The influence of simultaneous pancreas-kidney transplantation on the evolution of diabetic foot lesions and peripheral arterial disease.

PURPOSE: Simultaneous pancreas-kidney transplantation (SPKT) remains the best treatment option in patients with type 1 diabetes and chronic kidney failure. There are only a few studies addressing the potential ischemic deterioration of peripheral arterial disease (PAD) due to blood diverting from the iliac artery to the kidney graft. We aimed to evaluate diabetic foot lesions and PAD evolution in SPKT recipients and investigate if they are more frequent in ipsilateral lower limb of kidney graft. METHODS: We developed a retrospective cohort, including patients submitted to SPKT in our tertiary center, between 2000 and 2017. Diabetic foot lesions and PAD frequencies were compared in the period before and after transplantation. RESULTS: Two hundred and eleven patients were included, 50.2% (n = 106) female, with a median age at transplantation of 35 years (IQR 9). After a median follow-up period of 10 years (IQR 7), patient, kidney, and pancreatic graft survival were 90.5% (n = 191), 83.4% (n = 176), and 74.9% (n = 158), respectively. Before transplant, 2.8% (n = 6) had PAD and 5.3% (n = 11) had history of foot lesions. In post-transplant period, 17.1% (n = 36) patients presented PAD and 25.6% (n = 54) developed diabetic foot ulcers, 47.6% (n = 35) of which in the ipsilateral and 53.3% (n = 40) in the contralateral lower limb of the kidney graft (p = 0.48). Nine patients (4.3%) underwent major lower limb amputation, 3 (30%) ipsilateral and 7 (70%) contralateral to the kidney graft (p = 0.29). CONCLUSIONS: Diabetic foot lesions were not more frequent in the ipsilateral lower limb of the kidney graft, therefore downgrading the 'steal syndrome' role in these patients.

Maternofetal outcomes in early-onset gestational diabetes: does weight gain matter?

AIM: Women with early-onset gestational diabetes mellitus (GDM) have overall lower gestational weight gain (GWG) compared to those with later-onset GDM, albeit with usually worse maternofetal outcomes. We intent to investigate the association between inadequate GWG and maternofetal outcomes in pregnant women with early-onset GDM. METHODS: We performed a retrospective study of women with early-onset GDM based on the National Registry of GDM. Three study groups were defined according to the recommendations of the Institute of Medicine for GWG: excessive GWG (eGWG), adequate (aGWG) or insufficient (iGWG). RESULTS: A total of 8040 pregnant women were included: 27% (n = 2170) eGWG, 31% (n = 2492) aGWG and 42% (n = 3378) iGWG. Preeclampsia (4.3 vs 3 vs 1.6%, p < 0.001), polyhydramnios (3.1 vs 2.3 vs 1.8%, p = 0.008) and cesarean section (37.4 vs 34.1 vs 29.5%, p < 0.001) were significantly more frequent among women with eGWG. Additionally, there was a higher frequency of macrosomia (8.1 vs 3.6 vs 2.4%, p < 0.001), large-for-gestational-age (8.2 vs 3.7 vs 2.6%, p < 0.001) and birth trauma (2.6 vs 1.5 vs 1.1%, p < 0.001) in this group. On the other hand, fetal death (0.2 vs 0.2 vs 0.5%, p = 0.04), small-for-gestational-age (9 vs 10.3 vs 14.9, p < 0.001) and preterm delivery (5.6 vs 7.1 vs 7.5%, p = 0.03) were more frequent in iGWG group. CONCLUSIONS: Over two-thirds of pregnant women with early-onset GDM had inappropriate GWG, which was significantly associated with adverse maternofetal outcomes. Weight management must be a focus of special attention in women with early-onset GDM, beyond glycemic control, to achieve healthy pregnancy outcomes.

Mild periconceptional hyperglycemia: predictor of adverse fetomaternal outcomes in gestational diabetes?

AIM: To clarify whether mild first trimester hyperglycaemia (characteristic of early-onset GDM) is associated with higher incidence of congenital malformations and other adverse fetomaternal outcomes compared to women with second trimester hyperglycaemia (later-onset GDM). DESIGN AND METHODS: We analyzed the Portuguese National GDM database, containing data collected between 2011 and 2017. Two study groups were defined: Group 1-Women with GDM diagnosed during the first trimester (with fasting glycemia ≥ 92 and < 126 mg/dL); Group 2-Women with GDM diagnosed after the first 12 weeks of gestation, with either fasting glycemia or oral glucose tolerance test, according to the International Association of Pregnancy and Diabetes Study Group criteria. The fetomaternal characteristics of each group were compared. RESULTS: A total of 18.518 pregnant women diagnosed with GDM were included which 34.4% of them belonged to Group 1. Pregnant women from this group were significantly younger and had a higher median BMI than the women from the other group. Overall, there was no significant differences in maternal morbidity parameters between groups. Non-evolutive pregnancies were significantly more frequent along the present gestation in the group 1 (1.1% vs. 0.1%, p < 0.001), as was fetal death (0.6% vs. 0.2%, p < 0.001). Congenital malformations did not differ significantly between groups (3.2% vs. 2.8%, p = 0.155). CONCLUSIONS: The mild near conceptional hyperglycaemic state characteristic of an early-onset GDM seems to be associated with an increased prevalence of non-evolutive pregnancies and foetal deaths when compared to later-onset GDM.

Recycling organic wastes to agricultural land as a way to improve its quality: A field study to evaluate benefits and risks.

A field study was established to assess the effects of a sewage sludge (SS), a mixed municipal solid waste compost (MMSWC) and a compost produced from agricultural wastes (AWC), in a Vertisol, using Lolium multiflorum L. The amendments were applied for two consecutive years: 6, 12 and 24t dry matter ha-1 for SS, and the amendment doses for MMSWC and AWC were calculated to deliver the same amount of organic matter (OM) per unit area. The amendments had significant beneficial effects on some soil properties (e.g. soil OM, NKjeldahl, extractable P and K), and on plant productivity parameters (e.g. biomass yield, chlorophyll, foliar area). For instance, soil OM increased from 0.78% to 1.71, 2.48 and 2.51%, after two consecutive years of application of 24t dry matter ha-1 of SS, MMSWC and AWC, respectively, while the plant biomass obtained increased from 7.75tha-1 to 152.41, 78.14 and 29.26tha-1, for the same amendments. On the plant, effects were more pronounced for SS than for both compost applications, a consequence of its higher capacity to provide N to the plant in a readily available form. However, after two years of application, the effects on soil properties were more noticeable for both composts, as their OM is more resistant to mineralization, which endures their beneficial effects on soil. Cadmium, Cr, Ni and Pb pseudo-total concentrations, were not affected significantly by the application of the organic wastes to soil, in all tested doses, neither their extractability by 0.01M CaCl2. On the contrary, Cu and Zn pseudo-total concentrations increased significantly in the second year of the experiment, following the application of the higher rate of MMSWC and AWC, although their extractability remained very low (<0.5% of their pseudo-total fraction). Trace elements concentrations in the aboveground plant material were lower than their maximum tolerable levels for cattle, used as an indicator of risk of their entry into the human food chain. Despite these results, it is interesting to note that the SS promoted a significant increase in the foliar concentrations of Cu, Ni and Zn that did not happen in composts application, which can be explained by the reduction of the soil pH, as a consequence of SS degradation in soil. Concluding, if this type of organic wastes were to be used in a single application, the rate could be as high as 12 or even 24tha-1, however, if they are to be applied in an annual basis, the application rates should be lowered to assure their safe application (e.g. to 6tha-1). Moreover, it is advisable to use more stable and mature organic wastes, which have longer lasting positive effects on soil characteristics.

One hundred eleven simultaneous pancreas-kidney transplantations: 10-year experience from a single center in Portugal.

From May 2000 to May 2010, we performed 111 simultaneous pancreas-kidney transplants (SPKT) from cadaveric donors, by using enteric drainage and systemic vascular anastomosis. In 26 cases they showed 6 HLA mismatches. Immunosuppression included antithymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. The patients' mean age was 34 ± 6 years, and mean time from diabetes diagnosis was 23 ± 6 years; 107 patients had been on dialysis for 32 ± 24 months, and 4 had a preemptive status. Acute rejection episodes were detected in 20 patients (18%): in 3 cases they affected both organs, in 9 only the kidney, and in 8 only the pancreas. The incidence of complications needing reoperation was 28.8%. They were mostly pancreas graft-related, including bleeding, thrombosis, and infection. In more recent years, after a slight modification of surgical technique, we noted a decreased rate of complications. Six patients died from: 2 from cardiovascular or cerebrovascular disease, 3 from infection, and 1 from an unknown cause. Pancreas graft loss occurred in 26 and kidney graft loss in 12 patients. Four patients underwent a second pancreas and 5 a second kidney graft. Patients with surviving grafts showed good function: serum creatinine, 1.09 ± 0.23 mg/dL; fasting blood glucose, 79.7 ± 9.8 mg/dL; and HbA(1c), 4.88 ± 0.47%. Patient, kidney, and pancreas survival results were 96%, 96%, and 83% at 1; 94%, 91%, and 75% at 5; and 94%, 62%, and 69% at 10 years, respectively. These good results, compared with larger series and to recent pancreas transplant registry reports, are a strong motivation for the further development of this unique program in Portugal.

Pancreas-kidney transplantation: complications and readmissions in 9-years of follow-up.

Over 9 years, we have performed 93 simultaneous pancreas-kidney transplants (SPKT). The morbidity of this procedure is high compared with kidney transplantation alone; readmissions are frequent and costs are higher. Herein we have presented the complications during follow-up of these 93 patients. Their mean age was 34 +/- 6 years and prior dialysis time was 32 +/- 25 months. The median hospital stay on the first admission for the transplant procedure was 22 days, including 2 days in the intensive care unit. Bleeding, thrombosis, and infection were the most frequent reasons for prolonged hospitalization. Thirty patients underwent >or=1 surgical reinterventions. Incidence of acute rejection episodes was 11.8%. After discharge, 74.2% of the patients had 197 readmission episodes with infection being the main cause, urinary tract infections, the most frequent; however, systemic viral and fungal infections required the longest readmission periods. The need for surgical interventions, graft dysfunction, and vascular problems were the remaining causes of readmission. At the end of follow-up, 87 patients were alive, 86 with well-functioning kidneys and 74 with normal functioning pancreata. Global survival rates for patient, kidney, and pancreas were 96%, 95%, and 81% at 1-year; 93%, 90%, and 79% at 5-years; and 93%, 90% and 79% at 9-years. Although pancreas-kidney transplant patients are complex presenting many management difficulties, our overall results represent a positive stimulus for diabetic patients.

Bone mineral density after simultaneous kidney-pancreas transplantation: four years follow-up of 57 recipients.

Bone disease and an high risk of fractures are major problems in transplantation. Among diabetic patients undergoing simultaneous kidney-pancreas (SKP) transplantation, there are few studies assessing long-term effects on bone mass. The aim of this study was to evaluate bone mineral density (BMD) over 4 years follow-up after SKP transplantation. Fifty-seven patients had 22.8 +/- 5.3 years of prior diabetes, 65% were female, and the overall mean age was 24.3 +/- 5.93 years. At the time of transplantation, the lumbar spine and femoral neck T-scores were -1.75 +/- 1.05 and -1.95 +/- 0.73, respectively; 28% of subjects had evidence of osteoporosis. One year after transplantation, 77.6% of patients displayed improved lumbar T-scores to -1.33 +/- 0.94 (P = .044) with stable femoral neck T-scores. Bone densitometry enhanced gradually through the 4 years follow-up: lumbar T-score to -1.04 +/- 0.67 (P = .004) and femoral neck T-score to -1.69 +/- 0.49 (P = .12). At year 4, no osteoporosis cases were detected but 86.7% of patients did not receive steroids in the immunosuppressive regimen. The graft function remained stable (serum creatinine, 1.2 mg/dL; fasting glucose, 87.7 mg/dL). During the follow-up, BMD improved more significantly at cortical sites. Our study reports a reduced prevalence of fractures (8.7%) compared with the literature, which could be related to a steroid-sparing protocol and/or aggressively treatment of osteoporosis.

Steroid withdrawal in simultaneous pancreas-kidney transplantation: a 7-year report.

Simultaneous pancreas-kidney transplantation (SPK) is the treatment of choice for selected diabetic patients with end-stage renal disease. Maintenance steroid therapy is associated with significant morbidity and mortality among SPK transplant recipients. Steroid withdrawal regimens are becoming more common, albeit with reservations regarding its safety and efficacy. We performed a retrospective review of 77 SPK transplant recipients from May 2000 to December 2007. The subjects received induction therapy with thymoglobulin followed by maintenance immunosuppression with tacrolimus and mycophenolate mofetil. A late steroid withdrawal protocol was adopted. The rates of acute rejection, graft and patient survival, and side effects were analyzed. One-year patient, kidney, and pancreas survivals were 93%, 91%, and 86%, respectively. Eleven patients experienced acute rejection. Mean follow-up time was 1155.5 +/- 776.1 days. Prednisolone withdrawal was carried out between 6 and 12 months posttransplantation in 42 patients (77.8%) with at least 1 year follow-up; no case of acute rejection occurred. At present, 72 patients have a functioning kidney graft, and 65 patients also have a functioning pancreas graft. The mean serum creatinine is 1.12 +/- 0.49 mg/dL and the mean HbA1c concentration is 4.5% +/- 0.4%. The patients have a low prevalence of hypertension, hyperlipidemia, and obesity. Steroid withdrawal was successful and safe in the majority of in-study patients and safe without an increase of immune events. Our patient and graft outcomes are within other international SPK transplant units standards.

Pancreas-kidney transplantation and the evolution of pancreatic autoantibodies.

The recurrence or persistence of pancreatic autoantibodies after pancreas-kidney transplantation (PKT) is an intriguing finding. We prospectively analyzed 77 PKTs, searching for risk factors for the expression of these autoimmune markers and their impact on pancreas graft function. Among the 77 PKTs, 24.7% had 0 HLA matches, 20.8% displayed delayed graft function, and 14.3% had acute rejection episodes. Immunosuppression included antithymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF), and steroids. Sixty-five patients had both grafts functioning as a follow-up of more than 6 months. In 11 patients anti-glutamic acid decarboxylase (GAD) positivity persists (n = 8) or has recurred (n = 3), 4 of whom show increasing titers. Two patients maintain positive islet cell antibodies (ICA) and anti-GAD antibodies. The 9 patients positive for ICA included 2 who were negative before PKT and 7 who remain positive. The "positive" group (22 patients with positive ICA and/or anti-GAD) did not differ from the global group of 65 functioning PKT in terms of acute rejection episodes, HLA match, and steroid withdrawal. Among the positive patients, there were 2 with borderline glucose levels; however, among the entire "positive" group, the mean fasting glucose, HbA1c, and C-peptide measurements were not significantly different, when compared with the other 65 PKTs. In conclusion, pancreatic autoantibodies may be persistently positive or recur after PKT, despite appropriate immunosuppression. Its impact on long-term pancreas graft survival is unknown. We could not identify risk factors for their expression. An extended follow-up with monitoring and search for other risk factors may be necessary to increase our knowledge in this field.

Simultaneous pancreas-kidney transplantation: five-year results from a single center.

We report the 5-year results of our simultaneous pancreas-kidney transplantation (SPKT) program, started on May 2, 2000. Forty-two SPKT were performed on 42 type I diabetic patients with chronic renal failure. The procedure was performed with enteric diversion and vascular anastomosis to the iliac vessels. Immunosuppressive protocol included antithymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. The 24 women and 18 men had a mean age of 33.5 +/- 6.3 years and mean 22.8 +/- 14.2 years time of diabetes evolution. Forty patients had been on dialysis for 34.3 +/- 24.1 months, and two were preemptive transplantations. Acute rejection episodes were treated in eight patients (19.1%): in three cases they affected both organs; in two only the kidney was affected; and the other three were pancreas graft rejections. The incidence of postoperative complications requiring re-operation was 42.9%, mostly pancreas graft related. Two patients died, one due to cardiovascular disease; the other was transplant related. Three kidney grafts were lost, and the causes were immunologic, thrombosis, and patient death. Pancreas graft loss occurred in seven patients: thrombosis (n = 3); infection (n = 3); immunologic (n = 1). The patients with surviving grafts were doing well, with normal kidney and pancreas function: serum creatinine = 0.89 +/- 0.15 mg/dL; fasting blood glucose = 79 +/- 16 mg/dL; HbA1c = 4.7 +/- 1.1%. The 1-year patient, kidney, and pancreas survival rates were 97.3%, 94.6%, and 83.8% and 5-year values, 91.7%, 89.2%, and 78.7%, respectively. In conclusion, these results are similar to the most recent UNOS/IPTR reports, leading us to consider our experience with SPKT very positive.

[Squamous cell carcinoma of the face: therapeutic approach]. / Carcinoma espinho celular da face. Abordagem terapêutica.

Cutaneous squamous cell carcinoma is the most common metastatic skin cancer. The importance of early recognition and thorough treatment of premalignant lesions as well as the recognition of risk factors of the neoplasms that are most likely to metastasize must also be emphasized. A retrospective study of 126 patients, treated for primary squamous cell carcinoma of the face, was undertaken over a 7-year period. An attempt is made to define the major therapeutic modalities chosen, taking into consideration the specific anatomic location.