Fat-to-blood recirculation of partially dysfunctional PD-1+CD4 Tconv cells is associated with dysglycemia in human obesity.

Obesity is characterized by the accumulation of T cells in insulin-sensitive tissues, including the visceral adipose tissue (VAT), that can interfere with the insulin signaling pathway eventually leading to insulin resistance (IR) and type 2 diabetes. Here, we found that PD-1+CD4 conventional T (Tconv) cells, endowed with a transcriptomic and functional profile of partially dysfunctional cells, are diminished in VAT of obese patients with dysglycemia (OB-Dys), without a concomitant increase in apoptosis. These cells showed enhanced capacity to recirculate into the bloodstream and had a non-restricted TCRß repertoire divergent from that of normoglycemic obese and lean individuals. PD-1+CD4 Tconv were reduced in the circulation of OB-Dys, exhibited an altered migration potential, and were detected in the liver of patients with non-alcoholic steatohepatitis. The findings suggest a potential role for partially dysfunctional PD-1+CD4 Tconv cells as inter-organ mediators of IR in obese patients with dysglycemic.

Capecitabine-Induced Ileitis during Neoadjuvant Pelvic Radio-Chemotherapy for Locally Advanced Rectal Cancer: A Case Report with Literature Review.

We report on a clinical case of capecitabine-induced acute ileitis in a patient treated with pre-operative concurrent chemoradiation with capecitabine for locally advanced rectal cancer and provide a comprehensive literature review. This a rare, but life-threatening, clinical situation, that clinicians should be aware of. Severe persistent diarrhea is the most frequent clinical feature and computed tomography is a valid tool for diagnosis. Conservative management includes capecitabine withdrawal, antidiarrheal therapy and endovenous hydration, together with dietary modifications and broad-spectrum antibiotics. Pelvic irradiation represents an adjunctive risk factor, which may increase the likelihood of occurrence of terminal ileitis. Early recognition and prompt intervention are crucial for successful clinical management.

Advice of General Practitioner, of Surgeon, of Endocrinologist, and Self-determination: the Italian Road to Bariatric Surgery.

PURPOSE: Bariatric surgery (BS) is considered the most efficient treatment for severe obesity. International guidelines recommend multidisciplinary approach to BS (general practitioners, endocrinologists, surgeons, psychologists, or psychiatrists), and access to BS should be the final part of a protocol of treatment of obesity. However, there are indications that general practitioners (GPs) are not fully aware of the possible benefits of BS, that specialty physicians are reluctant to refer their patients to surgeons, and that patients with obesity choose self-management of their own obesity, including internet-based choices. There are no data on the pathways chosen by physicians and patients to undergo BS in the real world in Italy. METHODS: An exploratory exam was performed for 6 months in three pilot regions (Lombardy, Lazio, Campania) in twenty-three tertiary centers for the treatment of morbid obesity, to describe the real pathways to BS in Italy. RESULTS: Charts of 2686 patients (788 men and 1895 women, 75.5% in the age range 30-59 years) were evaluated by physicians and surgeons of the participating centers. A chronic condition of obesity was evident for the majority of patients, as indicated by duration of obesity, by presence of several associated medical problems, and by frequency of previous dietary attempts to weight loss. The vast majority (75.8%) patients were self-presenting or referred by bariatric surgeons, 24.2% patients referred by GPs and other specialists. Self-presenting patients were younger, more educated, more professional, and more mobile than patients referred by other physicians. Patients above the age of 40 years or with a duration of obesity greater than 10 years had a higher prevalence of all associated medical problems. CONCLUSIONS: The majority of patients referred to a tertiary center for the treatment of morbid obesity have a valid indication for BS. Most patients self-refer to the centers, with a minority referred by a GP or by specialists. Self-presenting patients are younger, more educated, more professional, and more mobile than patients referred by other physicians. Older patients and with a longer duration of obesity are probably representative of the conservative approach to BS, often regarded as the last resort in an endless story.

Role of nutritional ketosis in the improvement of metabolic parameters following bariatric surgery.

BACKGROUND: Ketone bodies (KB) might act as potential metabolic modulators besides serving as energy substrates. Bariatric metabolic surgery (BMS) offers a unique opportunity to study nutritional ketosis, as acute postoperative caloric restriction leads to increased lipolysis and circulating free fatty acids. AIM: To characterize the relationship between KB production, weight loss (WL) and metabolic changes following BMS. METHODS: For this retrospective study we enrolled male and female subjects aged 18-65 years who underwent BMS at a single Institution. Data on demographics, anthropometrics, body composition, laboratory values and urinary KB were collected. RESULTS: Thirty-nine patients had data available for analyses [74.4% women, mean age 46.5 ± 9.0 years, median body mass index 41.0 (38.5; 45.4) kg/m2, fat mass 45.2% ± 6.2%, 23.1% had diabetes, 43.6% arterial hypertension and 74.4% liver steatosis]. At 46.0 ± 13.6 d post-surgery, subjects had lost 12.0% ± 3.6% of pre-operative weight. Sixty-nine percent developed ketonuria. Those with nutritional ketosis were significantly younger [42.9 (37.6; 50.7) years vs 51.9 (48.3; 59.9) years, P = 0.018], and had significantly lower fasting glucose [89.5 (82.5; 96.3) mg/dL vs 96.0 (91.0; 105.3) mg/dL, P = 0.025] and triglyceride levels [108.0 (84.5; 152.5) mg/dL vs 152.0 (124.0; 186.0) mg/dL, P = 0.045] vs those with ketosis. At 6 mo, percent WL was greater in those with postoperative ketosis (-27.5% ± 5.1% vs 23.8% ± 4.3%, P = 0.035). Urinary KBs correlated with percent WL at 6 and 12 mo. Other metabolic changes were similar. CONCLUSION: Our data support the hypothesis that subjects with worse metabolic status have reduced ketogenic capacity and, thereby, exhibit a lower WL following BMS.

Renal Resistance Trend During Hypothermic Machine Perfusion Correlates With Preimplantation Biopsy Score in Transplantation of Kidneys From Extended Criteria Donors.

BACKGROUND: Graft quality from extended criteria donors (ECDs) is extremely wide, and a reliable evaluation parameter is required. So far, biopsy is widely used to evaluate ECD organs and to decide whether double (DKT) or single (SKT) kidney transplantation should be performed. The aim of this study is to compare renal resistance (RR) trend during hypothermic machine perfusion (HMP) with a preimplantation biopsy score. METHODS: From December 2014 to April 2020, HMP has been systematically applied to all organs from ECDs for at least 3 hours. All grafts underwent a preimplantation biopsy histologic assessment with Karpinski's score. SKTs or DKTs were performed accordingly. RR trend during the first 180 minutes of HMP was compared with the biopsy score. RESULTS: Eighty-three kidneys were used to perform 57 transplantations (31 SKTs and 26 DKTs). A biopsy confirmed suitability for transplantation in all cases, and the median score was 4 (range, 2-7). Kidneys with a score of 5 to 7 had significantly higher RR value than kidneys with a score of 0 to 4 at basal time (3.35 vs 2.71; P = .074), at 60 minutes (1.24 vs 0.94; P = .031), at 120 minutes (1.10 vs 0.81; P = .010), and at 180 minutes (1.00 vs 0.77; P = .022). A cutoff value of RR ≥0.88 at 120 minutes of perfusion had the best sensibility and specificity (0.71 and 0.75, respectively) to discriminate kidneys with a score of 5 to 7 from kidneys with a score of 0 to 4. No differences were found in postoperative outcomes between SKT and DKT recipients. CONCLUSIONS: RR trend during HMP correlates with the histologic score in ECD kidneys and can be used as a reliable parameter to evaluate graft quality.

Kidney Transplants From Donors on Extracorporeal Membrane Oxygenation Prior to Death Are Associated With Better Long-Term Renal Function Compared to Donors After Circulatory Death.

Donation after circulatory death (DCD) allows expansion of the donor pool. We report on 11 years of Italian experience by comparing the outcome of grafts from DCD and extracorporeal membrane oxygenation (ECMO) prior to death donation (EPD), a new donor category. We studied 58 kidney recipients from DCD or EPD and collected donor/recipient clinical characteristics. Primary non function (PNF) and delayed graft function (DGF) rates, dialysis need, hospitalization duration, and patient and graft survival rates were compared. The estimated glomerular filtration rate (eGFR) was measured throughout the follow-up. Better clinical outcomes were achieved with EPD than with DCD despite similar graft and patient survival rates The total warm ischemia time (WIT) was longer in the DCD group than in the EPD group. Pure WIT was the highest in the class II group. The DGF rate was higher in the DCD group than in the EPD group. PNF rate was similar in the groups. Dialysis need was the greatest and hospitalization the longest in the class II DCD group. eGFR was lower in the class II DCD group than in the EPD group. Our results indicate good clinical outcomes of kidney transplants from DCD despite the long "no-touch period" and show that ECMO in the procurement phase improves graft outcome, suggesting EPD as a source for pool expansion.

Enrichment of Tc1 cells and T cell resistance to suppression are associated with dysglycemia in the visceral fat in human obesity.

OBJECTIVE: Insulin resistance, defined as tissue inflammation leading to type 2 diabetes, is a feature of obesity. The immune system has been implicated in its pathogenesis, but the role of adaptive immunity in humans remains uncertain. Here, we aim to determine whether specific phenotypic and functional properties of visceral adipose tissue (VAT)-derived CD4 conventional T cells (Tconv) and CD8 T cells are associated with dysglycemia in human obesity. RESEARCH DESIGN AND METHODS: Peripheral blood and the stromal vascular fraction of obese patients without dysglycemia (n=23), with impaired fasting glucose or type 2 diabetes (n=17), and non-diabetic lean controls (n=11) were studied. Characterization of memory, activation profile, cytokine production, proliferative capacity, cytotoxic potential and transforming growth factor-ß-mediated suppression of CD4 Tconv and CD8 T cells was performed. Correlation between anthropometric/metabolic parameters and VAT-derived T cell subsets was determined. RESULTS: In the VAT of the overall obese population, reduced frequency of interferon-γ-producing or tumor necrosis factor-α-producing CD4 (ie, T helper 1, Th1) and CD8 (ie, cytotoxic type 1, Tc1) T cells, as well as interleukin-17-producing CD8 T cells (ie, Tc17), was evident when compared with lean controls. However, enrichment of Tc1 cells, together with the impaired ability of CD4 and CD8 T cells to be suppressed, distinguished the visceral fat of obese patients with dysglycemia from the one of non-diabetic obese patients. Moreover, accumulation of Th1 and Tc1 cells in the VAT correlated with anthropometric and metabolic parameters. CONCLUSIONS: Here, we define the VAT-specific characteristics of T cells in human obesity, showing that accumulation of Tc1 cells and T cell resistance to suppression can be harmful to the development of obesity-induced diabetes. These findings open new directions to investigate immunological targets in the obesity setting.

Leakage Risk Stratification After Laparoscopic Sleeve Gastrectomy (LSG): Is There a Role for Routine Postoperative CT Scan?

PURPOSE: Leakage of the gastric remnant after laparoscopic sleeve gastrectomy (LSG) represents an unpredictable, dreadful occurrence. Our aim was to assess whether routine postoperative CT scan is an effective tool for early prediction of leakage after LSG. MATERIALS AND METHODS: From a prospectively acquired database, all consecutive patients who underwent LSG between January 2015 and December 2018 were identified; within this database, all patients who were evaluated with at least one contrast-enhanced CT scan within 48 h from surgery were enrolled in this retrospective study. The selected CT findings included twisting of the gastric remnant, perigastric air bubbles, and hematoma; the antral segment proximal from the pylorus to the first staple firing was also analyzed in terms of distance (StP, stapler to pylorus distance) and linearity (LI, linearity index). RESULTS: After exclusions, 250 patients were included; 10 patients suffered from gastric leakage. Patients with perigastric hematoma and/or twisting of the distal part of the gastric remnant on routine postoperative CT scan were found to be more likely to develop leakage after LSG (p = 0.005 and p < 0.001, respectively). The mean StP was 45 ± 19.1 mm; the mean LI was 1.54 ± 0.4. Patients with subsequent development of leakage had significantly lower StP (26.7 ± 12.5 mm vs. 45.9 ± 18.9 mm; p = 0.001) and LI values (1.16 ± 0.11 vs. 1.55 ± 0.39; p = 0.002). CONCLUSION: Routine postoperative CT scan after LSG permits early stratification of leakage risk, thus providing an actual aid for patients' management.

Hypothermic Machine Perfusion as an Alternative to Biopsy Assessment in Transplantation of Kidneys Donated After Cardiocirculatory Death: A Pilot Study.

BACKGROUND: Transplantation of kidneys from donation after cardiocirculatory death (DCD) donors is becoming an ever-increasing reality. So far, biopsy histologic assessment is the main parameter for evaluation of graft suitability, but it has several drawbacks and has poor reliability. The aim of this study is to verify if real-time renal resistance (RR) measurement during hypothermic machine perfusion (HMP) can be used as a reliable parameter to evaluate the quality of grafts from DCD and extracorporeal membrane oxygenation (ECMO) donors. METHODS: From January 2015 to September 2018, HMP has been systematically applied to all organs from DCD and ECMO donors. All grafts underwent preimplantation biopsy histologic assessment with Karpinski's score. Single kidney transplants (SKTs) or double kidney transplants (DKTs) were performed according to biopsy score results. Kidneys were considered suitable for transplant if RR reached ≤ 1.0 within 3 hours of perfusion. RR trend and postoperative outcome were analyzed considering biopsy score and donor type. RESULTS: A total of 30 kidneys (15 from DCD and 15 from ECMO donors) were used to perform 26 transplants (22 SKTs and 4 DKTs). Considering RR trend, all grafts were considered suitable for transplant within 1 hour of perfusion. Biopsy confirmed this result in all cases, and median score was 3 (range, 0-7). SKT score kidneys had lower starting RR than DKT ones (1.88 vs 2.88; P = .04) but identical final RR (0.58 vs 0.57; P = .76). DKT recipients had faster postoperative creatinine reduction than SKT recipients but similar postoperative day 30 value (1.42 vs 1.15 mg/dL; P = .20). No differences were found between DCD and ECMO grafts in terms of RR trend and postoperative outcome. CONCLUSIONS: HMP can be an alternative to histologic biopsy assessment for evaluation of transplant suitability of DCD and ECMO kidneys. If acceptability threshold is reached, SKT can be performed in all cases. ECMO donors should be considered like DCD donors.

Renal Resistance Trend During Hypothermic Machine Perfusion Is More Predictive of Postoperative Outcome Than Biopsy Score: Preliminary Experience in 35 Consecutive Kidney Transplantations.

Hypothermic machine perfusion (HPM) grants a better postoperative outcome in transplantation of organs procured from extended criteria donors (ECDs) and donors after cardiac death (DCD). So far, the only available parameter for outcome prediction concerning those organs is pretransplant biopsy score. The aim of this study is to evaluate whether renal resistance (RR) trend during HPM may be used as a predictive marker for post-transplantation outcome. From December 2015 to present, HMP has been systematically applied to all organs from ECDs and DCD. All grafts underwent pretransplantation biopsy evaluation using Karpinski's histological score. Only organs that reached RR value ≤1.0 within 3 hours of perfusion were transplanted. Single kidney transplantation (SKT) or double kidney transplantation (DKT) were performed according to biopsy score results. Sixty-five HMPs were performed (58 from ECDs and 7 from DCD/ECMO donors). Fifteen kidneys were insufficiently reconditioned (RR > 1) and were therefore discarded. Forty-nine kidneys were transplanted, divided between 21 SKT and 14 DKT. Overall primary nonfunction (PNF) and delayed graft function (DGF) rate were 2.9 and 17.1%, respectively. DGF were more common in kidneys from DCD (67 vs. 7%; P = 0.004). Biopsy score did not correlate with PNF/DGF rate (P = 0.870) and postoperative creatinine trend (P = 0.796). Recipients of kidneys that reached RR ≤ 1.0 within 1 hour of HMP had a lower PNF/DGF rate (11 vs. 44%; P = 0.033) and faster serum creatinine decrease (POD10 creatinine: 1.79 mg/dL vs. 4.33 mg/dL; P = 0.019). RR trend is more predictive of post-transplantation outcome than biopsy score. Hence, RR trend should be taken into account in the pretransplantation evaluation of the organs.

Are there any relations among transplant centre volume, surgical technique and anatomy for donor graft selection? Ten-year multicentric Italian experience on mini-invasive living donor nephrectomy.

BACKGROUND: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. METHODS: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. RESULTS: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). CONCLUSIONS: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.

Regulatory T-cells from pancreatic lymphnodes of patients with type-1 diabetes express increased levels of microRNA miR-125a-5p that limits CCR2 expression.

Autoimmune type 1 diabetes (T1D) is thought to be caused by a defective immune regulation with regulatory T (Treg) cells playing a fundamental role in this process. Tolerance mechanisms depend on tunable responses that are sensitive to minor perturbations in the expression of molecules that can be carried out by multiple epigenetic mechanisms, including regulation by microRNAs. In this study, microRNA expression profile was investigated in Treg cells isolated from peripheral blood (PB) and from pancreatic draining lymph nodes (PLN) of T1D patients and non-diabetic subjects. Among 72 microRNAs analyzed, miR-125a-5p resulted specifically hyper-expressed in Treg cells purified from PLN of T1D patients. TNFR2 and CCR2 were identified as miR-125a-5p target genes. Elevated miR-125a-5p was detected in Treg cells isolated from PLN but not from PB of donors with T1D and was associated with reduced CCR2 expression. A specific beta-cell expression of the CCR2-ligand (CCL2) was observed in the pancreata of cadaveric donors, suggesting that beta-cells are prone to attract CCR2+ Treg cells. These novel data propose a mechanism, occurring in PLNs of T1D patients, involving increased expression of miR-125a-5p on Treg cells which results into reduced expression of CCR2, thus limiting their migration and eventual function in the pancreas.

[Surgical overview on kidney and pancreas transplantation]. / Problemi chirurgici nel trapianto di rene e di pancreas - Position paper.

The main purpose of this paper, written by a group of Italian expert transplant surgeons, is to provide clinical support and to help through the decision-making process over pre-transplant surgical procedures in potential kidney recipients, as well as selection of pancreas transplant candidates and perioperative management of kidney recipient. Current topics such as different approaches in minimally invasive donor nephrectomy, methods of graft preservation and treatment of failed allograft were addressed.

Utilization of organs from donors after circulatory death for vascularized pancreas and islet of Langerhans transplantation: recommendations from an expert group.

Donation after circulatory death (DCD) donors are increasingly being used as a source of pancreas allografts for vascularized organ and islet transplantation. We provide practice guidelines aiming to increase DCD pancreas utilization. We review risk assessment and donor selection criteria. We report suggested factors in donor and recipient clinical management and provide an overview of the activities and outcomes of vascularized pancreas and islet transplantation.

Duodenal stump fistula after gastric surgery for malignancies: a retrospective analysis of risk factors in a single centre experience.

BACKGROUND: Duodenal stump fistula (DSF) is the most severe surgical complication after gastrectomy. This study was designed to assess the incidence, to observe the consequences, and to identify the risk factors associated with DSF after gastrectomy. METHODS: All procedures involving total or sub-total gastrectomy for cancer, performed between January 1987 and June 2012 in a single institution, were prospectively entered into a computerized database. Risk factors analysis was performed between DSF patients, patients with complete uneventful postoperative course and patients with other major surgical complications. RESULTS: Over this 25 years period, 1287 gastrectomies were performed. DSF was present in 32 cases (2.5 %). Mean post-operative onset was 6.6 days. 19 patients were treated conservatively and 13 surgically. Mean DSF healing time was 31.2 and 45.2 days in the two groups, respectively. Mortality was registered in 3 cases (9.37 %), due to septic shock (2 cases) and bleeding (1 case). In monovariate analysis, heart disease (p < 0.001), pre-operative lymphocytes number (p = 0.003) and absence of manual reinforcement over duodenal stump (p < 0.001) were found to be DSF-specific risk factors, whereas liver cirrhosis (p = 0.002), pre-operative albumin levels (p < 0.001) and blood losses (p = 0.002) were found to be non-DSF-specific risk factors. In multivariate analysis heart disease (OR 5.18; p < 0.001), liver cirrhosis (OR 13.2; p < 0.001), bio-humoral nutritional status impairment (OR 2.29; p = 0.05), blood losses >300 mL (OR 4.47; p = 0.001) and absence of manual reinforcement over duodenal stump (OR 30.47; p < 0.001) were found to be independent risk factors for DSF development. CONCLUSIONS: Duodenal stump fistula still remains a life-threatening complication after gastric surgery. Co-morbidity factors, nutritional status impairment and surgical technical difficulties should be considered as important risk factors in developing this awful complication.

Apparent diffusion coefficient modifications in assessing gastro-oesophageal cancer response to neoadjuvant treatment: comparison with tumour regression grade at histology.

OBJECTIVES: To assess changes in apparent diffusion coefficient (ΔADC) and volume (ΔV) after neoadjuvant treatment (NT), and tumour regression grade (TRG) in gastro-oesophageal cancers (GEC), and to discriminate responders from non-responders. METHODS: Thirty-two patients with biopsy-proven locally-advanced GEC underwent diffusion weighted magnetic resonance imaging (DWI) pre- and post-NT. Lesion ADC, volume, ΔADC and ΔV were calculated. TRG 1-2-3 patients were classified as R; TRG 4-5 as non-responders. ΔADC-TRG and ΔV-TRG correlations, pre-NT and post-NT ADC, ΔADC and ΔV cut-off values for responders and non-responders were calculated. Two readers measured mean tumour ADCs and interobserver variability was calculated. (Spearman's and intraclass correlation coefficient [ICC]). RESULTS: The interobserver reproducibility was very good both for pre-NT (Spearman's rho = 0.8160; ICC = 0.8993) and post-NT (Spearman's rho = 0.8357; ICC = 0.8663). Responders showed lower pre-NT ADC (1.32 versus 1.63 × 10(-3) mm(2)/s; P = 0.002) and higher post-NT ADC (2.22 versus 1.51 × 10(-3) mm(2)/s; P = 0.001) than non-responders and ADC increased in responders (ΔADC, 85.45 versus -8.21 %; P = 0.00005). ΔADC inversely correlated with TRG (r = -0.71, P = 0.000004); no difference in ΔV between responders and non-responders (-50.92 % versus -14.12 %; P = 0.068) and no correlation ΔV-TRG (r = 0.02 P = 0.883) were observed. CONCLUSIONS: The ADC can be used to assess gastro-oesophageal tumour response to neoadjuvant treatment as a reliable expression of tumour regression. KEY POINTS: • DWI is now being used to assess many cancers. • Change in ADC measurements offer new information about oesophageal tumours. • ADC changes are more reliable than dimensional criteria in assessing neoadjuvant treatment. • Such ADC assessment could optimise management of locally advanced gastro-oesophageal cancers.

Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes.

OBJECTIVE: Autoimmune diseases, including type 1 diabetes, are thought to have a Th17-cell bias and/or a T-regulatory cell (Treg) defect. Understanding whether this is a hallmark of patients with type 1 diabetes is a crucial question that is still unsolved, largely due to the difficulties of accessing tissues targeted by the disease. RESEARCH DESIGN AND METHODS: We phenotypically and functionally characterized Th17 cells and Tregs residing in the pancreatic-draining lymph nodes (PLNs) of 19 patients with type 1 diabetes and 63 nondiabetic donors and those circulating in the peripheral blood of 14 type 1 diabetic patients and 11 healthy subjects. RESULTS: We found upregulation of Th17 immunity and functional defects in CD4(+)CD25(bright) Tregs in the PLNs of type 1 diabetic subjects but not in their peripheral blood. In addition, the proinsulin-specific Treg-mediated control was altered in the PLNs of diabetic patients. The dysfunctional Tregs isolated from diabetic subjects did not contain contaminant effector T cells and were all epigenetically imprinted to be suppressive, as defined by analysis of the Treg-specific demethylated region within the forkhead box P3 (FOXP3) locus. CONCLUSIONS: These data provide evidence for an unbalanced immune status in the PLNs of type 1 diabetic subjects, and treatments restoring the immune homeostasis in the target organ of these patients represent a potential therapeutic strategy.

Kidney-pancreas transplantation is associated with near-normal sexual function in uremic type 1 diabetic patients.

BACKGROUND: Sexual function is altered in patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD), thus affecting quality of life. The present study aimed to analyze sexual function in patients with T1D and ESRD (T1D+ESRD) who received a simultaneous kidney-pancreas (KP) or kidney-alone (KD) transplantation. METHODS: Ten KP, 10 KD, 9 T1D+ESRD patients and 11 healthy control subjects were evaluated according to the following parameters: (1) medical/sexual history and physical examination; (2) International Index of Erectile Function; (3) Beck's inventory for depression; (4) assessment of hormonal profile; (5) quantitative sensory testing of both hand and penile sensory thresholds; and (6) hemodynamic penile assessment. RESULTS: Controls and KP patients showed a higher rate of self-reported satisfactory erectile function as compared with KD and T1D+ESRD patients. Circulating androgens level resulted lower in both groups of transplanted patients and in patients with T1D+ESRD compared with healthy controls, albeit a relatively better profile was observed in KP. Both transplanted and T1D+ESRD patients showed peripheral hyposensitivity; however, healthy controls and KP showed better penile hemodynamic parameters compared with KD and T1D+ESRD. CONCLUSIONS: Our study demonstrates that sexual function, circulating sex steroids milieu, penile sensitivity, and hemodynamics are near-normalized for the most part in KP transplantation. Further studies are needed to assess the beneficial role and the overall impact of KP transplantation on sexual function in a long-term setting and a larger cohort of patients.

Risks and benefits of transplantation in the cure of type 1 diabetes: whole pancreas versus islet transplantation. A single center study.

BACKGROUND: Pancreas and islet transplantation are the only available options to replace beta-cell function in patients with type 1 diabetes. Great variability in terms of rate of success for both approaches is reported in the literature and it is difficult to compare the respective risks and benefits. OBJECTIVES: The aim of this study was to analyze risks and benefits of pancreas transplantation alone (PTA) and islet transplantation alone (ITA) by making use of the long-term experience of a single center where both transplantations are performed. We focused on the risks and benefits of both procedures, with the objective of better defining indications and providing evidence to support the decision-making process. The outcomes of 33 PTA and 33 ITA were analyzed, and pancreas and islet function (i.e., insulin independence), perioperative events, and long-term adverse events were recorded. RESULTS: We observed a higher rate of insulin independence in PTA (75%) versus ITA (59%), with the longer insulin independence among PTA patients receiving tacrolimus. The occurrence of adverse events was higher for PTA patients in terms of hospitalization length and frequency, re-intervention for surgical and immunological acute complications, CMV reactivation, and other infections. CONCLUSIONS: In conclusion, these results support the practice of listing patients for PTA when the metabolic control and the progression of chronic complications require a rapid normalization of glucose levels, with the exception of patients with cardiovascular disease, because of the high surgical risks. ITA is indicated when replacement of beta-cell mass is needed in patients with a high surgical risk.