The relationship between 6-thioguanine levels and remission outcomes in children with autoimmune hepatitis. Single center experience.

Aim of the study: The treatment of autoimmune hepatitis (AIH) is based on steroids and azathioprine (AZA). AZA is a pro-drug which is converted among others into 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP). The aim of the study was to determine the relationship between the AZA active metabolite 6-TG and both the biochemical and histological remission outcomes. Material and methods: The authors conducted a retrospective analysis of a single chart review. The sample size consisted of 44 pediatric patients with AIH. Biochemical remission was defined as an alanine aminotransferase (ALT) level below 40 U/l and histological remission was defined as a situation when the control biopsy revealed inflammation grade G1 (or lower) in the Batts-Ludwig score. Statistical analysis was applied to assess the difference in remission outcomes in patients with different levels of 6-TG. Results: In the benchmark variant of our statistical analysis, we found that the correlation between 6-TG and ALT in the sample was not statistically significant. Moreover, the difference between the mean levels of ALT in the populations in and without remission was not statistically significant (the p-value of the t-test was 0.16). Conclusions: Our results tend to support the claim that there is no statistically significant relationship between 6-TG concentration and remission (both biochemical and histological) in pediatric patients with AIH.

Therapeutic drug monitoring of mycophenolic acid (MPA) using volumetric absorptive microsampling (VAMS) in pediatric renal transplant recipients: ultra-high-performance liquid chromatography-tandem mass spectrometry analytical method development, cross-validation, and clinical application.

BACKGROUND: Mycophenolic acid (MPA) is widely used in posttransplant pharmacotherapy for pediatric patients after renal transplantation. Volumetric absorptive microsampling (VAMS) is a recent approach for sample collection, particularly during therapeutic drug monitoring (TDM). The recommended matrix for MPA determination is plasma (PL), and conversion between capillary-blood VAMS samples and PL concentrations is required for the appropriate interpretation of the results. METHODS: This study aimed to validate and develop a UHPLC-MS/MS method for MPA quantification in whole blood (WB), PL, and VAMS samples, with cross and clinical validation based on regression calculations. Methods were validated in the 0.10-15 µg/mL range for trough MPA concentration measurement according to the European Medicines Agency (EMA) guidelines. Fifty pediatric patients treated with MPA after renal transplantation were included in this study. PL and WB samples were obtained via venipuncture, whereas VAMS samples were collected after the fingerstick. The conversion from VAMSMPA to PLMPA concentration was performed using formulas based on hematocrit values and a regression model. RESULTS: LC-MS/MS methods were successfully developed and validated according to EMA guidelines. The cross-correlation between the methods was evaluated using Passing-Bablok regression, Bland-Altman bias plots, and predictive performance calculations. Clinical validation of the developed method was successfully performed, and the formula based on regression was successfully validated for VAMSMPA to PLMPA concentration and confirmed on an independent group of samples. CONCLUSIONS: This study is the first development of a triple matrix-based LC-MS/MS method for MPA determination in the pediatric population after renal transplantation. For the first time, the developed methods were cross-validated with routinely used HPLC-DAD protocol.

The Course of COVID-19 Infection in Patients After Pancreas and Kidney Transplantation: A Single-Center Observation.

Solid graft recipients are at an increased risk of serious complications and death. Out of 130 outpatient recipients of pancreas grafts at our Clinic, 20 patients (15.73%) had a confirmed severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2). Each patient had a different course of the disease, and the forms of infection varied from mild to severe and lethal. According to recommendations, after confirmation of the infection, mycophenolate mofetil was withdrawn and the immunosuppression was based on steroids and a calcineurin inhibitor. In this study, we performed an analysis of the course of COVID-19 infection in patients after pancreatic transplantation. Twenty pancreas recipients were confirmed to have COVID-19 infections; 4 of whom required hospitalization owing to severe complications. Patients reported weakness, excessive intensity of fatigue, shortness of breath with exertion, cough, and periodically increased temperature. Weakness and fatigue persisted in these patients for about 6 weeks. In 2 patients there was a need for oxygen supplementation and empirical antibiotic. Mortality was 5%, and there was 1 graftectomy. Deterioration of either kidney or pancreas graft were not observed in any other patients. The course of SARS-CoV-2 infection in solid graft recipients is similar to that of the rest of the population. Because of immunosuppression, recipients were accustomed to avoiding crowds and complying with obligations to wear masks.

Vascular Complications After Simultaneous Pancreas and Kidney Transplantation: A Case Report.

A 51-year-old patient with type I diabetes and end-stage renal disease was qualified for a simultaneous kidney and pancreas transplant. The procedure was performed in a typical manner: arterial anastomosis to the right common iliac artery, the graft's portal vein with inferior vena cava, and side-to-side duodenal intestinal anastomosis. The kidney was implanted retroperitoneally. Six months after the transplant, the patient reported pain in the right lower abdomen, and imaging examinations revealed arterial anastomosis. Reconstruction of the right common iliac artery was performed with a Gore-Tex prosthesis and the pancreatic artery reanastomosed to the right external iliac artery. After the surgery, the function of the transplanted pancreas deteriorated, the level of C-peptide was decreased, and the patient required low doses of insulin. After another 8 months, the imaging studies revealed an aneurysm located in the bifurcation of the aorta up to the anastomosis of the pancreatic graft artery with the iliac artery. The patient was qualified for the implantation of an endovascular of 2 prosthesis, which improved the graft's function. After another 2 months, the presence of an aneurysm at the endovascular prosthesis was found again. The patient was requalified for endovascular prosthesis implantation. Currently, there is no aneurysm but the function of the pancreas graft is impaired, though the kidney graft function is good. Patients after simultaneous kidney and pancreas transplant are a group of patients with an increased risk of vascular complications. Treatment should take place in a multidisciplinary center.

COVID-19 Vaccines in Pancreatic Transplant Recipients: A Single-Center Observative Study.

The SARS-CoV-2 pandemic was a real test of doctors' abilities to adapt and respond to patients' needs. The course of infection varied from influenza-like symptoms to severe infections with multi-organ failure and death. Therefore, the possibility of vaccination against the COVID-19 virus brought great hope. Since 2004, 240 pancreas and pancreas with kidney (simultaneous pancreas and kidney transplantation, pancreas after kidney, pancreas transplants alone) transplants were performed in our center. Currently, 130 transplant patients are under the care of the transplant clinic. All patients were informed about the possibility of vaccination against SARS-CoV-2 with the mRNA vaccine. The aim of the study was to evaluate the development of antibodies to SARS-CoV-2 in patients who had previously undergone transplantation. Fifty-three patients were vaccinated with the full double dose and 37 patients received an additional third dose. The level of antibodies in the IgM and IgG classes was assessed in patients' serum. The level of antibodies was assessed before administration of the vaccine and then after administration of the first and second doses. Most patients had no response to vaccination after 1 dose of the vaccine and 21 patients achieved therapeutic antibody levels after the full dose of vaccination. However, the highest titer of immunoglobulins was found in recipients who received the third dose. The use of vaccinations is safe and can protect the group of patients after pancreas transplantation from serious complications of SARS-CoV-2 infection despite the use of immunosuppressive drugs.

The Possibility of Using Paulownia elongata S. Y. Hu × Paulownia fortunei Hybrid for Phytoextraction of Toxic Elements from Post-Industrial Wastes with Biochar.

The potential of the Paulownia hybrid for the uptake and transport of 67 elements along with the physiological response of plants cultivated in highly contaminated post-industrial wastes (flotation tailings-FT, and mining sludge-MS) was investigated. Biochar (BR) was added to substrates to limit metal mobility and facilitate plant survival. Paulownia could effectively uptake and translocate B, Ca, K, P, Rb, Re and Ta. Despite severe growth retardation, chlorophyll biosynthesis was not depleted, while an increased carotenoid content was noted for plants cultivated in waste materials. In Paulownia leaves and roots hydroxybenzoic acids (C6-C1) were dominant phenolics, and hydroxycinnamic acids/phenylpropanoids (C6-C3) and flavonoids (C6-C3-C6) were also detected. Plant cultivation in wastes resulted in quantitative changes in the phenolic fraction, and a significant drop or total inhibition of particular phenolics. Cultivation in waste materials resulted in increased biosynthesis of malic and succinic acids in the roots of FT-cultivated plants, and malic and acetic acids in the case of MS/BR substrate. The obtained results indicate that the addition of biochar can support the adaptation of Paulownia seedlings growing on MS, however, in order to limit unfavorable changes in the plant, an optimal addition of waste is necessary.

The Course of SARS-CoV-2 in a Patient After a Recent Kidney Transplant: A Literature Review on COVID-19 Therapy.

BACKGROUND: Kidney transplant recipients are at high risk of severe complications and death due to coronavirus disease 2019 (COVID-19). METHODS: The first part of the article describes a case of COVID-19 in our patient after a recent kidney transplant. The second part of the article presents the outcome of literature search from multiple resources from April 2020 until March 2021. Abstracts were screened, followed by full-text review with data extraction. Part 2 discusses current treatment options of COVID-19, and part 3 refers to this treatment application in patients after solid organ transplant. RESULTS: We have summarized 45 studies from China, France, Italy, Spain, the United Kingdom, and the United States. Mortality rates from published studies were variable. Based on early data from Spain, 42% of patients who developed COVID-19 within 60 days of transplant died. According to results of the European Renal Association COVID-19 Database collaboration group, the 28-day COVID-19-related mortality is 21.3% for kidney transplant recipients, which is still markedly higher than what is observed in other populations. Acute kidney injury was common, and mycophenolate mofetil and mammalian target of rapamycin were discontinued in most patients. CONCLUSIONS: Effective therapy has been sought since the outbreak of the pandemic, and at the same time intensive work has been done to produce a vaccine that could effectively protect against the disease. Summing up the efforts of numerous groups of researchers from around the world that have been continued since the beginning of 2020, we may assume the following: (1) we still do not have causal drugs that would reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and allow its complete elimination, but antispike monoclonal antibodies against SARS-CoV-2 seem to be very promising, and (2) the withdrawal of antiproliferative and antimetabolic drugs and the continuation of steroids and calcineurin inhibitors is now a commonly accepted approach in patients after organ transplant.

Normal Pancreas Graft Appearance in Magnetic Resonance Diffusion Tensor Imaging (DTI).

BACKGROUND The main purpose of diagnostic imaging after pancreas transplantation is to exclude potential complications. As long as standard anatomical imaging such as sonography, contrast-enhanced computed tomography, and magnetic resonance imaging (MRI) are sufficient to display macroscopic vasculature, early changes within the graft caused by insufficient microperfusion will not be displayed for evaluation. MATERIAL AND METHODS Patients with pancreas allograft function in good condition were included in the study. No specific preparation was demanded before the MRI examination. The results of MRI were correlated with Igls criteria. It was a preliminary study to examine diffusion tensor imaging (DTI) value and safety in pancreas transplantation. RESULTS Our results indicated that higher fractional anisotropy (FA) values of the graft's head were associated with delayed graft function and insulin intake. We also compared grafts' images in early and late periods and found differences in T1 signal intensity values. DTI is a reliable noninvasive tool, requiring no contrast agent, to assess graft microstructure in correlation with its function, with FA values showing the most consistent results. By Igls criteria, no graft failure, 76% had optimal function, 10% had good function, and 14% had marginal function. CONCLUSIONS Our results suggest that DTI can be safely used in patients after pancreas transplantation and is advantageous in detecting early as well as late postoperative complications such as intra-abdominal fluid collection, malperfusion, and ischemia of the graft. Our findings correspond with clinical condition and Igls criteria. DTI is free of ionizing agents and is safe for kidney grafts.

Endovascular Treatment of Pseudoaneurysm After Simultaneous Pancreas-Kidney Transplant: A Case Report.

Pseudoaneurysm is a rare vascular complication in pancreas transplantation that can lead into life-threatening situations. A 44-year-old male patient after simultaneous pancreas-kidney transplant was admitted to the hospital for routine tests 3 months after surgery. A computed tomography scan and ultrasound examination were done, and a diagnosis of pseudoaneurysm was made. The patient was qualified for endovascular treatment. The pseudoaneurysm was closed using coils, and kidney and pancreas grafts stayed in proper condition. Endovascular interventions in patients after pancreas transplantation are safe and preferable in managing postoperative complications.

Influence of Peritoneal or Hemodialysis on Results of Simultaneous Pancreas and Kidney Transplant.

OBJECTIVES: The influence of peritoneal dialysis on outcomes after simultaneous pancreas and kidney transplant is still vague. In addition, whether peritoneal dialysis leads to a higher risk of infectious complications and higher mortality rates in these transplant patients has not been unambiguously confirmed. In this study, our aim was to verify whether dialysis type determined outcomes on the pancreas graft and whether dialysis type was a risk factor for graftectomy or recipient death. MATERIALS AND METHODS: Our study group included 44 simultaneous pancreas and kidney transplant patients. Analyzed parameters included type and duration of dialysis treatment, age, sex, long-term pancreas graft survival and patient survival, overall mortality, and number of graftectomies. RESULTS: Of 44 patients, 3 (7%) required a graftectomy. Mortality rate of the group was 5%. Of 44 patients, 33 had hemodialysis and 11 had peritoneal dialysis. In those who had hemodialysis, the mean duration of renal replacement therapy was 30.5 months, which was significantly longer than duration for those who had peritoneal dialysis (20.4 mo; P < .01). There were 3 graftectomies and 1 death in the hemodialysis group. In the peritoneal dialysis group, there were no graftectomies and 1 death, with no significant differences in the number of graftectomies and mortality rates between the groups. Long-term survival also did not differ between the groups. CONCLUSIONS: We found that type of dialysis did not affect outcomes in our group of simultaneous pancreas and kidney transplant patients. Before transplant, each patient requires an individual approach to treatment. The type of dialysis performed should not be viewed as a contradiction for transplant.

Endovascular Interventions in Vascular Complications After Simultaneous Pancreas and Kidney Transplantations: A Single-Center Experience.

BACKGROUND Vascular failures are serious complications in pancreas transplantation. Open surgery is a reliable and quick intervention method, but it carries a risk of infection and bleeding. Endovascular procedures are rare among patients after a SPK, but are becoming more frequently used. One of the main risks of the endovascular approach is that the renal function impairment caused by contrast agent. MATERIAL AND METHODS We performed a retrospective analysis of 200 transplanted pancreases at our center over the last 14 years. The analyses included those patients after pancreas transplantation who required the most challenging vascular interventions and ones that were non-standard for the procedure. RESULTS Severe vascular conditions requiring endovascular intervention were observed in 3% of SPKs. In one retransplanted patient, there was an acute ischemia of the lower extremity due to the narrowing of the common iliac artery following a previous transplantectomy, above the new pancreas graft anastomoses. In another patient, local inflammation led to the disruption of the external iliac artery on the level of transplantectomy, caused severe bleeding, and we had to implement a stent-graft to reconstruct the iliac artery wall. A third patient had a pseudoaneurysm demanding further treatment with a stent-graft implemented into the femoral artery due to a pseudoaneurysm of the right external iliac artery. CONCLUSIONS Intravenous interventions in patients with a transplanted or retransplanted pancreas are safe and feasible. It is a technically demanding procedure, but the risk of kidney graft function deterioration, as well as of bleeding due to the high dose of heparin used, is lower than with open vascular surgery.

Preoperative glucose abnormalities in patients with pancreatic tumours.

INTRODUCTION: Pancreatic cancer is a neoplasm characterised by poor prognosis. The only effective, possible treatment is radical surgery, but most patients do not qualify for surgery because of delayed diagnosis. AIM: To determine if assessment of endocrine pancreatic function could serve as a means of screening for pancreatic cancer. MATERIAL AND METHODS: This prospective study was conducted on a group of 50 patients diagnosed with pancreatic tumour, who were qualified for surgery. RESULTS: From 1.07.2010 to 4.07.2011 a further 50 patients were added to the study group. They had been admitted to the hospital with pancreatic tumours. During the preoperative period, nine of these people had been treated for diabetes, 14 were newly diagnosed with diabetes and 15 had been diagnosed with impaired glucose tolerance, but only 12 had a normal glucose profile. Afterwards, patients underwent the surgical treatment. Histopathological examination revealed that out of the 50 operated patients, 36 suffered from malignant disease, and of these only four had no impaired glucose tolerance before treatment. CONCLUSIONS: In most cases, patients with pancreatic tumours have impaired glucose tolerance. Screening patients over 50 years of age could speed up diagnosis and surgical treatment.

Laparoscopic distal pancreatectomy - new standard in the pancreatic surgery.

UNLABELLED: The improvement of laparoscopic techniques that we witnessed over the last decade, also applied to pancreatic surgery. Both worldwide and in Poland, increasingly more patients with lesions located within the body and tail of the pancreas are treated using laparoscopic distal pancreatectomy. The aim of the study was to compare the outcomes of laparoscopic and open distal pancreatectomy. MATERIAL AND METHOD: Between January 2009 and March 2013, 107 patients underwent distal pancreatectomy at a single institution: 39 using laparoscopic technique and 68 using open technique. This was a retrospective study. RESULTS: There were no significance differences with regard to duration of the surgical procedure, duration of hospitalization and complication rate between both groups. Statistically significant difference was found for the incidence of spleen preservation in patients undergoing laparoscopy, due to better visualization of the structures. In the group of patients with pancreatic cancer there was no significance difference in the incidence of malignancy found in the surgical margin. Our results are similar to that presented in the literature. CONCLUSIONS: Laparoscopic distal pancreatectomy is a safe method, with a higher rate of spleen preservation among the patients with the lesion located in the body and tail of the pancreas.

Alterations of basement membrane zone and cutaneous microvasculature in morphea and extragenital lichen sclerosus.

The aim of this study was to compare alterations of the basement membrane zone (BMZ) and to visualize changes within the skin vascular network in morphea and extragenital lichen sclerosus with the use of laser scanning confocal microscopy. This work was performed in eight plaques of morphea (three active and five inactive) and eight of lichen sclerosus (three of short duration and five long-lasting). Biopsy specimens from six healthy individuals served as controls. The biopsies were cut into 40-microm-thick sections, labeled with antibodies against beta4-intergin (a lamina lucida marker), collagen IV, and the N-terminal end of collagen VII (lamina densa markers) and C-terminal end of collagen VII (a sublamina densa marker) and studied using laser scanning confocal microscopy. Three-dimensional reconstruction of various regions of the BMZ showed a decreased number and size of the dermal papillae both in morphea and lichen sclerosus compared with normal skin. In morphea, the continuity of the BMZ at the level of lamina lucida, lamina densa, and sublamina densa was preserved whereas in LS numerous invaginations and holes were present in the BMZ at the level of the lamina lucida and lamina densa. Thus the alterations of the BMZ in morphea differ from those in lichen sclerosus. Three-dimensional reconstruction of the skin vascular network showed increased angiogenesis only in the early inflammatory stage of morphea, whereas in inactive morphea and lichen sclerosus various numbers of enlarged vessels were visible. The changes in the vascular network in morphea appear to be related to the activity of the disease.

Three-dimensional imaging reveals major changes in skin microvasculature in lipoid proteinosis and lichen sclerosus.

BACKGROUND: Lipoid proteinosis is a rare autosomal recessive disorder characterized by deposition of hyaline-like material in several organs, including skin. Pathogenic mutations have been found in the extracellular matrix protein 1 gene (ECM1). Recent studies have disclosed that ECM1 is also a target antigen for autoantibodies in patients with the acquired disease, lichen sclerosus. Both conditions have been reported to show abnormalities in dermal blood vessels but these changes have not been fully assessed. OBJECTIVE: The purpose of this study was to investigate the architecture of the cutaneous microvasculature in lipoid proteinosis and lichen sclerosus to better determine the role of ECM1 in the skin pathology observed in these disorders. METHODS: Labeling of skin biopsies (lipoid proteinosis, lichen sclerosus and control skin) with antibodies to type IV collagen and laminin-1 and reconstruction of the dermal blood vessels using laser confocal microscopy and computer imaging. RESULTS: In both lipoid proteinosis and lichen sclerosus there was reduplication of the basement membranes surrounding blood vessel walls. There were enlarged vessels in the mid and deep dermis that were orientated parallel to the dermal-epidermal junction. In addition, the normal capillary loop network in the dermal papillae, as well as the subcutaneous plexus and transverse connecting vessels were lacking in both disorders. CONCLUSION: This study demonstrates that skin microvasculature is grossly altered when ECM1 is targeted by inherited mutations (lipoid proteinosis) or acquired autoantibodies (lichen sclerosus) and that this glycoprotein appears to have an important role in regulating blood vessel physiology and anatomy in the skin.