis U shaped relationship of ePVS with mortality was revealed, present independently of age, sex, COVID-19 severity and comorbidity burden. In addition, higher ePVS was independently associated with higher tendency for mechanical ventilation, intensive care unit treatment, venous thromboembolism, major bleeding and bacteriemia and lower ePVS was independently associated with tendency for arterial thrombotic events. Higher ePVS, indicative of plasma volume expansion and inflammatory cytokine accumulation, may predispose respiratory deterioration and venous thromboembolism, despite less severe initial clinical presentation. Lower ePVS, indicative of hemoconcentration, may predispose arterial thrombotic events. Both may be associated with higher mortality in hospitalized COVID-19 patients

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