Prolonged islet allograft function is associated with female sex in patients after islet transplantation

Author(s):  
Joana R N Lemos ◽  
David A Baidal ◽  
Raffaella Poggioli ◽  
Virginia Fuenmayor ◽  
Carmen Chavez ◽  
...  

Abstract Background Islet transplantation (ITx) has proved to be effective in preventing severe hypoglycemia and improving metabolic control in selected subjects with T1D. Long-term graft function remains a challenge. Estrogens have been shown to protect β-cells from metabolic stresses and improve revascularization of transplanted human islets in the mouse. We aimed to evaluate the influence of sex in allograft survival of ITx recipients. Methods We analyzed a retrospective cohort of ITx recipients (n=56) followed-up for up to 20 years. Allograft failure was defined as a stimulated C-peptide <0.3 ng/ml during a mixed-meal tolerance test. Subjects were divided into recipients of at least one female donor (Group 1) and recipients of male donors only (Group 2). Results Group 1 subjects (n=25) were aged 41.5 ± 8.4 years and Group 2 subjects (n=22) 45.9 ± 7.3 years (P= 0.062). Female recipient frequency was 44.8% (n=13) in Group 1 and 55.2% (n=16) in Group 2 (P=0.145). Group 2 developed graft failure earlier than Group 1 [680 (286 – 1624) vs. 1906 (756 – 3256) days, P= 0.038]. We performed additional analyses on female recipients only from each group (Group 1, n= 16, Group 2, n=20). Female recipients in Group 1 exhibited prolonged allograft function compared to Group 2, after adjustment for confounders (OR: 28.6, CI: 1.3 – 619.1; P < 0.05). Conclusion Recipients of islets from at least one female donor exhibited prolonged graft survival compared to recipients of islets from exclusively male donors. In addition, female recipients exhibited prolonged survival compared to male recipients following ITx of at least one female donor.

2016 ◽  
Vol 62 (5) ◽  
pp. 62-63
Author(s):  
Tatyana Y. Tselovalnikova ◽  
Alla E. Yudina ◽  
Maria G. Pavlova ◽  
Alexey V. Zilov ◽  
Nadezhda A. Mazerkina ◽  
...  

Background. Endocrine consequences such as growth hormone deficiency (GHD), growth disturbances and metabolic disorders are common in childhood cancer survivors.Aim: to evaluate and compare the prevalence of growth disturbances and metabolic disorders in childhood posterior cranial fossa tumors (cPCFT) and acute lymphoblastic leukemia (cALL) survivors.Materials and methods. 40 subjects (21 men, 19 women) who had undergone treatment for cPCFT (group 1) and 25 subjects (9 men, 16 women) after treatment for cALL (group 2) were assessed. Group 1 underwent surgery, chemotherapy (CT) and craniospinal irradiation in a dose of 34.9 ± 1.6 Gy with a boost to the PCF 51.3 ± 9.2 Gy. Group 2 underwent CT (23 subjects were treated with ALL-BFM-90 protocol; 2 subjects were treated with ALL-MB-2002 protocol). All subjects of the group 2 received cranial irradiation in a dose 12,7±2 Gy. Age at the time of the survey in a group 1 and 2 – 19.8 ± 3.05 and 21.2±3.9 years; age at the time of treatment – 10.9 ± 3.4 and 6.9±3.4 years; follow-up – 7.2 ± 4.2 and 13.8±4.9 years, respectively. 16 age and sex matched healthy controls were included. Patient’s anthropometric and laboratory parameters were measured, GHD was diagnosed in group 1 by 2 tests – insulin tolerance test (ITT) and glucagon stimulation test (GST). In group 2 these tests didn't perform. At the time of the survey no one in both groups received GH replacement therapy. Only 5 subjects (3 boys and 2 girls) in group 1 were treated with recombinant human GH during childhood.Results.Final height SDS in the group 1 was significantly less than in the group 2 (p=0.001) and in healthy controls (p<0.001). In the group 1 and 2 there were significantly less patients reached target height compared to healthy controls (p<0.001). Subjects of group 1 rarely reached their target height in comparison to the group 2 (p=0.006). IGF-1 SDS was significantly less in the group 1 (-1.37±1.24) than in the group 2 (0.5±1.24, p<0.001). In group 1 GHD according to GST was diagnosed in 60% of subjects, according to ITT in 82.1% of subjects. Waist circumference was significantly bigger in group 2 compared to the group 1 (p=0.046) and to healthy controls (p=0.001). Overweight was registered in 10% of patients in group 1 and in 16% - in group 2. Dyslipidemia was diagnosed in 50% in group 1, in 19% in group 2 (p=0.226). In group 1 16.7% and in group 2 66.7% of subjects were insulin resistant.Conclusions. After treatment for cPCFT growth disturbances occurred more often than after cALL therapy. Metabolic disorders were diagnosed with different frequency in both cPCFT and cALL survivors. These patients need endocrinologist’ observation.


2021 ◽  
Vol 9 ◽  
Author(s):  
Saygin Abali ◽  
Serdar Beken ◽  
Eda Albayrak ◽  
Aysegul Inamlik ◽  
Burcu Bulum ◽  
...  

Introduction: The exact definition of small-for-gestational-age (SGA) infant is still controversial among clinicians. In this study, we aimed to understand which definition is better in terms of establishing both early postnatal problems and growth. In this way, we compared early neonatal problems and infancy growth of term infants with birth weight (BW) &lt; -2 SDS and with BW between 10th percentile (−1.28 SDS) and −2 SDS.Methods: A single center retrospective cohort study was conducted. Preterm infants, multiple gestations and newborns with any congenital anomalies were excluded from the study. Study group was defined as Group 1 (n = 37), infants BW &lt; −2.00 SDS; Group 2 (n = 129), between −1.28 and −2.00 SDS; and Group 3 (n = 137), randomly selected newborns with optimal-for-gestational-age (BW between −0.67 and +0.67 SDS) as a control group.Results: The incidence of severe hypoglycemia was highest in Group 1 (%10.8) and Group 2 and 3 had similar rates of severe hypoglycemia (0.8 and 0.7%, respectively). The incidence of polycythemia was 5.4% in Group 1 and was significantly higher than Group 3 (0.0%) while it was 2.3% in Group 2. Short stature (length &lt; −2 SDS) ratio at the age of 1 and 2 years were similar in each group. Overweight/obesity ratio at the age of 1 were 9.5, 20.8 and 16.7% in each group, respectively (p = 0.509).Conclusion: This study was planned as a pilot study to determine potential differences in the problems of hypoglycemia, polycythemia, and growth according to the differences in definition. Short term disturbances such as hypoglycemia and polycythemia are found to be higher in infants with a BW SDS below −2. From this point of view, of course, it will not be possible to change the routine applications immediately, however this study will be an initiative for discussions by making long-term studies.


2020 ◽  
Vol 12 (4) ◽  
Author(s):  
Ha Nguyen Thi Thu ◽  
Manh Bui Van ◽  
Dung Nguyen Thi Thuy ◽  
Kien Truong Quy ◽  
Duc Nguyen Van ◽  
...  

Background: Delayed graft function (DGF) and acute rejection (AR) are common complications in kidney transplant patients. Objectives: The study evaluated DGF and AR in highly sensitized patients and their effects on kidney function for six months post-transplantation. Methods: We enrolled 95 patients with kidney transplants from living donors who were divided into two groups. Group 1 included 47 highly sensitized patients with panel reactive antibody (PRA) < 20.0% and negative donor-specific antigen, and group 2 included 48 patients with negative PRA. All patients were followed for the state of DGF, AR, and kidney function for six months. Results: Group 1 showed a significantly higher proportion of DGF and AR than group 2 (27.7% versus 2.1%, P < 0.001 and 14.9% versus 2.1%, P = 0.031, respectively). The rates of positive PRA in DGF and AR patients were significantly higher than those in non-DGF and non-AR patients (92.9% versus 42.0%, P < 0.001 and 87.5% versus 46.0%, P = 0.031, respectively). Transplanted kidney function was significantly worse in patients with PRA and DGF and/or AR than in patients with negative PRA and non-DGF and non-AR only in the seventh-day post-transplantation. Conclusions: Kidney transplant in highly sensitized patients with positive PRA was related to the increased ratio of DGF and AR.


2011 ◽  
Vol 129 (5) ◽  
pp. 300-308 ◽  
Author(s):  
Lívia Nascimento de Matos ◽  
Guilherme de Vieira Giorelli ◽  
Amir Saado ◽  
Cristiane Bitencourt Dias

CONTEXT AND OBJECTIVE: Early diagnosis of prediabetes should be done to avoid complications relating to diabetes mellitus (DM). The aim here was to assess the prevalence of prediabetes among individuals at high risk of developing DM, and to seek variables relating to glucose intolerance (GI) among individuals with normal fasting plasma glucose (FPG). DESIGN AND SETTING: Cross-sectional study at Hospital do Servidor Público Estadual, São Paulo. METHODS: The FPG and glucose tolerance test (GTT) were analyzed, from which the subjects were divided as follows: group 1 (FPG and GTT both normal), group 2 (normal FPG but abnormal GTT), group 3 (abnormal FPG but normal GTT), and group 4 (FPG and GTT both abnormal). The subjects' clinical, laboratory and anthropometric profile was determined. RESULTS: 138 subjects were studied: 44 in group 1, 11 in group 2, 33 in group 3 and 50 in group 4. The prevalence of prediabetes was 68.0%. Group 4 individuals were older than group 1 individuals [69.0 (55.5-74.0) versus 58.9 ± 11.8 years; P < 0.05], with greater prevalence of risk conditions for DM [5.0 (4.0-5.0) versus 4.0 (3.0-5.0); P < 0.05]. Among individuals with normal FPG, GI prevalence was 20.0%. No variables analyzed correlated with GTT. CONCLUSION: The prevalence of prediabetes was 68.0%, and 20.0% of subjects with normal FPG had GI. Although some anthropometric, clinical and laboratory variables have been correlated with DM and prediabetes, none, except for GTT, was able to screen for GI among subjects with normal FPG in the present study


1995 ◽  
Vol 4 (3) ◽  
pp. 297-305 ◽  
Author(s):  
Ismail H. Al-Abdullah ◽  
M.S. Anil Kumar ◽  
Dawn Kelly-Sullivan ◽  
George M. Abouna

Transplantation of unpurified islets into the liver, unlike that of purified islets, causes portal hypertension and coagulopathy. The aim of this project was to determine the most suitable alternative site for transplantation of unpurified pancreatic islets in autotransplanted dogs. Twenty-five female mongrel dogs were divided into 5 groups depending on the site of islet transplantation: liver (3), spleen (7), skeletal muscle (5), omental pouch (6), and renal subcapsule (4). Pancreatic digestion of the total pancreatectomized specimen was carried out by distension of the pancreas with 1.5 mg/mL collagenase suspended in 250 mL Hanks' balanced salt solution using a semiautomatic method. The total number of islets equivalent isolated from 25 dogs was 90948 ± 6053. Only islets > 60 μm in diameter were counted, and the mean islet equivalent transplanted per kg body wt was 6762 ± 429. Islet function was achieved with transplantation into spleen in 71%, omental pouch in 50%, and muscle in 20%, but none in the renal subcapsule or liver groups. Glucose tolerance test at 30 d showed a mean K Value (decline in glucose, %/min) of 1.94 ± 0.73,0.79 ± 0.15 and 1.02 in the splenic, omental pouch and muscle groups, respectively. All animals in the liver group, 2 from the splenic group, and 2 from the renal subcapsule group died of diffuse bleeding. Four out of 5 dogs in the muscle group developed necrosis at the site of transplantation and the islets never functioned. This study demonstrates that in dogs, spleen and omental pouch appear to be suitable sites for transplantation of unpurified islets.


ISRN Urology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Nikhil Vasdev ◽  
John Moir ◽  
Muhammed T. Dosani ◽  
Robert Williams ◽  
Naeem Soomro ◽  
...  

Background. We present our centres successful endourological methodology of ex vivo ureteroscopy (EVFUS) in the management of these kidneys prior to renal transplantation. Patient and Methods. A retrospective analysis was performed of all living donors (n=157) identified to have asymptomatic incidental renal calculi from January 2004 until December 2008. The incidence of asymptomatic renal calculi was 3.2% (n=5). Donors were subdivided into 2 groups depending on whether theydonated the kidney with the renal calculus (Group 1) versus the opposite calculus-free kidney (Group 2). Results. All donors in Group 1 underwent a left laparoscopic donor nephrectomy. The calculi were extracted in all 3 cases using a 7.5 Fr flexible ureteroscope either prior to transplant (n=2) or on revascularization (n=1). There were no urological complications in either group. At a mean followup at 64 months there was no recurrent calculi formation in the recipient in Group 1. However, 1 recipient formed a calculus in group 2 at a follow up of 72 months. Conclusions. Renal calculi can be successfully retrieved during living-related transplantation at the time of transplant itself using EVUS. This is technically feasible and is associated with no compromise in ureteral integrity or renal allograft function.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Xinyu Li ◽  
Qiang Meng ◽  
Lei Zhang

Pancreatic islet transplantation as a therapeutic option for type 1 diabetes mellitus is gaining widespread attention because this approach can restore physiological insulin secretion, minimize the risk of hypoglycemic unawareness, and reduce the risk of death due to severe hypoglycemia. However, there are many obstacles contributing to the early mass loss of the islets and progressive islet loss in the late stages of clinical islet transplantation, including hypoxia injury, instant blood-mediated inflammatory reactions, inflammatory cytokines, immune rejection, metabolic exhaustion, and immunosuppression-related toxicity that is detrimental to the islet allograft. Here, we discuss the fate of intrahepatic islets infused through the portal vein and propose potential interventions to promote islet allograft survival and improve long-term graft function.


2011 ◽  
Vol 9 (1) ◽  
pp. 56-65
Author(s):  
Lucio Roberto Requião Moura ◽  
Eduardo José Tonato ◽  
Érika Arruda Ferraz ◽  
Thiago Corsi Filliponi ◽  
Rogério Chinen ◽  
...  

ABSTRACT Objective: To compare three different regimens of thymoglobulin induction. Methods: One hundred seventy two patients submitted to renal transplantation from a dead donor were divided into three groups according to the total number of thymoglobulin doses used in the post-transplantation surgery: Group 1, until 14 doses - May 2002 to June 2004 (n = 48); Group 2, until 7 doses - July 2004 to December 2006 (n = 57); Group 3, until 4 doses - January 2007 to July 2009 (n = 67). The three groups were compared according to the main outcomes. Results: The main demographic differences among the groups were: greater dialysis time in Group 3 (p < 0.001 for Group 1; and p = 0.04 for Group 2); donor age, greater in Groups 2 and 3 (p = 0.02; p = 0.01, respectively); and cold ischemia time progressively greater from Group 1 to 3: 19.5 ± 5.1 to 24.6 ± 5.7 hours (p < 0.001). In relation to the inhibitor of calcineurin, the relation Tac/Csa was 14.6/66.7% in Group 1, 78.9/12.3% in Group 2 and 100/0% in Group 3. Reflecting the increase in cold ischemia time, the incidence of delayed graft function was 64.6%, 68.4% e 82.1% in Groups 1, 2 and 3, respectively (p = ns). The incidence of acute rejection was similar in the three groups: 16.7% (1); 16.3% (2) and 16.4 (3) - p = ns. The prevalence of viremia for cytomegalovirus was 61.7% in Group 1, 66.1% in Group 2 and 83.3% in Group 3 (p = ns). There were no difference related to the number of infected cells with cytomegalovirus in antigenemia, according to the groups, however, patients in Group 3 had an earlier diagnosis: from 64.3 ± 28.5 days in Grup 2, to 47.1 ± 22.5 days, in Group 3, p < 0.001. Survival of the graft in one year was 89.6%, 92.9% and 91.0%, in Groups 1, 2 and 3, respectively (p = ns). The graft function was much better with the lower doses of thymoglobulin: Group 1: 57.0 ± 20.0 mL/min; Group 2: 67.0 ± 18.4 mL/min (p = 0.008); Group 3: 71.2 ± 18.4 mL/min (p < 0.001, Group 1 versus Group 3; p = 0.06, Group 1 versus Group 2). There was a significant reduction in the costs of induction protocol from U$ 7,567.02 to U$ 3,485.56 (p < 0.001). Conclusions: The total number of thymoglobulin doses for immunologic induction could be reduced in a safe and effective way, without a negative impact in graft rejection or survival, preserving renal function and being significantly cheaper.


2009 ◽  
Vol 161 (1) ◽  
pp. 37-42 ◽  
Author(s):  
C L Ronchi ◽  
C Giavoli ◽  
E Ferrante ◽  
E Verrua ◽  
S Bergamaschi ◽  
...  

ObjectiveRadiotherapy (RT) for pituitary adenomas, including GH-secreting ones, frequently leads to GH deficiency (GHD). Data on the effects of surgery alone (S) on dynamic GH secretion are limited. The aim of the study was to investigate the occurrence of GHD in acromegalic patients treated with different therapeutic options.Design and methodsFifty-six patients in remission from acromegaly, (33 F & 23 M, age: 54±13 years, body mass index (BMI): 28.4±4.1 kg/m2, 21 with adequately substituted pituitary deficiencies) treated by S alone (n=33, group 1) or followed by RT (n=23, group 2), were investigated for GHD by GHRH plus arginine testing, using BMI-adjusted cut-offs. Several metabolic and cardiovascular parameters (waist circumference, body fat percentage, blood pressure, fasting and post-oral glucose tolerance test glucose, HbA1c, insulin resistance and lipid profile) were evaluated in all the patients and 28 control subjects with known diagnosis of GHD.ResultsSerum GH peak after challenge was 8.0±9.7 μg/l, without any correlation with post-glucose GH nadir and IGF-1 levels. The GH response indicated severe GHD in 34 patients (61%) and partial GHD in 15 patients (27%). IGF-1 were below the normal range in 14 patients (25%). The frequency of GHD was similar in the two treatment groups (54% in group 1 and 70% in group 2). No significant differences in metabolic parameters were observed between acromegalic patients and controls with GHD.ConclusionsSevere GHD may occur in about 60% of patients treated for acromegaly, even when cured after S alone. Thus, a stimulation test (i.e. GHRH plus arginine) is recommended in all cured acromegalic patients, independently from previous treatment.


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