- MeSH
- Survival Analysis MeSH
- Drug Combinations MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Prospective Studies MeSH
- Graft Rejection complications therapy MeSH
- Sirolimus pharmacology therapeutic use MeSH
- Tacrolimus pharmacology therapeutic use MeSH
- Kidney Transplantation statistics & numerical data trends MeSH
- Check Tag
- Humans MeSH
BACKGROUND: In patients having undergone orthotopic heart transplantation, a number of complications exist that are known to be connected to both telomerase activity and telomere length. The aim of this study was to determine how telomere length in aortic DNA correlates with the subsequent post-transplantation development of the patients. MATERIALS AND METHODS: Between 2005 and 2015, we collected aortic samples from 376 heart recipients (age 50.8 ± 11.8 years) and 383 donors (age 38.6 ± 12.2 years). Relative telomere length in aortic tissue DNA was determined using quantitative PCR. RESULTS: Shorter telomere length was detected in heart allograft recipients compared to donors (P < 0.0001). Patients suffering acute cellular rejection had significantly shorter telomere length (P < 0.01) than patients without rejection. Shorter telomere length was observed in patients with implanted mechanical circulatory support before heart transplantation (P < 0.03), as well as in subjects with cardiac allograft vasculopathy (P < 0.05). Overall survival time after heart transplantation was associated with shorter donor telomeres (P < 0.004). CONCLUSIONS: Telomere length differed between donors and recipients independent of the sex and age of the patients. Our findings suggest a potential new linkage between the aortic telomere length of recipients and post-heart transplant complications. Further studies focusing on epigenetic modifications and gene regulation involved in telomere maintenance in transplanted patients should verify our results.
- MeSH
- Aorta physiology MeSH
- Tissue Donors MeSH
- Adult MeSH
- Transplantation, Homologous trends MeSH
- Middle Aged MeSH
- Humans MeSH
- Graft Rejection diagnosis genetics physiopathology MeSH
- Telomere physiology MeSH
- Heart Transplantation trends MeSH
- Telomere Shortening physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Caveolin-1 is a phosphoprotein that plays a crucial role in tissue remodeling and fibrotic pathways, controlling fibroblast function, proliferation, and apoptosis. Here we aimed to examine the association between the CAV1 rs4730751 gene polymorphism and kidney graft function, graft histology, and graft survival. This study enrolled 270 Caucasian deceased – donor renal transplant recipients. We found no statistically significant associations between CAV1 rs4730751 and delayed graft function, acute rejection, or chronic allograft dysfunction, as well as creatinine values at 1–60 months after transplantation, the risk of graft loss, dialysis or death after transplantation, or histopathological changes in kidney allograft biopsies. Our findings do not support an association between the CAV1 gene rs4730751 polymorphism and kidney allograft function in our population.
BACKGROUND: Delayed graft function (DGF) caused by ischemia/reperfusion injury (I/RI) negatively influences the outcome of kidney transplantation. This prospective single-center study characterized the intrarenal transcriptome during I/RI as a means of identifying genes associated with DGF development. METHODS: Characterization of the intrarenal transcription profile associated with I/RI was carried out on three sequential graft biopsies from respective allografts before and during transplantation. The intragraft expression of 92 candidate genes was measured using quantitative real-time reverse transcriptase polymerase chain reaction (2) in delayed (n=9) and primary function allografts (n=26). RESULTS: Cold storage was not associated with significant changes to the expression profile of the target gene transcripts; however, up-regulation of 16 genes associated with enhanced activation of innate and adaptive immune responses and apoptosis was observed after reperfusion. Multivariate logistic regression analysis revealed that higher tubular atrophy scores (ct) together with a lower expression of Netrin-1 might predict DGF development (training area under the receiver operating curve=0.89, cross-validated area under the receiver operating curve=0.81). CONCLUSIONS: Poor baseline tubular cell quality (defined by a higher rate of tubular atrophy) combined with the reduced potential of apoptotic survival factors represented by decreased Netrin-1 gene expression were associated with delayed kidney graft function.
- MeSH
- Principal Component Analysis MeSH
- Atrophy MeSH
- Biopsy MeSH
- Immunohistochemistry MeSH
- Kidney Tubules pathology MeSH
- Humans MeSH
- Logistic Models MeSH
- Tumor Suppressor Proteins analysis genetics MeSH
- Nerve Growth Factors analysis genetics MeSH
- Delayed Graft Function etiology metabolism pathology MeSH
- Prospective Studies MeSH
- Gene Expression Regulation MeSH
- Reperfusion Injury complications MeSH
- Kidney Transplantation adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Prevalence časných cévních rejekčních změn v aloštěpech ledvin u dětí u akutní rejekce (AR) byla 7,1 %. Morfologie odpovídala mírné a střední rejekční arteritidě (v1, v2), respektive celulární a obliterativní arteriopatii (CA, OA). Změny byly nalezeny 37. až 336. den po transplantaci ledviny (TPL). Doba funkce štěpů s cévními změnami byla značně kratší než tam, kde se cévní léze nevyskytly (p = 0,0018). Prevalence pozdních vaskulárních rejekčních změn u chronické rejekce (CR) byla 24,3 %. Ve třech případech byl zaznamenán obraz degenerativní endarteritidy (EAD) pozdního typu. Ve dvou z 9 vyšetřených štěpů (22,2 %) CR byla imunofluorescenčním vyšetřením (IF) prokázána silná difuzní vazba frakce komplementu C4d, v současnosti považovaná za korelát humorální rejekce. V těchto dvou případech byl průběh nepříznivý a skončil selháním štěpů. Humorální imunitní reakce při akutní a chronické rejekci (AHR, CHR) je nově vymezenou jednotkou v patologii rejekční nefropatie. Nález AHR je důležitý pro terapii i prognózu štěpu, kdežto význam CHR se dosud upřesňuje.
A study of early vascular rejection lesions in renal allografts in children showed their prevalence in 7.1% in acute rejection (AR). The morphology corresponded to mild or moderate rejection arteritis (v1, v2), or cellular and obliterative arteriopathy (CA, OA). The changes were found 37 to 336 days after renal transplantation (TPL), respectively. The functional period of grafts with early vascular lesions was considerably shorter than in cases where no vascular lesions developed (p=0.0018). A study of late vascular rejection lesions in renal allografts showed a prevalence of 24.3% in chronic rejection (CR). Degenerative endarteritis (EAD) was recorded in three cases. In two out of nine CR grafts examined (22.2%), strong diffuse linear binding of complement C4d fraction, which is at present considered to be a sign of humoral rejection, was proved by immunofluorescence. In these two cases, the course was unfavorable and the grafts failed. The humoral immune reaction in both acute and chronic rejection (AHR, CHR) is a recently defined unit in the pathology of rejection nephropathy. The finding of AHR is important in the treatment and prognosis of graft, whereas its significance in CHR is being assessed.
- MeSH
- Arteritis diagnosis MeSH
- Biopsy MeSH
- Endarteritis diagnosis MeSH
- Research Support as Topic MeSH
- Immunologic Techniques MeSH
- Complement System Proteins MeSH
- Humans MeSH
- Adolescent MeSH
- Graft Rejection MeSH
- Kidney Transplantation MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- Review MeSH
- Comparative Study MeSH
BACKGROUND: Malakoplakia is an unusual chronic inflammatory disease with distinctive histopathological features rarely involving the parenchyma of a transplanted kidney, and to date less than ten cases have been reported. METHODS AND RESULTS: We present a case of malakoplakia of a kidney graft in a 31 year old woman after simultaneous kidney and pancreas transplantation, which was successfully treated with quinolones. After the treatment of malakoplakia, she was monitored regularly, and her renal and pancreas grafts functioned well for the following 9 years, which is 12 years post transplantation. Moreover, 1 year after treatment of malakoplakia she became pregnant and gave birth to a healthy child. CONCLUSION: Evaluation of a kidney biopsy sample represents the key to diagnosis of malakoplakia which is important for correct patient management. Treatment with antibiotics with intracellular penetration (quinolone type) may result in curing the disease. According to our knowledge, this is the first case of allograft renal malakoplakia after combined kidney and pancreas transplantation.
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Quinolones therapeutic use MeSH
- Diabetes Mellitus, Type 1 surgery MeSH
- Adult MeSH
- Humans MeSH
- Malacoplakia diagnosis etiology drug therapy MeSH
- Kidney Diseases etiology drug therapy MeSH
- Kidney Transplantation adverse effects MeSH
- Pancreas Transplantation MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
Composite facial allotransplantation is emerging as a treatment option for severe facial disfigurements. The technical feasibility of facial transplantation has been demonstrated, and the initial clinical outcomes have been encouraging. We report an excellent functional and anatomical restoration 1 year after face transplantation. A 59-year-old male with severe disfigurement from electrical burn injury was treated with a facial allograft composed of bone and soft tissues to restore midfacial form and function. An initial potent antirejection treatment was tapered to minimal dose of immunosuppression. There were no surgical complications. The patient demonstrated facial redness during the initial postoperative months. One acute rejection episode was reversed with a brief methylprednisolone bolus treatment. Pathological analysis and the donor's medical history suggested that rosacea transferred from the donor caused the erythema, successfully treated with topical metronidazol. Significant restoration of nasal breathing, speech, feeding, sensation and animation was achieved. The patient was highly satisfied with the esthetic result, and regained much of his capacity for normal social life. Composite facial allotransplantation, along with minimal and well-tolerated immunosuppression, was successfully utilized to restore facial form and function in a patient with severe disfigurement of the midface.
- MeSH
- Middle Aged MeSH
- Humans MeSH
- Burns, Electric pathology surgery MeSH
- Facial Injuries pathology surgery MeSH
- Graft Rejection etiology MeSH
- Rosacea etiology pathology MeSH
- Facial Transplantation adverse effects methods pathology physiology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
BACKGROUND: Primary graft dysfunction (PGD) after lung transplantation (LuTx) contributes substantially to early postoperative morbidity. Both intraoperative transfusion of a large amount of blood products during the surgery and ischemia-reperfusion injury after allograft implantation play an important role in subsequent PGD development. METHODS: We have previously reported a randomized clinical trial of 67 patients where point of care (POC) targeted coagulopathy management and intraoperative administration of 5% albumin led to significant reduction of blood loss and blood product consumption during the lung transplantation surgery. A secondary analysis of the randomized clinical trial evaluating the effect of targeted coagulopathy management and intraoperative administration of 5% albumin on early lung allograft function after LuTx and 1-year survival was performed. RESULTS: Compared to the patients in the control (non-POC) group, those in study (POC) group showed significantly superior graft function, represented by the Horowitz index (at 72 h after transplantation 402.87 vs 308.03 with p < 0.001, difference between means: 94.84, 95% CI: 60.18-129.51). Furthermore, the maximum doses of norepinephrine administered during first 24 h were significantly lower in the POC group (0.193 vs 0.379 with p < 0.001, difference between the means: 0.186, 95% CI: 0.105-0.267). After dichotomization of PGD (0-1 vs 2-3), significant difference between the non-POC and POC group occurred only at time point 72, when PGD grade 2-3 developed in 25% (n = 9) and 3.2% (n = 1), respectively (p = 0.003). The difference in 1-year survival was not statistically significant (10 patients died in non-POC group vs. 4 patients died in POC group; p = 0.17). CONCLUSIONS: Utilization of a POC targeted coagulopathy management combined with Albumin 5% as primary resuscitative fluid may improve early lung allograft function, provide better circulatory stability during the early post-operative period, and have potential to decrease the incidence of PGD without negative effect on 1-year survival. TRIAL REGISTRATION: This clinical trial was registered at ClinicalTrials.gov (NCT03598907).
- MeSH
- Allografts MeSH
- Hemorrhage MeSH
- Humans MeSH
- Primary Graft Dysfunction * MeSH
- Reperfusion Injury * MeSH
- Lung Transplantation * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Úvod: Autoři předkládají střednědobé zkušenosti pracoviště s použitím čerstvých arteriálních allograftů v řešení infekce cévní protézy v aortální či aortofemorální pozici. Materiál a metodika: V letech 2001–2010 jsme operovali celkem 24 nemocných (23 s infektem cévní protézy v aortální, resp. aortofemorální pozici a 1x s metastatickou nepravou výdutí bifurkace AA) za použití čerstvého tepenného alloštěpu. Poměr M/Ž byl 15/9, průměrný věk souboru 65,8 (36–81) let. Z přidružených chorob dominovala této sestavě chronická onemocnění GIT. Nemocní prodělali před výkonem celkem 70 cévních operací (1–9; m. 2,9/pac.), medián mezi první a poslední operací byl 5,8 roku. Sedm nemocných bylo v sepsi (29,2 %), 3 měli aortoenterickou píštěl. Proveden 13x aortobifemorální bypass, 8x aortounifemorální bypass a 3x aortální, resp. aortobiiliacká náhrada v rozličných technických modifikacích včetně sekvenčních distálních rekonstrukcí. Tepenný allograft byl použit do 8–48 hodin po odběru (medián studené ischemie 20 hodin) a nemocným již perioperačně nasazen cyklosporin A. Výsledky: Hospitalizační mortalita byla 20,8 % (5/24), ve dvou případech zapříčiněná pooperačním krvácením z napojení alloštěpu či při jeho nekróze. Další úmrtí nesouvisela přímo s implantátem. Amputovali jsme dvě končetiny (8,3 %), ischemické již před operací. Medián sledování nemocných je 4,6 roku (3 m.–8 r.). Přežití do 3 let bylo 68,4 % a příčiny úmrtí nesouvisely v dohledaných případech se stavem allograftu. K pozdnímu uzávěru raménka došlo 2x, zúžení v průběhu štěpu jsme zaznamenali 2x a stenózy v distálních napojeních 3x. Stav byl vyřešen reoperací či intervenčně a četnost servisních výkonů tak dosáhla 20,5 % ve střednědobém sledování. Jeden allograft je sledován pro mírnou dilataci. Závěr: Krátce konzervovaný tepenný allograft si, za podmínek respektování ABO kompatibility a trvalé postimplantační imunosupresivní léčby zachovává svou anatomickou strukturu i funkci a v hostilním prostředí předchozího infektu představuje cennou alternativu chirurgické léčby infekce cévní protézy v aortofemorální pozici či mykotického aneuryzmatu.
Introduction: The mid-term experience with the use of the fresh arterial allografts in the treatment of aortic or aortofemoral prosthetic infection is presented. Material and methods: Between 2001–2010 24 patients (23 with the infected graft in aortic or aortofemoral position and one with a mycotic aneurysm of the aortic bifurcation) were operated with the use of the fresh arterial allograft. Male/female ratio was 15/9, average age 65.8 (36–81) years. The gastrointestinal comorbidities dominated this cohort. The total of 70 previous vascular operations (1–9; m. 2.9/patient) were performed with the median of 5.8 years between the first and the last procedure. Seven patients had sepsis (29.2%), aortoeneteric fistula occurred in three. Various technical modifications of the aortobifemoral (13), aortounifemoral (8) bypass, aortic and aortoiliac replacement (3) were performed including the sequential distal reconstructions. The arterial allograft was used within 8–48 hours following harvest (the median cold ischemic time of 20 hours) and all patients were given cyclosporine A perioperatively. Results: In-hospital mortality was 20.8% (5/24), twice caused by postoperative hemorrhage from either the aortic anastomosis or the graft necrosis. The remaining deaths were not related to the allograft itself. Two limbs, preoperatively ischemic, were amputated (8.3%). The median follow-up is 4.6 years (3 m.–8 yrs.). The three-years survival was 68.4% and the known causes of death had no relation to the allograft. The late occlusion of the graft limb occurred twice, stenoses within its course twice and three femoral anastomotic stenoses were disclosed. All were treated either surgically or by PTA/stent and the redo procedures’ rate has thus reached 20.5% in the mid-term follow-up interval. One graft has shown a slight diffuse dilatation since requiring but follow-up. Conclusions: Under the conditions of the ABO compatibility tolerance and ongoing postimplantation immunosuppression the shortly ischemic arterial graft helds its anatomic structure and function and within the hostile setting of the previous infection represents a valuable alternative of the surgical treatment of the vascular prosthetic infection in the aortofemoral position or of the mycotic aneurysm.
- Keywords
- imunosuprese,
- MeSH
- Aorta, Thoracic transplantation MeSH
- Aortic Aneurysm surgery MeSH
- Femoral Artery transplantation MeSH
- Blood Vessel Prosthesis adverse effects MeSH
- Adult MeSH
- Transplantation, Homologous MeSH
- Prosthesis-Related Infections surgery microbiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
