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Russian Journal of Transplantology and Artificial Organs

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Vol 25, No 1 (2023)
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Editorial

Clinical Transplantology

7-14 631
Abstract

 

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs).

Objective: to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19.

Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 ± 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up.

Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by rnseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 ± 3.2 days versus 4.6 ± 1.6 days in group 1, p < 0 .001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.

15-23 609
Abstract

Objective: to study the causes of graft loss and indications for repeat liver transplantation (rLT).

Materials and Methods. We studied the experience garnered from 250 orthotopic full-size cadaveric liver transplantations in 228 patients from 1998 to 2021. The severity of the patient’s condition at the time of intervention was estimated according to the MELD scale. Repeat surgeries were performed in 22 cases in 19 patients (analyzed group).

Results. Organ preservation parameters, length of stay in intensive care unit (ICU), severity of postoperative complications in primary transplantations in general and in the analyzed group did not differ significantly. The main causes of graft loss were graft arterial insufficiency (57.9%) and hepatic artery thrombosis (21%). Severe early allograft dysfunction (EAD) and primary nonfunction accounted for 10.5%, portal vein thrombosis occurred in 5%, and chronic graft rejection was noted in 5% of cases.

Conclusion. Arterial insufficiency is one of the leading causes of graft loss after liver transplantation. Early correction of arterial and biliary complications help in preserving graft viability.

24-30 459
Abstract

A clinical case of pancreas transplantation (PTx) based on an original technique is presented. The applied technique made it possible to prevent the spread and involvement of the abdominal organs in an inflammatory process caused by postoperative graft pancreatitis, and to preserve the pancreas graft.

31-37 550
Abstract

Hepatic artery thrombosis (HAT) following liver transplantation (LT) is a severe life-threatening complication that can lead to graft loss and mortality after LT. According to different reports, HAT incidence ranges from 2% to 9%. Modern endovascular and radiosurgical techniques allow for minimally invasive liver graft revascularization. Nonetheless, a major consequence of even a successful revascularization is ischemic cholangiopathy, which can lead to ischemic biliary strictures and anastomotic leak. The paper presents a clinical case of long-term complex treatment of combined complications of LT using minimally invasive endovascular and endoscopic techniques.

38-42 572
Abstract

Kidney transplantation (KT) is regarded as the most effective therapeutic approach for people with end-stage renal disease. However, for a number of reasons - constant increase in the incidence of diseases contributing to formation and development of chronic kidney disease, as well as continuing shortage of donor organs - 78-95% of patients in need of a kidney transplant do not receive the necessary treatment, and the waiting list stretches for several years. This paper presents the first outcomes of KT for chronic glomerulonephritis performed at St. Luke’s Clinical Hospital in St. Petersburg, in collaboration with the staff of Shumakov National Medical Research Center of Transplantology and Artificial Organs.

43-46 405
Abstract

This paper presents a clinical case of laparoscopic nephrectomy for a large (10 cm) renal sinus mass in an allograft kidney, followed by intrarenal urinary tract reconstruction with ureteral reimplantation. The surgery had an acceptable oncological outcome, without loss of kidney function. Regardless of the volume and extent of the tumor process, the use of minimally invasive, nephron-sparing treatment techniques takes a leading position in the treatment of renal cancer in kidney recipients. Intrarenal urinary tract reconstruction allows a kidney to be saved even if the tumor is significantly large and/or inoperable.

47-51 397
Abstract

The paper presents a clinical case of successful kidney transplantation (KTx) in a patient with end-stage chronic kidney disease (ESKD) resulting from familial Mediterranean fever (FMF). Pre-transplant preparation and posttransplant management tactics are presented. The authors conclude that ESKD can be effectively treated by KTx in a patient with FMF against the background of ongoing pathogenetic therapy in autoinflammation.

52-61 771
Abstract

Objective: to develop a personalized algorithm for extended-release tacrolimus in kidney recipients and to analyze its early outcomes in comparison with a retrospective control group.

Materials and methods. The first (I) control group «Standard Protocol» included 228 patients operated on at Botkin City Clinical Hospital from June 2018 to November 2021; tacrolimus was administered postoperatively in a starting standard dosage of 0.2 mg/kg. The second group (II) consisted of 75 patients operated from December 2021 to November 2022, whose postoperative treatment involved a personalized extended-release tacrolimus dosing protocol. Induction immunosuppression was similar in both groups. The target tacrolimus level in the early postoperative period was considered to be 10-12 ng/ml for all patients. The comparison criteria included incidence of Over-immunosuppression (tacrolimus C0 >15 ng/ml), incidence of acute rejection and infectious complications in the first month after surgery, incidence and duration of delayed graft function (DGF), and length of stay at the hospital.

Results. Over-immunosuppression was statistically significantly lower in the personalized protocol group, with 36.7% in group I and 87.5% in group II (p < 0.001). There was also a lower incidence of early infectious complications in group II: 5.4% vs. 13.2%, however, without reaching a level of statistical significance (p = 0.088). DGF incidence in group I and group II were 25.4% (58/228) and 22.7% (17/75), respectively. The length of stay at the hospital in group II was also statistically significantly lower: 13 versus 19 bed days (p = 0.033). In both subgroups, no patient developed acute rejection in the first month after surgery (p = 1).

Conclusion. The personalized dosing protocol that was developed for extended-release tacrolimus in kidney recipients achieves the target levels of the drug recommended for the early postoperative period with low risk of under-immunosuppression and associated acute graft rejection, with a significantly lower incidence of over-immunosuppression.

62-67 541
Abstract

Objective: to evaluate the role of physical activity (at sports games) in improving the quality of life of organ recipients.

Materials and methods. We examined 42 adult lung, heart, kidney and liver recipients, and patients undergoing renal replacement therapy (mean age 42.6 ± 12.09 years) - participants of the First Russian Transplant Games. The results were analyzed. Quality of life of the recipients was assessed using the nonspecific SF-36 questionnaire.

Results. After solid organ transplantation, the interviewed recipients answered that they try to lead an active lifestyle, to engage in accessible physical activities, and to participate in sports events intended for organ recipients. Assessment of the quality of life according to the SF-36 questionnaire showed that all the participants had high scores in terms of the physical and psychological component, which is associated with regular physical training and sports.

Conclusion. Physical exercise and active participation in sports activities are an important component in the socialization and rehabilitation of organ recipients. These two factors also improve the psychological and physical components of the quality of life of the recipients.

68-76 431
Abstract

Objective: to determine the efficacy of non-selective beta-blockers (NSBBs) in the primary prevention of bleeding esophageal varices and to assess their impact on the survival of patients with ascites enrolled in the liver transplant waiting list (LTWL).

Materials and methods. We carried out a retrospective comparative study of cirrhotic patients with severe ascites and esophageal varices without bleeding before enrollment in the LTWL. Primary prophylaxis of variceal bleeding included the use of NSBBs (n = 97, group 1). These drugs were not used in the other patients (n = 91, group 2).

Results. There were no significant differences between the groups in terms of clinical, laboratory and demographic parameters, MELD scores and Child-Turcotte-Pugh (CTP) classes for cirrhosis. Patient groups included in the study had no significant differences with respect to incidence of medium- and large-sized varices and incidence of severe ascites. Bleeding incidence was significantly lower in the NSBBs group than in the non-NSBBs group (52.6% and 95.6%, respectively, p = 0.0001).

Conclusion. NSBBs constitute an efficacious therapy in primary prophylaxis of esophageal variceal bleeding, thereby saving life and preventing delisting of patients with ascites from the LTWL.

Heart Transplantation and Assisted Circulation

77-89 997
Abstract

Implantable left ventricular assist device (LVAD) is a state-of-the-art treatment for adults and children with end-stage heart failure. The early and late period after LVAD implantation can be severely complicated. Right ventricular failure (RVF) still remains a common complication after LVAD implantation. RVF is the cause of reduced post-implant survival. We suggest that an additional temporary or permanent right ventricular assist device (RVAD) is an effective treatment for LVAD-associated RVF. In this clinical case report, we describe the medical history of a pediatric patient (14 years old) with severe heart failure (PediMACS Level 1) against a background of dilated cardiomyopathy. The patient required peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) prior to urgent LVAD (HM3) implantation. In the early post-LVAD implantation (1 POD) period, the patient presented with hemodynamic and echocardiographic events of acute RVF that was resistant to drug therapy (inotropic/vasopressor support, iNO) and required mechanical circulatory support (MCS) with a preoperatively implanted VA-ECMO. In the LVAD-associated RVF scenario, VA-ECMO as a means of total cardiac bypass is a non-physiological MCS method and, therefore, undesirable. In this clinical situation, our solution was to use a paracorporeal centrifugal blood pump for temporary right heart support. A RVAD was assembled using percutaneous cannulation in two sites and a modification of the pre-existing VA-ECMO circuit. For RVAD, we used an ECMO cannula previously installed through the femoral vein (26 F) and added a reverse venous cannula (22 F) through the right internal jugular vein into the pulmonary trunk. To facilitate the passage of the return cannula into the pulmonary artery, we used a contralateral sheath (6 F, 40 cm) and an Amplatz Super Stiff guidewire under radiological control. The oxygenator was removed from the circuit on day 2 of RVAD. Central hemodynamics (reduction in right atrial pressure (RAP) to 10 mm Hg, increase in pulmonary capillary wedge pressure (PCWP) to 14 mm Hg), as well as right ventricular (RV) and left ventricular (LV) volume characteristics all improved. These observations allowed us to optimize the performance of the implantable LVAD (increase in flow rate to 4.2 l/min or 2.1 l/min/m2). The duration of paracorporeal RVAD after LVAD implantation was 7 days with an average flow rate of 2.3 ± 0.2 l/min. Postoperative treatment in the intensive care unit (ICU) lasted for 15 days. The patient was discharged from the hospital on postoperative day 34.

90-98 638
Abstract

Chronic heart failure (CHF) against the background of congenital heart disease, mostly in early childhood, or various forms of cardiomyopathies, more common in teenage age, represents an important cause of morbidity and mortality in the pediatric population [1, 2]. Due to the increase in the number of patients suffering from refractory end-stage CHF over the last two decades, and the current shortage of donor organs in pediatric practice, the issue of long-term mechanical circulatory support (MCS) is becoming increasingly a pressing problem. Patient management is a multidisciplinary task, since prolonged use of anticoagulant and antiplatelet therapy to prevent ventricular thrombosis has potentially life-threatening complications - acute hemorrhagic stroke and bleeding of varying severity.

99-105 510
Abstract

Objective: comparative analysis of long-term outcomes following heart transplantation (HT) with prolonged and short cold ischemia.

Materials and methods. We analyzed the data of 29 orthotopic HT with >4 hours of cold ischemia. The transplant surgery was performed at Meshalkin National Medical Research Center between 2013 and the present time. Organs were obtained from donors from other regions. The control group consisted of 29 HTs with cold ischemia <4 hours, performed in the same period. The minimum distance between the transplant center and the donor base was about 250 km (Barnaul); the maximum distance was about 850 km (Krasnoyarsk). Recipient survival and postoperative peculiarities were analyzed.

Results. In-hospital survival in the prolonged cold ischemia group was 89.7% (n = 26) with 3 deaths (10.3%). In the second group (<240 min), in-hospital survival was 79.3% (n = 23) with 6 (20.7%) deaths. The Kaplan-Meier survival analysis showed no difference between the groups (Log-Rank Test, P 1/4 0.59). In addition, cold ischemia time did not increase the risk of graft rejection and the risk of transplant coronary artery disease (TCAD).

Conclusion. HT with cold ischemia >4 hours did not have worse outcomes than in short graft ischemia. This provides grounds for further accumulation of experience in the use of heart donors from remote locations.

106-112 453
Abstract

Objective: to investigate the efficiency of a device that generates pulsatile flow during constant-speed axial-flow pump operation for use in left ventricular assist devices.

Materials and methods. The pulsatile flow-generating device, hereinafter referred to as «pulsator», consists of a variable hydraulic resistance made in the form of a hull. A tube of elastic biocompatible material featuring an inner diameter of 11 mm is installed inside it. In the systolic phase of the left ventricle, due to systolic pressure, the elastic tube is fully opened, minimizing resistance to blood ejection. In the diastolic phase, due to suction action of the flow pump operating in constant revolutions, the elastic tube partially closes, creating additional hydraulic resistance to blood flow, which leads to reduced diastolic aortic pressure. Comparative assessment of axial-flow pump operation in pulsating and non-pulsating modes was carried out on a hydrodynamic stand that simulated the cardiovascular system. The following indices were calculated: arterial pressure pulsation (Ip), in-pump flow pulsation (AQ), energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE).

Results. When comparing axial-flow pump operation in pulsatile and continuous mode, arterial pressure pulsation index, in-pump pulsation index, and SHE index increased by 2.13 ± 0.2, 3.2 ± 0.2, and 2.7 ± 0.15 times, respectively, while EER index remained unchanged.

Regenerative Medicine and Cell Technologies

113-122 493
Abstract

The use of tissue-engineered products (TEP) from decellularized extracellular matrix (dECM) to treat deep skin lesions is a tissue engineering method that promotes regenerative healing. Cell-free preparations reproduce the hierarchical complexity of tissues, mimic structural, biochemical and mechanical signals that are necessary to attract cells, and are a source of bioactive molecules. The human umbilical cord biomaterial has a fetal phenotype with extra-embryonic origin, and therefore is available and has no ethical limitations in its use. The tissue engineering laboratory at Kirov Military Medical Academy developed and patented a TEP from the highly regenerative human umbilical cord in the form of matrix and hydrogel matrix. To study its regenerative potential, lyophilisates of tissue-engineered solid-state and hydrogel matrices were implanted around mini pig fullthickness wounds in vivo. The external signs of inflammatory response and the histological images of biopsy specimens from the lyophilizate implantation areas were analyzed. The effect of nutrient media, «conditioned» with lyophilizates of both matrices, on the viability and migration activity of fibroblast-like cells, isolated from mini pig skin, was investigated. The matrix lyophilisates showed good biocompatibility and bioactivity in in vitro and in vivo experiments. Implantation of the samples promoted faster formation of mature epidermis compared to the control.



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ISSN 1995-1191 (Print)