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Multiple myeloma (MM) is a malignant, incurable neoplastic disease. The currently used treatment significantly improves the prognosis and extends the survival time of patients. Unfortunately, a common side effect of the therapy is peripheral neuropathy, which may lead to dose reduction or complete treatment discontinuation/modification. In this study, we examined the changes in plasma levels of circulating miRNAs in myeloma patients to define potential factors characteristic for drug-induced peripheral neuropathy (DiPN). Global miRNA expression profile in the plasma of patients with MM during treatment was determined using miRNA microarray technology. Receiver operating characteristic (ROC) analysis allowed the identification of three miRNAs (miR-22-3p; miR-23a-3p; miR-24-3p) that could be a potential biomarker of PN. The most promising results were obtained for miR-22-3p, which was characterized by ROC area under curve (AUC) = 0.807. Our results suggest a relationship between the DiPN in patients with MM and the level of selected miRNAs in the plasma.

The launch of novel chemotherapeutic agents-in particular, proteasome inhibitors and immunomodulatory drugs-dramatically changed multiple myeloma (MM) therapy, improving the response rate and prolonging progression-free survival. However, none of the anti-MM drugs are deprived of side effects. Peripheral neuropathy (PN) seems to be one of the most pressing problems. Despite extensive research in this area, the pathogenesis of drug-induced peripheral neuropathy (DiPN) has not yet been fully elucidated. In the present study, we aimed to assess the potential relationship between proinflammatory factors and the development of PN in MM patients with particular emphasis on the application of VTD (bortezomib, thalidomide, dexamethasone) regimen. Our analysis identified increased concentrations of CCL2, IL-1β, and IFN-γ in plasma of MM patients during treatment, both with and without symptoms of PN, compared with untreated neuropathy-free MM patients. At the same time, the plasma concentration of IL-1β in patients with neuropathy was significantly increased compared with patients without PN before and during treatment. Moreover, the results were enhanced at the transcript level by performing global mRNA expression analysis using microarray technology. The most significant changes were observed in the expression of genes responsible for regulating immunological and apoptotic processes. An in-depth understanding of the mechanisms responsible for the development of DiPN might in the future reduce the incidence of PN and accelerate diagnosis, allowing the choice of neuropathy-free treatment strategies for MM.

BACKGROUND There are several genes and genetic loci affecting telomere length, including hTERT gene and BICD1 gene as well as polymorphisms within chromosome 18. It has been demonstrated that the age of the donor is a negative factor associated with long-term kidney allograft function, and that post-transplant complications accelerate transplanted organ aging, thus contributing to estimated glomerular filtration rate (eGFR) decreases. The aim of this study was a joint assessment of donors' and recipients' hTERT and BICD1 genes as well as chromosome 18 polymorphisms with regard to early kidney transplantation outcomes. MATERIAL AND METHODS The study enrolled 74 pairs of Polish Caucasian kidney allograft cadaveric donors (60% male, mean age 45.99±14.62) and recipients (50.0% male, mean age 48.89±13.50). The transplantation procedure (Tx) was performed between 2001 and 2012. All samples were genotyped in duplicate using Real-Time PCR. RESULTS This study showed that rs2735940 hTERT CX-TT donor-recipient genotype pair was associated with almost five times higher odds (OR=4.82; 95% CI: 1.32-18; p=0.016) of delayed graft function (DGF), and that rs2735940 hTERT, rs2630578 BICD1, and rs7235755 chromosome 18 polymorphisms combined pairs were not associated with acute rejection (AR). CONCLUSIONS In conclusion, both the donor's and the recipient's rs2735940 hTERT gene polymorphism was associated with early graft function after transplantation. The odds of DGF were almost five times higher for a combination of CX (CT or CC) donor genotype and TT recipient genotype. Joint assessment of donor-recipient genotype pairs provides more information for prediction of early kidney transplantation outcomes.

Transplantation is the preferred method of end stage renal insufficiency treatment due to better quality of life and extended life of transplanted patients. Currently a non-invasive test, which evaluates the risk of acute or chronic rejection or deterioration of the transplanted organ's function, is being sought. An increase of the transrenal DNA concentration in the urine of urinary tract infection patients and in renal graft recipients during an episode of acute rejection was observed. There were also reports on shortening of telomeres in transplanted organ chromosomes, as the result of accelerated aging of cells, and its connection with the onset of chronic allograft nephropathy and the degree of its completion, and thus the deterioration of kidney function. The aim of this paper is to describe the urine genetic analysis through determining the length of the telomeres and the content of transrenal DNA to monitor kidney function and to evaluate the prevalence of acute and chronic rejection in patients after kidney transplantation. The genetic analysis of the biological material collected from patients relies on the determination of transrenal DNA content and length of DNA telomeres isolated from the urine of kidney recipients. The presented methods assume that the genetic profile of the transplanted organ recipient as well as kidney donor can be determined, so the source of the genetic material in the urine of the patient can be identified. A measurable effect of these methods' use would be to complement the evaluation of the prevalence of acute and chronic rejection and transplanted kidney function with a modern, non-invasive method, which is the analysis of telomere length from sediment of urine and the content of transrenal DNA in the urine.

Background: The outcome of kidney allograft transplantation is associated with numerous donor-dependent and recipient-dependent immunological and non-immunological factors. Studies on genetic factors affecting the non-immunological aspects, like ageing of the kidney allograft and patient outcome are still lacking. The aim of this study was the analysis of relative telomere length (RTL; T/S ratio) in the biopsy specimens of the transplanted kidney allograft and its correlation with the delayed graft function (DGF), acute rejection (AR) and chronic allograft dysfunction (CAD)., Methods: The study enrolled 119 Caucasian kidney allograft recipients (64 M/55 F, mean age 47.32 ± 14.03; transplantation performed between 2001 and 2012). Organs were harvested from cadaveric donors (59.8 M/40.2 F, mean age 45.99 ± 14.62)., Results: There were significant differences in RTL assessed in kidney allograft biopsy specimens collected 3-6 months after transplantation between patients with DGF and without DGF (181.8 ± 82.0 vs. 284.6 ± 149.6; p < 0.05) and in RTL of kidney allograft biopsy specimens collected 18-60 months after transplantation between patients with AR and without AR (188.1 ± 162.1 vs. 263.3 ± 134.7; p = 0.047). There were significant differences in RTL assessed in kidney allograft biopsy specimens collected 12-24 months after transplantation between patients with CAD and without CAD (168.0 ± 120.0 vs. 282.1 ± 158.4; p = 0.038)., Conclusions: Duration of dialysis before transplantation and PRA influence the kidney allograft ageing. Telomere length assessed in biopsy specimens collected in the peri-transplant period predicts the long-term kidney allograft function. Complications of kidney transplantation, like DGF, AR and CAD are linked with the telomere length and thus, graft ageing.

Background/aims: It has been confirmed that telomere length (TL) correlates with chronological donor age and that telomere shortening is accelerated in allografts. The aim of this study was to analyse the associations between graft rs2735940 hTERT and rs2630578 BICD1 gene polymorphisms and rs7235755/rs2162440 chromosome 18 polymorphisms, relative TL and kidney function after transplantation., Methods: The study enrolled 119 Polish Caucasian kidney allograft recipients (64M/55F, mean age 47.3±14.0 years). The relative TL was assessed in biopsy specimens. To identify genotypes of the studied polymorphisms, real-time PCR was performed., Results: The graft rs2735940 hTERT gene polymorphism TT genotype was associated with a significantly lower risk of delayed graft function (DGF) (TT vs. TC+CC; OR=0, p=0.009) and significantly shorter TL in the '0' biopsy (TT vs. CC: 207±153 vs. 400±161, p=0.036). The graft rs2630578 BICD1 gene polymorphism CC genotype was associated with lower creatinine concentrations in the first month (CC vs. GC: 1.11±0.06 vs. 2.0±1.25 mg/dL, p=0.03). The AA genotype of the graft rs7235755 chromosome 18 polymorphism was associated with longer relative TL in specimens collected 12 to 60 months after transplantation (AA vs. GG+GA p=0.04; AA vs. GG: 489±152 vs. 246±145, p=0.035) and the presence of A allele was associated with higher creatinine concentrations one month after transplantation (GA+AA vs. GG p=0.026; GA vs. GG: 2.18±1.59 vs. 1.76±0.88 mg/dL, p=0.02). It was found that shorter TL in the first six months was associated with higher creatinine concentrations 12 and 18 months after transplantation (Rs=-0.32; p=0.07 and Rs=-0.54; p=0.006, respectively)., Conclusions: Graft rs2735940 hTERT and rs2630578 BICD1 gene polymorphisms and rs7235755/rs2162440 chromosome 18 polymorphisms, apart from the association with TL, affect early kidney function after transplantation. Relative TL correlated negatively with creatinine concentrations, allowing the use of TL as a predictor of long-term kidney function., (© 2015 S. Karger AG, Basel.)

The incidence of cardiovascular diseases in pregnancy is estimated at about 1%. Pregnant women suffer from rheumatic diseases of the heart valves, hypertension, congenital heart deffects, inflammatory and ischemic disorders or pathologies of the electrical conduction system of the heart. Myocarditis during pregnancy occurs very seldom. Few cases of severe myocarditis during gestation have been reported in the literature. This report presents a case of a 27-year-old Asian patient, at 8 weeks of gestation, diagnosed with an acute myocarditis. The woman was admitted to the hospital, presenting with early and nonspecific symptoms, (fever up of 38.5 degrees Celsiuss, abdominal pain and nausea). After temporary improvement, the patient's condition deteriorated. On the fourth day of the hospitalization, myocarditis led to heart failure and the patient had to be transffered to the Intensive Care Unit. Wide-spectrum antibiotics, glucocorticoids, diuretics, bisoprolol, as well as fluid and electrolyte supplementation, were administered. After 22 days of treatment the patient was discharged home in good condition. Afterwards she attended follow-up visits at the Gynecology-Obstetric Outpatient Clinic. She delivered a healthy son (2340 grams, 51 centimetres, Apgar 10) at 37 weeks of gestation. At present, she remains under the care of the Cardiac Clinic and requires small doses of bisoprolol because of periodic supraventricular arrhythmias.

The course of pregnancy and delivery in a patient after Fontan repair of double-outlet right ventricle is herein presented. She uneventfully delivered a healthy infant in good general condition at 38 weeks of gestation through a caesarean section, at 24 years after cardiosurgery. Although the patient demonstrated a good hemodynamic state after the operation and conceived while being clinically stable, a worsening of her general condition was observed. After a 4-year follow-up it was clear that pregnancy and delivery had a harmful effect on her cardiovascular function.

The purpose of the study was the assessment of the diagnostic possibilities and usefulness of 24-hour cassette EEG/ECG recording in the differential diagnosis of short attacks of consciousness disturbances and/or syncopal states, and demonstration of interrelations between arrhythmias and seizures of cerebral origin. 24-EEG/ECG was obtained in 71 patients, including 34 with cardiological history who had above disturbances. Recording of 24-EEG/ECG made possible establishing of correct diagnosis in 15 cases (21.1%): in 1 case it was sinus arrest, in 14--epilepsy. In another 5 cases (7%) arrhythmia or conduction disturbances were found which could have been the case of their attacks, they all were patients with cardiological history. The analysis of EEG/ECG records of 47 epileptic seizures in 16 patients showed that in 11 of them (69%) the seizures were associated with sinus tachycardia without other arrhythmias. These results demonstrated the complex cause-effect relationship of cardiocerebral disorders in the aetiology of these states, and the usefulness of 24-EEG/ECG in their detection.

A case of left ventricular outflow tract stenosis resulted from compression of the heart is presented. This symptomatic cardiovascular lesion was produced by extensive growth of mediastinal tumour. Numerous noninvasive methods were necessary to establish this difficult diagnosis. The patient underwent surgery that disclosed a benign process (of neurofibroma). After tumour's resection marked hemodynamic signs subsided.

We describe a 41 year-old patient with atrial septal defect combined with mitral stenosis, severe pulmonary hypertension and tricuspid regurgitation. Despite high pulmonary vascular resistance, surgical intervention was decided on. Follow up proved to be successful. The role of echocardiography and hemodynamics data to establish a preoperative diagnosis is discussed.

A case of recurrent tricuspid valve endocarditis after surgical closure of ventricular septal defect is presented. Intensive medical treatment lasting nearly ten years completely failed. There were still vegetations attached to the septal leaflet of the tricuspid valve with positive cultures (Ps. aeruginosa). Persistent sepsis without signs of heart failure required surgical intervention. Tricuspid valvuloplasty with excision of infected patch was successfully performed. Six months later the patient remained symptomless.

Unlabelled: To evaluate the suspected role of sympathetic nerve tone in pathogenesis of arrhythmogenic right ventricle dysplasia (ARVD), noradrenaline (NOR) and adrenaline (AD) plasma levels were determined by radioenzymatic method in 10 pts with ARVD (mean age 36 y, VT-8 pts, syncope-5) at rest and during peak exercise. 9 healthy men (mean age 28 y) served as control., Results: [table: see text], Conclusion: Significant increase of norepinephrine serum level during peak exercise suggests essential role of sympathetic nerve tone in pathogenesis of ARVD.

24-hours Holter's ecg monitoring was performed in 79 patients with the hypertrophic cardiomyopathy. Ventricular arrhythmias were recorded in 75.9% of patients, including those revealed in the second recording in 29.5% of patients. Subsequent ecg monitoring was especially useful in detection of complex forms of ventricular arrhythmias (in 27.5%). Average doses of verapamil and Beta-adrenergic blockers were not sufficient in the antiarrhythmic therapy. There was no close correlation between ventricular arrhythmias and a morphologic type of a cardiomyopathy. Patients with episodes of fainting or loss of consciousness require repeated Holter's ecg monitorings.

The aim of the study was to evaluate the usefulness of 24-hour automatic recording of blood pressure and cardiac rhythm in patients with borderline hypertension. The study was performed in 50 patients aged 38.8 +/- 13.1 using the Del Mar Avionics device. Mean time of recordings was 21.3 hours, and the mean number of blood pressure measurements per one patient was 52.4. Great fluctuations of systolic blood pressure (from 92.1 +/- 12.6 to 191 +/- 37.0 mm Hg) and diastolic one (from 57.3 +/- 11.4 to 118.9 +/- 13.8 mm Hg) were observed. Mean systolic blood pressure (125.6 +/- 10.6 mm Hg) was significantly lower than the mean value of last three ambulatory measurements (141.9 +/- 9.8; p less than 0.001). Also mean diastolic pressure was lower than that obtained in the out patient clinic (84.7 +/- 9.7 vs 91.9 +/- 3.2 mm Hg; p less than 0.001). Mean heart rate during the day was 86.2 +/- 10.7 and at night 69.7 +/- 10.5 beats per minute. Ventricular and/or supraventricular cardiac arrhythmias were observed in 14 (28%) of examined patients. Results of the study indicate, that 24-hour automatic blood pressure recording is the valuable method, affording possibilities for more precise estimation of blood pressure and its 24-hour fluctuations in patients with borderline hypertension.

In 79 patients aged 13-65 (mean 36.6) with different types of the hypertrophic cardiomyopathy ECG Holter's monitorings, M-mode and 2-dimensional echocardiographic examinations as well as hemodynamic ones were performed. Ventricular arrhythmias were observed in ECG Holter's recordings in 59.9% of patients. More frequent occurrence of higher grades (3, 4, 5 grades by Lown's classification) of ventricular arrhythmias were stated in patients with significantly thicker intraventricular septum, increase of a left ventricular ejection fraction and a lower left ventricular myocardial mass. There were observed 7 patients without significant forms of ventricular arrhythmias in ECG 24-hours monitoring, but with several, coexisting, well known in literature sudden cardiac death risk factors such as: history of cardiac arrest, sudden cardiac death occurrences in a family before the age of 50, preexcitation syndrome, ecg repolarization disorders, history of fainting, physical activity performance or mental stress. It was stated, that risk of severe ventricular arrhythmias occurrence or a sudden cardiac death in patients with coexisting several, above mentioned, risk factors is higher than in remaining patients with the hypertrophic cardiomyopathy.