Inhibition of Neutral Sphingomyelinase 2 by Novel Small Molecule Inhibitors Results in Decreased Release of Extracellular Vesicles by Vascular Smooth Muscle Cells and Attenuated Calcification.

Vascular calcification (VC) is an important contributor and prognostic factor in the pathogenesis of cardiovascular diseases. VC is an active process mediated by the release of extracellular vesicles by vascular smooth muscle cells (VSMCs), and the enzyme neutral sphingomyelinase 2 (nSMase2 or SMPD3) plays a key role. Upon activation, the enzyme catalyzes the hydrolysis of sphingomyelin, thereby generating ceramide and phosphocholine. This conversion mediates the release of exosomes, a type of extracellular vesicles (EVs), which ultimately forms the nidus for VC. nSMase2 therefore represents a drug target, the inhibition of which is thought to prevent or halt VC progression. In search of novel druglike small molecule inhibitors of nSMase2, we have used virtual ligand screening to identify potential ligands. From an in-silico collection of 48,6844 small druglike molecules, we selected 996 compounds after application of an in-house multi-step procedure combining different filtering and docking procedures. Selected compounds were functionally tested in vitro; from this, we identified 52 individual hit molecules that inhibited nSMase2 activity by more than 20% at a concentration of 150 µM. Further analysis showed that five compounds presented with IC50s lower than 2 µM. Of these, compounds ID 5728450 and ID 4011505 decreased human primary VSMC EV release and calcification in vitro. The hit molecules identified here represent new classes of nSMase2 inhibitors that may be developed into lead molecules for the therapeutic or prophylactic treatment of VC.

Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure.

BACKGROUND: Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC. METHODS: We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies. RESULTS: The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress. CONCLUSION: In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Early postoperative hemodynamic instability after heart transplantation - incidence and metabolic indicators.

BACKGROUND: Primary graft dysfunction (PGD) is the main cause of death in the first 30 days after heart transplantation (HTX), accounting for approximately 40% of mortality. The study's primary aim was to assess the incidence of PGD, following the International Society for Heart and Lung Transplantation consensus, and to compare it with the incidence of significant postoperative hypotension despite administration of high-dose inotropes and vasoconstrictors. The secondary aim of the study was to determine changes in biochemical markers that accompany the phenomenon. METHODS: Forty-five patients who underwent HTX between 2010 and 2015 were enrolled in this study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Hemodynamic instability was defined as significant postoperative hypotension (mean arterial pressure (MAP) < 60 mmHg) combined with a high inotrope score (> 10). Data for long-term mortality were obtained from the population registration office. RESULTS: PGD incidence was relatively low (17.8%); however, hemodynamic instability was common (40%). Among unstable patients, MAP was insufficient for end-organ perfusion (51.4 ± 9.5 mmHg) but no decrease in left ventricular function was observed (cardiac index, 2.65 ± 0.6 l/min/m2; left ventricular ejection fraction, 52.9 ± 15.5%). Within this group, mean systemic vascular resistance index (961 ± 288 dyn*s*m2/cm5) was low despite receiving high doses of vasoactive agent (norepinephrine 0.21 (0.06-0.27) µg/kg/min during first 24 h postoperatively and 0.21 (0.01-0.27) µg/kg/min during next 24 h postoperatively). After HTX, serum lactate levels were initially significantly higher in patients with hemodynamic instability (p = 0.002); however, impaired lactate clearance was not observed (p = 0.366), and lactate levels normalized within the first 24 h postoperatively. Postoperative hemodynamic instability altered the long-term outcome and increased 5-year mortality after HTX (p = 0.034). CONCLUSIONS: Hemodynamic instability is a more common phenomenon than PGD. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients.

Why should cardiac surgeons occlude the left atrial appendage percutaneously?

OBJECTIVES: Percutaneous left atrial appendage (LAA) occlusion (LAAO) is a procedure dominated by cardiologists. The aim of our study was to present the results of percutaneous LAAO performed solely by cardiac surgeons. METHODS: Two hundred twenty-three consecutive patients with nonvalvular atrial fibrillation underwent percutaneous LAAO in two cardiac surgery sites. In the first center, all 84 LAAO procedures were performed with the endocardial LAA occluders: 60 cases with the Amulet and 24 cases with the LAmbre. In the second center, all 139 LAAO procedures were performed with the LARIAT epicardial device. RESULTS: The mean CHA2 DS2 -VASc-score was 3.7 ± 1.8 points, and mean HAS-BLED score was 3.6 ± 1.2 points. The procedure was successful in 97.3% of cases. Procedural or device-related adverse events were noted in 4.4% (n = 10) of cases: one periprocedural cardiac arrest, one aortic injury, one gastrointestinal bleeding, three cases of vascular access complications, and four cardiac tamponades. After a follow-up of 40.3 ± 17.3 months, 78.4% of patients were alive, with the annual mortality rate of 5.3%. Compared to the predicted risk, the observed incidence of thromboembolism was lower by 71%, and the bleeding incidence was lower by 69%. CONCLUSIONS: Percutaneous LAAO procedures can be safely performed by cardiac surgeons, with no cardiological assistance. LAAO done by surgeons is safe and effective, and periprocedural and long-term outcomes are excellent. Cardiac surgeons should be trained in both types of LAAO: endocardial and epicardial.

Atrial septal defect surgery in adults--populational and epidemiological analysis.

UNLABELLED: Atrial septal defect (ASD) is one of the most common congenital heart diseases found in adolescents and adults. Shunt may lead to serious further complications, such as pulmonary hypertension and right heart chambers overload. The aim of this study was the analysis of the population of adult patients with ASD together with the frequency of the annuloplasty tricuspid ring implantation in ASD II and the necessity of anterior mitral valve cusp suturing due to the cleft accompanying ASD I. MATERIALS AND METHODS: The study group consisted of 58 males and 122 females aged 17 to 77. Individuals were divided into three age brackets: 17-30 years old--22%; 31-50--38,5% and 51-77--39,5%. RESULTS: In 92,8% of cases median sternotomy was performed. Other approaches were: right mini- thoracotomy 5%, 2,2% underwent lower hemisternotomy. There were 16 annuloplasties accompanying ASD closure: 13 in ASD II patients, 1 in PFO patient, 2 in ASD I patients. Average size of the pericardiac patch used to ASD type II correction was bigger in patients, who also underwent annuloplasty tricuspid ring implantation (Mann- Whitney U test: -2,25, p=0,024). CONCLUSION: Repair of ostium secundum and sinus venosus ASD can be performed safely via minithoracotomy endoscopic approach with similar outcomes as sternotomy. Beside the mitral cleft suturing in ASD I patients, annuloplasty tricuspid ring implantation is the most common additional procedure. ASD II patients, who had undergone such annuloplasties needed the bigger pericardial patches.

Personal Resources and Expectations and Health Behaviors Among Solid Organ Transplant Recipients-A Multicenter Study.

BACKGROUND: The long-term success of organ transplantation (Tx) depends on the transplant recipient's ability to self-manage symptoms, treatment, lifestyle changes, and psychosocial consequences. Health behavior (HB) determinants include personality traits such as optimism, self-efficacy, and health locus of control. PURPOSE: Assessing the relationship between personal resources and expectations and health behaviors of organ transplant recipients. MATERIAL AND METHODS: The study was conducted between 01/04/2018 and 30/10/2019 at 3 transplant centers in Poland. The study group consisted of 243 Tx recipients of kidney, heart, liver, and lung. The Health Behavior Inventory, Multidimensional Health Locus of Control Scale (MHLC), General Self-Efficacy Scale, Dispositional Optimism Scale, and Hospital Anxiety and Depression Scale were used to collect data. FINDINGS: The study group had medium levels of dispositional optimism (mean 15) and high levels of self-efficacy (mean 30.18). The MHLC scale was dominated by a belief in the influence of others and an internal locus of control over one's health. The respondents presented a high level of HB (mean 92.09). A positive relationship was found between personal resources (self-efficacy and optimism), MHLC and HB. The presence of depression and anxiety negatively affected personal resources and internal locus of health control and HB in terms of a positive mental attitude. Type of Tx differentiated internal locus of health control and HB. Predictors of HB were dispositional optimism, self-efficacy, influence of others with health locus of control, symptoms of depression, age and time since transplantation-explaining between 6.1% and 14.5% of health behavior categories. CONCLUSIONS: To improve health practices among organ recipients, strengthening their personal resources is recommended. It is necessary to form an internal locus of control for adherence to positive HB.

Outcomes and Complications after Left Ventricular Assist Device Implantation.

BACKGROUND: Heart transplantation is the treatment of choice for selected patients with end-stage heart failure. Persistent donor organ shortage causes a growing demand for mechanical circulatory support not only as a bridge to transplantation but mainly as a destination therapy (DT). METHODS: The aim of the study was to analyze the indications, comorbidities, and complications during the follow-up of all patients undergoing left ventricular assist device (LVAD) implantation with at least 12 months of follow-up time in one of the most experienced clinics in Poland between 2015 and 2023. RESULTS: There were 125 individuals with LVAD implantation, from which 90 had full 12 months of follow-up (85 males - 94%, 5 females - 6%), with a median age of 58 (50.25-63.75) years. The median body mass index was 27.12 (25.27-29.68). The etiology of heart failure was ischemic (n = 44, 49%), dilated cardiomyopathy (n = 44, 49%), and others. Preoperative echocardiography revealed a mean LV ejection fraction of 13.8% and a median LV dimension of 7.55 (6.92-8.2) cm. In 61 patients (68%), imaging confirmed pulmonary hypertension. Thirty-four patients (38%) had diabetes and 16 (18%) were active smokers. Median follow-up was 30 (17.25-42) months, with the longest period being about 82 months. 40 (44%) patients had kidney failure before LVAD implantation, and in 43 cases (48%), we observed relevant, transient deterioration of kidney function. Almost all patients (n = 82, 91%) suffered from anemia (Hb <13 g/dL in males and <12 g/dL in females) in different periods after LVAD implantation due to perioperative bleeding, gastrointestinal bleeding or unknown causes. The lowest Hb level was observed in the first week after LVAD implantation in 53 cases (58%). Median red cell concentrate transfusion demand before the discharge after surgery was 6 (2-8, 5) units. CONCLUSIONS: Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Anemia and kidney failure are the most frequent follow-up complications. Improved results and increased applicability and durability of LVADs have established this treatment option as an excellent alternative for patients with end-stage heart failure.

Driveline Infection in Patients With Left Ventricular Assist Devices Implanted as Destination Therapy.

BACKGROUND: Donor organ shortages cause increasing demand for mechanical circulatory support in patients with end-stage heart failure not only as a bridge to heart transplantation but mainly as a destination therapy. Improved results and increased applicability and durability of left ventricular assist devices (LVADs) have established this treatment option as an alternative to heart transplantation in selected patients. One of the most common complications after LVAD implantation is driveline infections (DLIs). METHODS: This study aimed to expand the understanding of DLI epidemiology and potential changes in implantation techniques regarding optimizing DLI prevention and treatment among all patients undergoing LVAD (Medtronic's Heartware HVAD and HeartMate 3 Abbott LVAD system) implantation with at least 12 months of follow-up time between 2015 and 2022. RESULTS: There were 120 individuals with LVAD implantation, of whom 90 had 12 months of follow-up (85 men [94%], 5 women [6%]) with a median age of 58 years (50.25-63.75). The median body mass index was 27.12 kg/m2 (25.27-29.68). Of the 90 patients, 43 had ischemic heart failure (48%), 43 had dilated cardiomyopathy (48%), and the remaining 3 had other etiologies (3%), such as postinflammatory, and the remaining 1 had congenital heart defect (1%). Preoperative echocardiography revealed a mean left ventricle ejection fraction of 13.8% and a median left ventricle dimension of 7.55 cm (6.92-8.2). Imaging confirmed pulmonary hypertension in 61 patients (68%). Thirty-four of the 90 patients had diabetes (38%), and 16 were active smokers (18%). Median follow-up was 30 months (17.25-42), with the longest period being 82 months. More than half of the patients (n = 52; 57%) experienced a DLI. The median time to the first episode of DLI was 13 months (6-25). The most common pathogen revealed in wound swab culture was methicillin-sensitive Staphylococcus aureus (n = 23; 44%), Pseudomonas aeruginosa (n = 9; 17%), Proteus mirabilis (n = 4; 7%), and others. We observed that deeper driveline implantation below the left rectus muscle and just above the posterior rectus sheath resulted in fewer DLIs and longer free-from-DLI follow-up time. There was no statistically significant difference in DLI frequency between patients with or without diabetes mellitus. CONCLUSIONS: Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of destination therapy. DLI is the most common complication after LVAD implantation. Optimal surgical techniques and early implementation of targeted antibiotics are crucial. Significant challenges remain in optimizing DLI prevention and treatment.

Advanced abdominal arterial calcification sparing kidney allograft--case report.

Excess and progressing arterial calcification is a frequent finding in patients with chronic kidney disease and in diabetics. Vascular calcification present in patients on dialysis, usually continues to progress (although possibly with slower rate) in patients after kidney transplantation. These observations are limited mostly to aorta and coronary arteries; virtually no data exist on progression in vascular calcification within the vasculature of transplanted kidney. The case report presents the patient with diabetes and non-functioning renal transplant back on dialysis with extremely severe intra-abdominal artery calcification, sparing renal artery of transplanted kidney. Calcification did not develop within transplanted kidney despite 10 years of exposition to diabetic environment and a few years of chronic kidney disease after transplantation, including CKD-T stage 5 for at least one year after re-starting of dialysis. To the best of our knowledge, this is the second report ever describing sparing of kidney graft from calcification despite disseminated calcification in other vascular beds. It is tempting to speculate that some "intrinsic" factors exist within the transplanted kidney that protects it from calcification despite exposure to procalcifying milieu of diabetes and uremia.

Right ventricular-pulmonary arterial coupling in patients with implanted left ventricular assist devices.

OBJECTIVE: Both the right ventricular (RV) contractile function and pulmonary arterial (PA) pressure influence clinical outcomes in patients supported with left ventricular assist devices (LVADs), but the impact of RV-PA coupling is unknown. This study aimed to determine the prognostic impact of RV-PA coupling in patients with implanted LVADs. METHODS: Patients with implanted third-generation LVADs were retrospectively enrolled. The RV-PA coupling was assessed preoperatively by the ratio of RV free wall strain (RVFWS) derived from speckle-tracking echocardiography and noninvasively measured peak RV systolic pressure (RVSP). The primary end point was a composite of all-cause mortality or right heart failure (RHF) hospitalization. Secondary end points consisted of all-cause mortality at a 12-month follow-up and RHF hospitalization. RESULTS: A total of 103 patients were screened, and 72 with good RV myocardial imaging were included. The median age was 57 years; 67 patients (93.1%) were men, and 41 (56,9%) had dilated cardiomyopathy. A receiver-operating characteristic analysis (AUC 0.703, 51.5% sensitivity, 94.9% specificity) was used to identify the optimal cutoff point (0.28%/mmHg) for the RVFWS/TAPSE threshold. Nineteen subjects (26.4%) had advanced RV-PA uncoupling. Event rates were estimated using the Kaplan-Meier method showing a strong association with an increased risk for the primary end point of death or RHF hospitalization (89.47% vs. 30.19%, p < 0.001). A similar observation applied to all-cause mortality (47.37% vs. 13.21%, p = 0.003) and RHF hospitalization (80.43% vs. 20%, p < 0.001). CONCLUSIONS: An advanced RV dysfunction assessed by RV-PA coupling may serve as a predictor of adverse outcomes in patients with implanted LVADs.

Nutritional Risk Assessment and Adverse Events in Patients Undergoing Left Ventricular Assist Device Implantation-A Retrospective Cohort Study Using Hospital Information System.

Clinical or subclinical malnutrition occurs in 30% to 70% of patients with advanced heart failure and increases the risk of postoperative adverse events. The main objective of this study was to assess the nutritional status of patients prior to left ventricular assist device (LVAD) implantation using different methods of malnutrition assessment and to evaluate the relationship between nutritional status and postoperative adverse events. A retrospective cohort study included 120 patients aged 26-74 years referred for LVAD surgery. Preoperative nutritional status (NRS-2002-Nutritional Risk Score 2002, NRI-Nutritional Risk Index, PNI-Prognostic Nutritional Index; TLC-total lymphocyte count) and postoperative adverse events were assessed. Moderate to severe malnutrition was found in 55.8%, 43.3%, 40.0%, and 20% of all patients, respectively, according to the PNI, NRI, TLC, and NRS-2002 scores. Patients with a TLC < 1200 cells/m3 had a higher risk of postoperative acute renal failure [hazard ratio (HR): 2.5; 95% confidence interval (95% CI): 1.01-6.3] and death during the observation period [HR = 2.1; 95% CI: 1.2-3.5]. Moderate to severe malnutrition was also associated with a significantly increased risk of in-hospital death [for the NRI score, HR = 4.9 (95% CI: 1.1-22.0); for the PNI score, HR = 5.0 (95% CI: 1.1-22.3)]. In conclusion, moderate to severe malnutrition prior to LVAD implantation has been identified as a risk factor for postoperative acute renal failure and mortality. Assessment of nutritional risk may improve patient selection and early initiation of nutritional support.

Outcomes in Patients With HeartMate3 Versus HeartWare Ventricular Assist Device Implanted as Destination Therapy.

BACKGROUND: Donor organ shortage caused a growing interest in mechanical circulatory support not only as a bridge to transplant but also as a destination therapy. Improved results and increased applicability and durability of left ventricular assist devices (LVADs) have established this treatment option as an alternative for patients with end-stage heart failure. METHODS: The aim of the study was to compare the early results, major complications, and the follow up of all patients undergoing HeartMate3 (HM3) LVAD and HeartWare Ventricular Assist Device (HVAD) system implantation in one of the most experienced Clinic in Poland between 2015 and 2020. RESULTS: There were 78 individuals (72 male, 92%; 6 female, 8%), with median age 57 years (range, 50-62 years). Until 2020 we implanted 47 (60%) HVADs and 31 (40%) HM3 LVADs. Patient characteristics were comparable between both groups apart from median left ventricle diameter (8.2 cm [range, 7.4-8.4 cm] in HM3 group vs 7.2 cm [range, 6.7-7.9 cm] in HVAD group; P < .01) The overall survival was 53.2% in the HVAD group and 77.4% in the HM3 group (P =.03). Mean survival time was higher in HM3 group (2.97 years [range, 2.43-3.5 years] vs 2.51 years [range, 1.94-3.08 years]; P < .05). Mean complication-free survival time was also higher in the HM3 group (2.16 years [range, 1.55-2.76] vs 1.61 [range, 1.16-2.06 years]; P < .05), with overall complication-free rate of 54.8% for HM3 vs 29.8% for HVAD (P = .27). Median hospitalization time was comparable (31 days [range, 25-39 days] in the HM3 group vs 32 days [range, 24-38 days] in the HVAD group; P = .49). CONCLUSIONS: Patients supported with the HM3 had significantly fewer major complications than HVAD. Moreover, the HVAD was associated with higher mortality.

How to Improve the Outcomes of LVAD Implantation?

BACKGROUND: Heart transplantation is the treatment of choice for selected patients with end-stage heart failure. Persistent donor organ shortage has resulted in a growing interest in mechanical circulatory support not only as a bridge to transplantation but also as a destination therapy. METHODS: The aim of the study was to analyze the indications, comorbidities, operative technique, complications, and follow-up of all patients undergoing left ventricular assist device implantation in one of the most experienced clinics in Poland between 2015 and 2020 and state the best timing of the procedure. RESULTS: This study included 78 individuals (72 males, 92%; 6 females, 8%) with a median age of 57 years (range, 50-62 years). The median body mass index was 27.12 (range, 25.2-29.5). The etiology of cardiomyopathy was ischemic (n = 31, 39%), dilated cardiomyopathy (n = 47, 60%), and others. Sixty-four patients presented with New York Heart Association class IV (82%). Leading heart rhythm was sinus (n = 31, 40%) and pacemaker rhythm (n = 47, 60%). Sixty-four patients had implantable cardioverter defibrillator implantation (82%). Preoperative echocardiography revealed a median left ventricle ejection fraction of 14.5% (range, 10%-15%) and LV dimension 7.55 cm (range, 6.9-8.275 cm). In 51 patients (65%), imaging confirmed pulmonary hypertension. The intensive care unit stay was 6 days (range, 4.25-11.75 days). Median time to extubation was 25 hours (range, 23.75-70 hours). The median time to discharge was 31.5 days (range, 25-31.85 days). In-hospital mortality was 12 patients (15%). Median follow-up time was 19.5 months (range, 11.25-31 months) months, with the longest follow-up of about 53 months. CONCLUSIONS: Appropriate selection of candidates and timing of left ventricular assist device implantation are critical for improved outcomes of destination therapy.

Osteomodulin attenuates smooth muscle cell osteogenic transition in vascular calcification.

RATIONALE: Vascular calcification is a prominent feature of late-stage diabetes, renal and cardiovascular disease (CVD), and has been linked to adverse events. Recent studies in patients reported that plasma levels of osteomodulin (OMD), a proteoglycan involved in bone mineralisation, associate with diabetes and CVD. We hypothesised that OMD could be implicated in these diseases via vascular calcification as a common underlying factor and aimed to investigate its role in this context. METHODS AND RESULTS: In patients with chronic kidney disease, plasma OMD levels correlated with markers of inflammation and bone turnover, with the protein present in calcified arterial media. Plasma OMD also associated with cardiac calcification and the protein was detected in calcified valve leaflets by immunohistochemistry. In patients with carotid atherosclerosis, circulating OMD was increased in association with plaque calcification as assessed by computed tomography. Transcriptomic and proteomic data showed that OMD was upregulated in atherosclerotic compared to control arteries, particularly in calcified plaques, where OMD expression correlated positively with markers of smooth muscle cells (SMCs), osteoblasts and glycoproteins. Immunostaining confirmed that OMD was abundantly present in calcified plaques, localised to extracellular matrix and regions rich in α-SMA+ cells. In vivo, OMD was enriched in SMCs around calcified nodules in aortic media of nephrectomised rats and in plaques from ApoE-/- mice on warfarin. In vitro experiments revealed that OMD mRNA was upregulated in SMCs stimulated with IFNγ, BMP2, TGFß1, phosphate and ß-glycerophosphate, and by administration of recombinant human OMD protein (rhOMD). Mechanistically, addition of rhOMD repressed the calcification process of SMCs treated with phosphate by maintaining their contractile phenotype along with enriched matrix organisation, thereby attenuating SMC osteoblastic transformation. Mechanistically, the role of OMD is exerted likely through its link with SMAD3 and TGFB1 signalling, and interplay with BMP2 in vascular tissues. CONCLUSION: We report a consistent association of both circulating and tissue OMD levels with cardiovascular calcification, highlighting the potential of OMD as a clinical biomarker. OMD was localised in medial and intimal α-SMA+ regions of calcified cardiovascular tissues, induced by pro-inflammatory and pro-osteogenic stimuli, while the presence of OMD in extracellular environment attenuated SMC calcification.

[Arterial embolisation for post-traumatic retroperitoneal bleeding]. / Embolizacja naczyn tetniczych jako metoda zaopatrzenia krwawien zaotrzewnowych u chorych niestabilnych hemodymicznie.

BACKGROUND: Road traffic accidents resulting in multiple organ trauma are among the leading causes of mortality among people under 45 years of age. Those with pelvic injury are at special risk, because of difficult haemostasis and massive bleeding of mixed origin. Various methods of treatment have been used, including laparotomy, direct clamping and ligation of affected vessels, retroperitoneal packing, and external/internal pelvic stabilisation. In selected cases, angioembolisation of various vessels can be used CASE REPORTS: A 24-year-old male patient was admitted after a road traffic accident, in which he suffered multiple injuries to the skull, abdomen and pelvis. An emergency laparotomy was performed, revealing ruptures of the spleen, mesentery, right ureter, and bladder, and a giant haematoma in the retroperitoneal space. The spleen was removed, and the traumatised organs temporarily repaired. The pelvis and femoral bones were stabilised externally. After surgery, the patient was transferred to the ITU; he was haemodynamically unstable due to coagulopathy and persistent bleeding from the superior gluteal artery. On the fourth day, angioembolisation of the latter was performed using three occluding coils that resulted in immediate control of the bleeding and haemodynamic stabilisation. DISCUSSION AND CONCLUSION: In selected cases of severe bleeding from a traumatic pelvic injury, angioembolisation can be used as a lifesaving technique, especially in patients with coagulopathy after ineffective surgical interventions.

Usefulness of ct scans and radiographs in the assessment of cervical spine injuries in polytrauma patients - own experience.

INTRODUCTION: This paper evaluates the usefulness of spiral CT and conventional radiographs in the assessment of cervical spine injuries in polytrauma patients. The data are used as a basis for determining a precise and quick method for the assessment of the severity of cervical spine injuries that is also possibly least inconvenient for the patient.This approach is important due to the high risk of cervical spine injuries in patients with severe polytrauma and head injuries, as appropriate diagnostic work-up will help avoid unnecessary examinations and shorten time to diagnosis. MATERIAL AND METHODS: The study population consisted of 46 polytrauma patients hospitalized at the Intensive Care Unit of the Regional Hospital in Olsztyn. The efficacy of the diagnosis of cervical spine injuries on the basis of conventional radiographs and spiral CT studies was compared. RESULTS: Conventional radiographs failed to cover the entire cervical spine in all patient, and the assessment of most radiographic images was either difficult or unclear. Spiral CT studies with reformations were able to provide complete image of injuries to bony structures in all patients. CONCLUSIONS: Spiral CT with reformations (MPR and VRT) should be the basic modality in the diagnosis of cervical spine fractures. An appropriate treatment method may be selected and mistakes in the interpretation of injuries may be avoided on the basis of CT studies. Its other advantages are the short time required to perform the scan and the possibility of supporting vital functions in polytrauma patients during the examination.

The comparison of the value of ct imaging and selected MRI sequences (including DWI) in the evaluation of axonal injuries.

BACKGROUND: Diffuse axonal injuries of the brain consist in the damage (overstretching or torsion) of white matter axons, as a result of the forces of energy waves, evoked in the moment of injury, together with its accelerating-retarding inertia effect. Patients with DAI are most frequently the casualties of high speed car accidents. Diffuse axonal injuries of the brain are one of the most common acute brain injuries, with lesions typically occurring in the periventricular white matter, corpus callosum, and on the borderline of the white and grey matter, subventricularly. The diagnosis of axonal injuries is difficult, as the majority of lesions found in DAI are of microscopic nature. MATERIAL/METHODS: The material included the evaluation of 8 patients with craniocerebral injuries, normal results of brain CT (or showing slight posttraumatic lesions), and in severe neurological clinical state (continuing coma), which was all suggestive of a diffuse axonal injury. The patients were subjected to brain MRI studies within an MRI trauma protocol including FLAIR and DWI sequences, as well as sagittal T2-weighed images, which shortened the diagnostic examination time and was sufficient for the visualisation of DAI-specific lesions. RESULTS: On MRI examination, seven patients were diagnosed with diffuse foci of high signal intensity, located in corpus callosum, basal ganglia, thalamus and brain stem, although the CT examination results were normal or revealing minor changes. The foci were most prominent in DWI images. DWI sequence showed a diffuse cytotoxic oedema of white matter in one case, in which the CT results were normal. CONCLUSIONS: The MRI examination with DWI should become a basic diagnostic tool in DAI. Due to patients' severe condition, the diagnostic process should be shortened. This could be done with the use of some selected sequences and projections of brain MRI, including transverse DWI and FLAIR, as well as T2-weighed images in sagittal plane, which reduces the time of the examination by approx. 12-15 minutes. Correct and quick diagnosis of a diffuse axonal injury is of major therapeutic and prognostic importance.

Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells.

Development of clinical stem cell interventions are hampered by immature cell progeny under current protocols. Human mesenchymal stem cells (hMSCs) are characterized by their ability to self-renew and differentiate into multiple lineages. Generating hMSCs from pluripotent stem cells (iPSCs) is an attractive avenue for cost-efficient and scalable production of cellular material. In this study we generate mature osteoblasts from iPSCs using a stable expandable MSC intermediate, refining established protocols. We investigated the timeframe and phenotype of cells under osteogenic conditions as well as the effect of menaquinone-7 (MK-7) on differentiation. From day 2 we noted a significant increase in RUNX2 expression under osteogenic conditions with MK-7, as well as decreases in ROS species production, increased cellular migration and changes to dynamics of collagen deposition when compared to differentiated cells that were not treated with MK-7. At day 21 OsteoMK-7 increased alkaline phosphatase activity and collagen deposition, as well as downregulated RUNX2 expression, suggesting to a mature cellular phenotype. Throughout we note no changes to expression of osteocalcin suggesting a non-canonical function of MK-7 in osteoblast differentiation. Together our data provide further mechanistic insight between basic and clinical studies on extrahepatic activity of MK-7. Our findings show that MK-7 promotes osteoblast maturation thereby increasing osteogenic differentiation.

The Bone-Vasculature Axis: Calcium Supplementation and the Role of Vitamin K.

Calcium supplements are broadly prescribed to treat osteoporosis either as monotherapy or together with vitamin D to enhance calcium absorption. It is still unclear whether calcium supplementation significantly contributes to the reduction of bone fragility and fracture risk. Data suggest that supplementing post-menopausal women with high doses of calcium has a detrimental impact on cardiovascular morbidity and mortality. Chronic kidney disease (CKD) patients are prone to vascular calcification in part due to impaired phosphate excretion. Calcium-based phosphate binders further increase risk of vascular calcification progression. In both bone and vascular tissue, vitamin K-dependent processes play an important role in calcium homeostasis and it is tempting to speculate that vitamin K supplementation might protect from the potentially untoward effects of calcium supplementation. This review provides an update on current literature on calcium supplementation among post-menopausal women and CKD patients and discusses underlying molecular mechanisms of vascular calcification. We propose therapeutic strategies with vitamin K2 treatment to prevent or hold progression of vascular calcification as a consequence of excessive calcium intake.

Absence of perioperative excessive bleeding in on-pump coronary artery bypass grafting cases performed by residents.

OBJECTIVES: On-pump coronary artery bypass grafting (CABG) is associated with elevated bleeding risk. Our aim was to evaluate the role of surgical experience in postoperative blood loss. METHODS: A propensity score-matched analysis was employed to compare on-pump CABG patients operated on by residents and specialists. End points included drainage volume and bleeding severity, as assessed by the Universal Definition of Perioperative Bleeding in cardiac surgery and E-CABG scale. RESULTS: A total of 212 matched pairs (c-statistics 0.693) were selected from patients operated on by residents (n = 294) and specialists (n = 4394) between October 2012 and May 2018. Patients did not differ in bleeding risk. There were no statistically significant differences in postoperative 6-, 12- and 24-h drainages between subjects operated on by residents and specialists, and there was no between-group difference in rethoracotomy or transfusion rate. There were no differences in Universal Definition of Perioperative Bleeding or E-CABG grades. In June 2018, after a median follow-up of 2.8 years (range 0.1-5.7 years), the overall survival was 94%, with no differences between the patients operated on by residents (95%) and specialists (92%) (P = 0.27). CONCLUSIONS: Patients undergoing on-pump CABG, when operated on by a resident, are not exposed to an elevated bleeding risk, as compared with patients operated on by experienced surgeons.