Generation of two hiPSC lines, (DMBi003-A and DMBi004-A), by reprogramming peripheral blood mononuclear cells and fibroblast-like synoviocytes from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects joints but should be considered as a syndrome that also includes extra-articular manifestations and comorbidities. Human-derived induced pluripotent stem cells (hiPSCs) and their differentiated derivatives may be of special interest in the investigation of complex pathophysiology of RA. In this study, we demonstrate and compare the generation of hiPSC from peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients. Application of three-dimensional cardiac microtissues constructed from RA specific iPSC-derivatives may be a useful approach to investigate RA comorbidities and cardiac protection or toxicity of anti-rheumatic drugs.

Complement Components in the Diagnosis and Treatment after Kidney Transplantation-Is There a Missing Link?

Currently, kidney transplantation is widely accepted as the renal replacement therapy allowing for the best quality of life and longest survival of patients developing end-stage renal disease. However, chronic transplant rejection, recurrence of previous kidney disease or newly acquired conditions, or immunosuppressive drug toxicity often lead to a deterioration of kidney allograft function over time. Complement components play an important role in the pathogenesis of kidney allograft impairment. Most studies on the role of complement in kidney graft function focus on humoral rejection; however, complement has also been associated with cell mediated rejection, post-transplant thrombotic microangiopathy, the recurrence of several glomerulopathies in the transplanted kidney, and transplant tolerance. Better understanding of the complement involvement in the transplanted kidney damage has led to the development of novel therapies that inhibit complement components and improve graft survival. The analysis of functional complotypes, based on the genotype of both graft recipient and donor, may become a valuable tool for assessing the risk of acute transplant rejection. The review summarizes current knowledge on the pathomechanisms of complement activation following kidney transplantation and the resulting diagnostic and therapeutic possibilities.

The Impact of Beta Blockers on Survival in Heart Transplant Recipients: Insights from the Zabrze HTx Registry.

INTRODUCTION: The data assessing the impact of beta blocker (BB) medication on survival in patients after heart transplantation (HTx) are scarce and unequivocal; therefore, we investigated this population. METHODS: We retrospectively analyzed the HTx Zabrze Registry of 380 consecutive patients who survived the 30-day postoperative period. RESULTS: The percentage of patients from the entire cohort taking BBs was as follows: atenolol 24 (17%), bisoprolol 67 (49%), carvedilol 11 (8%), metoprolol 28 (20%), and nebivolol 8 (6%). The patients receiving BBs were older (56.94 ± 14.68 years vs. 52.70 ± 15.35 years, p=0.008) and experienced an onset of HTx earlier in years (11.65 ± 7.04 vs. 7.24 ± 5.78 p ≤ 0.001). They also had higher hematocrit (0.40 ± 0.05 vs. 0.39 ± 0.05, p=0.022) and red blood cells (4.63 (106/µl) ± 0.71 vs. 4.45 (106/µl) ± 0.68, p=0.015). Survival according to BB medication did not differ among the groups (p=0.655) (log-rank test). Univariate Cox proportional hazard regression analysis revealed that the following parameters were associated with unfavorable diagnosis: serum concentration of albumin (g/l) HR: 0.87, 95% CI (0.81-0.94), p=0.0004; fibrinogen (mg/dl) HR: 1.006, 95% CI (1.002-1.008), p=0.0017; and C-reactive protein (mg/l) HR: 1.014, 95% CI (1.004-1.023), p=0.0044. CONCLUSIONS: The use of BBs in our cohort of patients after HTx was not associated with survival benefits.

Mechanical circulatory support restores eligibility for heart transplant in patients with significant pulmonary hypertension.

BACKGROUND: An increasing number of patients with end­stage heart failure implies a wider use of left ventricular assist devices (LVADs). Irreversible pulmonary hypertension (PH) is a predictor of unfavorable prognosis and a contraindication to orthotopic heart transplant (OHT). AIMS: The aim of this study was to evaluate the effect of continuous­flow LVAD (CF­LVAD) support on pulmonary pressure and pulmonary vascular resistance (PVR) as well as the impact of pre­LVAD hemodynamic parameters on survival during LVAD support. METHODS: Data collected from 106 patients who underwent CF­LVAD implantation in the years 2009 to 2018 (men, 95.3%; mean [SD] age, 51.8 [12] years; mean [SD] INTERMACS profile, 2.9 [1.6]; mean [SD] LVAD support time, 661 [520] days; follow­up until May 2019) were retrospectively analyzed. RESULTS: Right heart catheterization was performed before LVAD implantation in 94 patients (88.7%), after implantation-in 31 (29.2%), and before and after implantation-in 28 (26.4%). We observed mean pulmonary artery pressure (mPAP) >25 mm Hg in 65 patients (61.3%) and PVR >2.5 Wood units in 33 patients (31.1%) before LVAD implantation. A significant improvement after CF­LVAD implantation was noted in mPAP, pulmonary capillary wedge pressure, transpulmonary gradient, PVR, cardiac output (P <0.001 for all parameters), and cardiac index (P = 0.003). All patients with initially irreversible PH became eligible for OHT during LVAD support. Survival during LVAD support did not depend on initial mPAP and PVR. CONCLUSIONS: In patients with end­stage heart failure, CF­LVAD support leads to a significant reduction of pre­ and postcapillary PH. Survival on CF­LVAD support is independent of elevated mPAP and PVR before implantation, which suggests that LVADs decrease the risk associated with PH.

Right Heart Catheterization-Background, Physiological Basics, and Clinical Implications.

The idea of right heart catheterization (RHC) grew in the milieu of modern thinking about the cardiovascular system, influenced by the experiments of William Harvey, which were inspired by the treatises of Greek philosophers like Aristotle and Gallen, who made significant contributions to the subject. RHC was first discovered in the eighteenth century by William Hale and was subsequently systematically improved by outstanding experiments in the field of physiology, led by Cournand and Dickinson Richards, which finally resulted in the implementation of pulmonary artery catheters (PAC) into clinical practice by Jeremy Swan and William Ganz in the early 1970s. Despite its premature euphoric reception, some further analysis seemed not to share the early enthusiasm as far as the safety and effectiveness issues were concerned. Nonetheless, RHC kept its significant role in the diagnosis, prognostic evaluation, and decision-making of pulmonary hypertension and heart failure patients. Its role in the treatment of end-stage heart failure seems not to be fully understood, although it is promising. PAC-guided optimization of the treatment of patients with ventricular assist devices and its beneficial introduction into clinical practice remains a challenge for the near future.

Saphenous graft atherosclerosis as assessed by optical coherence tomography data for stenotic and non-stenotic lesions from the OCTOPUS registry.

INTRODUCTION: Coronary artery bypass grafting (CABG), although widely used for a long time in diffuse coronary artery disease (CAD), has serious limitations associated with graft aging and its degeneration. AIM: The relationship between saphenous vein graft (SVG) plaque morphology assessed by optical coherence tomography (OCT) and clinical findings has not been elucidated yet. MATERIAL AND METHODS: We compared the morphology of SVG in stenotic vs. non-stenotic lesions using OCT imaging in 29 patients hospitalized in our center within the OCTOPUS registry. RESULTS: Stenotic lesions were characterized by higher incidence of thin-cap fibroatheroma (TCFA) (33% vs. 0%, p = 0.0048), thrombus (28% vs. 0%, p = 0.0008), lipid-rich plaque (LRP) (75% vs. 35%, p = 0.0013) and plaque within the SVG valve (19% vs. 0%, p = 0.0114) as compared to non-stenotic lesions. Patients with intimal tearing or rupture (ITR) were older (75.8% vs. 68.9 years, p = 0.047) and had lower left ventricular ejection fraction (LVEF) (32.0% vs. 49.7%, p = 0.001) and glomerular filtration rate (GFR) (36.0 vs. 73.6 ml/min/1.73 m2, p = 0.010). Patients with calcified lesions vs. those without had lower high-density lipoprotein (HDL) cholesterol (33.2 vs. 44.1 mg/dl, p = 0.018), similarly to those with ruptured plaque vs. those without (28.3 vs. 41.7 mg/dl, p = 0.047). CONCLUSIONS: Presence of ITR was associated with advanced age, decreased LVEF and renal insufficiency. Decreased concentration of HDL was associated with higher occurrence of calcified and ruptured plaque.

The Role of Parathyroid Hormone and Vitamin D Serum Concentrations in Patients with Cardiovascular Diseases.

25-hydroxyvitamin D (25(OH)D) plays a crucial role in human homeostasis. Its deficiency (vitamin D deficiency-VDD), being common in European population, combined with elevated concentration of parathyroid hormone (PTH), represents a vicious cycle of mechanisms leading to heart failure (HF). Despite several papers published in that field, the effect of VDD and PTH concentration on cardiovascular system remains unequivocal; thus, the aim of the study was to compare these data among HF and non-HF patients being prospectively enrolled into the study during hospital stay in the cardiology ward. Patients with HF had higher PTH concentration (85.0 ± 52.6 versus 64.5 ± 31.7, p ≤ 0.02) compared to non-HF patients. Mean PTH values were associated with the clinical status expressed by the New York Heart Association class (NYHA class) ("0"-66.04, "I"-56.57, "II"-72.30, "III"-85.59, and "IV"-144.37 pg/ml, p ≤ 0.00004). Interestingly, neither 25(OH)D (31.5 versus 29.7 ng/ml, p ≤ ns) nor phosphorus (P) (1.23 versus 1.18 mmol/l, p ≤ ns) nor total calcium (Ca2+) concentration (2.33 versus 2.37 mmol/l, p ≤ ns) differed among the groups. Reassuming PTH serum concentration in contrary to 25(OH)D, P and Ca2+ are significantly raised among the patients with HF and shows significant relationship with the clinical status expressed by the NYHA class.

Corrigendum to "The Role of Parathyroid Hormone and Vitamin D Serum Concentrations in Patients with Cardiovascular Diseases".

[This corrects the article DOI: 10.1155/2018/5287573.].

Prediction models for different plaque morphology in non-significantly stenosed regions of saphenous vein grafts assessed with optical coherence tomography.

INTRODUCTION: Coronary artery bypass grafting (CABG) is a method of choice in treatment of diffuse coronary artery disease (CAD), although it has some limitations such as late saphenous vein graft (SVG) patency loss, which occurs in one fifth of all conduits at 5 years. Since atherosclerosis in SVG has diffuse characteristics, it appears that significantly and non-significantly stenosed lesions may have an equal impact on worse prognosis. AIM: To assess non-significant lesions of SVG by the use of optical coherence tomography (OCT) and investigate the clinical and laboratory findings with the potential impact on plaque composition. MATERIAL AND METHODS: Twenty-nine patients with 43 non-significant lesions were enrolled in the study. All variables were assessed using uni- and multivariable logistic regression analysis with each plaque morphology as a dependent variable. Odds ratio (OR) and 95% confidence interval (CI) were computed. RESULTS: Plaque rupture (PRT) was independently associated with age (OR = 1.49, 95% CI: 1.09-2.04, p = 0.015) and lower rates of high-density lipoproteins (HDL) cholesterol (OR = 0.67, 95% CI: 0.49-0.92, p = 0.016). Intimal tearing or rupture (ITR) was related to reduced GFR (OR = 0.52, 95% CI: 0.38-0.72, p = 0.0004). Lipid-rich plaque (LRP) was associated with raised platelet count (PLT) (OR = 1.51, 95% CI: 1.16-1.96, p = 0.004) and increased frequency of smoking (OR = 1.45, 95% CI: 1.12-1.89, p = 0.007). CONCLUSIONS: Atherosclerosis of SVG is not restricted to significantly stenosed lesions. Plaque composition is independently associated with different types of clinical and laboratory findings, mostly recognized as risk factors of CAD.

[Parathormone and vitamin d in heart failure - theoretical influence on disease development and potential therapy targets].

Vitamin D and parathormone (PTH) are hormones regulating calcium and phosphorus homeostasis. The aim of the article is to summarize the current knowledge in the field and to assess its impact on heart failure (HF) pathogenesis. PTH serum concentration being frequently elevated in patients with HF has negative impact on circulatory system stimulating myocardial fibrosis, wall thickening and reninangiotensin-aldosterone system (RAAS) activity. PTH reacts with smooth muscle cells receptors mediating adrenergic and chronotropic activation resulting in increased oxidative stress, endothelial dysfunction, intracellular calcium overload and has negative influence on prognosis in chronic HF patients. Vitamin D, which deficiency is common in developed countries, has widely distributed receptors including myocardium, endothelium and smooth muscle cells. Being an antiproliferative agent vitamin D modulates RAAS, regulates natriuretic peptides and myosine expression, suppresses inflammatory cytokines activity, has antiarrhytmic properties and increases myocardial contractility. It decreases arterial pressure, inhibits atherosclerosis progression and plays a protective role against inflammation including viral infections of cardiotropic potential. Optimal vitamin D serum concentration has potential protective impact on cardiovascular system.

Parathyroid hormone serum concentration in Central European patients with non-ischaemic heart failure as a potential marker of disease severity and poor prognosis.

INTRODUCTION: Parathyroid hormone (PTH) might be considered as a potential marker of disease severity and worse prognosis in heart failure (HF) patients. The aim of the study was to assess PTH, vitamin D, phosphorus (P), and total calcium (Ca2+) serum concentrations in Central European patients suffering from HF of non-ischaemic origin compared to non-HF volunteers.To evaluate potential correlations among the enumerated parameters, established markers of worse prognosis and declared sun exposure. MATERIAL AND METHODS: Serum intact-PTH, 25-OH vitamin D, P, and total Ca2+ concentrations were assessed in a group of HF patients and non-HF volunteers. Patients described their daily profile of sun exposure during the previous eight weeks as "above" or "below" seven hours a week. RESULTS: The mean PTH concentrations in the non-ischaemic HF group and control group were 79.5 pg/mL and 59.6 pg/mL, respectively (P = 0.009). Non-HF volunteers declaring higher sun exposure time had higher serum concentrations of vitamin D compared to those with lower sun exposure time (30.3 vs. 23.8 ng/mL, P < 0.05), unlike the HF patients (24.1 ng/mL vs. 23.2 ng/mL, P = ns). Multiple regression analysis revealed the relationship between age, NT-proBNP (N-terminal pro-brain natriuretic peptide), P, and PTH as a dependent variable. CONCLUSIONS: PTH is significantly elevated in non-ischaemic HF patients compared to non-HF volunteers and correlates with established factors of worse prognosis, including age, estimated glomerular filtration rate (eGFR), aspartate aminotransferase (AST), serum concentrations of creatinine, and NT-proBNP. Declared sun exposure did not affect the serum concentration of vitamin D in the HF group, in contrast to the control group.

Shoulder proprioception - lessons we learned from idiopathic frozen shoulder.

BACKGROUND: Of all the most frequent soft tissue disorders of the shoulder, idiopathic frozen shoulder (IFS) offers the greatest potential for studying proprioception. Studies concerning the presence of proprioception dysfunctions have failed to determine the potential for spontaneous healing of passive shoulder stabilizers (anterior and posterior capsule, middle and inferior gleno-humeral ligaments), its relationship with passive (PJPS) and active (AJPS) shoulder proprioception for internal and external rotation (IR, ER), as well as the isokinetic muscle performance of the internal and external rotators. This study investigates these dependencies in the case of arthroscopic release of IFS. METHODS: The study group comprised 23 patients (average aged 54.2) who underwent arthroscopic release due to IFS and 20 healthy volunteers. The average follow-up time was 29.2 months. The Biodex system was used for proprioception measurement in a modified neutral arm position and isokinetic evaluation. The results were analysed using the T-test, Wilcoxon and interclass correlation coefficient. P-values lower than 0.05 were considered significant. RESULTS: Statistically significant differences were found between involved (I) and uninvolved (U) shoulders only in the cases of PJPS and AJPS, peak torque, time to peak torque and acceleration time for ER (p < 0.05). No statistically significant difference was noted between PJPS IR and PJPS ER or between AJPS IR and AJPS ER (p > 0.05) for the U shoulders. CONCLUSIONS: The anatomical structure of anterior (capsule, middle and anterior band of inferior gleno-humeral ligament) and posterior (capsule and posterior band of inferior gleno-humeral ligament) passive shoulder restraints has no impact on the difference in PJPS values between ER and IR in a modified neutral shoulder position. The potential for spontaneous healing of the anterior and posterior passive shoulder restraints influences PJPS recovery after arthroscopic release of IFS. ER peak torque deficits negatively affect AJPS values. PJPS and AJPS of ER and IR can be measured with a high level of reproducibility using an isokinetic dynamometer with the arm in a modified neutral shoulder position. Differences greater than 15 % for PJPS and >24 % for AJPS for ER and IR can be helpful for future studies as baseline data for identification of particular passive and active shoulder stabilizers at risk.

Handheld Capillary Blood Lactate Analyzer as an Accessible and Cost-Effective Prognostic Tool for the Assessment of Death and Heart Failure Occurrence during Long-Term Follow-Up.

Impact of tissue lactate accumulation on prognosis after acute myocardial infarction (AMI) is biased. The study aimed to assess the prognostic role of lactate concentration (LC) in patients with AMI during one year of follow-up. 145 consecutive patients admitted due to AMI were enrolled. The data on the frequency of endpoint occurrence (defined as I, death; II, heart failure (HF); and III, recurrent myocardial infarction (re-MI)) were collected. The patients were divided into group A (LC below the cut-off value) and group B (LC above the cut-off value) for the endpoints according to receiver operating characteristic (ROC) analysis. The cumulative survival rate was 99% in group I-A and 85% in group I-B (p = 0.0004, log-rank test). The HF-free survival rate was 95% in group II-A and 82% in group II-B (p = 0.0095, log-rank test). The re-MI-free survival rate did not differ between groups. A multivariate Cox analysis showed a statistically significant influence of LC on death [Hazard Ratio (HR): 1.41, 95% Confidence Interval (CI) (1.13-1.76), and p = 0.002] and HF [HR: 1.21, 95% CI (1.05-1.4), and p = 0.007] with no impact on re-MI occurrence. LC in capillary blood may be considered a useful prognostic marker of late-onset heart failure and death after AMI.

The quantitative evaluation of the impact of viable medial meniscus graft type on the biochemical and biomechanical properties of the rabbit tibial cartilage.

BACKGROUND: Knowledge of the impact of viable medial meniscus allograft and autograft transplantation on biochemical and mechanical properties of cartilage is needed to understand the development of joint osteoarthritis. The purpose of this study was to evaluate this relationship 6 months after viable medial meniscal autograft and allograft transplantation. METHODS: Twenty rabbits were chosen for the study. The medial menisci were excised from 14 animals and stored under tissue culture conditions for 2 weeks. Seven menisci were implanted as autografts (group A) and seven as allografts (group B). The control group consisted of six animals which underwent arthrotomy. The tibial cartilage was used for mechanical and biochemical evaluation. RESULTS: The respective decreases of glycosaminoglycans (GAGs) and elasticity were 13.4 and 14.8% for group A and 30.4 and 32.6% for group B. The differences between group A and B and between each group and the control were statistically significant. The total collagen content was significantly lower in group B. CONCLUSIONS: The type of viable meniscal graft has an influence on the biochemical composition of the extracellular matrix (ECM) and biomechanical properties of the underlying tibial cartilage. A 1% decrease of glycosaminoglycan content is associated with a 1.1% decrease of cartilage elasticity. The average ratio of decrease of cartilage elasticity to that of the meniscus was 0.77 regardless of the type of meniscus graft. The viable allograft causes irreversible ECM disorder of the cartilage. Knowledge of the biochemical composition of the ECM meniscal grafts may serve as a predictor of their chondroprotective properties.

Evaluation of treatment strategy of acute knee infection after ACL reconstruction with hamstring.

BACKGROUND: Knee infection after anterior cruciate ligament reconstruction is a very serious complication. The aim of the paper is to present our experience relating diagnosis and management of this complication with concomitant graft salvage. MATERIAL AND METHODS: The study included 5 patients diagnosed with acute knee infection after anterior cruciate ligament arthroscopic reconstruction with hamstring with Rigid Fix graft fixation system. The treatment involved intravenous and oral antibiotic therapy combined with arthroscopic debridement and through drainage insertion. All patients were males with a mean age of 29 years. Evaluation was performed in reference to clinical symptoms of infection, laboratory tests results and effectiveness of the applied management. Mean observation period was 9.1 years (range from 7.2 to 10.5 years). RESULTS: Management that we undertook led to successful infection treatment with concomitant graft retention without the necessity to inspect the fixation site. There was no recurrence of infection during the 9.1 years of observation. CONCLUSIONS: 1. Plain monitoring of patient body temperature in the morning and in the afternoon at fixed times with the elimination of the effect of anti-inflammatory drugs on the temperature values enables early detection of acute knee infection after ACL reconstruction and rapid implementation of appropriate management. 2. Targeted antibiotic therapy combined with arthroscopic debridement and through drainage is an effective means of treatment of acute knee infection after anterior cruciate ligament arthroscopic reconstruction with hamstring without sacrificing the graft. 3. The conducted studies indicate that the primary source of infection is the knee joint and, consequently, there is no need to inspect graft fixation sites as long as the clinical symptoms from these sites do not cause suspicions of infection.

[Acute aortic syndrome mimicking anterior wall ST-elevation myocardial infarction]. / Ostry zespól aortalny imitujacy zawal serca sciany przedniej z uniesieniem odcinka ST.

We present a case of a 58-year-old man presenting with chest pain irradiating to the back and left arm, history of smoking and untreated hypertension. The anamnesis, symptoms and ECG findings consisting of ST elevation in leads aVR and V1-V2 suggested ST segment elevated myocardial infarction. Performed ECHO examination revealed possible acute aortic dissection. Considering haemodynamic instability, augmentation of chest pain and passing time which was obviously worsening the prognosis patient was submitted to aortography which finally proofed acute aortic dissection. Patient was subsequently transferred to cardiac surgery unit and successfully treated.