De novo HLA Class II antibodies are associated with the development of chronic but not acute antibody-mediated rejection after liver transplantation - a retrospective study.

Donor-specific antibodies (DSA) cause antibody-mediated rejection (AMR); however, their pathogenic role has not yet been adequately investigated after liver transplantation. The aim of our study was to analyse the clinical significance of DSA and complement-binding DSA for the prediction of AMR after liver transplantation. Our cohort included 120 liver recipients with assessed protocol biopsies one year post-transplant. All patients had defined HLA-specific and complement-binding (C1q + and C3d+) antibodies before and in regular intervals after transplantation. The incidence of DSA was evaluated in relation with clinical and histopathological data in the liver allografts. A higher occurrence of acute AMR was observed in recipients with preformed complement-binding DSA to HLA Class I antigens. Patients who developed chronic AMR had more frequently de novo-produced antibodies against HLA Class II antigens (P = 0.0002). A correlation was also found between de novo-formed C1q + and C3d+-binding antibodies to HLA Class II antigens and the development of chronic AMR (P = 0.043). Our study implies that preformed complement-binding DSA to HLA Class I antigens are related to increased risk of acute antibody-mediated rejection, while chronic AMR is more frequent in patients with de novo-produced antibodies to HLA Class II antigens after liver transplantation.

[Has been changed numbers and characteristics of patients with major amputations indicated for the diabetic foot in our department during last decade?] / Doslo v posledním desetiletí ke zmene poctu a charakteristik pacientu se syndromem diabetické nohy hospitalizovaných k vysoké amputaci na specializovaném podiatrickém pracovisti?

INTRODUCTION: One of the most serious complications of the diabetic foot (DF) is a major amputation, which is associated with poor patient prognosis. The occurrence of major amputations may be influenced by a variety of factors including deep infection caused by resistant pathogens.The aims of our study were to compare the incidence of major amputations in podiatric center, characteristics of amputated patients with the DF and other factors contributing to major amputations in last decade. METHODS: We included into our study all patients hospitalized for the DF in our center whose underwent major amputations from 9/2004 to 9/2006 (group 1) and from 9/2013 to 9/2015 (group 2). Risk factors such as severity of DF ulcers based on Texas classification, duration of previous anti-biotic therapy, the presence and severity of peripheral arterial disease (PAD) according to Graziani classification, the number of revascularizations, renal failure/hemodialysis, osteomyelitis, infectious agents found before amputations and their resistance were compared between the study groups. RESULTS: During the 1st study period (9/2004-9/2006) 373 patients were hospitalized for the DF, of whom 3.2 % underwent major amputation (12/373 - group 1), during the 2nd study period (9/2013-9/2015) 376 patients, of whom 5.1 % absolved major amputation (19/376 - group 2). As the numbers of major amputations as their indications were similar in both study groups. The study groups did not differ significantly in the age, BMI, duration and type of diabetes, duration of DF and severity of DF ulcers, the presence of renal failure/hemodialysis, osteomyelitis and PAD. Group 2 had milder forms of PAD by Graziani classification (4.4 ±1.4 vs 5.7 ± 0.9; p = 0.012) and a higher number of revascularizations before major amputations (2.5 ± 1.5 vs 1 ± 1; p = 0.003) compared to the group 1. These patients were significantly longer treated by antibiotics (5.4 ± 2.4 vs 2.5 ± 2 months; p = 0.002) and underwent more resections and minor amputations (3.1 ± 2.1 vs 0.9 ± 0.5; p = 0.0004) before major amputations in contrast to the group 1. There was a trend to higher incidence of Gram-negatives (65.1 % vs 61.5 %; NS) with a predominance of Enterobacteriacae species (60.7 % vs 56 %; NS) and a trend to the increase of Pseudomonas (25 % vs 18.8 %; NS) and Enterococci sp. (46.7 % vs 20 %; NS) in the group 2 compared to the group 1. The incidences as of MRSA, multidrug resistant Pseudomonas sp. of other resistant microbes were similar in both study groups. CONCLUSIONS: The incidence of major amputations in patients hospitalized for the DF remains unchanged during the last decade. The therapy of factors leading to amputations has evidently intensified. This is in accordance with the latest international recommendations for the therapy of DF. In the future, it is appropriate to focus on the improvement of detection and treatment of infection and ischemia in such risk group of patients.Key words: diabetic foot - major amputation.

IgA nephropathy in Czech patients--are we able reliably predict the outcome?

BACKGROUND/AIMS: The aim of our study was to retrospectively analyse data of 520 Czech patients with IgA nephropathy (IgAN) and to specify the risk factors affecting renal survival of IgAN patients. METHODS: Cox proportional hazards regression model was used to evaluate the effects of different variables on renal survival during a median follow up of six years. McNemar´s test was used to analyse the progression of renal function according to Bartosik´s formula. RESULTS: In our retrospective analysis of 520 Czech IgAN patients Cox proportional hazards regression model with five variables [hypertension, sex, GFR, proteinuria, age] was used. Significant regression coefficient was found for GFR, hypertension and proteinuria. Using stepwise algorithm GFR (OR = 3.09), hypertension (OR = 2.09) and proteinuria (OR = 1.97) were found as the most important factors for renal survival in our group of IgAN patients. Among patients with CKD 3 we found significantly better renal survival in patients with proteinuria < 1g/day compared to patients with higher proteinuria. We did not find the significant difference between predicted progression of renal function due to Bartosik´s formula and real progression of renal parametres assessed by GFR at the end of the follow up in our group of IgAN patients. CONCLUSION: Our retrospective study of 520 Czech IgAN patients confirmed GFR, hypertension and proteinuria as the most important factors affecting the prognosis of IgAN patients. We validated Toronto Bartosik´s formula to predict prognosis of IgAN patients.

The relationship between estimated GFR based on the CKD-EPI formula and renal inulin clearance in potential kidney donors.

It is not yet clear whether or not renal function in the living donor can be sufficiently assessed by estimated glomerular filtration rate (GFR) using creatinine-based equations. The present paper investigates the relationship between GFR values determined using renal inulin clearance (Cin) and those estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Our study was performed in 287 potential kidney donors with a mean age of 48 ± 10 years. Mean Cin was 1.47 ± 0.28 (1.10 - 2.50) mL/s/1.73 m2. Total bias when using the CKDEPI formula was -0.0183 mL/s/1.73 m2, precision 0.263 mL/s/1.73 m2, and accuracy 90.6% within ± 30% of Cin. The sensitivity of CKD-EPI to estimate a decrease in Cin below 1.33 mL/s/1.73 m2 was 50.5%, with an 85% specificity of detecting a value above the cutoff. Receiver-operating curve analysis for the above produced an area under the curve of 0.766 ± 0.0285 (CI 0.712 - 0.813). For donor screening purposes, CKD-EPI should be interpreted with great caution.

Risk factors for recurrence of diabetic foot ulcers: prospective follow-up analysis in the Eurodiale subgroup.

Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of and risk factors for DFU recurrence after healing during a 3-year follow-up period. At our site, 93 Eurodiale-enrolled patients had a healed DFU. Among these, 14 were not alive; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study, we assessed demographic factors (age, sex and distance from hospital); diabetes-related factors [duration, and glycated haemoglobin (HbA1c) levels]; comorbidities (obesity, renal failure, smoking and alcohol abuse) and DFU-related factors [peripheral arterial disease, ulcer infection, C-reactive protein (CRP) and; foot deformities]. During the 3-year follow-up period, a DFU had recurred in 42 patients (57.5%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location [odds ratio (OR) 8.62, 95% confidence interval (CI) 2.2-33.2]; presence of osteomyelitis (OR 5.17, 95% CI 1.4-18.7); HbA1c > 7.5% ([DCCT], OR 4.07, 95% CI 1.1-15.6) and CRP > 5 mg/l (OR 4.27, 95% CI 1.2-15.7). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3-year follow-up period, despite intensive foot care. The findings at diagnosis of the initial DFU were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) and define those at high risk for recurrence, but may be amenable to targeted interventions.

The retrospective analysis of 343 Czech patients with IgA nephropathy--one centre experience.

BACKGROUND: The aim of our study was to retrospectively analyse the clinical data and the histological findings of 343 patients (pts) followed up with IgA nephropathy (IgAN) in our department of nephrology. We have assessed the main demographic, clinical and histological data, and the medical treatment of IgAN pts. METHODS: Multivariate analysis was used to evaluate the effect of different variables on ≥50% increase of plasma creatinine level from baseline during a median follow-up of 4 years. RESULTS: In our group of IgAN pts, the male gender (68%) predominated over female gender (32%). At the time of renal biopsy, the median age of IgAN pts was 32.3 (18-90) years, the median level of serum creatinine was 119 µmol/L and the median level of proteinuria was 1.8 g/day. Most of the pts were found to have arterial hypertension (56.7%). The majority of the pts with arterial hypertension were treated with inhibitors of angiotensin-converting enzyme (80.4%) and the remaining pts (42.6%) were treated with angiotensin II receptor blockers. Fifty per cent of the pts (170 pts) were treated of corticosteroids, 21% of the pts (71 pts) used a combined immunosuppressive treatment of corticosteroids and cyclophosphamide, 8% of the pts (27 pts) took azathioprine, 1.5% of the pts (5 pts) took cyclosporine and 1.5% of the pts (5 pts) were given mycophenolate mofetil. Hypertension at presentation, fibrointimal proliferation of arterial vessels, interstitial fibrosis and interstitial inflammation were shown to be associated with ≥50% increase of plasma creatinine level from baseline in univariate analysis (P<0.05 for hypertension and fibrointimal proliferation; P<0.01 for interstitial fibrosis and inflammation). Using stepwise logistic regression presenting proteinuria>2 g/day [odds ratio (OR)=2.24, P<0.01], tubular atrophy (OR=4.97, P<0.01) and damage of tubular epithelium (OR=1.78, P<0.05) were found as risk factors for ≥50% increase of plasma creatinine level from baseline. CONCLUSION: Our retrospective analysis found valuable information not only about the clinical, laboratory and histological findings in IgAN pts but also information about the risk factors influencing the progression of renal insufficiency.

Prevalence and risk factors of polyomavirus BK replication in simultaneous pancreas/kidney transplant recipients from a single transplant center.

BACKGROUND: BK virus (BKV) replication is considered as a marker of risk for polyomavirus BK-associated nephropathy (PVAN). We evaluated the occurrence and risk factors for BKV DNA positivity following simultaneous pancreas/kidney transplantation (SPK). METHODS: Point prevalence of BK viruria and viremia was assessed in 183 SPK recipients. Real-time polymerase chain reaction was used with a detection threshold of 10(3) copies/mL. High-level BKV positivity was defined as viruria and/or viremia >10(7) and >10(4) copies/mL, respectively. BKV-positive patients were retested after 4-13 months and underwent an additional six-month clinical follow-up. RESULTS: Urine and serum BKV positivity was detected in 28 (17.3% of available samples) and 7 (3.8%) patients, with high-level viruria and viremia occurring in 6 (3.7%) and 3 (1.6%) patients, respectively. PVAN was biopsy-confirmed in 1 and suspected as a cause of progressive renal failure in another SPK recipient. Patients with single low-level viruria did not progress to high-level positivity or PVAN at follow-up. In multivariate analysis, pre-transplant diabetes duration and delayed graft function were independently associated with BKV positivity. CONCLUSIONS: Point prevalence of high-level BKV positivity and PVAN was low in SPK recipients from a single center. Diabetes duration and delayed graft function were independent risk factors for BKV replication.

Molecular networks involved in the immune control of BK polyomavirus.

BK polyomavirus infection is the important cause of virus-related nephropathy following kidney transplantation. BK virus reactivates in 30%-80% of kidney transplant recipients resulting in BK virus-related nephropathy in 1%-10% of cases. Currently, the molecular processes associated with asymptomatic infections in transplant patients infected with BK virus remain unclear. In this study we evaluate intrarenal molecular processes during different stages of BKV infection. The gene expression profiles of 90 target genes known to be associated with immune response were evaluated in kidney graft biopsy material using TaqMan low density array. Three patient groups were examined: control patients with no evidence of BK virus reactivation (n = 11), infected asymptomatic patients (n = 9), and patients with BK virus nephropathy (n = 10). Analysis of biopsies from asymptomatic viruria patients resulted in the identification of 5 differentially expressed genes (CD3E, CD68, CCR2, ICAM-1, and SKI) (P < 0.05), and functional analysis showed a significantly heightened presence of costimulatory signals (e.g., CD40/CD40L; P < 0.05). Gene ontology analysis revealed several biological networks associated with BKV immune control in comparison to the control group. This study demonstrated that asymptomatic BK viruria is associated with a different intrarenal regulation of several genes implicating in antiviral immune response.

A pilot study of systolic dyssynchrony index by real time three-dimensional echocardiography and Doppler tissue imaging parameters predicting the hemodynamic response to biventricular pacing in the early postoperative period after cardiac surgery.

OBJECTIVE: To evaluate systolic dyssynchrony index (SDI) measured by real time three-dimensional echocardiography (RT3DE) and Doppler tissue imaging (DTI) dyssynchrony parameters in predicting the hemodynamic response to biventricular (BIV) pacing in the early postoperative period after cardiac surgery. To compare right ventricular (RV) and BIV pacing using invasively measured hemodynamic values. METHODS: A prospective randomized clinical study enrolling 11 patients with ischemic heart disease, concomitant valvular heart disease, and left ventricular ejection fraction (LVEF) ≤ 35% comparing preoperative SDI by RT3DE and DTI LV dyssynchrony parameters to hemodynamic values obtained during RV or BIV sequential (DDD) epicardial pacing in the first 72 hours after cardiac surgery. RESULTS: BIV pacing produced a statistically significant higher cardiac output (CO) (6.27 ± 1.55 L/min) and cardiac index (CI) (3.44 ± 0.93 L/min per m(2) ) than RV pacing (CO 5.44 ± 0.97 L/min, CI 3.03 ± 0.83 L/min per m(2) , P < 0.05). We found a statistically moderate correlation between preoperative SDI by RT3DE and CO (r = 0.596, P < 0.05) and a nonsignificant correlation to CI (r = 0.535, P < 0.10) during BIV pacing. No correlation was observed between DTI dyssynchrony parameters and measured hemodynamic values. BIV pacing reduced the ICU stay and inotropic support requirements of patients after heart surgery. CONCLUSIONS: SDI measured preoperatively using RT3DE can predict CO during BIV pacing in the early postoperative period after cardiac surgery. BIV pacing is more hemodynamically effective than RV pacing in patients with LV dysfunction after coronary artery bypass grafting with or without a valve procedure.

Delayed Sleep-Wake Phase Disorder: Can Polysomnography Be Useful?

BACKGROUND: Delayed sleep-wake phase disorder (DSWPD) is a chronic condition with a multifactorial etiology that primarily affects adolescents, significantly influencing their quality of life. In clinical practice, the contribution of intrinsic and behavioral factors is difficult to determine. The aim of our study was to compare data from clinical interviews, sleep diaries, actigraphy, and nocturnal polysomnography (PSG) in a cohort of adolescents with DSWPD and to assess psychiatric/neurodevelopmental comorbidity. METHODS: Thirty-one patients (22 male; mean age 15.4 ± 2.2 years, range 12 to 19 years) with a diagnosis of DSWPD based on detailed history, sleep diary, and actigraphy underwent nocturnal polysomnography (PSG) and neurological, psychological, and psychiatric examination. RESULTS: Attention-deficit/hyperactivity disorder (ADHD) was present in 14 cases (45%), specific learning difficulties in nine (29%), and mood disorder (anxiety/depression) in 16 patients (52%). PSG revealed sleep-onset delay in only 12 (38%) cases. No differences in clinical data or psychiatric comorbidity between the group with sleep delay and the group with normal sleep onset were detected. Decreased total sleep time, sleep efficiency, rapid eye movement (REM) sleep, and prolonged REM sleep latency were observed in patients with delayed sleep onset. CONCLUSIONS: PSG showed delayed sleep timing in only 38% of patients with a diagnosis of DSWPD based on diagnostic criteria of the International Classification of Sleep Disorders. We suggest that PSG can provide useful information regarding the prevailing etiology (biological versus behavioral) if dim light melatonin onset testing is not available.

Central Disorders of Hypersomnolence: Association with Fatigue, Depression and Sleep Inertia Prevailing in Women.

Fatigue, depression, and sleep inertia are frequently underdiagnosed manifestations in narcolepsy and idiopathic hypersomnia. Our cross-sectional study design included diagnostic interview accompanied by assessment instruments and aimed to explore how these factors influence disease severity as well as to elucidate any sex predisposition. One hundred and forty-eight subjects (female 63%) were divided into narcolepsy type 1 (NT1; n = 87, female = 61%), narcolepsy type 2 (NT2; n = 22, female = 59%), and idiopathic hypersomnia (IH; n = 39, female = 69%). All subjects completed a set of questionnaires: Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scales (HADS), Fatigue Severity Scale (FSS), and Sleep Inertia Questionnaire (SIQ). In narcoleptic subjects, questionnaire data were correlated with the Narcolepsy Severity Scale (NSS), and in subjects with idiopathic hypersomnia, with the Idiopathic Hypersomnia Severity Scale (IHSS). The highest correlation in narcoleptic subjects was found between NSS and ESS (r = 0.658; p < 0.0001), as well as FSS (r = 0.506; p < 0.0001), while in subjects with idiopathic hypersomnia, the most prominent positive correlations were found between IHSS and SIQ (r = 0.894; p < 0.0001), FSS (r = 0.812; p < 0.0001), HADS depression scale (r = 0.649; p = 0.0005), and HADS anxiety scale (r = 0.528; p < 0.0001). ESS showed an analogic correlation with disease severity (r = 0.606; p < 0.0001). HADS anxiety and depression scores were higher in females (p < 0.05 and p < 0.01), with similar results for FSS and SIQ scales (p < 0.05 for both), and a trend toward higher ESS values in females (p = 0.057). Our study illustrates that more attention should be focused on pathophysiological mechanisms and associations of fatigue, depression, as well as sleep inertia in these diseases; they influence the course of both illnesses, particularly in women.

A prospective longitudinal study of BK virus infection in 120 Czech renal transplant recipients.

Polyomavirus BK (BKV) is a common human polyomavirus that rarely causes clinical symptoms in immunocompetent individuals. However, BK virus reactivation occurs in 20-40% of kidney transplant patients and 1-10% of cases present with BK virus-associated nephropathy (BKVN) and reduced kidney allograft survival. In this study, 120 consecutive renal allograft recipients were monitored for BK virus replication by real-time PCR (qPCR) in the blood and urine during the first year post-transplantation and risk factors for BK viremia, viruria, and polyoma BKV-associated nephropathy were evaluated. Receiver operating characteristic curve analysis was used to determine the cutoff points for assessing the risk of developing BKVN. In total, 1,243 samples were tested. BK-DNAuria >10(7) copies/ml and BK-DNAemia >10(4) copies/ml were found in 25.8% and 5% of the samples screened, respectively, during the 12 month follow-up period. BKVN was confirmed histologically in 3/120 patients and viremic patients were treated with dialysis for longer time periods and had higher levels of panel [corrected] reactive antibodies. Patients with viruria were also treated longer with dialysis and had impaired graft function 12 months post-transplantation. Patients with sustained viruria exhibited more acute rejection episodes than patients with transient viruria. Using receiver operating characteristic curve analysis, the cutoff point for viremia and viruria was redefined to 10(3) copies/ml serum for BK viremia and a cutoff point of 6.7 × 10(7) copies/ml in urine. In conclusion, polyoma BK viremia and viruria are frequent findings in kidney transplant recipients that warrant intensive monitoring as a means of preventing graft failure [corrected].

Association of advanced vasculopathy and transforming growth factor-beta1 gene expression with immunoglobulin A nephropathy progression.

BACKGROUND: The mechanism of IgA nephropathy (IgAN) progression remains ill-defined. In this prospective study, the prognostic role of clinical, histological and molecular markers over a 2-year follow-up was evaluated. METHODS: Fifty-one patients with biopsy-proven IgAN were followed for 24 months. Besides routine histology, the intrarenal gene expressions of cytokines and chemokines were quantified by reverse transcription quantitative real-time polymerase chain reaction, and the presence of lymphocytes and macrophages were immunohistochemically examined. RESULTS: Higher transforming growth factor-ß1 and severe chronic vasculopathy (but not glomerulosclerosis, interstitial fibrosis or lymphocyte infiltrate) were associated with the IgAN progression 24 months after biopsy. The gene expression of chemokine (C-C motif) ligands 2 and 5, hepatocyte growth factor, bone morphogenic protein-7 and transforming growth factor-ß1 and the interstitial infiltrate of T and B lymphocytes and macrophages were significantly associated with serum creatinine and glomerular filtration rate at the time of biopsy. The intrarenal chemokine (C-C motif) ligand 2 and hepatocyte growth factor gene expression were associated with the proteinuria. CONCLUSIONS: Besides the known risk factors for chronic kidney disease, advanced vasculopathy and molecular signatures of fibrogenesis were associated with the IgAN progression.

The hemodynamic effect of right ventricle (RV), RT3DE targeted left ventricle (LV) and biventricular (BIV) pacing in the early postoperative period after cardiac surgery.

BACKGROUND: Congestive heart failure negatively impacts the prognosis in patients after cardiac surgery. The aim of our study was to assess the value of targeted cardiac resynchronization therapy (CRT) within 72 hours after cardiac surgery in patients with mechanical dyssynchrony, who had an ejection fraction ≤ 35%, QRS ≥150 ms or between 120 and 150 ms. METHODS: A prospective randomized trial based on three-dimensional echocardiography (RT3DE) and optimized sequential dual-chamber (DDD ) pacing in patients after cardiac surgery. DDD epicardial pacing (Medtronic coaxial epicardial leads 6495) was provided by a modified Medtronic INSYNC III Pacemaker (Medtronic Inc., Minneapolis, MN, USA). SUMMARY OF RESULTS: The study included 21 patients with ischemic heart disease (HD) or valvular HD (16 men, 5 women, average age 69 years) with left ventricle (LV) dysfunction after cardiac surgery . Patients with biventricular (BIV) (CO 6.7 ± 1.7 L/min, CI 3.5 ± 0.8 L/min/m(2) ) and LV (CO 6.2 ± 1.5 L/min, CI 3.2 ± 0.7 L/min/m(2) ) pacing had statistically significantly higher CO and CI than patients with right ventricular (RV) (CO 5.4 ± 1.4 L/min, CI 2.8 ± 0.6 L/min/m(2) ) pacing (BIV vs RV P ≤ 0.001; LV vs RV P ≤ 0.05; BIV vs LV P ≤ 0.05). CONCLUSIONS: RT3DE targeted and optimized CRT in the early postperative period after cardiac surgery provided better hemodynamic results than RV pacing.

Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding.

Administration of nonselective beta-blockers in prophylaxis of first variceal bleeding is not suitable for all patients. Thus, we evaluated endoscopic variceal band ligation (EVBL) in primary prevention of bleeding in patients with cirrhosis and large esophageal varices. A total of 73 consecutive patients with liver cirrhosis and large esophageal varices without a history of gastrointestinal bleeding were randomized to receive either EVBL or propranolol and were followed for up to 18 months. Forty patients underwent EVBL and 33 patients received propranolol. Variceal bleeding occurred in 2 patients in the EVBL (5%) and in 2 patients in the propranolol group (6%, NS). The 18 month actuarial risk for first variceal bleed was 5% in the EVBL (95% CI, 0-12%) and 20% in the propranolol group (95% CI, 0-49%, NS). The actuarial probability of death at 18 months of follow-up was 5% (95% CI, 0-11%) in the EVBL group and 7% (95% CI, 0-17%, NS) in the propranolol arm. In conclusion, EVBL was an effective and safe alternative to propranolol in primary prophylaxis of bleeding in patients with large esophageal varices.

The consumption of the carp meat and plasma lipids in secondary prevention in the heart ischemic disease patients.

OBJECTIVES: Omega-3 fatty acids (FA) have been shown to be protective against cardiovascular diseases (CVD). The effect of the consumption of carp meat on CVD risk factors has not yet been examined in detail. We ascertained the influence of a diet enriched with carp meat with an elevated content of omega-3FA (200 g twice weekly for 4 weeks) in a group of subjects after cardiac revascularization surgery for ischemic heart disease with a follow-up spa treatment. DESIGN: After cardiac revascularization surgery, the probands consumed either a standard spa diet (56 individuals, 41 males, 15 females, age 41-80 years) or a diet enriched with two portions of carp meat (87 individuals, 64 males, 23 females, age 50-82 years). The differences in body mass index (kg/m²), blood pressure, plasma lipids and C-reactive protein (CRP) of the groups were analyzed. RESULTS: In the group with a higher consumption of carp meat, significantly greater improvements in lipid parameters in comparison to the standard spa diet were detected (total cholesterol p<0.001, triglycerides p<0.001, LDL-C p<0.001, CRP p<0.001, HDL-C p<0.001). No differences between these groups in blood pressure and body mass index were found. CONCLUSION: We conclude that the diet enriched with carp meat significantly improved plasma lipid parameters in patients after major cardiac revascularization surgery.

Effect of genotype on the disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment.

A genetic predisposition has been identified in 30% of idiopathic pulmonary fibrosis (IPF) cases. Although it is highly probable that the genotype affects the disease susceptibility and course in almost all patients, the specific genotype goes undetected. The aim of the present study was to explore the effects of variants of the genes encoding interleukin-4 (IL-4), mucin 5B (MUC5B), toll interacting protein (TOLLIP), surfactant protein A (SFPTA), transforming growth factor-ß (TGF-ß) and transporters associated with antigen processing (TAP1 and TAP2) on the course of IPF. A total of 50 patients with IPF were enrolled, and variants of these genes were assessed. Lung function at the time of diagnosis and after 6, 12 and 18 months, and the number of acute exacerbations and deaths in each observation period were measured. ANOVA was used to test the association between gene polymorphisms and the decrease in lung function. There was no significant effect of the gene polymorphisms on the outcomes of patients up to 6 months during the observation period. After 12 months, an effect of an IL-4 single nucleotide polymorphism (SNP) (rs 2070874) on patient outcomes was observed [relative risk (RR) for T allele: 5.6; 95% confidence interval (CI), 0.79-39.0; P=0.053]. The RR of progression in patients with the IL-4 SNP (rs 2243250) and the CT and TT genotypes was 4.3 (95% CI, 1.1-17.5; P=0.046). A total of 18 months after the diagnosis of IPF, an effect of the TOLLIP polymorphism on patient outcome was detected (rs 111521887; risk allele GC; RR: 7.2; 95% CI, 0.97-53.6; P=0.052). Thus, IL-4 and TOLLIP gene polymorphisms may represent disease course-modifying factors, but not drivers of IPF.

Main Factors Predicting Nonresponders to Autologous Cell Therapy for Critical Limb Ischemia in Patients With Diabetic Foot.

Autologous cell therapy (ACT) is a new treatment for patients with no-option critical limb ischemia (NO-CLI). We evaluated the factors involved in the nonresponse to ACT in patients with CLI and diabetic foot. Diabetic patients (n = 72) with NO-CLI treated using ACT in our foot clinic over a period of 8 years were divided into responders (n = 57) and nonresponders (n = 15). Nonresponder was defined as an insufficient increase in transcutaneous oxygen pressure by <5 mm Hg, 3 months after ACT. Patient demographics, diabetes duration and treatment, and comorbidities as well as a cellular response to ACT, limb-related factors, and the presence of inherited thrombotic disorders were compared between the 2 groups. The main independent predictors for an impaired response to ACT were heterozygote Leiden mutation (OR 10.5; 95% CI, 1.72-4) and homozygote methylenetetrahydrofolate reductase (MTHFR 677) mutation (OR 3.36; 95% CI, 1.0-14.3) in stepwise logistic regression. Univariate analysis showed that lower mean protein C levels (P = .041) were present in nonresponders compared with responders. In conclusion, the significant predictors of an impaired response to ACT in diabetic patients with NO-CLI were inherited thrombotic disorders.

Developmental Language Disorder: Wake and Sleep Epileptiform Discharges and Co-morbid Neurodevelopmental Disorders.

Developmental language disorder (DLD) is frequently associated with other developmental diseases and may lead to a handicap through adolescence or adulthood. The aim of our retrospective study was to characterize DLD subgroups, their etiological factors and clinical comorbidities, and the role of epileptiform discharges in wake and sleep recordings. Fifty-five children (42 male, mean age 6.2 ± 1.4 years, range 4-9 years) were included in the present study and underwent phoniatric, psychologic, neurologic, as well as wake and nocturnal electroencephalography (EEG) or polysomnography (PSG) examinations. A receptive form of DLD was determined in 34 children (63.0%), and an expressive form was found in 20 children (37.0%). Poor cooperation in one child did not permit exact classification. DLD children with the receptive form had significantly lower mean phonemic hearing (79.1% ± 10.9) in comparison with those with the expressive form (89.7% ± 6.2, p < 0.001). A high amount of perinatal risk factors was found in both groups (50.9%) as well as comorbid developmental diseases. Developmental motor coordination disorder was diagnosed in 33 children (61.1%), and attention deficit or hyperactivity disorder was diagnosed in 39 children (70.9%). Almost one half of DLD children (49.1%) showed abnormalities on the wake EEG; epileptiform discharges were found in 20 children (36.4%). Nocturnal EEG and PSG recordings showed enhanced epileptiform discharges, and they were found in 30 children (55.6%, p = 0.01). The wake EEG showed focal discharges predominantly in the temporal or temporo-parieto-occipital regions bilaterally, while in the sleep recordings, focal activity was shifted to the fronto-temporo-central areas (p < 0.001). Almost all epileptiform discharges appeared in non-rapid eye movement (NREM) sleep. A close connection was found between DLD and perinatal risk factors, as well as neurodevelopmental disorders. Epileptiform discharges showed an enhancement in nocturnal sleep, and the distribution of focal discharges changed.

Sleep-related rhythmic movements and rhythmic movement disorder beyond early childhood.

INTRODUCTION: Sleep-related rhythmic movements (SRRMs) are common in young children and become less prevalent with increasing age. When SRRMs significantly interfere with sleep and/or affect daytime functioning, potentially resulting in injury, rhythmic movement disorder (SRRMD) is diagnosed. OBJECTIVE: The aim of our study was to assess clinical comorbidities, types of SRRMs, sleep stage/wakefulness distribution during night, and age-dependence of these parameters. MATERIAL AND METHODS: In sum, 45 patients (age range 1-26 years, mean age 10.56 ± 6.4 years, 29 men) were clinically examined for SRRMs or SRRMD. Nocturnal polysomnography (PSG) was recorded in 38 patients. To evaluate clinical and sleep comorbidity, the cohort of 38 patients was divided according to age into four groups: (1) younger than 5 years (N = 7), (2) 5-9 years (N = 12), (3) 10-14 years (N = 11), and (4) ≥ 15 years (N = 8). RESULTS: A clear relationship between perinatal risk factors and developmental disorders (attention deficit hyperactivity disorder - ADHD, specific learning disability) was found which extended population prevalence at least five times. A total of 62 recordings were evaluated in 38 patients; SRRMs were found in PSG in 31 of 38 patients (82%). No age-dependent correlation between type of SRRMs and sleep stage/wakefulness distribution during the night was observed. However, when all recordings were correlated together, rolling stereotypes occurred more frequently in REM sleep, and rocking stereotypes in superficial NREM sleep. CONCLUSION: Developmental disorders and perinatal risk factors were connected with SRRMs and SRRMD in children and young adults. Rolling movements were significantly associated with REM stage and rocking stereotypes with superficial NREM sleep, independent of age.