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Summary Background Randomised controlled trials have shown that bariatric surgery is more effective than conventional treatment for the short-term control of type-2 diabetes. However, published studies are characterised by a relatively short follow-up. We aimed to assess 5 year outcomes from our randomised trial designed to compare surgery with conventional medical treatment for the treatment of type 2 diabetes in obese patients. Methods We did our open-label, randomised controlled trial at one diabetes centre in Italy. Patients aged 30–60 years with a body-mass index of 35 kg/m 2 or more and a history of type 2 diabetes lasting at least 5 years were randomly assigned (1:1:1), via a computer-generated randomisation procedure, to receive either medical treatment or surgery by Roux-en-Y gastric bypass or biliopancreatic diversion. Participants were aware of treatment allocation before the operation and study investigators were aware from the point of randomisation. The primary endpoint was the rate of diabetes remission at 2 years, defined as a glycated haemaglobin A 1c (HbA 1c ) concentration of 6·5% or less (≤47·5 mmol/mol) and a fasting glucose concentration of 5·6 mmol/L or less without active pharmacological treatment for 1 year. Here we analyse glycaemic and metabolic control, cardiovascular risk, medication use, quality of life, and long-term complications 5 years after randomisation. Analysis was by intention to treat for the primary endpoint and by per protocol for the 5 year follow-up. This study is registered with ClinicalTrials.gov, number NCT00888836. Findings Between April 27, 2009, and Oct 31, 2009, we randomly assigned 60 patients to receive either medical treatment (n=20) or surgery by gastric bypass (n=20) or biliopancreatic diversion (n=20); 53 (88%) patients completed 5 years' follow-up. Overall, 19 (50%) of the 38 surgical patients (seven [37%] of 19 in the gastric bypass group and 12 [63%] of 19 in the bilipancreatic diversion group) maintained diabetes remission at 5 years, compared with none of the 15 medically treated patients (p=0·0007). We recorded relapse of hyperglycaemia in eight (53%) of the 15 patients who achieved 2 year remission in the gastric bypass group and seven (37%) of the 19 patients who achieved 2 year remission in the biliopancreatic diversion group. Eight (42%) patients who underwent gastric bypass and 13 (68%) patients who underwent biliopancreatic diversion had an HbA 1c concentration of 6·5% or less (≤47·5 mmol/mol) with or without medication, compared with four (27%) medically treated patients (p=0·0457). Surgical patients lost more weight than medically treated patients, but weight changes did not predict diabetes remission or relapse after surgery. Both surgical procedures were associated with significantly lower plasma lipids, cardiovascular risk, and medication use. Five major complications of diabetes (including one fatal myocardial infarction) arose in four (27%) patients in the medical group compared with only one complication in the gastric bypass group and no complications in the biliopancreatic diversion group. No late complications or deaths occurred in the surgery groups. Nutritional side-effects were noted mainly after biliopancreatic diversion. Interpretation Surgery is more effective than medical treatment for the long-term control of obese patients with type 2 diabetes and should be considered in the treatment algorithm of this disease. However, continued monitoring of glycaemic control is warranted because of potential relapse of hyperglycaemia. Funding Catholic University of Rome.

Diabesity is a term often used to indicate the association of type-2 diabetes mellitus (T2DM) with obesity; the prevalence of both conditions is rapidly increasing worldwide and has reached epidemic proportions. Insulin resistance represents the major determinant of T2DM, which becomes manifest once relative β-cell failure ensues and insulin secretion is no longer sufficient to compensate for insulin resistance. In recent years, gastrointestinal surgery has emerged as the most effective option for the treatment of obesity and diabetes, with level-1 evidence of diabetes remission. Restrictive gastric operations such as gastric banding can improve insulin resistance in proportion to weight loss, while gastrointestinal bypass procedures, such as roux-en-y gastric-bypass (RYGB) and biliopancreatic diversion (BPD), can improve glucose homeostasis even before a significant weight loss is reached, suggesting weight-independent mechanisms of action. Studies comparing RYGB to BPD show that RYGB primarily enhances insulin secretion and reduces hepatic glucose output, whereas BPD rapidly improves glycemia primarily through the normalization of insulin sensitivity. Given the fact that BPD involves a significantly longer bypass of the proximal intestine than RYGB, these data suggest that the exclusion of a greater length of small bowel from the transit of food may cause broader and more profound influence on insulin sensitivity.

We report an extraordinarily rare case of a 17-year-old male with an extraskeletal Ewing's sarcoma (ESS) of the kidney and a massive thrombosis involving the inferior vena cava (IVC), from the iliac axis to the right atrium. This onset resembled renal cell carcinoma (RCC), although histological examination revealed it was an extraskeletal Ewing's sarcoma/peripheral neuro-ectodermal tumor (EES/PNET). EES/PNET should benefit from neoadjuvant chemotherapy to reduce the risk of metastasis and of recurrent disease due to delay in suitable treatment. Therefore, in the presence of a renal mass with tumor extension of IVC, it is reasonable to bear in mind that other tumors, apart from RCC, could occur. In such cases, a US or CT-scan guided biopsy could be useful.

Bilio-pancreatic diversion (BPD) induces permanent weight loss in previously severe obese patients through a malabsorptive mechanism. The aim of the study was to evaluate the modifications of circulating thyroid hormones after BPD, a surgical procedure which interferes with the entero-hepatic circulation of biliary metabolites. Forty-five patients were studied before and 2 years after BPD. Thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid antibodies, iodine urinary excretion, lipid profile, insulin and glucose plasma levels were assessed. The insulin-resistance HOMA IR index was calculated, and colour Doppler ultrasonography of the neck was performed. The subjects (23%) had subclinical hypothyroidism prior to BPD (TSH levels above the normal range with normal fT3 and fT4 levels). After 2 years 40.42% of the population showed subclinical hypothyroidism, while 6.3% became frankly hypothyroid, all of them with no evidence of auto-immune thyroiditis. Most of the patients, who became sub-clinically hypothyroid only following BPD, had already thyroid alterations at the sonogram (multi-nodular euthyroid goiter and thyroidal cysts) prior to surgery. BPD increases the prevalence of subclinical or even frank hypothyroidism, without causing a defect in thyroid function itself, through several integrated mechanisms. (1) It induces iodine malabsorption, which is partially compensated by iodine excretion contraction. (2) The entero-hepatic open circulation determines fT3 loss, which induces subclinical or frank hypothyroidism in patients with pre-existing thyroid alterations, interfering also with the weight loss progress. Iodine supplementation should be recommended in those patients reporting thyroid alterations at the sonogram prior to BPD, LT4 therapy should be strictly monitored in patients suffering of subclinical hypopthiroidism and T3 therapy should eventually be considered for patients diagnosed with frank hypothyroidism prior to BPD.

The indications for liver transplantation among patients with post-hepatitis B virus (HBV)-related cirrhosis have changed over the past 35 years. We reviewed the long-term results of 47 patients treated with liver transplantation for HBV-related cirrhosis. Patients were classified into 3 groups according to the perioperative regimen. In the initial experience, no immunoprophylaxis was adopted (no-IP; n = 5). From 1988–1996, an immunoprophylaxis scheme was adopted (HBIg; n = 16). From 1997–2007, we adopted the combination of lamivudine and HBIg (LAM-HBIg; n = 26). We calculated the prevalence of serological reinfection and patient survival at 1 to 20 years, using the 3 regimens. The recurrence rate was 75% in the group of untreated patients; 30% in the HBIg group; and 9% in the LAM-HBIg group. The overall survival was 67% at 5 years, and 64% at 10 and 20 years. The long-term survival for each of the 3 therapeutic approaches, namely, for the patients who did not receive any treatment, for the HBIg group, and for the LAM-HBIg group, were 20%, 50%, and 84%, respectively. We suggest to use the LAM-HBIg combination.

OBJECTIVE—Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women. RESEARCH DESIGN AND METHODS—Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 ± 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method. RESULTS—No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P ≤ 0.01) as was the decrease in dehydroepiandrosterone (P ≤ 0.05 and P ≤ 0.01, respectively). CBG decreased from 51.50 ± 12.76 to 34.33 ± 7.24 mg/l (P ≤ 0.01) following BPD. FCI increased from 11.15 ± 2.85 to 18.16 ± 6.82 (P ≤ 0.05). Insulin secretion decreased (52.04 ± 16.71 vs. 30.62 ± 16.32 nmol/m−2; P ≤ 0.05), and insulin sensitivity increased by 163% (P ≤ 0.0001). Serum CBG was related to BMI (r0 = 0.708; P = 0.0001), body weight (r0 = 0.643; P = 0.0001), body fat percent (r0 = 0.462; P = 0.001), C-reactive protein (r0 = 0.619; P = 0.004), and leptin (r0 = 0.579; P = 0.007) and negatively to M value (r0 = −0.603; P = 0.005). CONCLUSIONS—After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity.

Obesity has been defined as a “multi-metabolic and hormonal disease state”. Although significant advances have been made in the knowledge of how obesity develops and progresses, our understanding of its etiology and physiopathology is still incomplete.

We assessed the safety and clinical efficacy of the Molecular Adsorbent Recirculating System (MARS) in liver failure patients admitted to our intensive care unit (ICU) from May 2000 to February 2006. Of 28 adult patients with bilirubin >15 mg/dL and hepatic encephalopathy (HE) grade ≥2 or hepato-renal syndrome, 22 patients were included in the study, because 6 patients were older than 65 years of age or showed recent alcohol abuse or extrahepatic malignancy. Patients were assigned to 2 groups according to whether MARS therapy was associated with a transplantation procedure: 11 patients received MARS therapy and liver transplantation (OLT group) and 11 patients received MARS therapy alone (non-OLT group). Five of 11 patients in the OLT group were listed for transplantation and 6 patients with graft failure for retransplantation. The patients in the OLT and non-OLT groups were similar in MELD, SOFA, and SAPS scores. All patients were stable and free from complications. MARS significantly reduced bilirubin, bile acids, and blood urea nitrogen (BUN) levels in both groups (P < .05), whereas a significant decrease in ammonia level was observed in the OLT group. Patient survival rates at 3 and 6 months in the OLT group were 91% and 73%, respectively, and in the non-OLT group, 9% and 9%, respectively (P < .001). MARS was safe and well tolerated, improving biochemical parameters, neurological function, and pruritus. In terms of survival, the use of MARS alone was not effective due to the high rate of multiple organ failure. Nevertheless, the association of MARS with a transplant/retransplantation procedure was highly effective.

Currently, there are no data in the literature regarding the pathophysiological mechanisms involved in the rapid resolution of type 2 diabetes after bariatric surgery, which was reported as an additional benefit of the surgical treatment for morbid obesity. With this question in mind, insulin sensitivity, using euglycemic-hyperinsulinemic clamp, and insulin secretion, by the C-peptide deconvolution method after an oral glucose load, together with the circulating levels of intestinal incretins and adipocytokines, have been studied in 10 diabetic morbidly obese subjects before and shortly after biliopancreatic diversion (BPD) to avoid the weight loss interference. Diabetes disappeared 1 week after BPD, while insulin sensitivity (32.96 ± 4.3 to 65.73 ± 3.22 μmol · kg fat-free mass−1 · min−1 at 1 week and to 64.73 ± 3.42 μmol · kg fat-free mass−1 · min−1 at 4 weeks; P < 0.0001) was fully normalized. Fasting insulin secretion rate (148.16 ± 20.07 to 70.0.2 ± 8.14 and 83.24 ± 8.28 pmol/min per m2; P < 0.01) and total insulin output (43.76 ± 4.07 to 25.48 ± 1.69 and 30.50 ± 4.71 nmol/m2; P < 0.05) dramatically decreased, while a significant improvement in β-cell glucose sensitivity was observed. Both fasting and glucose-stimulated gastrointestinal polypeptide (13.40 ± 1.99 to 6.58 ± 1.72 pmol/l at 1 week and 5.83 ± 0.80 pmol/l at 4 weeks) significantly (P < 0.001) decreased, while glucagon-like peptide 1 significantly increased (1.75 ± 0.16 to 3.42 ± 0.41 pmol/l at 1 week and 3.62 ± 0.21 pmol/l at 4 weeks; P < 0.001). BPD determines a prompt reversibility of type 2 diabetes by normalizing peripheral insulin sensitivity and enhancing β-cell sensitivity to glucose, these changes occurring very early after the operation. This operation may affect the enteroinsular axis function by diverting nutrients away from the proximal gastrointestinal tract and by delivering incompletely digested nutrients to the ileum.

Aim of the present study was to assess, in a pair-matched analysis design, risk factors for post-transplant diabetes mellitus (PTDM) in renal transplant recipients (KTx). The incidence of PTDM was evaluated in 538 consecutive KTx in relation to their baseline immunosuppression. PTDM was defined according to the 2003 American Diabetes Association and World Health Organization experts committee definition. As risk factors for PTDM development were considered: age, family history of diabetes, body mass index (BMI), baseline immunosuppression, doses and blood levels of the immunosuppressive agents used. Baseline immunosuppression consisted of CSA, TAC and SRL + CNI. Thirty-two pair-matched controls were identified among the 538 KTx and included in the risk analysis. Significant risk factors for the development of PTDM were identified in the family history of diabetes (P < 0.02) and BMI (P < 0.05). Higher BMI and positive family history for diabetes mellitus were significant risk factors for the development of PTDM, regardless of the immunosuppressive agent used.

Background. The outcome of liver transplantation (LTx) has been correlated with several donor and recipient factors. Methods. A database of 191 consecutive LTx cases was analyzed using Kaplan-Meier and Cox regression statistics based on 80 variables. To avoid additional effects of late events on patient survival, the chosen endpoint was 6 months. Data were evaluated using SPSS statistical software. Results. Kaplan-Meier analysis revealed a difference in 1- to 6-month graft survival between patients transplanted with organs from donors older versus younger than 60 years (Breslow, P

Background. Botulinum toxin induces healing in patients with idiopathic anal fissures. Methods. One hundred-fifty patients with posterior anal fissures were treated with botulinum toxin injected in the internal anal sphincter on each side of the anterior midline. Subjects were randomized into 2 treatment groups based on the number of units of botulinum toxin injected. Patients in group I were treated with 20 units of botulinum toxin and, if the fissure persisted, were retreated with 30 units. Patients in group II were treated with 30 units and retreated with 50 units, if the fissure persisted. Results. The 2 groups were comparable in age, gender distribution, duration of symptoms, resting pressure, and maximum voluntary pressure at anorectal manometry. One month after the injection, examinations revealed complete healing in 55 patients (73%) from group I and 65 patients (87%) from group II ( P =.04). Five patients from group II reported a mild incontinence of flatus that lasted 2 weeks after the treatment and disappeared spontaneously. The values of the resting anal pressure ( P =.3) and the maximum voluntary pressure ( P =.2) did not differ between the 2 groups. At 2 months' evaluation, a healing scar was found in 67 patients (89%) from group I and 72 patients (96%) from group II. A relapse of the fissure was observed in 6 patients (8%) from group I who had a healing scar at 1 month, and 2 other patients never healed. A persistent fissure was present in 3 patients from group II who had no other symptoms. Conclusions. Botulinum toxin injected into the internal anal sphincter is effective in managing anal fissures and avoiding permanent complications. All patients were treated with the active drug and healed after 1 or 2 successive treatments. The results also confirm that higher doses account for a higher success rate, with little increase in complications or side effects, which is probably related to the diffusion of the toxin to the external sphincter. (Surgery 2002;131:179-84.)

Increasing information suggests that absorption profiling may be superior to trough level monitoring for optimal concentration control of cyclosporine microemulsion (Neoral) therapy, and that CsA exposure early post-transplant may correlate significantly with reduced risk of acute graft rejection. This randomized, prospective, multicenter international concentration-controlled study was conducted in 21 renal transplant centers in 8 countries to test and compare the clinical feasibility, functionality, accuracy, precision and prediction of rejection by cyclosporine microemulsion absorption profiling to conventional trough-level drug monitoring. Primary or second renal allograft recipients treated with basiliximab, cyclosporine microemulsion and prednisone immunosuppression were randomized to two study groups in which cyclosporine microemulsion therapy was monitored using a multipointalgorithm or by trough levels. The two study arms were comparable in terms of baseline characteristics, treatment and clinical outcomes. Treatment failure, consisting of acute rejection, graft loss or death, occurred with equal incidence in the two groups (30% and 33%, respectively). Diagnostic feasibility, measured as the proportion of samples obtained within the designated time window, was marginally lower in area under the time-concentration curve (AUC) than in trough groups, but the therapeutic accuracy and precision were comparable or superior in the AUC group. Cox regression analysis performed across study groups showed a highly significant correlation between the predicted probability of acute rejection and cyclosporine (CsA) exposure measured by AUC over the entire 12-h dosage interval (AUC[0-12]) (p = 0.0068), AUC over the first 4 h of the 12-h dosage interval (AUC[0-4]) (p = 0.0014) or 2h post-dose (C2) CsA level (p = 0.0027). Day 3 dose- and weight-corrected C2 values (EMIT equivalent) separated patients into low (200 microg/L/mg/kg dose), intermediate (200-350 microg/L/mg/kg dose) and high absorber categories (350 microg/L/mg/kg dose), defining those at greatest risk. Within these categories, C2 values above approximately 1500 microg/L by day 3 post-transplant were associated with the lowest predicted probability of rejection. Comparable analysis by Cox regression using C0 levels did notreach statistical significance. Absorption profiling is a feasible, accurate and precise method for monitoring cyclosporine microemulsion therapy in clinical practice and, as shown in the companion article, may be simplified by the use of single-point C2 concentrations which accurately predict individual AUC[0-4] exposure levels. Both cyclosporine microemulsion relative absorption (i.e. dose- and weight-corrected exposure) and CsA exposure (measured by predicted AUC or C2 levels) are closely correlated with the risk of rejection, and define patients at high and low risk of acute graft rejection. Trough (C0) levels are not closely correlated with either CsA exposure or rejection risk, and should not be considered reliable for monitoring cyclosporine microemulsion therapy.

Background. Surgical repair of rectocele does not always alleviate symptoms related to difficulty in defecation, and some patients have impaired fecal continence after surgical treatment. To avoid complications of surgical repair, we investigated the efficacy of botulinum toxin in treating patients with symptomatic rectocele. Methods. Fourteen female patients with anterior rectocele were included in the study. The patients were studied by using anorectal manometry and defecography, and then treated with a total of 30 units of type A botulinum toxin, injected into 3 sites, 2 on either side of the puborectalis muscle and the third anteriorly in the external anal sphincter, under ultrasonographic guidance. Results. After 2 months, symptomatic improvement was noted in 9 patients (P =.0003). At the same time, rectocele depth (mean +/- SD) was reduced from 4.3 +/- 0.6 cm to 1.8 +/- 0.5 cm (P =.0000001) and rectocele area from 9.2 +/- 1.3 cm(2) to 2.8 +/- 1.6 cm(2) (P =.0000001). Anorectal manometry demonstrated decreased tone during straining from 70 +/- 28 mm Hg at baseline to 41 +/- 19 mm Hg at 1 month (P =.003) and to 41 +/- 22 mm Hg at 2 months (P =.005). No permanent complications were observed in any patient for a mean follow-up period of 18 +/- 4 months. At 1 year evaluation, incomplete or digitally assisted rectal voiding was not reported by any patient, and a rectocele was not found at physical examination. Four recurrent, asymptomatic rectoceles were noted at defecography. Conclusions. Botulinum toxin injections should be considered as a simple therapeutic approach in patients with anterior rectocele. The treatment is safe and less expensive than surgical repair. A more precise method of toxin injections under transrectal ultrasonography accounts for the high success rate. Repeated injections may be necessary to maintain the clinical improvement.

Sex mismatch is a well-known risk factor for chronic rejection of liver allografts, but the mechanisms involved remain unclear. Since experimental observations suggest that female liver is more sensitive to reperfusion injury than male liver, we assessed the influence of gender on oxidative stress. Livers from male and female rats were exposed to warm ischemia and reperfused by an oxygenated buffer. Chemiluminescence was continuously recorded. Reduced and oxidized glutathione and malondialdheyde lactic dehydrogenase values were also determined. Chemiluminescence increased during reperfusion in both groups, but was significantly greater in livers from female rats. Malondyaldheide and lactic dehydrogenase progressively increased in all animals, reaching significantly greater values in female rats. Livers from female rats showed an increase in all the parameters of oxidative stress compared to male animals. A greater susceptibility to reperfusion injury may be evoked as an alternative mechanism to explain the poor outcome of female organ after liver transplantation.

To assess the effectiveness of biliopancreatic diversion (BPD) in the treatment of morbid obesity and to evaluate how the procedure affects body weight.Fourteen morbidly obese subjects studied before and 30 months after BPD and fifteen healthy volunteers matched for age, sex and height (controls).Comparison of the following parameters were made in the study groups before surgery and 30 months after BPD and with those of the controls group: fat mass, fat-free mass, non-protein substrate oxidation, basal metabolic rate, plasma glucose, insulin and free fatty acid concentrations.Obese subjects lost 60.38+/-10.71 kg of weight during 18 months following surgery and then remained stable for another 12 months, when this study was performed. Weight loss was substantially due to a loss of fat mass (FM: 60.13+/-13.01 kg before and 19.02+/-8.61 kg after BPD; p0.001). FM were not statistically different between post-obese subjects and controls; however, post-obese patients retained significantly more fat free mass (FFM) than controls. Subsequently, basal metabolic rates of post-obese subjects were higher than those of the control group (p0.05). Fasting non-protein respiratory quotient (npRQ) was significantly lower before BPD than 30 months after the surgery (0.798+/-0.04 vs. 0.90+/-0.048, p0.001), suggesting that, while obese, patients oxidized more lipids than carbohydrates. Moreover, fasting and two-hour plasma glucose and insulin concentrations decreased significantly after BPD to values comparable to those of the control group.Weight loss in obese patients after BPD is mainly due to lipid malabsorption, but increased energy expenditure associated with retaining a high FFM in physically active post-obese subjects may also play a role, enabling them to maintain long-term reduced body weights.

In recent studies, nonstandard donors and high Model for End-stage Liver Disease (MELD) values have been indicated as risk factors for both graft survival and patient survival. A recent debate concerns which donor and recipient match guarantees the best results in terms of early and late survival. To emphasize the role of the donor–recipient match, we have reported herein a complex case of a patient who changed his preoperative risk status, being transplanted three times using donors of different risk levels. At each transplant, the patient moved to a higher MELD class: first transplant MELD = 22; second transplant MELD = 37; third transplant MELD = 38. Only at the third transplant did the patient recover. Besides the liver, almost all his organs (kidneys, heart, lungs) recovered in a few weeks, as well. Unfortunately, severe cortical and subcortical brain damage remained a crucial limiting impairment, leading to death 5 months later, due to pulmonary infection, yet with a perfectly working liver. We underlined the role of donor factors to predict the outcome after liver transplantation in the MELD era.

Successful treatment of chronic hepatitis C virus (HCV) infection can prevent reinfection after orthotopic liver transplantation (OLT). Pegylated interferon (PEG-IFN) may ameliorate virological response (VR), making the risk-to-benefit ratio of therapy favorable in waiting list patients. From January 2001 to April 2006, we treated 15 HCV cirrhotics with PEG-IFN alpha-2b (1.5 microg/kg/week) and ribavirin (RIBA; >or=10.6 mg/kg/d). Their mean age was 51.5 years. There were 9 men. In 6 cases the genotype was 1b. With Child-Pugh scores >or=9 (range 9-12) and Model for End-Stage Liver Disease (MELD) scores >or=14 (range, 14-22). Adverse events occurred in all subjects: thrombocytopenia (

BACKGROUND Obesity is characterised by growth hormone (GH) abnormalities, including a blunted response to stimulation and a 'paradoxical' increase after meals. The blunted GH release is reversed by a surgical intestinal bypass procedure. However, this does not mean that normal GH dynamics have been restored. The present study assessed whether post-surgical weight reduction in obese patients normalised the modulation of GH release produced by metabolic fuels. SUBJECTS Ten obese female subjects, aged 23-54 y, were studied before and after biliopancreatic diversion (BPD). All patients, after surgery, had experienced a significant reduction in body weight (mean body mass index (BMI) 25.78 +/- 1.01 kg/m2 vs 44.68 +/- 1.73 kg/m2). Two groups were also studied as controls: Ten normal body weight female subjects and ten patients suffering from anorexia nervosa (AN, mean BMI 17.46 +/- 1.12 kg/m2). MEASUREMENTS We have studied the GH response to a GH releasing hormone (GHRH) bolus (1 microg/kg i.v., at 13.00 h) before and after a standard meal. RESULTS In post-BPD subjects, the GH response to GHRH in the fasting state, was clearly augmented in comparison with the pre-BPD values (peak values 18.06 +/- 4.56 vs 3.24 +/- 0.68 microg/L). In post-BPD subjects the postprandial GH response was further augmented in comparison with the fasting test (peak 30.12 +/- 4.99 microg/L, P < 0.05). This pattern was similar to that observed in anorexic patients. CONCLUSION The surgical procedure restores a normal GH response to GHRH in the fasting state, but the 'paradoxical' GH response after meals remains present, suggesting a persistent GH derangement in such patients, which is not related to body weight per se. The surgical procedure makes obese patients similar to anorexics, in the relationships between metabolic fuels and GH secretion. The persistence of the GH postprandial response to GHRH in post-BPD subjects suggests a role for metabolic fuels in the regulation of somatostatin (SRIF) secretion.

Background: The goal of the present work is to present an effective surgical approach for the treatment of a medically-resisitant form of hyperlipidemia. Methods: Two siblings with familial lipoprotein-lipase deficiency and subsequent hyperchylomicronemia, widespread skin xanthomas and severe insulin-resistant diabetes mellitus came to our observation after several unsuccessful attempts at medical treatment. In order to lower plasma lipids through lipid malabsorption, a modified bilio-pancreatic diversion operation was employed. The rationale in deciding to use this surgical approach was based also on the likely hypothesis that diabetes, in these subjects, was secondary to high circulating and tissue levels of lipids. Insulin sensitivity in the two treated subjects, as well as in 24 healthy volunteers constituting the control group, was assessed by euglycemic hyperinsulinemic clamp and indirect calorimetry, obtaining total end-clamp glucose uptake (M) and end-clamp glucose oxidation (ECGO) rates. Results: Within 3 weeks of surgery, plasma triglycerides and cholesterol levels had decreased from 4500 and 500 mg/dl (with dietary restrictions) to lower than 450 and 150 mg/dl (on a free, lipid-rich diet) respectively. Fasting plasma glucose levels had decreased from above 300 (under daily repeated subcutaneous injections of insulin) to 80-100 mg/dl (without administration of insulin or oral hypoglycemic agents). Body weight and fat free mass were maintained in both subjects after surgery. In both patients, before surgery M and ECGO were significantly lower than in normal subjects, while after surgery they were not significantly different from normal subjects, confirming the positive metabolic effect of the operation. Conclusion: The surgical option used in these patients may represent an interesting and effective new possibility for treatment of those severe cases of hyperlipemia leading otherwise to metabolic complications and a low quality of life.

Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.

Sepsis is characterized by an abnormal increase in plasma proline (PRO) level, which tends to be related to the severity of disease. This study has been performed to assess the relationship between changes in plasma PRO and levels and doses of other amino acids (AA) in critically ill septic patients undergoing total parenteral nutrition (TPN). Sixteen septic patients receiving TPN were randomly divided into two groups: 8 patients (Group A) received TPN with a standard AA solution, and 8 patients (Group B) with a modified AA solution (isonitrogenous, branchedchain AA enriched, with unchanged PRO concentration). Serial determinations of plasma AA profiles and of other variables were performed in each patient for a total of 396 measurements. In Group A mean plasma PRO level was 372μM/L; changes in PRO were tightly correlated with changes in the levels of most of the other AA, and the highest PRO levels characterized the more severely unbalanced septic metabolic profiles. In Group B, plasma levels of PRO and of the other AA (except glutamate, aspartate, taurine and the three branched-chain AA) decreased. The decrease in PRO level was well correlated with the increased branched-chain AA dose and with simultaneous decreases in plasma lactate and respiratory quotient. These changes could be related to a specific effect of branched-chain AA on septic metabolic derangement and on PRO metabolism, and to an improved balance between protein synthesis and catabolism.

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery (POI); and after reaching stable body weight, at least 2 years after surgery (POII). A group of 7 control subjects (C), matched groupwise for sex, age and BMI with POII patients, was also studied. The M value at POI was significantly higher than at Ob (49.12 ± 8.57 vs 18.14 ± 8.57 μmol · kg−1· min−1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 ± 7.23 vs 9.42 ± 3.91 μmol · kg−1· min−1) and was not significantly different between POII and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 ± 223.9 vs 1039.6 ± 283.4 vs 616.0 ± 77.6 μmol · l−1). The same applied to basal plasma triglycerides (2.07 ± 0.77 vs 1.36 ± 0.49 vs 0.80 ± 0.19 g · l−1). Weight decreased mainly in the late postoperative period (POI to POII 124.28 ± 11.22 to 69.71 ± 11.78, 83 % of total decrement), rather than in the early postoperative period (Ob to POI 135.25 ± 14.99 to 124.28 ± 11.22 kg, 17 % of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance. [Diabetologia (1997) 40: 599–605]

Measurement of inosine-monophosphate dehydrogenase (IMPDH) activity or gene expression was used as a further approach in pharmacokinetics (PK)/pharmacodynamic (PD)-guided mycophenolate mofetil (MMF) therapy. Forty-four de novo kidney transplant patients were enrolled; 35 of these completed the study, and were followed for 24 weeks for clinical status, PK parameters, IMPDH activity and IMPDH1/2 gene expression. IMPDH activity and expression were measured in peripheral blood mononuclear cells before transplant and at week 2,4,12 and 24, drawn before (t0) and 2 h (t2 h) after MMF administration. No significant correlation was found between IMPDH activity/expression and PK parameters. For both genes, significant enhancement in t2 h expression was observed, then decreases towards week 24 with a trend following steroid dosages. Seven patients experienced acute rejection (AR) and exhibited significantly higher pre-transplant expression of both IMPDH1 (median 3.42 vs. 0.84; p=0.0025), and IMPDH2 genes (135 vs. 104; p=0.0218) with respect to non-rejecting patients. A significant association was also found between pre-transplant IMPDH1 mRNA and haematological complications (p=0.032). This study suggests that high steroid dosages may influence IMPDH1/2 expression, hampering their use as a PD biomarker, particularly during the early post-transplant period. The measurement of pre-transplant levels of IMPDH1/2 may contribute to prediction of individual drug responsiveness to improve the clinical management of patients in MMF therapy.

The effectiveness of restrictive procedures has been inferior to that of malabsorbitive ones. Recent variants of restrictive procedures, i.e., gastric banding and sleeve gastrectomy, confirm the strive for more efficacious solutions with less complications. We investigated the balance between effectiveness and complications for a new restrictive procedure, a Transoral Endoscopic Vertical Gastroplasty (TOGa®)Seventy-nine morbidly obese patients were submitted to one out of three surgical procedures: TOGa® (29 patients), laparoscopic gastric bypass (LRYGBP; 20 patients), and biliopancreatic diversion (BPD; 30 patients). Mean BMI were 41.7 (35.4-46.6), 44.8 (36.4-54), and 47.5 (41-60.3), respectively. All the patients reached a 2-year follow-up.In TOGa® group BMI, respectively at 12 and 24 months, was 34.5 and 35.5, with 44 and 48.3% of patients with BMI lower than 35. In LRYGBP group, BMI was 30.7 and 29.2 kg/m(2), with 80 and 85% of patients with BMI 35. In BPD group, BMI was 30 and 29.6 kg/m(2), with 100 and 93.3% of patients with BMI 35. In TOGa® group, 59% of patients with an initial BMI 45 reached a BMI 35, in comparison to 48% recorded in the whole group and to 14.3% in patients with initial BMI ≥ 45.In selected patients, TOGa®, was associated with good results after two years in terms of weight loss, even in comparison with LRYGBP and BPD. Minimal trauma, absence of complications, and short hospital stay justify this procedure for patients with low BMI.

Insulin resistance is a common feature in obese patients. To evaluate the modifications in insulin sensitivity after a bariatric operation such as Bilio-pancreatic diversion (BPD), three groups of subjects (14 normal controls (N); seven ex-obese patients (X) with at least 2 years at weight-stable conditions after BPD surgery; and eight morbidly obese patients (0)) were studied with intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The ratio of the area under the curve (AUC) for glucose over that of insulin was used as a measure of insulin sensitivity. All the following tests were conducted as Bonferroni-corrected pairwise t-tests, in case overall ANOVA was significant. No significant difference was found between N and X subjects, while obese patients showed a reduced AUCg/AUCI ratio with respect to the normal controls (O vs N: 0.01164 +/- 0.00039 vs 0.02392 +/- 0.0039, p0.05). IVGTT, AUCS: significant differences were found in each case: N vs X: 0.0591 +/- 0.0075 vs 0.1402 +/- 0.0399, p0.05; N vs 0:0.0591 +/- 0.0075 vs 0.0223 +/- 0.0031, p0.01; X vs 0:0.1402 +/- 0.0399 vs 0.0223 +/- 0.0031, p0.05. IVGTT-derived data were also analyzed using the minimal model of glucose kinetics; with this method, glucose effectiveness was significantly different between normal subject and obese subjects (0.0248 +/- 0.00288 Vs 0.00906 +/- 0.00135 per min, p0.001). The insulin sensitivity index was not significantly different between normal and ex-obese subjects, while both of these groups were significantly different from obese patients (N vs 0: 12.04 x 10sup5; +/- 2.61 x 10sup5; vs 3.29 x 10sup5; +/- 0.61 x 10sup5;, p0.066; X vs 0: 16.42 x 10sup5; +/- 4.23 x 10sup5; vs 3.29 x 10(1)+/- 0.61 x 10sup5; per min per pM, p0.02). In conclusion, the present study indicates that, after a body weight reduction operation capable of almost re-establishing ideal body weight like BPD, obese individuals with a family history of obesity show a normalization of insulin response to glucose load.

Introduction The extremely good results of renal transplantation have favored the use of pre-emptive procedures for treatment of patients with end-stage renal disease before entering dialysis, but still some concerns exist about patient survival. The aim of this study was to analyze the evolution of death rates and the causes of mortality among recipients of procedures performed between 1970 and 2007. Methods We examined the outcomes at 1, 5, 10, and 15 years follow-up of 793 adults who underwent primary or repeat renal transplantation from living or deceased donors between January 1, 1970 and December 31, 2007. To evaluate the impact of immunosuppressive regimens on patient survivals, we considered 3 time intervals: the precyclosporine era, the cyclosporine era, and the postcyclosporine era. Results During follow-up 115/793 (14.5%) renal transplant recipients died. There was a significant decrease in the overall mortality rate over the years. Patients who underwent transplantation more recently in the postcyclosporine era (1997–2007) showed a mortality rate of 1.8% (7/394) at 1 year and 3.3% (13/394) at 5 years, significantly lower than in previous periods. There was no significant change in the most frequent causes of death: cardiovascular diseases and sepsis. Conclusion Our data indicated a significant improvement in patient survival after renal transplantation over the last decade. These data are significantly better than those reported for dialysis treatment thus supporting the strategy of pre-emptive transplantation for end-stage renal disease.

Parathyromatosis is the most severe type of recurrent secondary hyperparathyroidism (SHPT) after parathyroidectomy (PTX) in haemodialysis patients. It is difficult to completely remove all foci of parathyroid tissue and neck re-explorations are often required. Here, we report for the first time a case of recurrent SHPT due to parathyromatosis treated by radio-guided PTX. A haemodialysed 48-year-old woman with recurrent SHPT due to parathyromatosis was treated by radio-guided PTX. Preoperatively Ultrasonography, (99)Tc-SestaMIBI scintigraphy and magnetic resonances of the neck and thorax were performed. The preoperative imaging techniques detected four parathyroid nodules, while intraoperative gamma probe identified six nodules (three in atypical site). No frozen sections were performed during surgery. Post-operative intact parathyroid hormone levels were stabilized in the range 300-500 pg/mL during the 26 month follow-up by means of cinacalcet and paricalcitol therapy. In cases of parathyromatosis, the preoperative imaging techniques are inadequate, while intraoperative gamma probe is useful to detect the parathyroid tissue and allows a more extensive cytoreduction because it ensures the removal of undetectable and ectopic parathyroid foci. The operative time is reduced and frozen sections are unnecessary. However, the radio-guided PTX do not rule out parathyromatosis recurrence and complementary medical treatment is appropriate.

Intra-abdominal infections (IAIs) are defined as an inflammatory response of the peritoneum to microorganisms and their toxins, which results in purulent exudate in the abdominal cavity. They have two major manifestations: generalized peritonitis and IA abscess. Mortality rates for peritonitis, regardless of diagnostic and therapeutic developments in recent years, remain unacceptably high and still represent one of the greatest challenges for surgeons. Drainage, debridement, and definitive surgical management are the usual consecutive steps to be carried out, but in many circumstances, the procedure has to be tailored to the individual patient. Successful source control and antibiotic management is associated with illness resolution. Progression or failure to resolve organ dysfunction suggests disease persistence and the need for further intervention. Particular interest has been given to severe acute pancreas and its diagnosis and management, as well as to mediastinitis and pleural infection disease. Furthermore, we discuss the two most important sources of infection in surgery: wound and urinary tract.

Background. The usefulness of the combination of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) parathyroid scintigraphy and ultrasonography to detect para- thyroid glands (PTGs) in secondary hyperparathyroidism (SHPT) is still controversial. Methods. In all, 21 patients with SHPT underwent parathyr- oidectomy. The sensitivity and specificity of ultrasonography and scintigraphy related to site, size, hyperplasia type of PTG, concomitant thyroid disease, and the frequency of intraopera- tive frozen sections were determined. Results. The sensitivities of scintigraphy and ultrasonogra- phy were 62% and 55%, and the specificity was 95% for both procedures. The sensitivity of combined techniques was 73%. The scintigraphy detected 7/9 (78%) ectopic PTGs, whereas ultrasonography was always negative. A PTG maximum longi- tudinal diameter

Human herpevirus 8 (HHV8) DNA sequences have been found in lesions from patients with Kaposi's sarcoma (KS) in several forms including immunosuppressed transplant patients. We wanted to study the transmission of HHV8 in kidney transplant recipients and to assess the risk of development of KS related to the viral infection in this group of patients. We tested sera of 120 renal transplant recipients with serological assay for antibodies to HHV8 antigens before transplantation and then we tested sera of 66 patients of the same group after transplantation. Antibodies were detectable in 27.5 % of the patients before transplantation. In the seropositive population 15.1 % developed KS and in the negative group 1.1 %. Analysing 66 posttransplant sera we noticed that 24 % of the seronegative patients became positive after transplantation. Our data suggest that being positive for HHV8 before transplantation could be an important risk factor for the development of KS.

Background and aims Transoral gastroplasty (TOGA) recently emerged as a new, feasible and relatively safe technique for the surgical treatment of obesity. However, so far there are no data on the effects on insulin sensitivity in the literature. Our aim is to evaluate the effect of TOGA on insulin sensitivity and secretion. Methods and results Nine glucose normo-tolerant obese subjects (age:41±6years; BMI:42.49±1.03kg/m 2 ) were studied. Fat-free mass (FM) and fat mass (FM) were assessed by bioelectrical impedance; plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT) before and 3months after the operation. Insulin sensitivity was calculated using the oral-glucose insulin-sensitivity index, and insulin secretion by C-peptide deconvolution. Three months after surgery, a significant ( P =0.008) reduction of BMI to 35.65±0.65kg/m 2 , with a decrease of FM and FFM from 57.22±2.19 to 41.46±3.02kg ( P =0.008) and from 59.52±1.36 to 56.67±1.10kg ( P =0.048) respectively, was observed. Insulinemia was significantly reduced at fast and at 120min after OGTT; in contrast, no significant change in glucose concentration was observed. Insulin sensitivity significantly increased (348.45±20.08 vs. 421.18±20.84ml/min/m 2 , P =0.038) and the incremental area of insulin secretion rate (total ISR) significantly decreased (from 235.05±27.50 to 124.77±14.50nmol/min/m 2 , P =0.021). Total ISR correlated with weight, BMI and FM ( r =0.522, P =0.028; r =0.541, P =0.020; r =0.463, P =0.049, respectively). BMI represented the most powerful predictor of ISR decrease ( R 2 =0.541, P =0.020). Conclusion Transoral gastroplasty allows a significant weight loss 3months after the intervention as well as an amelioration of insulin sensitivity with subsequent reduction of the insulin secretion.

To aim of the study was to investigate the effect of bilio-pancreatic diversion (BPD) on type 2 diabetes in patients with BMI35 kg/m(2).OGTTs were performed and anthropometric data were compared between five diabetes patients (BMI 27-33 kg/m(2)) following BPD and seven diabetes patients after a low-energy diet. Insulin secretion was computed by C-peptide deconvolution. A euglycaemic-hyperinsulinaemic clamp was performed only in the BPD group and the M value measured.One month after BPD, fasting and 2 h post-OGTT glycaemia decreased from 15.22 +/- 3.22 to 6.22 +/- 0.51 mmol/l (p = 0.043), while insulin sensitivity increased significantly. No significant changes were observed in the low-energy diet group. Insulin secretion did not differ significantly after either intervention. Diabetes amelioration (change in HbA(1c) level) was observed up to 18 months after BPD without pharmacological therapy.BPD can achieve adequate control of type 2 diabetes also in patients with BMI35 kg/m(2). The rapid postoperative remission of diabetes is primarily related to an improvement in insulin sensitivity.

Cinacalcet efficacy is limited in severe secondary hyperparathyroidism (SHPT) and its effect on parathyroid gland (PTG) volume and morphology have not been sufficiently investigated. We evaluated the effect of cinacalcet treatment for one year on the laboratory parameters of calcium-phosphorus metabolism and PTG ultrasound (US) patterns in hemodialysis (HD) patients with severe SHPT and US results indicative of nodular hyperplasia. Thirteen HD patients with severe SHPT (intact parathyroid hormone >700 pg/mL), US/scintigraphic evidence of at least one PTG with a diameter >7 mm, and high surgical risk or refusal of surgery were included. The patients were treated with cinacalcet. The initial dose of 30 mg was increased up to 180 mg once daily. At baseline and after one year of cinacalcet treatment a neck US was performed, providing data on 22 parathyroid glands in eight patients. The mean diameter at baseline and at one year was 12.6 +/- 5.9 and 13.0 +/- 5.3 mm, respectively (P = 0.46). Similarly, the mean volume at baseline and at one year was 513.4 +/- 416.3 and 556.8 +/- 480.8 mm(3), respectively (P = 0.18). The US structural score remained unchanged in 16 parathyroid glands and increased in 6 (P < 0.03), while the vascular score remained unchanged in 16 parathyroid glands and decreased in 6 (P = 0.25). Thus it can be concluded that cinacalcet treatment for one year in HD patients with severe SHPT is not associated with significant changes in parathyroid gland US patterns.

Various artificial liver support systems are currently used in patients with decompensated chronic liver disease or acute liver failure as a bridge to recovery or to orthotopic liver transplantation (OLT). Between June 2004 and September 2006, 9 subjects were treated with plasma exchange (PE) for acute decompensation on chronic liver disease or chronic decompensation in end-stage liver disease. All of them were awaiting OLT or were listed at the moment of decompensation. Grade II to III hepatic encephalopathy (HE) was present in 4 patients, significant renal dysfunction in 3 patients, and ascites in 6 patients. Baseline serum total bilirubin was 35.1 ± 11.2 mg/dL (mean value ± SD). The patients underwent a mean of 12.1 2-hour exchanges over 1 to 8 weeks. The 3 who recovered were alive after a mean follow-up of 22.7 ± 10.3 months. There were 3 patients who underwent transplantation and 3 who died due to liver failure during treatment. Only subjects with acute decompensation and without HE or significant renal dysfunction survived without OLT. PE did not significantly modify the grade of HE or the renal function. PE seemed to be a safe, long-term, effective therapeutic option for acute decompensation among subjects with chronic liver disease without brain or renal dysfunction.

In liver transplantation the identification of risk factors and the risk quantification for each single case represent a field of great interest. There are donor-related and recipient-related risk factors. Donor risk index (DRI) was retrospectively calculated in 223 liver transplant cases. We did not include patients with preoperative diagnosis of hepatocarcinoma and retransplants. The cases were stratified into two classes according to the DRI (low risk, DRI1.7, and high risk, DRIor= 1.7). A new index, namely the organ patient index (OPI) was calculated adding the Model for End-stage Liver Disease (MELD) score to the DRI. Patients were stratified into two classes according to the OPI (low risk, OPIor= 2.85, and high risk, OPI2.85). The cases with low DRI (n=144) showed better survival than the cases with high DRI (n=82; P.02). The cases with low OPI (n=173) showed better survival than cases with high OPI (n=50; P.01). The OPI predicted outcomes better than DRI, increasing the gap in the long-term graft survival between the low- and the high-risk class. The inclusion of the MELD in the new index allowed better prediction of graft survival.

Background About 50% of kidney-transplant patients undergo organ rejection within 10 years. Chronic allograft nephropathy (CAN) represents the dominant cause of kidney transplant failure and accounts for 50–80% of graft loss in long-term surviving patients. CAN pathogenesis is multifactorial and not-completely elucidated; several reports indicate TGF-β1 and platelet-derived growth factor (PDGF)-BB expression in CAN suggesting a possible role of these factors in the allograft arteriosclerosis and graft failure. Methods We investigated the plasma expression concentrations of human growth factors with enzyme-linked immunosorbent assays and appropriate statistical analysis. Results We present evidences showing statistically significant association of CAN with a specific balance between TGF Beat1 and PDGF-BB plasma concentrations, in 129 kidney-transplant patients and 15 healthy controls. Odds ratios were computed to correlate expression-levels with CAN occurrence. Conclusion We believe these data may suggest a novel non-invasive method to identify early molecular markers of graft deterioration.

A four-year prospective study of distal revascularization in diabetics with trophic damage of the limbs is presented. Thirty-two infrapopliteal bypasses in 32 limbs of 31 diabetic patients were performed. One-year and three-year graft patency rates were 68% and 59% respectively. Limb salvage was obtained in every case of surgical success.

Background: The role ofparathyroid glands (PTG) ultrasonography (US) in hemodialysis patients with secondary hyperparathyroidism (SHPT) is still controversial. The present study aimed at evaluating the relationship between US findings and SHPT degree as well as therapeutic outcome. Methods: Twenty hemodialysis patients with moderate SHPT and 15 with severe SHPT underwent US to assess the PTG number, maximum longitudinal diameter (MLD), structural (1 – hypoechoic, 2 – slight heterogeneous, 3 – high heterogeneous, 4 – nodular) and vascular patterns (1 – slight, 2 – medium and 3 – high). Results: PTG number, MLD and US patterns were correlated with iPTH levels. MLD of patients with moderate or severe SHPT was 7.2 ± 2.3 and 15 ± 5.1 mm (p < 0.001). Most patients with moderate SHPT showed a single PTG with an MLD 9 mm and 3–4 structural and vascular patterns. Thirteen patients were responders to treatment and 22 nonresponders. In nonresponders, a higher number of PTG was observed as well as higher echostructural and vascular patterns. In 14 patients who underwent parathyroidectomy, no differences were found between PTG US MLD and pathology diameter. All PTG with evidence of 3–4 structural and vascular score at ultrasound showed nodular hyperplasia at pathological examination. Conclusions: The adopted classification of US findings is correlated with SHPT degree and therapeutic outcome and might be an adjunctive predictive method useful to assess the SHPT severity and to plan the therapeutic strategy.

Insulin resistance is a strong biological marker of both obesity and type 2 diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. Biliopancreatic diversion (BPD), inducing a massive lipid malabsorption, leads to a reversion of type 2 diabetes. To elucidate the mechanisms of diabetes reversibility, the expression of genes involved in glucose and free fatty acids (FFAs) metabolism was investigated in skeletal muscle biopsies from obese, type 2 diabetic subjects. Peripheral insulin sensitivity and insulin secretion was also measured. Eight Caucasian obese diabetic patients (BMI 52.1±1.85 kg/m2) were studied before and 3 years after BPD. The mRNA levels were estimated by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), insulin sensitivity by the euglycemic–hyperinsulinemic clamp and insulin secretion using a model describing the relationship between insulin secretion and glucose concentration. Whole-body glucose uptake (M), normalized by fat-free mass, significantly increased in post-obese subjects (P

We reviewed the incidence and the impact of posttransplant lymphoproliferative disorders (PTLDs) on patient survival among a consecutive series of 255 patients. Five cases of PTLD were observed in adults: two cases were early (less than 1 year) and three cases, late lymphomas. The EBV positivity and the degree of immunosuppression were the main risk factors. We labeled cases as early or late according to whether the time elapsed from the transplant to the first clinical evidence of PTLD was less than 12 months. The median time from transplant to diagnosis of PTLD was 8 (early) and 108 (late) months. All cases were treated by reduction in immunosuppressive therapy with conventional chemotherapy and rituximab. The early cases with lymphoma located at the hepatic hilum died due to local complications (biliary sepsis and hemobilia), after an initial partial response to chemotherapy. The three patients with late cases are in remission after a mean follow-up of 23 months.

Everolimus (EVL) has shown a potential to reduce nephrotoxicity associated with cyclosporine (CsA) while providing similar protection against rejection. We analyzed the incidence of acute rejection episodes (ARE) among 20 cadaveric renal transplant recipients treated with the combination of EVL + CsA. Immunosuppression consisted of basiliximab induction given pretransplant and on day 4 posttransplant; EVL at a starting dose of 1.5 mg/day followed by concentration control to trough levels of 3 to 8 ng/mL by day 7; CsA at a starting dose of 4 mg/kg per day and then concentration controlled with C2 monitoring (C2 500–700 ng/mL); and steroids in a tapering regimen to reach 5 mg by day 30. The overall incidence of ARE was 25%. On postoperative day 7, patients with ARE showed significantly lower mean EVL trough concentrations compared with those not experiencing ARE (NO ARE: 2.2 ± 2.1 ng/mL vs 4.8 ± 2.4 ng/mL) ( P = .05). The CsA C2 values were close to the lower end of the target range on day 3 (583 ± 334 ng/mL). All rejecting grafts were functioning at 3 months posttransplantations, but mean serum creatinine was higher in the ARE group (ARE 2.2 ± 0.7 mg/dL vs 1.1 ± 0.2 NO ARE; P = .04). In conclusion, whenever EVL is used in combination with CsA to protect kidney transplant patients against the risk of acute rejection, a threshold of 3 ng/mL must be reached in the first week posttransplantation. We suggest careful monitoring of EVL exposure and increased EVL starting doses.