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Abstract: Detection of the very first step of polyelectrolyte adsorption onto a solid support is of great importance for understanding mechanisms of solid surface modification. It was shown that streaming potential and contact angle measurements can be successfully used for polyelectrolyte (PE) adsorption characterization in a broad range of surface coverage. Cationic polyallylamine hydrochloride (PAH) was used for the formation of the layer. The electrokinetic characteristics of the substrate covered by the PAH layer were compared with contact angles measured under wet (captive air bubble/substrate in water) and dry (sessile water droplet/dried substrate) conditions. It has been demonstrated that contact angle values determined under both conditions are in good agreement. The observed rapid increase in the contact angle from zero for the bare mica surface to the value close to one characteristic of the PAH monolayer appears in the same PAH coverage range as zeta potential value changes due to adsorption. These results show that wettability can be as sensitive to the presence of small amounts of adsorbed species as electrokinetic measurements. [Copyright &y& Elsevier]

Abstract: Multilayer adsorption of polyelectrolytes on mica and electrochemically oxidized titanium was studied by the streaming potential method using a parallel-plate channel arrangement. Streaming potential data were complemented by wetting angle measurements. Two types of polyelectrolytes (PE) were used: polyallylamine hydrochloride (PAH), of a cationic type, and polysodium 4-styrenesulfonate (PSS) of an anionic type (both having molecular weight of ∼70,000). Layer by layer adsorption of polyelectrolytes from NaCl and TRIS solutions of various concentrations was studied in situ. It was demonstrated that after completing a bilayer, periodic variations in the apparent zeta potential between positive and negative values appeared for multilayers terminated by PAH and PSS, respectively. This was in accordance with zeta potential of the polymers in the bulk measured by electrophoresis. It also was observed that streaming potential data correlated well with the wetting angle characteristics of dried polyelectrolyte films. Variations in the contact angle between 70° for PAH and 40° for PSS were exactly in phase with the variation in the zeta potential. The stability of polyelectrolyte films against prolong washing (reaching 24h) was determined using the streaming potential method. It was revealed that both for mica and titanium, the PSS layer was considerably more resistant to washing, compared to the PAH layer. The experimental data obtained were consistent with a model postulating particle-like adsorption of polyelectrolytes. [Copyright &y& Elsevier]

Abstract: Adsorption of a cationic polyelectrolyte, polyallylamine hydrochloride (PAH), having a molecular weight of 70,000 on mica was characterized by the streaming potential method and by deposition of negative polystyrene latex particles. Formation of PAH layers was followed by determining the apparent zeta potential of surface ζ as function of bulk PAH concentration. The zeta potential was calculated from the streaming potential measured in the parallel-plate channel formed by two mica plates precovered by the polyelectrolyte. The experimental data were expressed as the dependence of the reduced zeta potential on the PAH coverage , calculated using the convective diffusion theory. It was found that for the ionic strength of 10−2 M, the dependence of on can be reflected by the theoretical model formulated previously for surfaces covered by colloid particles. The electrokinetic measurements were complemented by particle deposition experiments on PAH-covered mica surfaces. A direct correlation between the polymer coverage and the initial deposition rate of particles, as well as the jamming coverage, was found. For the initial deposition rate attained the value predicted from the convective diffusion theory for homogeneous surfaces. The initial deposition rates for surfaces modified by PAH were compared with previous experimental and theoretical results obtained for heterogeneous surfaces formed by preadsorption of colloid particles. It was revealed that negative latex deposition occurred at surfaces exhibiting negative apparent zeta potential, which explained the anomalous deposition of particles observed in previous works. It was suggested that the combined electrokinetic and particle deposition methods can be used for detecting adsorbed polyelectrolytes at surfaces for coverage range of a percent. This enables one to measure bulk polyelectrolyte concentrations at the level of 0.05 ppm. [Copyright &y& Elsevier]

Monocyte-T-cell interactions were studied in pokeweed mitogen (PWM)-activated cell cultures. We addressed the question of monocyte changes in PWM-stimulated cultures of T cells and monocytes and found, by flow cytometric analysis, that PWM activation led to a loss of cells with monocyte or macrophage phenotype (CD14, HLA-DR, HLA-DQ) within 48 hr of culture in the presence of T cells (CD4+ T cells), but not in cultures of pure monocytes. Chemiluminescence measurements revealed that phagocytic stimulation of monocytic superoxide release was impaired in PWM-stimulated cultures of monocytes plus T cells, but not in PWM-stimulated cultures of pure monocytes. Furthermore, PWM induced the secretion of interferon-gamma (IFN-γ) in primary cultures oft cells supplemented with 20% of monocytes, whereas in subsequent secondary cultures of these cells PWM induced IFN-γ only when monocytes were added. We conclude from these flow cytometric and functional analyses that monocytes are efficiently eliminated from PWM-activated T-cell/monocyte cultures by CD4+ T lymphocytes. [ABSTRACT FROM AUTHOR]

In the T suppressor circuit which affects contact sensitivity, the T acceptor cell trace) armed with T suppressor factor (TsF) and then triggered by antigen and major histocompatibility complex products (I-J) releases non-specific inhibitor (nsINH). These non-specific inhibitor(s) affect both the efferent and afferent stage of the contact sensitivity reaction and were originally detected by the inhibition of the passive transfer of contact sensitivity. The nsINH also blocks the induction of contact sensitivity when given intravenously at the time of immunization but has no effect when given at the time of challenge. Similarly, it blocks proliferation in the regional lymph nodes induced by contact sensitizer in a dose-dependent fashion; it acts when given at the time of immunization but not 1 day later. This effect is antigen non-specific and H-2 unrestricted. The nsINH bears I-J determinants as shown by affinity chromatography on monoclonal antibody. The nsINH comes from the Tacc and is not a breakdown product of the TsF. This is shown by the fact that, when the Tacc and TsF have I-J of different genotypes, the genotype of the nsINH corresponds to that of the Tacc. Parallel measurements of inhibition of lymphoproliferation and of passive transfer show that the nsINH has a molecular weight of 50-60 Kd and a pi around 6.8 and suggest that similar or identical molecules block both the afferent and efferent stage of the contact sensitivity reaction. [ABSTRACT FROM AUTHOR]

The water soluble, chemically reactive thioglycollic acid thioether derivatives of oxazolone and picryl chloride were synthesized and tested for their ability to prevent the development of contact sensitivity. Mice given two injections of these agents showed partial or complete unresponsiveness when subsequently sensitized and challenged with oxazolone and picryl chloride, respectively. This unrespon siveness was associated with T suppressor cells, Ts-eff(cs), which blocked the efferent stage of the con- tact sensitivity reaction, i.e. the passive transfer of contact sensitivity. These Ts-eff (a) were entirely specific when tested with the corresponding antigen. However, the suppression which they caused had a non-specific final common pathway. Cells from mice injected with the oxazolone and picryl thioethers and painted with the corresponding contact sensitizer produced a suppressor factor in vitro. This factor specifically blocked passive transfer by immune cells incubated in it. It also armed macrophages which then caused suppression. These macrophages were most effective when injected intraperitoneally. The suppressor factor had a molecular weight between 30,000 and 100,000 and the α-oxazolone factor was absorbed by oxazolone-albumin Seph arose and could be eluted with oxazolone-∊-aminocaproic acid. It was also absorbed by concanavalin-A-sepharose and could be eluted with α-methylmannoside. It is proposed that the ability of water soluble, chemically reactive haptenes to evoke a Ts-eff(cs) population may be relevent to the rarity of severe drug reactions following the injection of chemically reactive drugs. [ABSTRACT FROM AUTHOR]

Anti-picrylsuppressor factor was prepared in the standard way, i.e. by culturing lymphoid cells from mice injected with picrysulphonic acid and then painted with picryl chloride and taking the supernatant fluid. It was assessed by its ability to depress the passive transfer of contact sensitivity by immune cells incubated in it. The factor can be specifically absorbed by picryl (but not oxazolone) albumin sepharose beads and can be specifically eluted by picryl (but not oxazolone) ϵ-aminocaproic acid and by picryl-ϵ-N-lysine. These findings emphasise the role of the hapten epitope in the binding of a specific T cell product. The factor can also be absorbed by Concanavalin A sepharose and can be eluted by an appropriate sugar such as ɑ-methylmannoside, but not by an inappropriate sugar such as lactose. It was possible to undertake two sequential affinity chromatography steps—first absorption with picryl albumin sepharose and elution with picryl-ϵ-N-lysine followed immediately by absorption by Con A sepharose and elution with α-methylmannoside. The availability of sequential affinity chromatography provides a simple approach to the purification of specific T suppressor factor. [ABSTRACT FROM AUTHOR]

Human erythrocytes O,Rh+(D) coated with hyperimmune human anti-serum formed rosettes primarily with monocytes in peripheral blood mononuclear cell suspensions. The rosetting cells (EAhu-FRC). separated on a Lymphoprep gradient were found in the pellet and were up to 95% pure monocytes as judged by cytochemical criteria. A two step procedure involving depletion of T lymphocytes followed by the isolation of EAhu-RFC yielded monocytes up to 98% pure. The isolated cells did not respond to mitogens in vitro, but they act as accessory cells in mitogen-induced T lymphocyte proliferation. This simple method may be useful in studying monocyte function in human disease as it does not require a large amount of blood. [ABSTRACT FROM AUTHOR]

Human peripheral blood mononuclear cells freed from polymorphs reduce nitroblue tetrazolium (NBT). This reduction is due to monocytes, i.e. adherent, phagocytic, esterase-positive cells with Fc receptors. Monocytes allowed lo phagocytose zymosan show increased NBT reduction which under optimal conditions is 12.2 ± 24 × 10-9 mol·hr-1-10-6 monocytes. Monocytes which have phagocylosed zymosan depress the mitogen response of human lymphocytes to PHA. This effect of 'activated' monocytes is due to a soluble inhibitory mediator which appears in the supernatant after culture for 24 hr. Its appearance requires protein synthesis. It is suggested that NBT reduction of peripheral blood mononuclear cells can be used as a test for the state of monocyte activation in disease. The possibility that activated monocytes may depress blast transformation in vitro in disease states is discussed. [ABSTRACT FROM AUTHOR]

Contact sensitivity was produced in mice by painting the skin with picryl chloride and was assessed by the increase in ear thickness following local challenge. Contact, sensitivity was passively transferred by immune lymph node and spleen cells taken at 4 days. The mice were then challenged immediately and the reactions read at 24 and 48 hr. Immune lymph node and spleen cells taken at day 8 virtually fail to transfer. Experiment showed that they contain cells which suppress passive transfer. These are demonstrated by mixing approximately equal numbers of 4-day cells, which transfer contact sensitivity, and cells taken at later times and injecting them intravenously into recipients. These suppressor cells' can be demonstrated by day 6 and are still present at day 11 after immunization. The precursors of the suppressor cells are sensitive to cyclophosphamide. Irradiation of immune mice 2 days before taking cells also selectively inactivates the suppressor cells. When mice are pretreated with cyclophosphamide before immunization or irradiated 2 days before transfer, the lymph node and spleen cells taken on day 9 after immunization transfer contact sensitivity. In contrast the same number of cells from untreated mice were inactive. This suggests that the cells which mediate passive transfer or their precursors may occur in an inhibited form in lymph nodes and spleen at later times after immunization. These suppressor cells in immune mice differ from the T suppressor cells produced by the injection of picryl sulphonic acid-an agent which causes unresponsiveness: (1) the precursors of the T suppressor cells resist cyclophosphamide; (2) the T suppressor cells are found in mice treated so as to produce unresponsiveness while the other type of suppressor cells occurs in mice immunized for contact sensitivity. However, both types of suppressor cells are selectively inactivated by irradiation as compared with the cells which mediate contact sensitivity and both are able to act on the effector stage of contact sensitivity. [ABSTRACT FROM AUTHOR]

It has been shown that CBA mouse lymphocytes cultured in the presence of allogeneic fibroblasts or syngeneic polyoma virus-induced tumour cells became specifically immunized. These immunized lymphocytes, however, are by themselves non-cytotoxic and only cause target cell killing when mixed with normal macrophages. The reaction is immunologically specific and seems to depend on the antigenic differences between lymphocytes and target cells. The mechanism of the interaction between the immunized lymphocytes and the normal macrophages in the cytotoxic killing of target cells is discussed. [ABSTRACT FROM AUTHOR]

Analyzes the induction phase of contact sensitivity by footpad transfer of regional lymph node cells. Role of T cells in the injected population; Activity of cells from T-deprived mice; Stages in the inductive phase of the cell-mediated immune response.

The regulation of the immune responses by antibody administered passively on peritoneal exudate cells (PEG) was studied in guinea-pigs. The immunogenicity of sheep red blood cells (SRBC) associated with PEC for the induction of delayed hypersensitivity (DH) to soluble erythrocyte antigen was enhanced when PEG were incubated with anti-SRBG antibody. In contrast, the antibody response to SRBC was depressed. This phenomenon was only observed with specific antibody and was partially blocked when PEG covered with anti- SRBC antibody were incubated with rabbit anti-guinea-pig globulin serum. Comparable amounts of anti-SRBC antibody injected separately had no enhancing effect. Anti-SRBC sera from which the cytophilic antibody activity had been removed were inactive. PEG-associated SRBC were usually more immunogenic than the same amount of `free' SRBC for the induction of delayed hypersensitivity and always more immunogenic for antibody production. These observations suggested that macrophage cytophilic antibody might be involved in the regulation of the immune response and play a role in the preferential induction of delayed hypersensitivity in the studied system. [ABSTRACT FROM AUTHOR]

Lymph node and spleen cells from normal mice were cultured for 3 days with polyoma virus-induced tumour, Ehrlich's ascites turnout or leukaemia L 1210 cells. This resulted in in vitro immunization of the lymphocytes, which were then transferred to irradiated target cells labelled with 51Cr. Normal, i.e. non-immune thioglycollate-stimulated peritoneal macrophages were also added to some tubes. Non-immune macrophages mixed with immunized lymphocytes showed a significantly increased ability to destroy tumour ceils as compared with macrophages in the absence of immunized lymphocytes. The immunized lymphocytes were almost entirely inactive alone. When the number of macrophages was kept constant the cytotoxicity was dependent on the number of viable immunized lymphocytes placed on the target cells. Immunized lymphocytes, in the presence of macrophages, only exhibited strong killing of the target cells against which they had been immunized; some lysis of ‘bystander’ cells was, however, seen provided specific target cells were present. Macrophage monolayers exposed to immunized lymphocytes upon contact with specific antigen became ‘armed’ and showed a significant cytotoxicity for specific target cells. When immunized lymphocytes and normal macrophages were treated with actinomycin D and puromycin, cytotoxicity was inhibited in the immunized lymphocytes but not in the macrophages. The possible mechanism of normal macrophage cooperation with immunized lymphocytes in the cytotoxic killing reaction is discussed. Results presented in this paper favour the view that immunologically specific cytophilic factor (presumptive cytophilic antibody) is involved in the macrophage-mediated cytotoxicity in the system studied. [ABSTRACT FROM AUTHOR]

Mice were rendered specifically unresponsive to picryl chloride by pretreatment with picryl sulphonic acid. These mice fail to develop contact sensitivity, as judged by increment of car thickness, when, subsequently sensitized on the abdomen and challenged 6 days later with picryl chloride on the car. These mice were not in a pure state of classical immune tolerance. This was shown in two ways. (1) Cells from unresponsive donors were injected intravenously into normal CBA mice. The mice were then sensitized on the same day and challenged 6 days later. 'Unresponsive' (but not a variety of control) lymph node cells impaired the development of contact sensitivity to picryl chloride. The impairment was immunologically specific and 'unresponsive' cells did not impair the development of contact sensitivity to 'oxazolone'. (2) Unresponsive mice were irradiated and restored with 'unresponsive' bone marrow cells. They regained immune competence to picryl chloride when injected with normal lymph node cells and sensitized on the same day, and failed to regain competence when injected with unresponsive lymph node cells. The distinctive finding was that the injection of a mixture of normal and unresponsive lymph node cells failed to restore immune competence. Similar results were obtained when irradiated but otherwise normal recipients were used. Unresponsive cells also impaired the passive (adoptive) transfer of contact sensitivity. These results show that lymph node cells from mice which are unresponsive to picryl chloride actively and specifically impair the induction or manifestation of contact sensitivity to picryl chloride. It was concluded that this form of unresponsiveness is not classical tolerance and the hypothesis is put forward that the unresponsiveness is due at least in part to antibody mediated depression of contact sensitivity. [ABSTRACT FROM AUTHOR]

Macrophages can be obtained about 99 per cent pure and in a yield of about 50 per cent by ficoll (polysucrose) density gradient centrifugation of mouse peritoneal exudate cells. The macrophages appear in the lighter fractions. The lymphocytes appear in the denser fractions and can be further purified on a polystyrene bead, rayon wool column. The method also separates guinea-pig and rat peritoneal exudate cells. Peritoneal exudate macrophages take up colloidal radioactive gold in vivo. However, macrophages differ in the ability to take up colloidal gold and the macrophages which phagocytose the most gold appear in the lightest fraction after density gradient centrifugation. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the immunohistological components of chronic inflammation in endarterectomy lesions. Therefore, in 24 patients endarterectomy specimens were obtained from coronary arteries during CABG surgery (16 from RCA and 8 from LCA) and immunohistologically analyzed using avidin-biotin method (LSAB®/AP) with monoclonal antibodies. Macrophages and CD3 lymphocytes were counted under 200× magnification but MHC class II and ICAM-1 adhesion molecules were analyzed semi-quantitatively (scale from 0 to 3+). The mean macrophages density was 47.8±9.8 cells per mm2 and mean CD3 lymphocyte density was 1.3±0.6 cells per mm2. Lack or weak expression of HLA-DR (0–1+) on macrophages was found in 17 of 24 cases (70.8%). In the remaining seven cases (29.2%) there was a moderate and strong expression (2+ and 3+) of HLA-DR antigens. Similarly, no or weak ICAM-1 expression on macrophages was detected in 19 cases (79.2%). These cells were positively stained for ICAM-1 in only five cases (20.8%). Our data suggest that in advanced primary atherosclerotic lesions chronic inflammation is still present. On the other hand, the small number of activated inflammatory cells and the absence of positively stained endothelium suggests that inflammatory process tends to be burnt-out. [Copyright &y& Elsevier]

The cesium salts Cs xH3− xPW12O40 of Cs content x = 2 up to x = 3 were tested as the catalysts in the gas and liquid phase reactions. Dehydration of ethanol and transesterification of triglycerides with methanol were selected as the catalytic reactions. Apart from the standard preparation, the catalysts were prepared by two-stage procedure with methanol or water as a solvent. The Cs-salts were characterized by FT-IR, XRD, scanning electron microscopy and energy dispersive X-ray techniques. In turn, the influence of Cs-salts composition on the pH and conductivity of their aqueous colloidal solutions was investigated. The results obtained by the latter techniques were also characteristic for acidity of surface layer of colloidal particles because of surface layer-solution equilibrium. It has been shown that the secondary structure of acidic cesium salts existing in crystalline samples (solid solution of H3PW12O40 in Cs3PW12O40) changes after contacting with polar medium to the system consisting most probably of Cs3PW12O40 core with epitaxial layer of heteropolyacid. This is result of the protons migration from bulk to surface layer of primary particles enhanced by polar medium. It strongly influences the surface acidity of primary particles as well as the activity of Cs-salts in transesterification of triglycerides with methanol. In such polar medium, Cs2HPW12O40 salt becomes the most active catalyst, more active than Cs2.5H0.5PW12O40. An accumulation of partial glycerides and in particular glycerol on the surface of primary particles of Cs-salts resulted in relatively low maximum conversion of triglycerides, most probably due to partial blockage of the catalytic centers. This effect and the almost constant activity of Cs-salts under recycling use in the transesterification experiments are considered to be experimental evidences that methanolysis over Cs-salts was accomplished with the participation of surface protons. [ABSTRACT FROM AUTHOR]

Abstract: Most methods used in the risk assessment of heart transplant candidates do not include new biomarkers. Aims: The aim of the study was to examine the value of NTproBNP and hsCRP and their combined use together with HFSS score in the risk assessment of patients with heart failure enlisted for heart transplantation. Methods: Data of 658 patients enlisted for heart transplantation in all active transplantation centers were stored in a prospective registry. The composite end point-death or urgent transplantation was recorded during the follow-up. Results: Death or urgent transplantation was recorded in 161 (24%) of pts. 102 (15%) patients died and 59 (9%) were transplanted urgently. Kaplan-Meier curves for risk of death or urgent transplantation where highly significant when pts were stratified by the quartiles of NT proBNP (P < .000001) or quartiles according to the hsCRP level on admission (P < .002). In the multivariate Cox proportional hazard model, the significance was observed for NTproBNP (P < .01) and HFSS (P < .02), and borderline significance for hsCRP (P = .057). When ROC analyses of the area under the curve (AUC) values were considered, AUC area was for HFSS – 0.645, for NTproBNP – 0.653 and for hsCRP – 0.566. When all those variables were included together in the model, the AUC value rose to 0.6943. Based on those results a weighted risk model with all three parameters was proposed. Conclusion: HFSS, NTproBNP and hsCRP levels are independent stratification variables of survival or need for urgent heart transplantation. Their predictive value is moderately increased when they are analyzed together. [Copyright &y& Elsevier]

The immunogenicity of antigens associated with peritoneal exudate cells was compared with the immunogenicity of free antigens for the induction of delayed hypersensitivity. Oil induced peritoneal exudate cells were incubated with antigens labelled with radioactive iodine, washed and injected intraperitoneally into recipient guinea-pigs. Comparable amounts of free antigens were also injected. All sixteen inbred guinea-pigs given human or bovine gamma-globulin associated with peritoneal exudate cells gave positive reactions (greater than 5 mm) while the eighteen guinea-pigs given free antigens failed to show a reaction. Similar results were obtained with serum albumins in inbred guinea-pigs. The increased immunogenicity of antigens associated with peritoneal exudate cells was also seen in outbred guinea-pigs. Pretreatment with Freund's complete adjuvant did not depress the immunogenicity of antigens associated with peritoneal exudate cells and actually increased the induration of the 24-hour reaction to picrylated human scrum albumin and human serum albumin associated with peritoneal exudate cells. [ABSTRACT FROM AUTHOR]

Abstract: Oxidized low-density lipoproteins (ox-LDL) have been shown to be strongly atherogenic and immunogenic in experimental animals and in humans. Autoantibodies against ox-LDL and its various epitopes have been detected in sera and in atherosclerotic lesions. LDL oxidation may also lead to generation of oxidized derivatives of cholesterol (eg, 7-ketocholesterol [7-ketoCh]), which are characterized by high levels of cytotoxicity, muta- and carcinogenicity, as well as immunosuppressive effects and probable immunogenic properties. The aim of this study was to quantify autoantibodies to 7-ketoCh in sera from patients after orthotopic heart transplantation (OHT). IgG antibodies were measured in sera from 81 patients after OHT and 73 healthy volunteers using and enzyme-linked immunosorbent assay (ELISA) method. For the antigen we used 7-ketoCh hemisuccinate conjugated to bovine serum albumin. Anti-7-ketoCh antibodies were detected in all examined sera. Their concentrations were significantly higher among OHT patients than the control group, namely, 109.0 ± 109.7 vs 53.5 ± 20.0 U/mL (P < .005). Also, we observed a direct relationship between antibody concentration and time after OHT. Our results showed that the low molecular product of LDL oxidation, 7-ketoCh, was immunogenic possibly playing a role in the progression of atherosclerosis among OHT patients. [Copyright &y& Elsevier]

The anti-inflammatory effects of pentoxfylline are associated with a number of clinical benefits. These include reduction in mortality in patients who have undergone bone marrow transplants or suffer peritonitis. In infants with sepsis, a reduction in mortality has also been associated with pentoxyfylline administration. The anti-inflammatory effects of pentoxyfylline, as well as its bronchodilator, diuretic and respiratory muscle stimulant effects suggest it may have a useful role in BPD. Interim analysis of a prophylactic trial suggests pentoxyfylline may reduce treatment requirements after the neonatal period and that, in established BPD, pentoxyfylline and dexamethasone may be of similar efficacy. [ABSTRACT FROM AUTHOR]

Abstract Background The diagnosis of acute cellular rejection (ACR) is a major objective in the management of heart transplant recipients. The aim of this study was to assess the utility of speckle-tracking derived parameters in identifying patients at risk of graft rejection. Methods A prospective, single-center study was carried out involving 45 consecutive heart transplant patients who underwent a total of 220 routine endomyocardial biopsies (EMBs) with correlative echocardiographic examination. Results No significant ACR (grade 0-1R) was seen in 190 biopsies (81.2% of the ACR-free group), and moderate ACR requiring specific treatment (grade 2R) was detected in 30 biopsies (13.6% of the ACR group). Grade 3R was not observed. All longitudinal left ventricular (LV) and right ventricular (RV) strain parameters were greater in the ACR-free group than in patients with ACR, while no differences were observed between radial and circumferential strain parameters. In our analysis, we selected RV free wall longitudinal strain (RV FW) ≤ 16.8% and 4-chamber longitudinal strain (4CH LS) ≤ 13.8%, which related to the presence of ACR requiring treatment. We assigned 1 point for each parameter (minimum 0, maximum 2 points) and derived a new echocardiographic index, the Strain Rejection Score (SRS). Our proposed approach—a combination of the 2 abovementioned indices—for screening patients at risk of ACR ≥ 2R, when expressed by a score 2 points, showed good specificity, strong negative predictive value, and the highest area under the curve. Conclusions Our study demonstrated that combination of 4CH LS and RV FW as a new echocardiographic index, the Strain Rejection Score, can be useful as a noninvasive assessment of ACR during the first year of follow-up after heart transplant. Highlights • Noninvasive detection of rejection is a major objective in the management of heart transplant recipients. • We evaluated a new echocardiographic index, Strain Rejection Score (SRS), in the assessment of cardiac allograft rejection. • The new index includes RV free wall longitudinal strain and 4-chamber longitudinal strain analysis. • According to our results, SRS is sufficient for use as an auxiliary diagnostic tool for identifying most patients with a high degree of ACR suspicion. [ABSTRACT FROM AUTHOR]

Abstract Background Left ventricular assist devices (LVADs) are used for treatment of end-stage heart failure. Outcomes are dependent on right ventricle (RV) function. Prediction of RV function after LVAD implantation is crucial for device selection and patient outcome. The aim of our study was to compare early LVAD course in patients with optimal and borderline echocardiographic parameters of RV function. Material and methods We retrospectively reviewed 24 male patients with LVAD implantation. The following echocardiographic data of RV function were collected: FAC (fractional area change) with optimal value > 20%, tricuspid annulus plane systolic excursion >15 mm, RV diameter < 50mm, and right-to-left ventricle ratio < 0.57 (RV/LV). Patients were divided into group 1 (12 patients) with transthoracic echocardiography parameters in optimal ranges and group 2 (12 patients) with suboptimal transthoracic echocardiography findings. Study endpoints were mortality, discharge from the intensive care unit, and RV dysfunction. Demographics, postoperative clinical outcomes, comorbidities, complications, and results in a 30-day period were analyzed between groups. Results Echocardiography parameters differed significantly between groups 1 and 2 according to FAC (31.8% vs 24.08%; P =.005), RV4 (45.08 mm vs 51.69 mm; P =.02), and RV/LV ratio (0.6 vs 0.7; P =.009). Patients did not differ according to course of disease, comorbidities before implantation, or complications. One patient from each group died. Patients in group 2 experienced more pulmonary hypertension, required increased doses of catecholamines, and stayed in the intensive care unit longer. No RV dysfunction was noted. Conclusions Borderline FAC, tricuspid annulus plane systolic excursion, and RV4 add RV/LV ratio prolonged recovery after LVAD implantation even with no RV failure. Parameters chosen for qualification are in safe ranges. Highlights • Prediction of RV function for LVAD implantation is crucial for patient outcome. • We showed comparable outcome between groups of optimal and borderline RV function. • Our results with the continuous flow LVAD are encouraging; there was no RV dysfunction. [ABSTRACT FROM AUTHOR]

Abstract Background Model for End-Stage Liver Disease (MELD) score predicts multisystem dysfunction and death in patients with heart failure (HF). Left ventricular assist devices (LVADs) have been used for the treatment of end-stage HF. Aim of the study We evaluated the prognostic values of MELD, MELD-XI, and MELD-Na scores in patients with POLVAD MEV LVAD. Materials and methods We retrospectively analyzed data of 25 consecutive pulsatile flow POLVAD MEV LVAD patients (22 men and 3 women) divided in 2 groups: Group S (survivors), 20 patients (18 men and 2 women), and Group NS (nonsurvivors), 5 patients (4 men and 1 woman). Patients were qualified in INTERMACS class 1 (7 patients) and class 2 (18 patients). Clinical data and laboratory parameters for MELD, MELD-XI, and MELD-Na score calculation were obtained on postoperative days 1, 2, and 3. Study endpoints were mortality or 30 days survival. MELD scores and complications were compared between Groups S and NS. Results 20 patients survived, and 5 (4 men and 1 woman) died during observation. Demographics did not differ. MELD scores were insignificantly higher in patients who died (Group 2). Values were as follows: 1. MELD preoperatively (21.71 vs 15.28, P =.225) in day 1 (22.03 vs 17.14, P =.126), day 2 (20.52 vs 17.03, P =.296); 2. MELD-XI preoperatively (19.28 vs 16.39, P =.48), day 1 (21.55 vs 18.14, P =.2662), day 2 (20.45 vs 17.2, P =.461); and 3. MELD-Na preoperatively (20.78 vs 18.7, P =.46), day 1 23.68 vs 18.12, P =.083), day 2 (22.00 vs 19.19, P =.295) consecutively. Conclusions The MELD scores do not identify patients with pulsatile LVAD at high risk for mortality in our series. Further investigation is needed. Highlights • Mechanical circulatory system POLVAD MEV is used for treatment of heart failure. • MELD scores have predictive value for heart failure patients. • Assessment of predictive value of the MELD score after POLVAD MEV. • MELD scores do not predict morbidity or mortality in patients with POLVAD MEV. [ABSTRACT FROM AUTHOR]

Abstract Background Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration is elevated in patients with pulmonary hypertension (PH); however, its role in the detection of PH associated with lung disease is not well established. Aim The aim of this study was to assess the value of NT-proBNP in the detection of PH in patients with end-stage lung disease (esLD) referred for lung transplantation. Materials and methods The study population consisted of 65 patients: 37 with idiopathic pulmonary fibrosis (IPF), 20 with chronic obstructive pulmonary disease, and 8 patients with other interstitial lung diseases (75% men, mean age 53.3 ± 9.5 years). Serum concentration of NT-proBNP was assessed with an immunoradiometric assay kit. The mean pulmonary artery pressure (mPAP) was measured using a Swan-Ganz catheter. PH was defined as mPAP ≥ 25 mm Hg. Results Median NT-proBNP concentrations were significantly higher in patients with PH than in patients without PH: 139 (49–1236) pg/mL vs 67 (38–116) pg/mL, respectively; P =.016. Receiver operating characteristic (ROC) analysis revealed that NT-proBNP concentration higher than 131.5 pg/mL was a predictor of PH with good specificity (81%) and positive predictive value (78.9%) but low sensitivity (55.6%) and negative predictive value (58.6%). The area under the ROC curve of serum NT-proBNP concentration for PH was 0.71 (95% confidence interval 0.57–0.85, P =.039). Conclusion Serum concentration of NT-proBNP may be useful in the diagnosis of PH in patients with esLD referred for lung transplantation. Highlights • The usefulness of NT-proBNP in the diagnosis of hypoxic pulmonary hypertension was assessed. • Elevated serum concentration of NT-proBNP in patients with end-stage lung diseases referred for lung transplantation may reflect early changes in pulmonary circulation as well as right ventricle dysfunction. • NT-proBNP is useful as a non-invasive predictor for pulmonary hypertension in patients with end-stage lung diseases, that is, candidates for lung transplantation. [ABSTRACT FROM AUTHOR]

Abstract Background Red blood cell markers (RBCM) have been found to be predictors of mortality in various populations. However, there is no information regarding the association between the values of RBCM and long-term outcomes after orthotopic heart transplantation (OHT). The aim of this study was to assess whether the values of inflammatory markers and RBCM obtained directly before OHT are associated with mortality in patients diagnosed as having end-stage heart failure undergoing OHT. Methods We retrospectively analyzed data of 173 nonanemic adult patients diagnosed as having end-stage heart failure undergoing primary OHT between 2007 and 2014. Clinical and laboratory data were obtained at the time of admission for the OHT. RBCM were analyzed using an automated blood counter (Sysmex XS-1000i and XE-2100, Sysmex Corporation, Kobe, Japan). Results Mean age of the patients was 54 (41–59) and 72% of them were male. During the observation period, the mortality rate was 32%. Multivariable analysis of Cox proportional hazard confirmed that elevated pretransplantation red blood cell distribution width value (hazard ratio [HR], 1.38 [1.25–1.48], P <.001) was the sole independent predictor of death during long-term follow-up. Other red blood cell distribution width such as mean corpuscular volume, mean corpuscular hemoglobin concentration, and mean corpuscular hemoglobin (HR, 0.88 [0.84–0.91]; P <.001; HR, 0.75 [0.53–1.05]; P <.05; HR, 0.78 [0.64–0.96]; P <.05, respectively) had predictive value in univariable analysis. Conclusions In summary, we have demonstrated that elevated red blood cell distribution width immediately before OHT is an independent predictor of all-cause mortality in heart transplant recipients. Other factors associated with posttransplantation mortality include lower values of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Highlights • We identified the perioperative risk factors impacting the occurrence of death. • We have demonstrated that elevated RDW immediately before OHT is an independent predictor of all-cause mortality in heart transplant recipients. • Other factors associated with posttransplantation mortality include lower values of MCV, MCH, and MCHC—hematologic indices related to iron stores. [ABSTRACT FROM AUTHOR]

Abstract Background Pulmonary hypertension (PH) is a common complication in end-stage lung disease (esLD). The aim of this study was to establish the best threshold values for mean, systolic, and diastolic artery pressure (mPAP, dPAP, and sPAP, respectively) to identify patients with esLD referred for lung transplantation and to predict 1-year prognosis. Methods Sixty-five patients were enrolled in the study (75% men) with a mean age of 53.3 ± 9.5 years; 31% had chronic obstructive pulmonary disease (COPD), 57% had idiopathic pulmonary fibrosis (IPF), and 12% had interstitial lung diseases (ILDs). The mean period of observation was 14.4 ± 5 months. We assessed invasively mPAP, dPAP, and sPAP, as well as pulmonary capillary wedge pressure (PCWP), using a Swan-Ganz catheter. Receiver-operating characteristic (ROC) curves were constructed to identify the best cutoff points for mPAP, dPAP, and sPAP to predict survival. The study endpoint was defined as 1-year mortality before transplantation. Survival analysis was completed according to the Kaplan-Meier method. Results During follow-up, 30 (46.1%) patients died and 19 (29%) underwent lung transplantation. Based on ROC curve analysis, we estimated mPAP ≥30 mm Hg, dPAP ≥20 mm Hg, and sPAP ≥44 mm Hg as the best threshold values with the highest sensitivity (70%, 70%, and 73%, respectively) and specificity (76%, 69%, and 72%, respectively) and the acceptable area under curve (0.67, 0.68, and 0.72, respectively). The negative predictive values for mPAP, dPAP, and sPAP were higher than the positive predictive values (79%, 77%, and 81% vs 67%, 61%, and 64%, respectively). We also constructed Kaplan-Meier curves for mPAP, dPAP, and sPAP threshold values. There were significant differences in 1-year survival between patients with and without PH for mPAP, dPAP, and sPAP threshold values (P =.005, P =.035, and P <.001; respectively). Conclusion Elevated mPAP, dPAP, and sPAP are related to worse prognosis in patients with esLD referred for lung transplantation. Highlights • The best cutoff values of mean, diastolic, and systolic pulmonary artery pressure for predicting 1-year survival in patients with end-stage diseases referred for lung transplantation were assessed. • Mean, diastolic, and systolic pulmonary artery pressure are related to a worse prognosis in patients with end-stage lung diseases. • The right heart catheterization in patients with end-stage lung diseases, candidates for lung transplantation is an important part of the prognostic assessment in this group of patients. [ABSTRACT FROM AUTHOR]

Statistical properties of surfaces covered by particles deposited under the influence of gravity are investigated by means of optical microscopy and image analysis. The radial distribution function of the particle configurations is determined over a wide coverage range. Special attention is paid to the fluctuations of the number of particles on small surfaces which contain information upon the deposition process. A first analysis of these fluctuations is presented within a mean field approximation. All results are compared to the ballistic process which proves to be a good model. On the contrary, the observations are not compatible with a simple random sequential adsorption model. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess thyroid status before and during left ventricular assist device (LVAD) support and to estimate an impact of thyroid status at LVAD implantation on survival. We retrospectively analyzed thyroid function profile including thyroid- stimulating hormone (TSH), free triiodothyronine (fT 3), and free thyroxine (fT 4) in a group of all consecutive 147 patients (93.2%- male, BMI-26.7 ±5.6, mean and median INTERMACS profile- 3; 53% -ischemic etiology of heart failure) implanted with continuous-flow LVAD in our institution within years 2009-2021 (54%-HeartMate3; 40%- HeartWare; 6%- Heart Mate II). One year survival was 78.3%. Fifteen percent of patients received amiodarone, whereas 20.4%- supplementation of levothyroxine and 2% - thyreostatic treatment during LVAD support. Statistical methods used were: ROC curves, when Youden factor > 0.27- Chi 2 test, analysis of variance, Bonferroni test. Mean values of TSH, fT 3 and fT 4 were respectively 2.33 ± 1.69 uIU/ml; 2.14± 0.56 pg/ml; 1.25 ± 0.36 ng/dl before, 2.95 ± 3.18 uIU/ml; 2.47±1.35 pg/ml; 1.11 ±0.27 uIU/ml and 2.0 ±1.27 ng/dl; 2.43 ±0.42 pg/ml; 1.22 ± 0.25 ng/dl at 3 months and at 12 months post LVAD implantation. Mortality risk was 2.8 times lower for patients presenting TSH ≥ 1.29 uIU/ml (p= 0.01) and 3.8 times lower for patients presenting fT 3 ≥ 1.93 uIU/ml (p=0.003) at LVAD implantation. TSH significantly decreased between 3 and 12 months of LVAD support (Bonferroni test, p<0.009), whereas fT3 increased significantly after 3 and 12 months as compared to values before LVAD implantation (Bonferroni test, p < 0.039 and p<0.041 respectively). Thyroid function may have an impact on survival in patients with end-stage heart failure implanted with LVAD. Thyroid status surveillance and its corrections could improve the overall prognosis in this group of patients. Further studies are needed to confirm this thesis. [ABSTRACT FROM AUTHOR]

Background Left ventricular assist device (LVAD) support is increasingly used in patients with heart failure. The right ventricle (RV) plays a main role in LVAD support. Little is known about the effects of pulsatile Polvad MEV devices or continuouseconds flow pumps on RV function. We compared hemodynamic parameters of RV in patients after implantation of Polvad MEV (PM) and Heartware (HW) or Heartmate II (HMII) LVADs. Methods Forty-four patients were retrospectively reviewed after implantation of PM (group P; n = 24 [21 M, 3 F]) or HW or HMII (group C; n = 20 [20 M, 0 F]) LVADs from April 2007 to February 2014. Hemodynamic data—mean pulmonary pressure (mPAP), central venous pressure (CVP), cardiac output (CO), and cardiac index (CI)—were collected before surgery, after surgery, and every 2 hours in the intensive care unit, with the time points numbered from 1 to 120. Right ventricular work (RVW) was calculated according to the equation: RCW = CO × (mPAP − CVP) × 0.0144 (g·m). Results Baseline characteristic of the patients were similar. mPAP values were similar between groups. CVP values were higher in group P, significantly at time points 5 and 7–33. CO values were higher in group C, significantly from point 3 and almost all the time to point 43. CI reached significance at point 9, 12–14, 16–19, and 30–41. RCW was higher in group P before implantation. Post-implantation RCW values were higher in group C, significantly at time points 19, 20, 32–34, 51–53, and 55–57. Conclusions Continuous-flow pumps more effectively optimize RV function than pulsatile LVADs, which can result in more effective prevention of RV failure or insuffiency in that group. [ABSTRACT FROM AUTHOR]

Background The Model for End-Stage Liver Disease (MELD) scoring system incorporating a combination of hepatic and renal laboratory parameters does not adequately reflect the degree of multi-organ dysfunction in patients with heart failure, who need oral anticoagulation. In order to exclude the impact of oral anticoagulation on the international normalized ratio (INR), we used the MELD excluding INR (MELD-XI) score. The aims of the study were to calculate the individual preoperative MELD-XI score and its ability to predict 1-year mortality after heart transplantation and to identify other preoperative laboratory prognostic parameters. Methods We retrospectively analysed data of 87 consecutive adults undergoing heart transplantation between 2011 and 2014. Clinical data and laboratory parameters for the calculation of the MELD-XI score were obtained at the time of admission for the heart transplantation. Results The average age of the patients was 48.8 ± 13.3 years and 68.9% of them were male. During the observation period, the mortality rate was 18.4%. Multivariate analysis of Cox proportional hazard confirmed that the pretransplantation MELD-XI score (hazard ratio [HR] = 1.625 [1.286–2.053]; P < .001), sodium serum concentration (HR = 0.824 [0.677–1.001]; P < .05) and highly sensitive C-reactive protein (hs-CRP) serum concentration (HR = 1.045 [1.008–1.083]; P < .02) were independent predictors of death during the first year after heart transplantation. Area under the receiver operating characteristic (ROC) curve (AUC) indicated a good discriminatory power of MELD-XI (AUC 0.997; P < .04) and plasma sodium concentration (AUC 0.901; P < .01) in death prediction. Conclusions Our study confirms that the pretransplantation MELD-XI score, as well as serum sodium and hsCRP concentrations, may be used to estimate postoperative risk in heart transplant recipients during a 1-year follow-up. [ABSTRACT FROM AUTHOR]

Background Cardiac allograft vasculopathy (CAV) still remains to be one of the most important limiting factors for heart transplant recipients' long-term survival. The aim of our study was to identify the perioperative risk factors impacting the occurrence of CAV during the long-term follow-up. Methods We retrospectively analysed the data from 198 consecutive adult patients, who underwent heart transplantation between 2007 and 2012, in whom at least one routine coronarography (CAG) was performed. CAV onset was defined as any lesion seen at least at one routine CAG. Results The average follow-up was 63.6 ± 14.7 months. The frequency of CAV in the analysed population was 36 (18.1%). Multivariate stepwise logistic regression analysis confirmed that NT-proBNP plasma concentration directly before heart transplant [logNT-proBNP OR = 16.455 (4.587–31.036), P < .0001], fibrinogen plasma concentration a month after heart transplant [OR = 1.022 (1.009–1.035), P < .001] and occurrence of diabetes [OR = 12.355 (1.417–35.750), P < .001], were independent predictors of CAV. Area under the ROC curves (AUC) indicated a well discriminatory power of plasma fibrinogen [AUC 0.9278, P < .001] and plasma NTproBNP concentration [AUC 0.9514, P < .001] in CAV prediction. The optimal cut-off value of fibrinogen was 509 mg/dL, and of NT-proBNP was 10080 pg/mL. Conclusions Our data show that NT-proBNP and fibrinogen plasma concentrations as well as occurence of diabetes, both preexisting and new onset after heart transplant can be used to identify patients at risk of developing CAV. [ABSTRACT FROM AUTHOR]

Background Limited data exist about the effects of continuous-flow versus pulsatile-flow left ventricular assist devices (LVADs) on end-organ function. We hypothesized that a pulsatile Polvad MEV (PM) would result in outcomes similar to those of similarly ill patients implanted with a continuous-flow LVAD (Heartware [HW] or Heartmate II [HMII]). We aimed to compare renal, hepatic, and hematologic functions in the 1st 30 days of support. Methods We retrospectively reviewed patients with 24 PM (21 M, 3 F; group P) and 15 HW and 5 HMII (20 M, 0 F); group C LVAD implantations from April 2007 to February 2014. Creatinine, bilirubin, aspartate (AST) and alanine (ALT) transaminases, hematocrit, platelet count, international normalized ratio (INR), and activated partial thromboplastin time (APTT) parameters were analyzed before implantation and during 30 days of support. Demographic parameters were similar. Results No significant differences were found between the groups regarding baseline renal, hepatic, or hematologic function. Baseline INR and APTT were significantly higher in group P. Levels of creatinine were similar between groups. They increased from baseline to postoperative day (POD) 1 and then decreased. Bilirubin levels were insignificantly higher in group P. Transaminases were significantly higher in group P (AST in PODs 3–6, ALT in PODs 3–7). INR values were significantly higher at baseline and in POD 0. APTT values were insignificantly higher in group P. Conclusions The use of LVAD improved renal and hepatic function in our series. Patients in group P had more decreased hepatic function and presented slower regeneration. [ABSTRACT FROM AUTHOR]

Background The evaluation of prognosis and determination of a long-term treatment strategy is an important element of management in patients with heart failure (HF). Methods The aim of the study was to determine the prognostic value of the Model for End-Stage Liver Disease (MELD) and its modifications, MELD and serum sodium (MELD-Na) and MELD excluding the international normalized ratio (MELD-XI), as well as other independent risk factors for death during a 4-year follow-up. We analyzed retrospectively 143 patients with advanced HF, evaluated for heart transplant between 2009 and 2011. Patients using warfarin were excluded from the study. The long-term follow-up data were obtained during follow-up visits and/or phone contact with the patients or their families. Results The age of the patients was 54 (48–59) years and 88.1% of patients were male. Mortality rate during the follow-up period was 49%. The MELD scores (hazard ratio [HR], 1.12; P < .001), as well as serum high-sensitivity C-reactive protein (hs-CRP; HR, 1.01; P < .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; HR, 1.01; P < .05) levels, were independent risk factors for death. Receiver operator characteristic analysis indicated that a MELD cutoff of 10 (area under the curve [AUC], 0.756; P < .0001], MELD-XI cutoff of 13.0 (AUC, 0.720; P < .0001), MELD-Na cutoff of 13.0 (AUC, 0.813; P < .0001), hs-CRP cutoff of 4.02 (AUC, 0.686; P < .001), and NT-proBNP cutoff of 1055 (AUC, 0.722; P < .001) were the best predictive values as predictors of death. Conclusions MELD, MELD-Na, and MELD-XI scores are prognostic factors for death during a 4-year follow-up. A high MELD score is an independent prognostic factor for death. NT-proBNP and hs-CRP serum concentrations are other independent factors influencing death. [ABSTRACT FROM AUTHOR]

Background Mechanical circulatory support is increasingly used in patients with heart failure as a bridge to transplant or recovery. Results of use the Polish POLVAD MEV pulsatile circulatory support system and its comparison with novel devices never was done. We compared the course of patients with left ventricular circulatory support (left ventricular assist device [LVAD]) supported by POLVAD MEV or continuous flow devices Heart Mate II (HM II) and Heart Ware (HW) in single-center cohort. Methods We retrospectively reviewed 44 patients who underwent Polvad Mev (group P; n = 24 [21M/3F]) or HW or HM II (group C; n = 20 [20M/0F]) implantation between April 2007 and February 2014. Patients were in INTERMACS 1 (6 in group P and 1 in group C) or 2. Preimplant demographics, and perioperative and postoperative clinical outcomes were reviewed between groups. We analyzed baseline signs of heart failure, comorbidities, complications, and the 30- and 90-day results. Results Among the groups, age, gender, weight, and cause of heart failure were comparable. Patients in group C suffered more frequently from hypercholesterolemia preoperatively. Patients in group P had more pulmonary complications (7 vs 0) after LVAD implantation and stay longer on intensive care unit than patients in group C (17.61 ± 16.96 vs 9.56 ± 9.42; P = .047). After exclusion, INTERMACS 1 patients it was not significant (14.8 ± 10.8 vs 9.8 ± 9.6 days; P = .065), the 30- and 90-day mortality was comparable. Conclusions Implantation of pulsatile POLVAD MEV and continuous flow devices as LVAD support provides comparable results. A greater number of complications in group P can cause increased mortality over a longer observation period. [ABSTRACT FROM AUTHOR]

Background The role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). Material and Methods The study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 ± 5.3 years) without clinical symptoms of ischemic heart disease. The control group consisted myocardial fragments taken from 10 male heart valve and pulmonary artery donors with diagnosed cerebral death (age 40 ± 2.3 years). BRCA1 was detected immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity of BRCA1 expression was semiquantitatively assessed for cardiocytes, small vessels including capillaries, and interstitial cells. The significances between groups were estimated using the Mann-Whitney U test. Results All IDCM cases were positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes showed very intense staining and typical cardiomyopathic cardiocytes were stained weakly forming mosaic. Control cases showed weak-to-moderate uniform staining. Intensity of staining was significantly higher in IDCM cardiocytes, whereas small vessels and interstitial were stained similarly in both groups. Conclusions IDCM adverse remodeling results in more intense but nonuniform BRCA1 expression. This phenomenon seems to reflect IDCM biology: lower BRCA1 expression in myocytes with lower anti-apoptotic and DNA damage repair activity, with the opposite in hypertrophied myofibers. [ABSTRACT FROM AUTHOR]

The number of transplantations from an anti-HBcore positive donor to a seronegative recipient is still low. We present the first documented case in the history of the Silesian Center for Heart Diseases in Zabrze of a successful retransplantation from an HBcAb (+) donor to a seronegative recipient. A 45-year-old male patient after HTX in 2014 due to NICM was admitted with the signs and symptoms of heart failure. Severe mitral and tricuspid regurgitation and impaired systolic function of the graft were observed (LVEF 25%, RV hypokinesis). Vasculopathy was excluded, endomyocardial biopsy revealed no signs of acute cellular rejection (ACR 0). Due to the further deterioration, a decision of urgent heart retransplantation was made. A suitable donor with positive HBcAb antibodies and a negative HBs antigen was reported. After obtaining written informed consent, urgent orthotopic heart retransplantation was performed. The patient was vaccinated against hepatitis B, but the level of antibodies was undetectable. Pre-transplantation prophylaxis with lamivudine combined with subsequent valgancyclovir CMV prophylaxis was made. Active inflammatory cardiomyopathy of the explanted heart was diagnosed (histological examination). Inflammation of the transplanted heart was present despite no signs of cellular rejection in the endomyocardial biopsy. After the retransplantation signs of ACR in the 3a class were observed twice in the two first biopsies. High levels of GGTP (max. 692 U/l) and ALP (max. 214 U/l) were found in the second month after the transplantation. Transaminase and bilirubin levels were normal, abdominal US showed no pathology. The results improved in the follow-up. No manifestation of ACR and normal graft function were observed. After three months, valganciclovir prophylaxis was completed. The patient still received lamivudine (up to one year). In the repeated assessments, negative HBs antigen and low anti-HBs titers were found. We present a case report of heart retransplantation due to graft failure from an anti-HBcore positive and HBs antigen negative donor to a seronegative recipient. Based on anatomopathological and histopathological examination of the explanted graft, we also suggest that acute cellular rejection in the transplanted heart may exist despite negative findings in right-sided endomyocardial biopsy. [ABSTRACT FROM AUTHOR]

Continuous-flow left ventricular assist devices (CF-LVADs) have been extensively used in a strategy of bridge to orthotopic heart transplant due to increasing number of patients with end-stage heart failure and worldwide shortage of heart donors. However, usage of CF-LVADs is not free from limitations such as device-related adverse events, including pump thrombosis (PT). The purpose of this study was to develop an early PT detection algorithm based on the basic parameters monitored by the implanted device. We analyzed the power consumption recorded by pump controller, normalized with respect to impeller speed. The signal was transformed to Open-High-Low-Close form with the averaging window of 4 hours, which enabled calculation of Typical Price (TP) technical indicator. We then developed an algorithm that learns patient's usual TP values over two consecutive days. Later such an algorithm was able to analyze each subsequent data point and indicate whether the probability of thrombotic event meets predetermined threshold. We retrospectively reviewed log files of 101 patients implanted with HeartWare pump (HVAD). Seventeen had suspected or confirmed PT (21 events) according to INTERMACS definitions. Our algorithm classified correctly all cases with 100% sensitivity and 100% specificity. Based on abnormally high power consumption (Fig 1A) and TP evaluation, the algorithm alerted at least 40% probability of pump thrombosis (Fig 1B) preceding the onset of PT by 5.4 days on average. In the worst-case scenario, the threshold was reached 16 hours prior to the event. Our study shows that it is possible to predict PT events with use of a dedicated, custom-made algorithm. Automatic event detection and alarming could enable earlier medical management of PT and improve prognosis in patients implanted with HVAD. [ABSTRACT FROM AUTHOR]

Speckle-tracking echocardiography analysis may identify minor, subtle myocardial dysfunction not detectable by standard echocardiography. This study aimed to explore longitudinal left ventricular (LV) and right ventricular (RV) function in relation to acute cellular rejections (ACRs) degree ≥ 2R and their response to intensify therapy with intravenous steroids. 45 adult heart transplant recipients were prospectively assessed from January 2016 until May 2017. Among the biopsy specimens with ACR grade ≥ 2R, we identified those that underwent echocardiography before the episode of ACR, at the time of pathologic diagnosis, and during therapeutic intervention with 3 days of receiving intravenous steroids. 23 patients (51%) had at least 1 episode of moderate ACR during follow-up, and all these episodes were asymptomatic, with LVEF remaining in the normal range. Complete strain data in the ACR group were collected for 15 patients for all three time points. The cases of biopsy-proven ACR grade 2R were associated with marked reductions in GLS, 4-chamber longitudinal strain (4CH LS), systolic strain rate (SR), RV free wall longitudinal strain (RV FW) and increase of LV mechanical dyssynchrony (SD-TPS) (Tab. 1). There was an acute improvement of all LV and RV longitudinal strain parameters in reaction to appropriate immunosuppressive therapy for ACR in addition to no significant regression of LV mechanical dispersion (Tab. 2). Measurements of LV and RV longitudinal strain are promising tools for the noninvasive assessment of ACR and to guide the pharmacological treatment of rejection. [ABSTRACT FROM AUTHOR]

The aim of study was to echocardiographicly evaluate right ventricular function as a predictor of outcome in COVID 19 patients (pts) who underwent heart transplantation using RV strain and speckle tracking. 15 pts (mean age 47, 12 male 3 female) underwent heart transplantation from October 2020 to May 2021. All pts underwent transthoracic echocardiography for the evaluation of RV free wall longitudinal peak systolic strain RVFWSL, TAPSE, RVd1, RVd2, RVd3, FAC, TRVmax, IVC diam and S'. All pts were PCR positive for SARSCoV2 and had cough, fever and malaise indicative of COVD19, therefore were also radiological signs of COVID19 pneumonia. Also HS troponin, procalcitonin and CRP were elevated. They were treated with antiviral drugs and immune - based therapy including corticosteroids and convalescent plasma, and received standard triple regimen of calcineurin inhibitors (tacrolimus), antimetabolite (Mycophenolan Mofetil).All echocardiographic measurements were obtained from apical 4-chamber RV with focusing on the lateral wall. RvV free wall longitudinal peak systolic strain (RVFWSL) were significantly reduced during infection compared to post infection time (-15% vs -20) and RV four-chamber strain (RV4CSL) (-11,3% vs 21%). The RV function correlated with recovery time among heart transplant patients which was longer and also correlates significantly with acute cellular rejection in myocardial biopsy (10 patients -66,6% had 2R by ISHLT). In comparison to 2D measurement (RV diameter 28+/- 35, TAPSE 17+/-22, FAC 34+/-45) we did not observe significant difference during infection and post infection time. The study confirms that RV4CSL and RVFWSL are independent predictors of outcome in COVID 19 patients who undergo Heart transplantation. [ABSTRACT FROM AUTHOR]

Orthotopic heart transplantation remains the treatment of choice for endstage heart failure. In the face of the COVID19 pandemic, managing patients with advance HF before and after OHT has become an increasing challenge in both: in immunosuppression treatment and postoperative managements including biopsy protocol We retrospectively evaluated the outcomes of all patients who underwent OTH from March 2020 to February 2021 at Silesian Heart Diseases Center, Zabrze, Poland. Due to global pandemic of COVID19 several challenges including reduced numbers of myocardial biopsies were done 88 patients (67 male, 21 female) underwent OHT. During this period of time the COVID-19 infections were at high level in Poland. Both donor and recipients were tested for SARSCOV2 within 48 hrs of the procedure and none tested positive. We employed strict protocol of hand hygiene, PPE usage, isolation and regular staff PCR testing. We elected to reduce the routine myocardial biopsy rate from 4to1 in first month in order to reduce exposure of the patients to the potential of COVID19 disease. All patients received a standard triple regimen of calcineurin inhibitor (tacrolimus), antimetabolite (mycophenolate mofetil) and methylprednisolone. The level of immunosuppressive medications was done every day. 20 of 88 patients underwent first biopsy at 7 - 10 days post-operatively, and 3 more biopsies at one-month interval. The first myocardial biopsies did not demonstrate acute cellular rejection. We observed acute cellular rejection (2R grade) among 3 patients (15%) in second myocardial biopsy and they were treated with methylprednisolone 1gram iv for 3 days and after we return to previous prednisone dose. Third myocardial biopsy did not demonstrated acute cellular rejection. All of patients were discharged from the hospital at day14 days, and followed up in OPD once a week till the next admission. Ultrasonography including strain echo parameters of left and right ventricle, lab tests and the level of immunosuppression were done during each OPD visit. OHT recipients who underwent reduced numbers of myocardial biopsies appear to have reasonable outcomes (including adequate home support) compared to recipients with standard protocol. We have shown that successful heart transplantation could be performed during of COVID19 disease pandemic. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) remains one of the most dangerous viruses emerging in patients (pts) after heart transplant (HTx). A number of prevention strategies are available. However, there is no single recommended strategy to prevent the infection. Pre-emptive strategies implicate regular follow-ups and costs connected with the diagnostic protocols. In turn, generalized prophylaxis is connected with drug-related adverse effects and the cost of antiviral drugs. The purpose is to compare the pre-emptive therapy model with generalized prophylaxis and to find the strategy best matching our pts. Consecutive pts transplanted between May 2015 and May 2020 were enrolled in the study. To guide the pre-emptive strategy, the pp65 antigen was assessed in the 4th and 12th week after transplantation and additionally in the case of a suspected infection. As generalized prophylaxis, we used valganciclovir 900mg daily (dose adjusted to the renal function) for 110 days after transplant.130 pts were enrolled in the pre-emptive strategy (mean age at the time of transplant 54.6 ±12 years) 8 D+R-, 9 D-R-, 113 D±R+, according to CMV baseline serostatus. Generalized prophylaxis was implemented in 128 pts (mean age 55.2±11.6 years), 18 D+R-, 3 D-R-, 107 D±R+, respectively. In the pre-emptive strategy group, none of the pts with D-R- developed CMV infection. In the group of D±R+, 24 infections occurred, i.e. 5 symptomatic infections, 3 co-infections (> 3 months after HTx). None of the pts died due to CMV. In the D+R- group, 7 of 8 pts developed overt infection, and 4 of them died in the course of CMV infection. In the pre-emptive strategy group, prophylaxis was ceased in 7 patients due to drug-related adverse effects. CMV infection occurred in 2 pts (D+R-, after drug cessation). None of the pts developed CMV infection during the prophylaxis period. In 4 pts, CMV infection occurred after the prophylaxis period (D±R+: 3, D+R-: 1, respectively). None of the pts died due to CMV. Pre-emptive therapy with the use of pp65 antigen may be safely applied in the D-R- group. In the D+R- group, this model of pre-emptive therapy is completely insufficient. In the D±R+ group, testing should be done more frequently or generalized prophylaxis should be applied. Infections other than CMV should prompt the workup for CMV, also in the late period after HTx. [ABSTRACT FROM AUTHOR]