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S transfuzijo povezana volumska preobremenitev oz. TACO je najpogostejša respiracijska neželena transfuzijska reakcija (NTR). Pri TACO se med transfuzijo ali v 12 urah po njej pri dovzetnih bolnikih razvijeta kardiogeni pljučni edem in dihalna stiska zaradi volumske preobremenitve s tekočinami. Ogroženi so novorojenčki in dojenčki, starostniki, bolniki s srčnim popuščanjem, bolniki s hudo anemijo ter bolniki s pozitivno tekočinsko bilanco. Tvegana sta hitra transfuzija in večji volumen transfundiranih krvnih komponent. Bolnike s TACO zdravimo z dodajanjem kisika, intravenskimi diuretiki, nitrati in morfinskimi pripravki ter po potrebi z neinvazivnim ali invazivnim mehanskim predihavanjem. Čeprav je TACO v zadnjih letih v razvitem svetu najpogostejši vzrok za zbolevnost in za smrtni izid transfuzije, se ga pogosto spregleda in zato ne prijavi hemovigilančni službi. K temu prispevajo tako pomanjkljivo (pre)poznavanje simptomov in znakov TACO ter prekrivanje kliničnih slik pri kritično bolnih, kot tudi zahtevno razlikovanje od drugih dveh primarnih respiracijskih NTR: s transfuzijo povezane akutne okvare pljuč oz. TRALI in s transfuzijo povezane dispneje oz. TAD. S pregledom svetovne literature smo v članku povzeli najnovejša dognanja o patofiziologiji, klinični sliki in zdravljenju ter preprečevanju TACO. Podrobno opisujemo ISBT/IHN/AABB definicijo TACO iz leta 2018. Posebno pozornost smo namenili prikazu razlik med TACO, TRALI in TAD, ki bodo zdravnikom v pomoč pri diagnosticiranju. Za preprečevanje hudih posledic pri bolnikih je nujno potrebno znanje o preprečevanju, prepoznavanju in zdravljenju respiracijskih NTR. Enako velja za prijavljanje NTR hemovigilančni službi.

ABSTRACT Despite immense interest in biomarker applications of extracellular vesicles (EVs) from blood, our understanding of circulating EVs under physiological conditions in healthy humans remains limited. Using imaging and multiplex bead‐based flow cytometry, we comprehensively quantified circulating EVs with respect to their cellular origin in a large cohort of healthy blood donors. We assessed coefficients of variations to characterize their biological variation and explored demographic, clinical, and lifestyle factors contributing to observed variation. Cell‐specific circulating EV subsets show a wide range of concentrations that do not correlate with cell‐of‐origin concentrations in blood, suggesting steady‐state EV subset concentrations are regulated by complex mechanisms, which differ even for EV subsets from the same cell type. Interestingly, tetraspanin+ circulating EVs largely originate from platelets and to a lesser extent from lymphocytes. Principal component analysis (PCA) and association analyses demonstrate high biological inter‐individual variation in circulating EVs across healthy humans, which are only partly explained by the influence of sex, menopausal status, age and smoking on specific circulating EV and/or tetraspanin+ circulating EV subsets. No global influence of the explored subject's factors on circulating EVs was detected. Our findings provide the first comprehensive, quantitative data towards the cell‐origin atlas of plasma EVs, with important implications in the clinical use of EVs as biomarkers.

Background and Objectives: Most patients who are successfully resuscitated from cardiac arrest remain comatose, and only half regain consciousness 72 h after the arrest. Neuroprognostication methods can be complex and even inconclusive. As mitochondrial components have been identified as markers of post-cardiac-arrest injury and associated with survival, we aimed to investigate cytochrome c and mtDNA in comatose patients after cardiac arrest to compare neurological outcomes and to evaluate the markers’ neuroprognostic value. Materials and Methods: This prospective observational study included 86 comatose post-cardiac-arrest patients and 10 healthy controls. Cytochrome c and mtDNA were determined at admission. Neuron-specific enolase (NSE) was measured after 72 h. Additional neuroprognostication methods were performed when patients remained unconscious. Cerebral performance category (CPC) was determined. Results: Cytochrome c was elevated in patients compared to healthy controls (2.029 [0.85–4.97] ng/mL vs. 0 [0.0–0.16], p < 0.001) but not mtDNA (95,228 [52,566–194,060] vs. 41,466 [28,199–104,708] copies/μL, p = 0.074). Compared to patients with CPC 1–2, patients with CPC 3–5 had higher cytochrome c (1.735 [0.717–3.40] vs. 4.109 [1.149–8.457] ng/mL, p = 0.011), with no differences in mtDNA (87,855 [47,598–172,464] vs. 126,452 [69,447–260,334] copies/μL, p = 0.208). Patients with CPC 1–2 and CPC 3–5 differed in all neuroprognostication methods. In patients with good vs. poor neurological outcome, ROC AUC was 0.664 (p = 0.011) for cytochrome c, 0.582 (p = 0.208) for mtDNA, and 0.860 (p < 0.001) for NSE. The correlation between NSE and cytochrome c was moderate, with a coefficient of 0.576 (p < 0.001). Conclusions: Cytochrome c was higher in comatose patients after cardiac arrest compared to healthy controls and higher in post-cardiac-arrest patients with poor neurological outcomes. Although cytochrome c correlated with NSE, its neuroprognostic value was poor. We found no differences in mtDNA.

The aim of the present study was to determine the lactation stage effect on the concentration of essential and selected toxic elements in the sheep’s milk of Dubrovačka ruda. The research was conducted with 23 sheep, average age of 4 years, of 3rd lactation, while the milk samples were taken during the early (60th day), middle (90th day) and late (120th day) lactation stage. The sheep were selected according to uniformed body development, adequate health status, body condition, equable age (4 years), parity (3rd lactation), stage of lactation (±7 days) and litter size (single). Sheep were reared on the extensive Mediterranean pastures, reared indoors afterwards, fed with hay ad libitum and feed mixtures in average 0.5 kg/day. Milk sample was collected during morning milking from each sheep. The digested samples were analyzed with continuous flow hydride generation technique using inductively coupled plasma for Ca, Mg, K, P, Na, Cu, Fe, Zn, Mn, Ni, Mo, Co, Cr, Cd and Pb concentrations. Significant increase of Mg, Na, Se, Mn, Mo and Cd concentrations were found in milk as well as decrease of K concentration during the lactation. Although the concentration of Ca, Cu, Cr and As in milk during the lactation is increased, the differences between the lactation stages were not observed. Concentrations of P, Fe, Ni, Pb and Hg in milk of Dubrovačka ruda did not differ during the lactation. The low concentrations of Cr, Cd, Pb, As, Hg in milk indicate the safety for consumers and preserved environment of Dubrovnik-Neretva County.

Respiratory transfusion-related reactions are not very frequent, partly also because recognition and reporting transfusion reactions is still underemphasized. Tis article describes the most important respiratory transfusion reactions, their pathophysiology, clinical picture and treatment strategies. Respiratory transfusion related reactions can be primary or secondary. The most important primary transfusion-related reactions are TRALI - transfusion-related acute lung injury, TACO – transfusion-associated circulatory overload, and TAD - transfusion-associated dyspnea. TRALI is immuneassociated injury of alveolar basal membrane, which becomes highly permeable and causes noncardiogenic pulmonary edema. Treatment of TRALI is mainly supportive with oxygen, fluids (in case of hypotension) and in cases of severe acute respiratory failure also mechanic ventilation. TACO is caused by volume overload in predisposed individuals, such as patients with heart failure, the elderly, infants, patients with anemia and patients with positive fluid balance. Clinical picture is that of a typical pulmonary cardiogenic edema, and the therapy is classical: oxygen and diuretics, and in severe cases also non-invasive or invasive mechanical ventilation. TAD is usually a mild reaction of unknown cause and cannot be classified as TACO or TRALI, nor can it be ascribed to patient’s preexisting diseases. Although the transfusion-related reactions are not very common, knowledge about them can prevent serious consequences. On the one hand preventive measures should be sought, and on the other early recognition is beneficial, so that proper treatment can take place.