First World Consensus Conference on pancreas transplantation: Part II - recommendations.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Serum endocan and endothelial dysfunction in childhood acute lymphoblastic leukemia survivors: a tertiary center experience.

BACKGROUND: An increased risk of cardiovascular complications is reported in survivors of childhood acute lymphoblastic leukemia (ALL). Early identification of impaired vascular health may allow for early interventions to improve outcomes. AIM: The study was conducted to assess the endothelial dysfunction in ALL survivors using a new marker, serum endocan, and measurement of the mean common carotid arteries intima media thickness (cIMT). METHODS: A case-control study was conducted on 100 childhood ALL survivors (aged 6-18 years), with 80 healthy age and sex-matched children as a control group. Lipid profile, hepatitis markers, and serum ferritin where measured, in addition to the measurement of serum endocan. and cIMT by B-mode high-resolution ultrasonography for all study participants. RESULTS: Triglycerides, total cholesterol, post prandial glucose, and serum ferritin were significantly higher in ALL survivors than controls (p < 0.05). Dyslipidemia was detected in 6% of ALL survivors. ALL survivors showed statistically higher serum endocan levels (470.41 ± 556.1 ng/l, versus, 225.94 ± 185.2 ng/l, respectively) and increased cIMT levels compared with the control group (0.650 ± 0.129 mm versus 0.320 ± 0.095 mm, respectively) p < 0.05. Serum endocan was positively correlated with cIMT and blood cholesterol. CONCLUSIONS: The survivors of childhood ALL demonstrated an elevated level of serum endocan and increased cIMT. These can be used as predictors of endothelial dysfunction, and, as a consequence, the risk of developing premature atherosclerosis.

Diagnostic performance of rapid antigen test for COVID-19 and the effect of viral load, sampling time, subject's clinical and laboratory parameters on test accuracy.

BACKGROUND: Egypt was among the first 10 countries in Africa that experienced COVID-19 cases. The sudden surge in the number of cases is overwhelming the capacity of the national healthcare system, particularly in developing countries. Central to the containment of the ongoing pandemic is the availability of rapid and accurate diagnostic tests that could pinpoint patients at early disease stages. In the current study, we aimed to (1) Evaluate the diagnostic performance of the rapid antigen test (RAT) "Standard™ Q COVID-19 Ag" against reverse transcriptase quantitative real-time PCR (RT-qPCR) in eighty-three swabs collected from COVID-19 suspected individuals showing various demographic features, clinical and radiological findings. (2) Test whether measuring laboratory parameters in participant's blood would enhance the predictive accuracy of RAT. (3) Identify the most important features that determine the results of both RAT and RT-qPCR. METHODS: Diagnostic measurements (e.g. sensitivity, specificity, etc.) and receiver operating characteristic curve were used to assess the clinical performance of "Standard™ Q COVID-19 Ag". We used the support vector machine (SVM) model to investigate whether measuring laboratory indices would enhance the accuracy of RAT. Moreover, a random forest classification model was used to determine the most important determinants of the results of RAT and RT-qPCR for COVID-19 diagnosis. RESULTS: The sensitivity, specificity, and accuracy of RAT were 78.2, 64.2, and 75.9%, respectively. Samples with high viral load and those that were collected within one-week post-symptoms showed the highest sensitivity and accuracy. The SVM modeling showed that measuring laboratory indices did not enhance the predictive accuracy of RAT. CONCLUSION: "Standard™ Q COVID-19 Ag" should not be used alone for COVID-19 diagnosis due to its low diagnostic performance relative to the RT-qPCR. RAT is best used at the early disease stage and in patients with high viral load.

Factor VIII inhibitor development in Egyptian hemophilia patients: does intron 22 inversion mutation play a role?

BACKGROUND: Hemophilia A (HA) is an X-linked recessive bleeding disorder characterized by qualitative and quantitative deficiency of factor VIII (FVIII). The development of inhibitor antibodies against FVIII is the most challenging complication of treatment. Mutations in the FVIII gene is one of the genetic factors that leads to development of FVIII inhibitors especially intron 22 inversion (Inv22). OBJECTIVES: This study was carried out to assess the frequency of Inv22 of FVIII gene in Egyptian patients with hemophilia A and its role as a risk factor for developing inhibitors. PATIENTS AND METHODS: Seventy-two patients with severe HA and 48 patients with moderate HA were enrolled in the current study. All patients were treated on demand with either plasma-derived factor VIII or recombinant factor VIII concentrates. Genotyping of FVIII Inv22 was performed by LD-PCR while the presence and magnitude of inhibitor activity in blood was determined by the Bethesda assay. RESULTS: Around 23% of all hemophilia cases had positive Inv22. Intron 22 inversion mutation was detected in 6 and 33% of patients with moderate and severe HA respectively. Twenty-one cases (18%) of all hemophilic patients developed inhibitors. Thirty-7% of patients with Inv22 had inhibitor in their blood, almost all, but one, had severe HA. The risk of an inhibitor development during replacement therapy was four folds higher among Inv22 positive cases as compared with mutation negative peers (OR 4.3, 95% CI 1.6-11.9, P = 0.003). CONCLUSIONS: The prevalence of Inv22 of F VIII in Egyptian hemophiliacs is nearly like that of other population. This mutation was more frequently detected among severe hemophilic patients as compared with moderately affected peers. The presence of Inv22 mutation significantly predispose to FVIII inhibitor development.

Unexplained fever after pancreas transplantation.

BACKGROUND: Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. METHODS: We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas-kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. RESULTS: Twenty-three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post-transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy-proven rejection, graft loss, death, or documented infections compared to UF-free patients during the first-year post-transplant. CONCLUSION: UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first-year post-transplant.

3D Printed Vascularized Device for Subcutaneous Transplantation of Human Islets.

Transplantation of pancreatic islets or stem cell derived insulin secreting cells is an attractive treatment strategy for diabetes. However, islet transplantation is associated with several challenges including function-loss associated with dispersion and limited vascularization as well as the need for continuous immunosuppression. To overcome these limitations, here we present a novel 3D printed and functionalized encapsulation system for subcutaneous engraftment of islets or islet like cells. The devices were 3D printed with polylactic acid and the surfaces treated and patterned to increase the hydrophilicity, cell attachment, and proliferation. Surface treated encapsulation systems were implanted with growth factor enriched platelet gel, which helped to create a vascularized environment before loading human islets. The device protected the encapsulated islets from acute hypoxia and kept them functional. The adaptability of the encapsulation system was demonstrated by refilling some of the experimental groups transcutaneously with additional islets.

Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies.

Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m(2) or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up.

Paraoxonase-1 and oxidative status in common Mediterranean ß-thalassaemia mutations trait, and their relations to atherosclerosis.

AIMS: Investigation of paraoxonase-1 (PON1) activity with oxidative status parameters and the increased susceptibility to atherogenesis in ß-thalassaemia-trait (BTT) subjects. METHODS: Sixty BTT subjects and 20 age- and sex-matched healthy controls were enrolled in the study. Serum PON1, total antioxidant capacity (TAC), malondialdehyde (MDA) and carotid artery intima-media thickness (CIMT) were determined. Qualitative detection of ß-thalassaemia mutations was carried out. RESULTS: Serum PON1 activity and TAC were significantly lower in BTT subjects than in controls (p<0.001), while MDA and CIMT were significantly higher (p<0.001). In BTT subjects, TAC, MDA, and CIMT levels were significantly correlated with serum PON1 (r=0.945, -0.900, 0.940 and -0.922 respectively). Serum TAC and MDA were significantly correlated (r=-0.979). CONCLUSIONS: Oxidative stress is increased, while serum PON1 activity is decreased in BTT subjects. Decrease in PON1 activity is associated with the degree of oxidative stress, anaemia and increase in CIMT. Therefore, BTT subjects may be more prone to development of atherosclerosis.

Does aflatoxin as an environmental mycotoxin adversely affect the renal and hepatic functions of Egyptian lactating mothers and their infants? A preliminary report.

BACKGROUNDS/AIMS: Aflatoxin as a mycotoxin constitutes a real human threat. Its presence in human milk was previously reported in different countries. This work is the first Egyptian report that aimed to assess the presence of aflatoxin in both mothers' milk and the infants' sera and studied its correlation with infants' kidney functions. METHODS: Fifty healthy breast lactating mothers and their infants who were exclusively breast fed for at least 4 months were included. All of them were subjected to thorough laboratory evaluation including determination of aflatoxin concentration by high performance liquid chromatography. RESULTS: Twenty-four mothers (48%) and their infants had been contaminated with aflatoxin with the following mean contamination levels (ng/ml); mothers' serum of 8.9+/-4.2, mothers' milk of 1.9+/-0.6 and infants' serum of 1.8+/-0.9. The presence of this contamination level is not associated with renal or hepatic dysfunction. CONCLUSION: Mothers and their infants in our locality showed a relatively high aflatoxin contamination rate. We did not find a correlation of this contamination level and either renal or hepatic dysfunction.

Study of ochratoxin A as an environmental risk that causes renal injury in breast-fed Egyptian infants.

Ochratoxin A (OTA) constitutes a real human threat. Its presence in human milk has previously been reported in different countries. This study is the first Egyptian report on the presence of OTA in both mothers' milk and infants' sera, addressing its correlation with infants' kidney functions, which was not previously addressed in the literature. Fifty healthy breast-lactating mothers and their infants who were exclusively breast-fed for at least 4 months were included. All of them were subjected to a thorough laboratory evaluation including determination of OTA concentration by high-performance liquid chromatography. Thirty-six mothers (72%) and their infants had been contaminated with OTA. Univariate analysis showed that the presence of OTA was associated with significantly higher levels of urinary beta2 microglobulin and microalbuminuria. Multivariate logistic regression analysis showed that there was a significant correlation between a higher OTA level in infants' sera and the degree of microalbuminuria. Mothers and their infants in our locality are exposed to a high OTA contamination rate (72%). To establish the role of OTA in causation of future renal dysfunction for infants, large controlled studies are warranted.