Transplantation of Pancreatic Islets Into the Omentum Using a Biocompatible Plasma-Thrombin Gel: First Experience at the Institute for Clinical and Experimental Medicine in Prague.

BACKGROUND: Islet transplantation represents an established therapeutic option for people with type 1 diabetes who have hypoglycemia unawareness syndrome and frequent problematic hypoglycemic episodes when other methods comprising diabetes education and use of technological support fail. Because the current standard method of islet infusion into the liver has some limitations, novel approaches are under investigation. METHODS: We report our first results with 2 cases of islet transplantation into an omental pouch using a biocompatible plasma-fibrin gel. The recipients received 12,350 and 5,350 islet equivalents per kilogram that were mixed with autologous plasma, seeded during a laparoscopic procedure on the omentum, overlaid with human thrombin solution, and fixed by flapping the omentum over. RESULTS: During a 9-month follow-up, neither patient experienced any moderate or severe hypoglycemia. Their glucose control significantly improved, insulin dose decreased by approximately 50%, and C-peptide at 1 year was 0.22 and 0.14 pmol/mL, respectively. The postoperative course was uneventful, but C-peptide production in the first patient progressively declined at 1 year and hypoglycemic episodes recurred. CONCLUSIONS: Though the results for these first 2 cases are not fully satisfactory, we have demonstrated the feasibility, safety, and ability of this novel method to restore insulin production. Further refinements to improve immediate islet survival seem necessary.

Predictive Potential of Flow Cytometry Crossmatching in Deceased Donor Kidney Transplant Recipients Subjected to Peritransplant Desensitization.

Recipient sensitization is a major risk factor of antibody-mediated rejection (ABMR) and inferior graft survival. The predictive effect of solid-phase human leukocyte antigen antibody testing and flow cytometry crossmatch (FCXM) in the era of peritransplant desensitization remains poorly understood. This observational retrospective single-center study with 108 donor-specific antibody (DSA)-positive deceased donor kidney allograft recipients who had undergone peritransplant desensitization aimed to analyze variables affecting graft outcome. ABMR rates were highest among patients with positive pretransplant FCXM vs. FCXM-negative (76 vs. 18.7%, p < 0.001) and with donor-specific antibody mean fluorescence intensity (DSA MFI) > 5,000 vs. <5,000 (54.5 vs. 28%, p = 0.01) despite desensitization. In univariable Cox regression, FCXM positivity, retransplantation, recipient gender, immunodominant DSA MFI, DSA number, and peak panel reactive antibodies were found to be associated with ABMR occurrence. In multivariable Cox regression adjusted for desensitization treatment (AUC = 0.810), only FCXM positivity (HR = 4.6, p = 0.001) and DSA number (HR = 1.47, p = 0.039) remained significant. In conclusion, our data suggest that pretransplant FCXM and DSA number, but not DSA MFI, are independent predictors of ABMR in patients who received peritransplant desensitization.

Hybrid Repair Combined with Fresh Arterial Allograft Extra-Anatomical Reconstruction: The Treatment of Infrarenal Abdominal Aneurysm above an Aortobifemoral Bypass Complicated by an Infected Pseudoaneurysm in the Left Groin.

INTRODUCTION: A 72-year-old male patient was admitted into our centre with large infected pseudoaneurysm (PSA) in the left groin. The patient underwent a CT angiography (CTA) that confirmed a large partly thrombosed 6.5 × 5.5 cm PSA in the left groin arising from the distal anastomosis of the aortobifemoral bypass (ABF). Furthermore, the CTA revealed 11 cm juxtarenal abdominal aortic aneurysm (JAAA) from which the proximal anastomosis of the ABF was arising. METHOD: Aorto-uni-iliac stent graft Cook was placed from the right groin trough native severely stenotic right iliac arteries with proximal landing zone below the renal arteries, excluding the JAAA and the ABF. The distal landing zone was in the common iliac artery maintaining patent right internal iliac artery. Afterwards, a femoro-femoral crossover bypass from right to left was performed using a fresh arterial allograft. Postprocedurally, the hospital stay was uneventful. The left groin PSA cultures came positive for Staphylococcus epidermidis and Corynebacterium tuberculostearicum, both sensitive to vancomycin and rifampicin. RESULT: The patient underwent intravenous ATB treatment with vancomycin for two weeks, followed by four weeks of oral rifampicin. The patient was discharged on the 20th postoperative days. CONCLUSION: Hybrid repair combining aortic stent graft and extra-anatomical bypass in the treatment of infected distal parts of an aortofemoral bypass is an acceptable treatment modality.

The Effect of Different Thawing Rates on Cryopreserved Human Iliac Arteries Allograft's Structural Damage and Mechanical Properties.

INTRODUCTION: The rate of thawing of cryopreserved human iliac arteries allografts (CHIAA) directly affects the severeness of structural changes that occur during this process. METHOD: The experiment was performed on ten CHIAA. The 10% dimethylsulphoxide in 6% hydroxyethyl starch solution was used as the cryoprotectant; all CHIAA were cooled at a controlled rate and stored in the vapor phase of liquid nitrogen (-194°C). Two thawing protocols were tested: (1) placing the CHIAA in a water bath at 37°C, and (2) the CHIAA were thawed in a controlled environment at 5°C. All samples underwent analysis under a scanning electron microscope. Testing of the mechanical properties of the CHIAA was evaluated on a custom-built single axis strain testing machine. Longitudinal and circumferential samples were prepared from each tested CHIAA. RESULTS: Ultrastructural analysis revealed that all five CHIAA thawed during the thawing protocol 1 which showed significantly more damage to the subendothelial structures when compared to the samples thawed in protocol 2. Mechanical properties: Thawing protocol 1-longitudinal UTS 2, 53 ± 0, 47 MPa at relative strain 1, 27 ± 0, 12 and circumferential UTS 1, 94 ± 0, 27 MPa at relative strain 1, 33 ± 0, 09. Thawing protocol 2-longitudinal ultimate tensile strain (UTS) 2, 42 ± 0, 34 MPa at relative strain 1, 32 ± 0, 09 and circumferential UTS 1, 98 ± 0, 26 MPa at relative strain 1, 29 ± 0, 07. Comparing UTS showed no statistical difference between thawing methods. CONCLUSION: Despite the significant differences in structural changes of presented thawing protocols, the ultimate tensile strain showed no statistical difference between thawing methods.

Crossing borders to facilitate live donor kidney transplantation: the Czech-Austrian kidney paired donation program - a retrospective study.

Kidney paired donation (KPD) is a valuable tool to overcome immunological barriers in living donor transplantation. While small national registries encounter difficulties in finding compatible matches, multi-national KPD may be a useful strategy to facilitate transplantation. The Czech (Prague) and Austrian (Vienna) KPD programs, both initiated in 2011, were merged in 2015. A bi-national algorithm allowed for ABO- and low-level HLA antibody-incompatible exchanges, including the option of altruistic donor-initiated domino chains. Between 2011 and 2019, 222 recipients and their incompatible donors were registered. Of those, 95.7% (Prague) and 67.9% (Vienna) entered into KPD registries, and 81 patients received a transplant (95% 3-year graft survival). Inclusion of ABO-incompatible pairs in the Czech program contributed to higher KPD transplant rates (42.6% vs. 23.6% in Austria). After 2015 (11 bi-national match runs), the median pool size increased to 18 pairs, yielding 33 transplants (8 via cross-border exchanges). While matching rates doubled in Austria (from 9.1% to 18.8%), rates decreased in the Czech program, partly due to implementation of more stringent HLA antibody thresholds. Our results demonstrate the feasibility of merging small national KPD programs to increase pool sizes and may encourage the implementation of multi-national registries to expand the full potential of KPD.

Sirolimus vs mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study.

The study was intended to compare pancreas graft survival rates in two groups of pancreas and kidney transplant recipients prospectively randomized to treatment either with sirolimus or MMF. From 2002 to 2013, 238 type 1 diabetic recipients with end-stage kidney disease were randomized 1:1 to sirolimus or MMF treatment. Noncensored pancreas survival at 5 years was 76.4 and 71.6% for sirolimus and MMF groups, respectively (P > .05). Death-censored pancreas survival was better in the sirolimus group (P = .037). After removal of early graft losses pancreas survival did not differ between groups (MMF 83.1% vs sirolimus 91.6%, P = .11). Nonsignificantly more grafts were lost due to rejection in the MMF group (10 vs 5; P = .19). Cumulative patient 5-year survival was 96% in the MMF group and 91% in the sirolimus group (P > .05). Five-year cumulative noncensored kidney graft survival rates did not statistically differ (85.6% in the sirolimus group and 88.8% in MMF group). Recipients treated with MMF had significantly more episodes of gastrointestinal bleeding (7 vs 0, P = .007). More recipients in the sirolimus group required corrective surgery due to incisional hernias (21 vs 12, P = .019). ClinicalTrials No.: NCT03582878.

Simultaneous living donor orthotopic renal transplantation and bilateral nephrectomy for recurrent renal cell carcinoma and renal failure: case report and review of literature.

BACKGROUND: We report the case of a 43-year-old female patient with systemic lupus erythematosus, class III lupus nephritis, with predialysis creatinine levels around 350 µmol/L (3.95 mg/dL) after partial resection of the left kidney with histologically verified papillary carcinoma in 2010. Preoperative computed tomography of the abdomen revealed a small 8 mm tumor in the left upper kidney pole. The patient was indicated for simultaneous bilateral nephrectomy and orthotopic renal transplantation with the aim to minimize invasiveness of the procedure as well as for curable tumor removal. METHOD: The procedure was performed under the full anesthesia trough upper middle laparotomy. As the first step, bilateral transperitoneal nephrectomy was performed. The live donor surgery started in a parallel theater to shorten the cold ischemic time of the graft. The renal graft had singe vessels and ureter; it was placed into the recipient's right orthotopic position. End-to-end anastomosis of the right renal vein and artery anastomosis were performed; ureter was anastomosed end-to-end using recipient's ureter. RESULTS: The postoperative period was uneventful with repeatedly excellent ultrasonography check-up of the graft's perfusion. The patient was discharged after 13 days with a good renal function of the graft (urea: 15 mmol/L, creatinine 160 µmol/L [1.80 mg/dL]). CONCLUSION: Orthotopic renal transplantation is a technically challenging but valid alternative for patients who are unsuitable candidates for heterotopic renal transplantation or in cases where there is a clear benefit of orthotopic renal transplantation.

The Effects of Diuresis, Duration of Dialysis and Age on Lower Urinary Tract Function in Urologically Healthy Male Patients on the Waiting List for Kidney Transplant.

PURPOSE: This work investigated the effects of diuresis, duration of dialysis and age on lower urinary tract function in urologically healthy males on the waiting list for kidney transplant. MATERIALS AND METHODS: The study included all men who had kidney transplants at our centre between January 2009 and December 2014 who had normal urological findings prior to inclusion on the list. Diuresis, the duration of haemodialysis, age, and parameters of function of the lower urinary tract as determined by filling and voiding cystometry were evaluated. RESULTS: The study included 127 men (median age, 59 years; median diuresis, 250 mL; median duration of dialysis, 469.5 days). We found that greater diuresis was accompanied by significantly higher FDV, FDV/Cmax, NDV,Cmax and compliance and by significantly lower Pdet.max, PdetQmax and BOOI. Longer duration of dialysis was accompanied by significantly lower FDV, NDV and Cmax, compliance and Qmax.p and with significantlyhigher Pdet.max, PdetQmax and BOOI. Older age was associated with significantly higher Pdet.max and with significantly lower compliance. Worsening of the basic parameters of the storage function of the lower urinary tract occurred when diuresis decreased to 500-750 mL, when the duration of dialysis was one year and when patients were older than 54 years. CONCLUSION: In healthy male patients on the waiting list for kidney transplant, there were connections between the occurrence of dysfunctions of the lower urinary tract and diuresis, duration of dialysis and age. Patients should be monitored for dysfunctions of the lower urinary tract before and after transplantation.

Benefits of Islet Transplantation as an Alternative to Pancreas Transplantation: Retrospective Study of More Than 10 Ten Years of Experience in a Single Center.

BACKGROUND: Pancreas transplantation (PTx) represents the method of choice in type 1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. In 2005, the Institute for Clinical and Experimental Medicine (IKEM) launched a program to investigate the safety potential of islet transplantation (ITx) in comparison to PTx. AIM: This study aims to compare the results of PTx and ITx regarding severe hypoglycemia elimination, metabolic control, and complication rate. METHODS: We analyzed the results of 30 patients undergoing ITx and 49 patients treated with PTx. All patients were C-peptide-negative and suffered from hypoglycemia unawareness syndrome. Patients in the ITx group received a mean number of 12,349 (6,387-15,331) IEQ/kg/person administered percutaneously into the portal vein under local anesthesia and radiological control. The islet number was reached by 1-3 applications, as needed. In both groups, we evaluated glycated hemoglobin, insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia, and complications. We used the Mann Whitney test, Wilcoxon signed-rank test, and paired t-test for analysis. We also individually assessed the ITx outcomes for each patient according to recently suggested criteria established at the EPITA meeting in Igls. RESULTS: Most of the recipients showed a significant improvement in metabolic control one and two years after ITx, with a significant decrease in HbA1c, significant elevation of fasting and stimulated C-peptide, and a markedly significant reduction in insulin dose and the frequency of severe hypoglycemia. Seventeen percent of ITx recipients were temporarily insulin-independent. The results in the PTx group were comparable to those in the ITx group, with 73% graft survival and insulin independence in year 1, 68% 2 years and 55% 5 years after transplantation. There was a higher rate of complications related to the procedure in the PTx group. Severe hypoglycemia was eliminated in the majority of both ITx and PTx recipients. CONCLUSION: This report proves the successful initiation of pancreatic islet transplantation in a center with a well-established PTx program. ITx has been shown to be the method of choice for hypoglycemia unawareness syndrome, and may be considered for application in clinical practice if conservative options are exhausted.

Molecular patterns of diffuse and nodular parathyroid hyperplasia in long-term hemodialysis.

Secondary hyperparathyroidism is a well-known complication of end-stage renal disease (ESRD). Both nodular and diffuse parathyroid hyperplasia occur in ESRD patients. However, their distinct molecular mechanisms remain poorly understood. Parathyroid tissue obtained from ESRD patients who had undergone parathyroidectomy was used for Illumina transcriptome screening and subsequently for discriminatory gene analysis, pathway mapping, and gene annotation enrichment analysis. Results were further validated using quantitative RT-PCR on the independent larger cohort. Microarray screening proved homogeneity of gene transcripts in hemodialysis patients compared with the transplant cohort and primary hyperparathyroidism; therefore, further experiments were performed in hemodialysis patients only. Enrichment analysis conducted on 485 differentially expressed genes between nodular and diffuse parathyroid hyperplasia revealed highly significant differences in Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes database in ribosome structure (P = 3.70 × 10-18). Next, quantitative RT-PCR validation of the top differently expressed genes from microarray analysis proved higher expression of RAN guanine nucleotide release factor (RANGRF; P < 0.001), calcyclin-binding protein (CACYBP; P < 0.05), and exocyst complex component 8 (EXOC8; P < 0.05) and lower expression of peptidylprolyl cis/trans-isomerase and NIMA-interacting 1 (PIN1; P < 0.01) mRNA in nodular hyperplasia. Multivariate analysis revealed higher RANGRF and lower PIN1 expression along with parathyroid weight to be associated with nodular hyperplasia. In conclusion, our study suggests the RANGRF transcript, which controls RNA metabolism, to be likely involved in pathways associated with the switch to nodular parathyroid growth. This transcript, along with PIN1 transcript, which influences parathyroid hormone secretion, may represent new therapeutical targets to cure secondary hyperparathyroidism.

[Eversion carotid endarterectomy: evaluation of results after changing the operation technique]. / Everzní endarterektomie arterie carotis interna: hodnocení výsledku po zmene operacní techniky.

BACKGROUND: Stroke is the third most common cause of mortality, and carotid artery stenosis causes up to 30% of all ischemic strokes. Eversion CEA (ECEA) has been proposed as an acceptable alternative to the standard bifurcation endarterectomy in many patients. This study was designed to analyze the long-term durability of ECEA in symptomatic and asymptomatic patients. Data were retrospectively reviewed to determine the incidence of major adverse cardiovascular events (MACEs) within 30 days of surgery, late survival, and the incidence of restenosis. METHODS AND RESULTS: From January 1999 to June 2010, 344 ECEAs were performed on 324 patients (34% female, 38% symptomatic). The mean follow-up period was 30 months. CONCLUSIONS: MACEs occurred in 28 patients (8.6%). The overall incidence of stroke or death after ECEA was 1.7% and 0.9% at discharge. The overall incidence of stoke or death after CEA was 4.3% and 21% (14 strokes, 69 deaths, 8 of which were stroke-related). The overall occurrence of any restenosis (> 50%) after CEA was 4.3% (14 of 324 procedures).