Dariusz Janczak

Carotid body removal for treatment of chronic systolic heart failure

BACKGROUND Augmented reflex response from peripheral chemoreceptors characterises chronic heart failure (CHF), contributes to autonomic imbalance and exercise intolerance and predicts poor outcome. METHODS AND RESULTS We present a case of a 56-year-old male patient with ischaemic CHF, who underwent surgical, unilateral carotid body resection to reduce peripheral chemosensitivity. At 2-month and 6-month follow-ups, we document a persistent decrease in peripheral chemosensitivity accompanied by an improvement in exercise capacity, sleep disordered breathing and quality of life. Autonomic balance was favourably affected as evidenced by improved heart rate variability and augmented cardiac baroreflex sensitivity. There were no procedure-related adverse events. CONCLUSIONS Denervation of a carotid body may offer a clinical strategy to restore autonomic balance and improve morbidity in heart failure (NCT01653821).

Dissociation between blood pressure and heart rate response to hypoxia after bilateral carotid body removal in men with systolic heart failure

What is the central question of this study? Carotid body denervation removes the ventilatory response to acute hypoxia, although haemodynamic responses to acute hypoxia after carotid body removal have not been described conclusively in humans. What is the main finding and its importance? Carotid body removal results in dissociation of heart rate and blood pressure responses to hypoxia in human subjects. While the heart rate response (tachycardia) is maintained, there is a significant attenuation of the blood pressure response (hypertension), which indicates the existence of different sensory afferent pathways in the haemodynamic response to hypoxia that has important clinical implications for this novel therapeutic modality.

Carotid body resection for sympathetic modulation in systolic heart failure: results from first-in-man study.

Augmented reflex responses from peripheral chemoreceptors, which are mainly localized in the carotid bodies (CBs), characterize patients with systolic heart failure and contribute to adrenergic hyperactivation. We investigated whether surgical resection of CBs in these patients can be performed safely to decrease sympathetic tone.

Vascular complications after the treatment with Ilizarov external fixators.

Iatrogenic vascular injuries from external fixation in orthopaedics and traumatology are frequent. Three cases of vascular injuries after the treatment with Ilizarov external fixators were treated at our institution. These include two cases of pseudoaneurysms and one case of acute ischaemia of the lower limb. Two patients became symptomatic only after removal of the fixator. In all cases, the diagnosis was made by color flow duplex sonography. All vascular injuries needed surgical repair.Iatrogenic vascular injuries from external fixation in orthopaedics and traumatology are frequent. Three cases of vascular injuries after the treatment with Ilizarov external fixators were treated at our institution. These include two cases of pseudoaneurysms and one case of acute ischaemia of the lower limb. Two patients became symptomatic only after removal of the fixator. In all cases, the diagnosis was made by color flow duplex sonography. All vascular injuries needed surgical repair.

The increased risk of post-transplant diabetes mellitus in peritoneal dialysis-treated kidney allograft recipients

BACKGROUND Post-transplant diabetes mellitus (PTDM) is a common metabolic complication in kidney allograft recipients, significantly contributing to the elevated cardiovascular morbidity after renal transplantation and increased risk of chronic transplant dysfunction. The aim of the present investigation was to evaluate the factors influencing PTDM development. Under particular consideration were the elements, existing before the transplantation, especially the modality of dialysis treatment significance, i.e. haemodialysis (HD) versus peritoneal dialysis (PD). METHODS Three hundred and seventy-seven consecutive outpatients who underwent renal transplantation (RTx) in our institution between January 2003 and December 2005 were analysed. PTDM was diagnosed according to the current American Diabetic Association/World Health Organization criteria. Statistical inference was conducted by means of univariate methods (one factor versus PTDM) and multivariate methods in frames of generalized linear model. RESULTS In the study group, 72 patients (23.4%) developed PTDM after RTx (55 HD and 17 PD patients). PTDM incidence at 3, 6 and 12 months was 15.9%, 22.1% and 23.4%, respectively. The mean interval from transplantation to the onset of PTDM was 3.08 ± 2.73 months. In univariate analysis, the factors associated with the elevated risk of PTDM appearance were older recipient age, positive family history of diabetes, hypertensive nephropathy as end-stage renal disease cause, higher body mass index at transplantation, treatment by PD, and the graft from an older donor. In multivariate verification, statistical significance remained: older recipient age (P < 0.001), positive family history of diabetes (P = 0.002), and treatment by PD (P = 0.007). CONCLUSIONS Treatment by PD appears to be a possible novel factor, not yet reported, which may increase the risk of PTDM development.

Kidney ischemic injury genes expressed after donor brain death are predictive for the outcome of kidney transplantation.

The results of deceased donor kidney transplantation largely depend on the extent of organ injury induced by brain death and the transplantation procedure. In this study, we analyzed the preprocurement intragraft expression of 29 genes involved in apoptosis, tissue injury, immune cell migration, and activation. We also assessed their influence on allograft function. Before flushing with cold solution we obtained 50 kidney core biopsies of deceased donor kidneys immediately after organ retrieval. The control group included 18 biopsies obtained from living donors. Gene expression was analyzed with low-density arrays (Taqman). LCN2/lipocalin-2 is considered a biomarker of kidney epithelial ischemic injury with a renoprotective function. HAVCR1/KIM-1 is associated with acute tubular injury. Comparison of deceased donor kidneys to control organs revealed a significantly higher expression of LCN2 (8.0-fold P=.0006) and HAVCR1 (4.7-fold, P<.0001). Their expressions positively correlated with serum creatinine concentrations after 6 months after transplantation: LCN2 (r=.65, P<.0001), HAVCR1 (r=.44, P=.006). Kidneys displaying delayed graft function and/or an acute rejection episode in the first 6 months after showed higher LCN2 expression compared to event-free ones (1.7-fold, P=.027). A significantly higher increase in expression of TLR2 (5.2-fold), Interleukin (IL) 18 (4.6-fold), HMGB1 (4.1-fold), GUSB (2.4-fold), CASP3 (2.0-fold) FAS (1.8-fold), and TP53 (1.6-fold) was observed among deceased donor kidneys compared with the control group. Their expression levels were not related to clinical outcomes: however, they showed significant correlations with one another (r>.6, P<.0001). We also observed a slightly reduced expression of IL10 (0.6-fold, P=.004). Our data suggested that increased LCN2 and HAVCR1 expression observed in the kidneys after donor brain death were hallmarks of the organ injury process. LCN2 expression level in retrieved kidneys can predict kidney transplantation outcomes.

Adventitial lymphatics of internal carotid artery in healthy and atherosclerotic vessels

OBJECTIVES Presence of lymphatics in adventitia of major arteries remains controversial. Presence of lymphatics in adventitia of internal carotid artery was not documented and its relation to atherosclerosis was not studied. The aim of our study was to evaluate presence of lymphatic vessels in adventitia of internal carotid artery in healthy and atherosclerotic arteries. METHODS Fragments of arterial wall of internal carotid artery were obtained during the surgical eversion endarterectomy in 15 patients with internal carotid artery stenosis and 2 healthy organ donors. 21 arteries were studied. Patients age ranged from 56 to 77 years. Fragments of arterial wall were embeded in paraffin. Lymphatics of arterial adventitia were visualized with immunohistochemistry using LYVE-1 and anty-podoplanin antibodies. RESULTS The lymphatic vessels were visualized in adventitia of 20 carotid arteries. The serial sections have revealed that both LYVE-1 and podoplanin have identical specificity for lymphatic endothelium Number of lymphatics in adventitia significantly correlated with thickness of intima (p<0.046). CONCLUSIONS Lymphatics are present in adventitia of internal carotid artery. Number of adventitial lymphatics increases with severity of atherosclerosis measured as intimal thickness.

Duration of Brain Death and Cold Ischemia Time, But Not Warm Ischemia Time, Increases Expression of Genes Associated With Apoptosis in Transplanted Kidneys From Deceased Donors

Apoptosis is one of the most important mechanisms leading to kidney graft injury during transplantation. The aim of this study was to assess the expression of genes involved in apoptosis in transplanted kidneys derived from deceased donors (DD) at various stages of the transplant procedure, seventy eight transplanted kidneys procured from 43 DD were included in this study. As a baseline control for gene expressions we used six kidney allografts obtained from living donors (LD). Three core biopsies were performed: biopsy 1--5 minutes before organ perfusion in the donor; biopsy 2--at the end of cold ischemia before kidney implantation; and biopsy 3--30 minutes after reperfusion. Tumor protein p53 (TP53), caspase-3 (CASP3), B-cell lymphoma 2 protein (Bcl2), and heme oxygenase 1 (HO-1) gene expression levels were determined using custom-designed low-density arrays (TaqMan assay). Comparison of gene expression between DD and LD kidneys revealed greater expression of all genes in kidneys from DD in all biopsies; however, only CASP3 expression in biopsy 1 and TP53 expression in biopsy 3 were statistically significant. Prolongation duration of brain death beyond 10 hours in DD resulted in a significantly decreased CASP3 expression in biopsy 1. When the cold ischemia time (CIT) was longer than 24 hours, the expressions of Bcl2, TP53, and CASP3 were significantly higher compared to kidneys with ClT<24 hours. There was no correlation between warm ischemia time and gene expression in biopsy 3. CASP3 and TP53 expression only in biopsy 1 were significantly higher among kidney allografts with delayed (DGF) compared with immediate graft function. In conclusion expression of genes involved in apoptosis was more pronounced in kidney allografts from deceased donors. A prolonged donor brain-death period beyond 10 hours resulted in decreased CASP3 expression. CIT longer than 24 hours was associated with increased expressions of Bcl2, TP53, and CASP3. CASP3 and TP53 expressions were significantly higher among kidneys allografts displaying DGF.

Estimated Glomerular Filtration Rate Evolution Between 6 and 24 Months Predicts Long-Term Kidney Transplant Survival Among Patients With Inferior Graft Function

UNLABELLED One-year serum creatinine and other clinical and immunologic factors remain uncertain predictors of long-term kidney allograft outcomes. The aim of our retrospective study was to evaluate the prognostic significance of the estimated glomerular filtration rate (eGFR) monitoring of patients with suboptimal kidney allograft function. The analysis included 332 patients (median age, 43 years), who received deceased donor kidney transplantations between 1995 and 2007 with graft function for at least 1.5 years (median follow-up, 7 years). We examined the eGFR (the 4-variable Modification of Diets in Renal Disease [MDRD] equation) at 6 month posttranspant and every 6 months thereafter. Based on eGFR stratification (>60, 50-60, 40-49, and <40 mL/min per 1.73 m(2)) at 6 months we divided the patients into 4 groups. We identified patients with eGFR improvement (as judged by >20% increment between 6 and 24 months), versus stable or declining eGFR courses. RESULTS Among the groups, the eGFR improved among 47% of patients. Demographic characteristics including time on dialysis, human leukocyte antigen matching, cold ischemia times were similar across groups. A greater incidence of disadvantageous characteristics was observed among the deteriorating groups: older donor, higher delayed graft function incidence, as well as more frequent and severe acute rejection episodes. Excellent and comparable 5-year graft survivals were noticed among patients with improved eGFR between 6 and 24 months (97%, 100%, 100%, 94%). CONCLUSION Assessment of eGFR was a valuable biomarker for long-term kidney transplant outcomes among patients with inferior renal transplant function. A tendency to improve eGFR between 6 and 24 months posttransplant was advantageous for graft survival, possibly indicating state of immunologic quiescence.

Clavien Classification of Complications After 150 Laparoscopic Pyeloplasties

OBJECTIVES To compare the complications of laparoscopic pyeloplasty observed in 3 periods of our learning curve using the Clavien classification. METHODS We reviewed and retrospectively analyzed the records of 150 cases of laparoscopic pyeloplasty performed for primary ureteropelvic junction obstruction at our center. All patients were divided into 3 groups according to the order of the case number (1-50, 51-100, 101-150) to compare the intergroup differences in the preoperative data and perioperative parameters. The postoperative complications were subdivided according to the 5-grade Clavien classification of surgical complications. The groups of patients with and without complications were compared with respect to age, degree of hydronephrosis, positive urine culture before surgery, concomitant nephrolithiasis, crossing vessel, and the type of operation performed (dismembered vs nondismembered). RESULTS The success rate was 90.5%. The mean follow-up was 53.7 months (range 5-103). Intraoperative complications occurred in 9 (6%) of 150 patients and postoperative complications in 27 (18%) of 150 patients. No statistically significant differences were seen between the incidence of intra- and postoperative complications among the compared groups. The only statistically significant difference among the groups with and without complications was the presence of a positive urine culture (19% vs 6%, respectively). CONCLUSIONS The most common complications were connected with stent obstruction, and they did not seem dependent on surgeon experience. Patients with a preoperative positive urine culture might have a greater risk of postoperative complications.