In sepsis, platelets may become activated via toll-like receptors (TLRs), causing microvascular thrombosis. Megakaryocytes (MKs) also express these receptors; thus, severe infection may modulate thrombopoiesis. To explore the relevance of altered miRNAs in platelet activation upon sepsis, we first investigated sepsis-induced miRNA expression in platelets of septic patients. The effect of abnormal Dicer level on miRNA expression was also evaluated. miRNAs were profiled in septic vs. normal platelets using TaqMan Open Array. We validated platelet miR-26b with its target SELP (P-selectin) mRNA levels and correlated them with clinical outcomes. The impact of sepsis on MK transcriptome was analyzed in MEG-01 cells after lipopolysaccharide (LPS) treatment by RNA-seq. Sepsis-reduced miR-26b was further studied using Dicer1 siRNA and calpain inhibition in MEG-01 cells. Out of 390 platelet miRNAs detected, there were 121 significantly decreased, and 61 upregulated in sepsis vs. controls. Septic platelets showed attenuated miR-26b, which were associated with disease severity and mortality. SELP mRNA level was elevated in sepsis, especially in platelets with increased mean platelet volume, causing higher P-selectin expression. Downregulation of Dicer1 generated lower miR-26b with higher SELP mRNA, while calpeptin restored miR-26b in MEG-01 cells. In conclusion, decreased miR-26b in MKs and platelets contributes to an increased level of platelet activation status in sepsis.
Abstract:Horseshoe kidney is a fusion anomaly found in approximately one in 400-600 people. Due to vascular and ureteral variations, transplantation with a horseshoe kidney presents a technical challenge. In our case, the isthmus connected the upper poles and contained parenchyma. It consisted of three renal arteries, fi ve veins collected to the inferior vena cava, and two ureters and pyelons. It was implanted en bloc to the left side retroperitoneally. During the early period, cellular and humoral rejection was confi rmed and treated. For a urine leak, double J catheters were implanted into both ureters. Later, the fi rst catheter was removed. Subsequently, urinary sepsis developed, necessitating graftectomy. The uncommon anatomy of ureters and antibody-mediated rejection (AMR) may both be factors for a ureter tip necrosis led to an infected urinoma. After other Hungarian authors, we also report a horseshoe kidney transplantation that was technically successful. However, after an adequately treated but severe acute humoral rejection, the patient developed sepsis, and the kidney had to be removed. We conclude that transplantation with horseshoe kidney is technically feasible but may increase the risk for urinary complications and resultant infections. Careful consideration of risk and benefi t is advised when a transplant professional is faced with this option.
Aneszteziológiai és Intenzív Terápiás Klinika, DebrecenA COVID-19-fertőzéses, kritikus állapotba került betegek körében a cardiorespiratoricus rendszer összeomlása a következő mechanizmusok útján történhet: (1) citokinvihar, haemophagocytosis -szeptikus sokk, (2) uralhatatlan hypoxaemia, (3) specifikus szervelégtelenségek, illetve többszervi elégtelenség részjelenségeként. Ebben az összefoglalóban a fenti állapotok ellátásának és megelőzésének jelenleg rendelkezésre álló terápiás opcióit tekintjük át. A szeptikus sokk kezelésére az utóbbi években egyre gyakrabban és biztató sikerességgel kerül alkalmazásra a citokinek eltávolítása CytoSorb-haemoperfusióval. A konvencionális, mechanikus lélegeztetéssel már nem kezelhető hypoxaemia esetén szóba jön az inhalált nitrogén-oxid (iNO), az inhalációs formában bejuttatott epoprosztenol és a venovenosus extracorporalis membránoxigenizáció (VV-ECMO). A többnyire késői fázisban fellépő szervelégtelenségek gyakori komponense az akut veseelégtelenség, amely a rendelkezésre álló folyamatos vesepótló kezelések valamelyikének indítását igényli. Orv Hetil. 2020; 161(17): 704-709.
In this Escherichia coli induced porcine model, severe sepsis was evident by conventional criteria at 4 hours while several - mostly hypoxemia induced - biomarkers were already altered by 2 hours.
The pathophysiology of hemorheological and microcirculatory disturbances in septic process -mostly during the early hours-still not clarified in all the details, yet. In anesthetized pigs living E. coli (ATCC 25922 strain) was administered intravenously with an increasing concentration and the animals were observed for 8 hours. Before the intervention and in every 2 hours arterial (cannulated femoral artery) and venous (cannulated external jugular vein) blood samples were collected for hemorheological laboratory tests: blood and plasma viscosity, ESR, leukocyte anti-sedimentation rate, erythrocyte deformability (together with osmoscan parameters) and erythrocyte aggregation (using light-transmission and laser back-scattering methods) Control animals were stable over the 8-hour anesthesia, while septic animals died by the 6th hours in a fulminant sepsis. Over the experimental period, the tendency of impairment in erythrocyte deformability (together with osmotic gradient ektacytometry parameters) and the controversial decreasing of erythrocyte aggregation values (declining all aggregation index values, elongating t 1/2 ) were well detected in this porcine model during the early hours (4-6) of fulminant sepsis. The in vitro effect of these bacteria on erythrocytes' micro-rheological parameter was similar: decreasing red blood cell deformability and lowering aggregation. Further studies are needed to clarify the early micro-rheological changes of bacteremia and the developing sepsis.
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