The prospective validation of a scoring system to assess mucosal cleanliness during EGD.

BACKGROUND AND AIMS: Cleanliness of the mucosa of the upper GI (UGI) tract is critical for performing a high-quality EGD. The aim of this study was to validate a recently developed UGI cleanliness scale (the Polprep: Effective Assessment of Cleanliness in Esophagogastroduodenoscopy [PEACE] system) in the detection of clinically significant lesions (CSLs) in the UGI tract. METHODS: Patients who underwent a complete diagnostic EGD were prospectively enrolled from August 2021 to October 2022. The UGI tract (esophagus, stomach, and duodenum) cleanliness was scored from 0 to 3 for each segment. The primary outcomes were the detection of CSLs and PEACE scores. RESULTS: Of 995 patients enrolled from 5 centers, adequate cleanliness (AQ; all scores ≥2) was found in 929 patients. In multivariate regression analysis, AQ was associated with the number of diagnosed CSLs (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.06-3.01; P = .03). Other factors related to CSL detection were duration of EGD (OR, 1.29, 95% CI, 1.23-1.35, P < .001), male sex (OR, 1.33, 95% CI, 1.04-1.71; P = .025), and EGD indication (dyspepsia, alarm symptoms, gastritis surveillance, other indications vs GERD) (OR, 0.43 [95% CI, 0.31-0.6, P < .001], OR, 0.44 [95% CI, 0.28-0.67, P < .001], OR, 0.44 [95% CI, 0.25-0.76; P = .004], and OR, 0.44 [95% CI, 0.31-0.62; P < .001], respectively). Twenty-seven patients were diagnosed with UGI neoplasia, all in patients with adequate cleanliness of the UGI tract. CONCLUSIONS: Adequate cleanliness of the UGI tract as assessed with the PEACE system was associated with a significantly higher detection rate of CSLs during EGD. The relationship of this scale with UGI neoplasia detection warrants further investigation.

Scoring system assessing mucosal visibility of upper gastrointestinal tract: The POLPREP scale.

BACKGROUND AND AIM: The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS: To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS: The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS: The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.

Hypogelsolinemia and Decrease in Blood Plasma Sphingosine-1-Phosphate in Patients Diagnosed with Severe Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a frequent hospitalization cause of patients suffering from gastrointestinal disorders. Gelsolin has an ability to bind bioactive lipids including different sphingolipids engaged in inflammatory response. Importantly, hypogelsolinemia was observed in patients with different states of acute and chronic inflammation. AIMS: The aim of the present study was to assess the interplay of blood plasma gelsolin and blood plasma sphingosine-1-phosphate (S1P) concentration in patients diagnosed with acute pancreatitis. MATERIALS AND METHODS: To assess the concentration of gelsolin and S1P, immunoblotting and HPLC technique were employed, respectively. Additionally, the concentrations of amylase, lipase, C-reactive protein (CRP), procalcitonin (PCT) and the number of white blood cells (WBC) and platelet (PLT) were recorded. RESULTS: We found that both pGSN and S1P concentrations in the plasma of the AP patients were significantly lower (pGSN ~ 15-165 mg/L; S1P ~ 100-360 pmol/mL) when compared to the levels of pGSN and S1P in a control group (pGSN ~ 130-240 mg/L; S1P ~ 260-400 pmol/mL). Additionally, higher concentrations of CRP, WBC, amylase and lipase were associated with low level of gelsolin in the blood of AP patients. No correlations between the level of PCT and PLT with gelsolin concentration were noticed. CONCLUSION: Plasma gelsolin and S1P levels decrease during severe acute pancreatitis. Simultaneous assessment of pGSN and S1P can be useful in development of more accurate diagnostic strategies for patients with severe acute pancreatitis.

Daily Changes in Channel Occupancy in the 868 MHz ISM Band.

Due to the rapid development of Internet of Things (IoT) systems operating in industrial, scientific and medical (ISM) frequency bands, many researchers have attempted to determine the amount of interference that can be expected in such systems. The basic information required for this purpose is the current occupancy of frequency channels in various geographical locations. It is known that the occupancy measurement must last long enough to allow for the detection of low duty cycle transmissions. In this paper, it is shown that fulfilling only this criterion may lead to unreliable results being obtained. In two measurement campaigns performed in two different locations, the occupancy of a selected sub-band in the 868 MHz ISM band was determined on the basis of two hour-long observations repeated several times a day. During a typical day, the ratio of the maximum and the minimum result depended on the location and reached a value of eight; however, on one day, a period of abnormally high channel usage reaching 65% was observed in the location in which typical values did not exceed 1%.

Channel Occupancy Measurements in 868 MHz ISM Band in Residential Areas.

The rapid development of Internet of Things (IoT) has led to more and more devices using ISM frequency bands. Because they are not time synchronized, medium access collisions are unavoidable. The probability of such a collision is usually reasonably low; however, it increases with the number of transmitters competing for the same frequency channel. For this reason, ISM bands' occupancy is regularly monitored by researchers. This paper presents the results of the measurement campaign during which a selected part of the 868 MHz ISM frequency band was monitored for the presence of transmissions in six locations in various residential areas in Warsaw, Poland. For the purpose of the campaign, a dedicated measurement set-up comprising a software-defined radio (SDR) module was assembled. The measurements results showed that the channel occupancy is in most cases lower than 1% with a maximum observed value of 2%. The paper presents selected characteristics of the detected signals. Additionally, distribution over time of the detected signals was used together with the Monte Carlo simulations to analyze how long idle time blocks are available for new transmitters that could be deployed in the band under testing.

Sphingolipids metabolism in the salivary glands of rats with obesity and streptozotocin induced diabetes.

Diabetes is considered a major public health problem affecting millions of individuals worldwide. Remarkably, scientific reports regarding salivary glands sphingolipid metabolism in diabetes are virtually non-existent. This is odd given the well-established link between the both in other tissues (e.g., skeletal muscles, liver) and the key role of these glands in oral health preservation. The aim of this paper is to examine sphingolipids metabolism in the salivary glands in (pre)diabetes (evoked by high fat diet feeding or streptozotocin). Wistar rats were allocated into three groups: control, HFD-, or STZ-diabetes. The content of major sphingolipid classes in the parotid (PSG) and submandibular (SMSG) glands was assessed via chromatography. Additionally, Western blot analyses were employed for the evaluation of key sphingolipid signaling pathway enzyme levels. No changes in ceramide content in the PSG were found, whereas an increase in ceramide concentration for SMSG of the STZ group was observed. This was accompanied by an elevation in SPT1 level. Probably also sphingomyelin hydrolysis was increased in the SMSG of the STZ-diabetic rats, since we observed a significant drop in the amount of SM. PSG and SMSG respond differently to (pre)diabetes, with clearer pattern presented by the later gland. An activation of sphingomyelin signaling pathway was observed in the course of STZ-diabetes, that is, metabolic condition with rapid onset/progression. Whereas, chronic HFD lead to an inhibition of sphingomyelin signaling pathway in the salivary glands (manifested in an inhibition of ceramide de novo synthesis and accumulation of S1P).

Plasma Sphingolipids in Acute Pancreatitis.

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder associated with systemic inflammatory response syndrome and, in the case of severe AP, a mortality rate ranging from 36% to 50%. Standard clinical treatment of AP includes intensive hydration, analgesia, and management of complications. Unfortunately, the direct treatment of AP at the level of its molecular pathomechanism has not yet been established. Recent studies indicate that the sphingolipid signaling pathway may be one of the important factors contributing to the development of inflammation in pancreatic diseases. In the current study, we sought to investigate this promising route. We examined the plasma sphingolipid profile of 44 patients with acute pancreatitis, dividing them into three groups: mild, moderate and severe AP. Samples were collected from these groups at days 1, 3 and 7 following their hospital admission. We demonstrated significant changes in blood plasma sphingolipids in relation to the time course of AP. We also found an inhibition of de novo ceramide synthesis in mild and moderate AP. However, the most important and novel finding was a significant elevation in sphingosine-1-phosphate (S1P) (a downstream metabolite of ceramide) in mild AP, as well as a dramatic reduction in the lipid molecule content in the early stage (days 1 and 3) of severe AP. This strongly indicates that plasma S1P could serve as a prognostic marker of AP severity.

The Effects of AS160 Modulation on Fatty Acid Transporters Expression and Lipid Profile in L6 Myotubes.

BACKGROUND/AIMS: AS160 is a key intracellular regulator of energy utilization in cells. It was shown to regulate GLUT4 translocation from intracellular depots to the plasma membrane, with subsequent changes in facilitated glucose uptake into the skeletal muscles. Similarly, also free fatty acids (FFAs) transmembrane transport seems to be largely protein-mediated. Therefore, the objective of this study was to examine the effects of moderate AS160 depletion (-82% mRNA, -25% of protein content) on the expression of fatty acid transporters and subsequent changes in lipid profile in L6 myotubes. RESULTS: Surprisingly, moderate down regulation of AS160 expression was followed by increased AS160 phosphorylation (∼40%). These resulted in a greater expression of fatty acid transporters, namely FABPpm and FAT/CD36, with subsequently increased FAs cellular influx. No changes in the expression of FATP1 and 4 were noticed. Accordingly, we have observed a reduction in total TAG content. This was mainly caused by a significant changes in TAG fatty acids composition favouring a decrease in the amount of palmitic and stearic fatty acid moieties. In contrast, our experimental intervention led to distinctively increased total content of DAG and PL, but concomitantly decreased the content of all measured sphingolipids, e.g. SFA, SA1P, CER, SFO and S1P, in the AS160 knockdown group. CONCLUSIONS: Modulation of AS160 level and activity led to significant increase in the concentration of DAG and PL, which was associated with changes in FAs composition and expression of fatty acid transporters. Interestingly, the intervention also simultaneously decreased the content of sphingolipids.

Variation in blood levels of hormones in obese patients following weight reduction induced by endoscopic and surgical bariatric therapies.

BACKGROUND: Beneficial clinical effects of weight reduction following bariatric therapies is not fully understood and maybe related to the complex interactions between leptin, adiponectin, visfatin, omentin, and ghrelin. The aim of study was to investigate their timeline changes associated with weight reduction and their profile in relation to the type of treatment and its efficacy. METHODS: Circulating hormones levels were analyzed before and after endoscopic and surgical procedures in 67 obese patients and compared to non-obese healthy controls. RESULTS: Obese patients had higher leptin levels and lower levels of adiponectin, visfatin, omentin, and ghrelin than non-obese controls. During the consecutive follow-up visits after treatment, there was a gradual decrease in leptin levels and an increase in adiponectin levels to the levels observed in non-obese. At 50-54weeks, the ghrelin levels were lower and the levels of adiponectin and visfatin, but not omentin, were higher compared to their baseline values. BMI correlated with ghrelin and leptin levels. The percentage of total weight loss correlated positively with adiponectin levels and negatively with leptin levels. Patients with adequate weight loss had a significantly lower leptin concentration than those with treatment failure. There were timeline variations in hormone levels between endoscopic and bariatric therapies, however there were no significant differences in the median their concentration at 50-54weeks after therapy. CONCLUSION: Our study supports observations that weight loss itself, rather than the procedure type, is responsible for hormonal variation. The leptin levels reflect the best the body weight changes after bariatric therapies.

Effect of streptozotocin-induced diabetes on lipids metabolism in the salivary glands.

BACKGROUND: Diabetes is one of the most common metabolic diseases. Moreover, previous studies indicate that diabetes may cause changes in the salivary glands phenotype and in the composition of saliva itself. Therefore, the main objective of this study was to determine the effects of streptozotocin induced diabetes on lipid profile of the rat salivary glands. METHODS: Male Wistar rats were divided into two groups: control and STZ-induced diabetes. At the end of the experiment all animals were sacrificed and samples of the parotid and submandibular salivary glands were excised. Major lipid fractions concentrations were determined by means of chromatography (TLC and GC). RESULTS: We observed a significant increase (∼3.5 fold) in the level of triacylglycerol in both the parotid and submandibular salivary glands of diabetic rats. The abovementioned changes were accompanied by significant, although less dramatic (i.e. from -60% to -90%), decrements in the levels of other lipid classes (phospholipids, free fatty acids and diacylglycerol). CONCLUSIONS: In our study we have showed, presumably for the first time, that streptozotocin induced diabetes causes decrement in PH content with subsequent atrophy and malfunction in both parotid and submandibular salivary glands. Another novel finding of our research is that diabetic rats were characterized by an increased TG accumulation in both parotid and submandibular salivary glands. The later one could be a clinical manifestation of diabetes.

The Role of PGC-1α in the Development of Insulin Resistance in Skeletal Muscle - Revisited.

Currently, obesity is a predominant medical condition and an important risk factor for the development of several diseases, including type 2 diabetes mellitus. Importantly, most research has indicated lipid-induced insulin resistance in skeletal muscles is a key link between the aforementioned pathological conditions. PGC-1α is a prominent regulator of myocellular energy metabolism orchestrating gene transcription programming in response to numerous environmental stimuli. Moreover, it is widely acknowledged that mitochondrial metabolism (primary metabolic target of PGC-1α) disturbances are widely acknowledged contributors to type 2 diabetes development. Therefore, it seems surprising that the exact physiological contribution of PGC-1α in the development of insulin resistance in skeletal muscle remains poorly understood. This review aims to reconcile these allegedly different findings by looking for a common denominator in the role(s) of PGC-1α in respect to lipid-induced insulin resistance in skeletal muscle. Our scrutiny of the literature indicates that interventions at the level of PGC-1α may exert beneficial effects on myocytes in respect to lipid-induced insulin resistance. The latter takes place as a result of a positive net energy balance (fatty acids oxidation surpassing their accumulation rate). Moreover, the aforementioned effects may not necessarily be limited to physically active states. They seem to occur, however, only within a physiologically observed range in muscle cells (approximately 1-fold changes in PGC-1α protein expression).

Hyperthyroidism evokes myocardial ceramide accumulation.

BACKGROUND: Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. METHODS: Male Wistar rats were treated for 10 days with triiodothyronine (T3) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. RESULTS: We have demonstrated that prolonged, in vivo, T3 treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), ß-hydroxyacyl-CoA dehydrogenase (ß-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). CONCLUSIONS: We conclude that prolonged T3 treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.

Inhibition of ceramide de novo synthesis reduces liver lipid accumulation in rats with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is an insulin resistance-related hepatic disorder which can transform to cirrhosis. Insulin resistance deregulates hepatic lipid metabolism, leading to accumulation of cytotoxic lipids including ceramide and diacylglycerols. Myriocin, obtained from fungi traditionally used in Chinese medicine in an effort to attain eternal youth, is a potent pharmacological inhibitor of ceramide de novo synthesis. We examined whether inhibition of ceramide de novo synthesis with myriocin ameliorate hepatic lipid accumulation and reverse NAFLD. METHODS: The experiment was carried out on male Wistar rats. The animals were divided into four groups: (i) control group, fed standard rodent diet, (ii) group, fed standard diet also treated with myriocin for 7 days, (iii) group, fed high-fat diet for 5 weeks, (iv) group, fed high-fat diet and treated with myriocin. In liver samples sphingolipids: ceramide, sphingosine and sphingosine-1-phosphatate and neutral lipids, such as diacylglycerols and triacylglycerols were measured. In peripheral blood samples, glucose and insulin levels and aminotransferases activities were measured. RESULTS: High-fat diet feeding caused NAFLD, confirmed by histological assessment, with increased hepatic lipids accumulation and whole-body insulin resistance. After treating with inhibitor of ceramide de novo synthesis, decrease in hepatic ceramide and other toxic lipids were noticed. Moreover, histological analysis of liver samples revealed that inhibition of ceramide de novo synthesis reduced hepatic steatosis. CONCLUSIONS: Inhibition of ceramide de novo synthesis reduced hepatic lipid accumulation in rats with NAFLD, this led to amelioration of hepatic steatosis.

Effect of COVID-19 on the prevalence of bystanders performing cardiopulmonary resuscitation: A systematic review and meta-analysis.

BACKGROUND: The importance of bystander cardiopulmonary resuscitation (CPR) during out-of-hospital cardiac arrests is especially important in the context of coronavirus disease 2029 (COVID-19) because it can significantly influence survival outcomes. The objective of this meta-analysis was to examine the primary outcomes of bystander CPR during the pandemic and pre-pandemic periods. METHODS: A search was conducted in the PubMed Central, Scopus, and EMBASE databases, as well as the Cochrane Central Register of Controlled Trials database, up to December 10, 2023. In cases where the value of I² was greater than or equal to 50% or the Q-test indicated that the p-value was less than or equal to 0.05, the studies were considered to be heterogeneous. Sensitivity assessment was performed using the leave-one-out methodology. The study protocol was registered in PROSPERO with the ID number CRD42023494912. RESULTS: Twenty-five articles were included in this meta-analysis. Pooled analysis showed that bystander CPR frequency during the COVID-19 pandemic was 38.8%, compared to 44.8% for the pre-pandemic period (odds ratio: 1.04; 95% confidence interval: 0.93-1.16; p = 0.48). CONCLUSIONS: The article's conclusions indicate that the COVID-19 pandemic influenced a reduction in bystander CPR compared to the pre-pandemic period, but this difference was not statistically significant. Further research is recommended to understand attitudes, including the fears of witnesses, before performing CPR on patients with suspected or confirmed infectious diseases. The study highlights the importance of bystander intervention in emergency situations and the impact of a pandemic on public health response behaviors.

Diagnostic and prognostic performance of the neutrophil-to-lymphocyte ratio in acute coronary syndromes: A meta-analysis of 90 studies including 45 990 patients.

BACKGROUND: Cardiovascular disease is a leading cause of mortality worldwide and is likely to rise. Acute coronary syndrome (ACS) is consequent on inflammation. As a common and cost-effective inflammatory biomarker, the neutrophil-to-lymphocyte ratio (NLR) may be beneficial in cardiovascular medicine. AIMS: This meta-analysis examines the diagnostic and prognostic performance of the NLR in ACS. METHODS: We systematically searched PubMed Central, Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov databases. The search spanned from databases inception to January 10, 2024. The findings were aggregated into normalized mean differences with 95% confidence intervals. RESULTS: Ninety articles, with 45 990 participants, were included. Pooled analysis of the NLR varied and was higher in ST-segment elevation myocardial infarction (STEMI) vs. non-ST-segment elevation myocardial infarction patients (4.94 ± 3.24 vs. 3.24 ± 2.74), acute myocardial infarction vs. unstable angina (4.47 ± 3.43 vs. 2.97 ± 1.58), ACS vs. stable angina (SA) (5.45 ± 4.28 vs. 2.46 ± 2.15), and ACS vs. controls (5.31 ± 4.01 vs. 2.46 ± 2.45). The NLR also was associated with ACS mortality, with survivors having lower results (3.67 ± 2.72 vs. 5.56 ± 3.93). Subanalysis showed that differences in the NLR were observed in STEMI survivors (4.28 ± 3.24 vs. 6.79 ± 3.98). Of ACS patients with major cardiovascular events (MACE) vs. without MACE, the NLR was 6.29 ± 4.89 vs. 3.82 ± 4.12. In STEMI patients, the NLR differed between those with and without MACE (6.99 ± 5.27 vs. 4.99 ± 4.12). CONCLUSIONS: The NLR is an effective tool for differentiating between different types of ACS. A high NLR is associated with ACS and increased MACE at 30 days. The NLR also appears to be a good predictor of MACE risk, at least in STEMI patients.

Robotic versus Laparoscopic Liver Resections for Colorectal Metastases: A Systematic Review and Meta-Analysis.

Colorectal cancer is the third most common cancer worldwide, and the liver is the most common localization of metastatic disease. The incidence of minimally invasive liver surgery is increasing, and robotic surgery (RLR) is believed to overcome some limitations of a laparoscopic approach (LRL). We performed a systematic review and meta-analysis of operative and short-term oncologic outcomes of the laparoscopic versus robotic-assisted liver resection for colorectal liver metastases. An online search of PubMed, Embase, Scopus, and the Cochrane databases was performed. Eight studies involving 3210 patients were considered eligible for the meta-analysis. In the LRL group, a higher conversion to open rate (12.4%) was observed compared to the RLR (6.7%; p = <0.001). 30-day mortality was 0.7% for the LRL group compared to 0.5% for the RLR group (p = 0.76). Mortality in longer periods among LLR and RLR amounted to 18.2% vs. 8.0% for 1-year mortality (p = 0.07), 34.1% vs. 26.7% for 2-year mortality (p = 0.13), and 52.3% vs. 48.3% for 3-year mortality (p = 0.46). The length of hospital stay was 5.6 ± 2.5 vs. 5.8 ± 2.1 days, respectively (p = 0.47). There were no significant differences between the incidence of individual complications in the LRL and RLR groups (p = 0.78). Laparoscopic or robotic approaches for colorectal liver metastases are comparable in terms of safety and effectiveness. There are significant advantages to robotic surgery, although there is still no long-term evidence concerning overall survival, and the number of patients operated on using RLR remains small.

The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society.

Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.

[The role of sphingolipids in selected cardiovascular diseases]. / Rola sfingolipidów w wybranych chorobach ukladu krazenia.

Bioactive sphingolipids are engaged with numerous cellular processes such as cell differentiation, proliferation and apoptosis. Sphingolipid metabolism in heart is regulated by physical exercise and PPARs. Ceramide, the main second messenger of sphingomyelin pathway of signal transduction, was found to be involved in development of cardiac dysfunction after ischemia/reperfusion. On the other hand ceramide derivative sphingosine- 1- phosphate has been shown to exert potent cardioprotective action and guards cardiomyocytes against ischemic/reperfusion injury. Pharmacological compounds, which regulate metabolism of sphingolipids can be potentially useful in treatment of selected cardiovascular diseases. The aim of this work is critical review of physiological and pathological role of sphingolipids in circulatory system.