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Background: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)., Patients and Methods: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested., Results: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival., (© 2024. Society of Surgical Oncology.)

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery., (© 2023. The Author(s).)

Purpose: Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future., Methods: A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus., Results: Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders., Conclusions: Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Open pancreatoduodenectomy with vein resection (OPD-VR) is now standard of care in patients who responded to neoadjuvant therapies. Feasibility of robotic pancreatoduodenectomy (RPD) with vein resection (RPD-VR) was shown, but no study provided a detailed description of the technical challenges associated with this formidable operation. Herein, we describe the trips and tricks for technically successful RPD-VR., Methods: The vascular techniques used in RPD-VR were borrowed from OPD-VR, as well as from our experience with robotic transplantation of both kidney and pancreas. Vein resection was classified into 4 types according to the international study group of pancreatic surgery. Each type of vein resection was described in detail and shown in a video., Results: Between October 2008 and November 2021, a total of 783 pancreatoduodenectomies were performed, including 233 OPDs-VR (29.7%). RPD was performed in 256 patients (32.6%), and RPDs-VR in 36 patients (4.5% of all pancreatoduodenectomies; 15.4% of all pancreatoduodenectomies with vein resection; 14.0% of all RPDs). In RPD-VR vein resections were: 4 type 1 (11.1%), 10 type 2 (27.8%), 12 type 3 (33.3%) and 10 type 4 (27.8%). Vascular patches used in type 2 resections were made of peritoneum (n = 8), greater saphenous vein (n = 1), and deceased donor aorta (n = 1). Interposition grafts used in type 4 resections were internal left jugular vein (n = 8), venous graft from deceased donor (n = 1) and spiral saphenous vein graft (n = 1). There was one conversion to open surgery (2.8%). Ninety-day mortality was 8.3%. There was one (2.8%) partial vein thrombosis, treated with heparin infusion., Conclusions: We have reported 36 technically successful RPDs-VR. We hope that the tips and tricks provided herein can contribute to safer implementation of RPD-VR. Based on our experience, and according to data from the literature, we strongly advise that RPD-VR is performed by expert surgeons at high volume centers., (© 2023. The Author(s).)

Background: Triangle pancreatoduodenectomy adds to the conventional procedure the en bloc removal of the retroperitoneal lympho-neural tissue included in the triangular area bounded by the common hepatic artery (CHA), the superior mesenteric artery (SMA), and the superior mesenteric vein/portal vein. We herein aim to show the feasibility of "cold" triangle robotic pancreaticoduodenectomy (C-Tr-RPD) for pancreatic cancer (PDAC)., Methods: Cold dissection corresponds to sharp arterial divestment performed using only the tips of robotic scissors. After division of the gastroduodenal artery, triangle dissection begins by lateral-to-medial divestment of the CHA and anterior-to-posterior clearance of the right side of the celiac trunk. Next, after a wide Kocher maneuver, the origin of the SMA, and the celiac trunk are identified. After mobilization of the first jejunal loop and attached mesentery, the SMA is identified at the level of the first jejunal vein and is divested along the right margin working in a distal-to-proximal direction. Vein resection and reconstruction can be performed as required. C-Tr-RPD was considered feasible if triangle dissection was successfully completed without conversion to open surgery or need to use energy devices. Postoperative complications and pathology results are presented in detail., Results: One hundred twenty-seven consecutive C-Tr-RPDs were successfully performed. There were three conversions to open surgery (2.3%), because of pneumoperitoneum intolerance (n = 2) and difficult digestive reconstruction. Thirty-four patients (26.7%) required associated vascular procedures. No pseudoaneurysm of the gastroduodenal artery was observed. Twenty-eight patients (22.0%) developed severe postoperative complications (≥ grade III). Overall 90-day mortality was 7.1%, declining to 2.3% after completion of the learning curve. The median number of examined lymph nodes was 42 (33-51). The rate of R1 resection (7 margins < 1 mm) was 44.1%., Conclusion: C-Tr-RPD is feasible, carries a risk of surgical complications commensurate to the magnitude of the procedure, and improves staging of PDAC., (© 2022. The Author(s).)

Several studies have showed good/excellent results of thermal-ablation (TA) to reduce volume of benign thyroid nodule (TN). Nevertheless, no systematic review has reported information about clinical achievements with TA. Being the latter of high interest, this systematic review was undertaken to achieve high evidence about the efficacy of TA in reducing TN-related symptoms and cosmetic concerns. Radiofrequency (RFA) and laser (LA) therapies were considered. A comprehensive literature search of online databases was performed on January 2022 looking for studies reporting clinical results obtained by RFA or LA in terms of VAS (namely, Visual Analogic Scale) and cosmetic concerns. Initially, 318 records were found and 14 were finally included in the meta-analysis. VAS data were available in all RFA studies and the pooled mean reduction was of 3.09 points with significant heterogeneity. Cosmetic score data were available in 11 RFA studies and the pooled mean reduction was of 1.45 with significant heterogeneity. Regarding LA studies, 4 series reported VAS data and the pooled mean reduction was of 2.61 points with significant heterogeneity. The analysis of LA data about cosmetic concerns was not performed due to data paucity. Importantly, heterogeneities were not explained by meta-regression analyses using several covariates (i.e., baseline TN volume, follow-up duration, volume reduction rate). This systematic review showed that clinical data about TN TA efficacy are sparse and affected by high unexplained inconsistency. International societies should give indication about how we should clinically select and evaluate patients undergoing TN TA., (© 2022. The Author(s).)

Introduction: There are limited numbers of high-volume centers performing minimally invasive pancreatoduodenectomy (MIPD) routinely. Several approaches to MIPD have been described. Aim of this analysis was to show the learning curve of three different approaches to MIPD. Focus was on determining the number of cases necessary to obtain proficient level in MIPD., Patients and Methods: Retrospective study wherein outcomes of 300 consecutive patients at three centers-at each center the initial 100 consecutive patients undergoing MIPD for malignant and benign tumors of the head of the pancreas and perimpullary area, performed by three experienced surgeons were collected and analyzed., Results: Overall, 300 patients after MIPD were included: the three different cohorts (laparoscopic n = 100, hybrid n = 100, robotic n = 100). CUSUM analysis of operating time in each center demonstrated that the plateau for laparoscopic PD was n = 61, for hybrid PDes was n = 32 and for robotic PD was n = 68. Median operative time for laparoscopic, hybrid, and robotic approaches was 395 min, 404 min, 510 min, respectively. Intraoperative blood loss for laparoscopic PD, hybrid PD, and robotic PD was 250 ml, 250 ml, and 413 ml, respectively. Delayed gastric emptying occurred 12% in laparoscopic cohort, 10% in hybrid, and 53% in robotic cohort. Major complications (Clavien-Dindo III/IV) rate for laparoscopic PD, hybrid PD, and robotic PD was 32%, 37%, and 22% with 5% death in each cohorts, respectively., Conclusion: This analysis of the learning curve of three European centers found a shorter learning curve with hybrid PD as compared to laparoscopic and robotic PD. In implementation of a MIPD program, a stepwise approach might be beneficial., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The 4 th International Conference on Controversies in Vitamin D was held as a virtual meeting in September, 2020, gathering together leading international scientific and medical experts in vitamin D. Since vitamin D has a crucial role in skeletal and extra-skeletal systems, the aim of the Conference was to discuss improved management of vitamin D dosing, therapeutic levels and form or route of administration in the general population and in different clinical conditions. A tailored approach, based on the specific mechanisms underlying vitamin D deficiency in different diseases that were discussed, was recommended. Specifically, in comparison to healthy populations, higher levels of vitamin D and greater amounts of vitamin D were deemed necessary in osteoporosis, diabetes mellitus, obesity (particularly after bariatric surgery), and in those treated with glucocorticoids. Emerging and still open issues were related to target vitamin D levels and the role of vitamin D supplementation in COVID-19 since low vitamin D may predispose to SARS-CoV-2 infection and to worse COVID-19 outcomes. Finally, whereas oral daily cholecalciferol appears to be the preferred choice for vitamin D supplementation in the general population, and in most clinical conditions, active vitamin D analogs may be indicated in patients with hypoparathyroidism and severe kidney and liver insufficiency. Parenteral vitamin D administration could be helpful in malabsorption syndromes or in states of vitamin D resistance.Specific guidelines for desired levels of vitamin D should be tailored to the different conditions affecting vitamin D metabolism with the goal to define disease-specific normative values., (© 2021. The Author(s).)

Background: The recent development of 3D vision in laparoscopic and robotic surgical systems raises the question of whether these two procedures are equivalent. The aim of this study was to evaluate the surgical and long-term oncological outcomes of 3D laparoscopic (3D-LLR) and robotic liver resection (RLR) for hepatocellular carcinoma (HCC)., Methods: The data for operative time, morbidity, margins, and survival were reviewed for 3D-LLR and compared with RLR., Results: From 2011 to 2017, 93 patients with HCC, including 58 (62%) with cirrhosis, underwent 3D-LLR [49 (53%)] or RLR [44 (47%)]. No difference was observed in operative time (269 vs. 252 min; p = 0.52), overall (27% vs. RLR: 16%; p = 0.49) and severe morbidity (4% vs. 2%; p = 0.77) or in the surgical margin width (9 vs. 11 mm; p = 0.30) between the 3D-LLR and RLR groups. The 3-year overall and recurrence-free survival rates after 3D-LLR and RLR were 82% and 24% and 91% (p = 0.16) and 48% (p = 0.18), respectively., Conclusions: The 3D-LLR and RLR systems provide comparable surgical margins with similar short- and long-term oncological outcomes.

We retrospectively studied the association between changes in exercise capacity at discharge from a home-based exercise program and the risk of all-cause mortality among patients with peripheral artery disease (PAD) and claudication. The records of 1076 consecutive PAD patients were assessed between 2003 and 2013. The exercise program was prescribed during a few visits and executed at home at symptom-free walking speed. Ankle-Brachial Index (ABI) and maximal speed (S max ) on an incremental treadmill test were recorded at baseline and discharge. The number and date of deaths and hospitalizations for a 10-year period were collected from the regional registry. A total of 865 PAD patients completed the program (completers), while 221 left the program for health reasons (n = 128, diseased) or for nonhealth reasons (n = 83, quitters). Among the completers, the mortality rate (27%) was significantly lower (p < 0.001) than that of both the diseased (49 deaths, 38%) and the quitters (45 deaths, 54%). The completers (71 ± 9 years; 88% exercise sessions completed) showed significant improvements in the lowest ABI (from 0.62 ± 0.18 to 0.67 ± 0.19) and S max (from 3.3 ± 1.1 to 3.8 ± 1.1 km h -1 ) at discharge. The completers who reached the clinically important difference of S max  ≥ 0.4 km h -1 at follow-up showed a significantly lower mortality risk (25% vs. 30%; HR 0.72; 95% CI 0.55-0.93) as well a lower rate of hospitalizations (p < 0.001). In conclusion, in PAD patients, active participation in a home-based exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly for those who attained a moderate increase in exercise capacity.

Background: No study has shown the oncologic non-inferiority of robotic pancreatoduodenectomy (RPD) versus open pancreatoduodenectomy (OPD) for pancreatic cancer (PC)., Methods: This is a single institution propensity score matched study comparing RPD and ODP for resectable PC, based on factors predictive of R1 resection (≤ 1 mm). Only patients operated on after completion of the learning curve in both procedures and for whom circumferential margins were assessed according to the Leeds pathology protocol were included. The primary study endpoint was the rate of R1 resection. Secondary study endpoints were as follows: number of examined lymph nodes (N), rate of perioperative transfusions, percentage of patients receiving adjuvant therapies, occurrence of local recurrence, overall survival, disease-free survival, and sample size calculation for randomized controlled trials (RCT)., Results: Factors associated with R1 resection were tumor diameter, number of positive N, N ratio, logarithm odds of positive N, and duodenal infiltration. The matching process identified 20 RPDs and 24 OPDs. All RPDs were completed robotically. R1 resection was identified in 11 RPDs (55.0%) and in 10 OPDs (41.7%) (p = 0.38). There was no difference in the rate of R1 at each margin as well as in the proportion of patients with multiple R1 margins. RPD and OPD were also equivalent with respect to all secondary study endpoints, with a trend towards lower rate of blood transfusions in RPD. Based on the figures presented herein, a non-inferiority RCT comparing RPD and OPD having the rate of R1 resection as the primary study endpoint requires 3355 pairs., Conclusions: RPD and OPD achieved the same rate of R1 resections in resectable PC. RPD was also non-inferior to OPD with respect to all secondary study endpoints. Because of the high number of patients required to run a RCT, further assessment of RPD for PC would require the implementation of an international registry.

Background: Improvement in morbidity of pancreatoduodenectomy (PD) largely depends on the reduction in the incidence of clinically relevant (CR) postoperative pancreatic fistula (POPF)., Methods: After internal validation of the clinical risk score (CRS) of POPF, and identification of other predictive factors for POPF, robotic (RPD), and open (OPD) PDs were stratified into risk categories and matched by propensity scores. The primary endpoint of this study was incidence of CR-POPF. Secondary endpoints were 90-day morbidity and mortality, and sample size calculation for randomized controlled trials (RCT)., Results: No patient undergoing RPD was classified at negligible risk for POPF, and no CR-POPF occurred in 7 RPD at low risk. The matching process identified 48 and 11 pairs at intermediate and high risk for POPF, respectively. In the intermediate-risk group, RPD was associated with higher rates of CR-POPF (31.3% vs 12.5%) (p = 0.0026), with equivalent incidence of grade C POPF. In the high-risk group, CR-POPF occurred frequently, but in similar percentages, after either procedures. Starting from an unadjusted point estimate of the effect size of 1.71 (0.91-3.21), the pair-matched odds ratio for CR-POPF after RPD was 2.80 (1.01-7.78) for the intermediate-risk group, and 0.20 (0.01-4.17) for the high-risk group. Overall morbidity and mortality were equivalent in matched study groups. Sample size calculation for a non-inferiority RCT demonstrated that a total of 31,669 PDs would be required to randomize 682 patients at intermediate risk and 1852 patients at high risk., Conclusions: In patients at intermediate risk, RPD is associated with higher rates of CR-POPF. Incidence of grade C POPF is similar in RPD and OPD, making overall morbidity and mortality also equivalent. A RCT, with risk stratification for POPF, would require an enormous number of patients. Implementation of an international registry could be the next step in the assessment of RPD.

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a new procedure aimed at promoting the overgrowth of small future liver remnants (FLR). The role of ALPPS in hilar cholangiocarcinoma (h-CCA) is currently considered marginal because liver split in the presence of bile duct obstruction increases postoperative morbidity and mortality (Schadde et al. in Ann Surg 260:829-836,2014; Nadalin et al. in Z Gastroenterol 52:35-42,2014). Virtual liver split (Gall et al. in Ann Surg 261:e45-e46,2015) could improve the outcome of ALPPS in h-CCA., Methods: A 64-year-old woman with a type IIIA h-CCA without evidence of vascular involvement had a small FLR (FLR/body weight: 0.47 cm 3 /kg). After bilateral percutaneous biliary drainage (PBD) and bilirubin normalization, the patient was planned for laparoscopic step 1 ALPPS using microwave ablation (MWA). Because of possible challenge in hilar dissection in this tumor type, robotic assistance was preferred to conventional laparoscopy for step 1., Results: The patient recovered promptly from step 1, with a 68 % increase in the volume of FLR by postoperative day (POD) 10 (FLR/body weight of 0.79 cm 3 /kg). On POD 15, the patient underwent open right hepatectomy with en bloc resection of the caudate lobe, bile duct bifurcation, and extrahepatic biliary duct (T2N1M0R0). Estimated blood loss was negligible during step 1 and 150 mL during step 2. The patient recovered well. Chemotherapy was started 6 weeks after ALPPS stage 2, and was well tolerated and full course. Twenty months after resection the patient is alive, well, and disease-free., Conclusions: Laparoscopic ALPPS (Machado et al. in Ann Surg 256:e13,2012) and MWA on the intended split line (Gringeri and Boetto in Ann Surg 261:e42-e43,2015) have been recently described. The combination of these techniques with PBD allowed successful ALPPS in a patient with h-CCA.

Non-alcoholic fatty liver diseases are the hepatic manifestation of metabolic syndrome. According to the classical pattern of NAFLD progression, de novo fatty acid synthesis has been incriminated in NAFLD progression. However, this hypothesis has been challenged by the re-evaluation of NAFLD development mechanisms together with the description of the role of lipogenic genes in NAFLD and with the recent observation that PGC-1β, a nuclear receptor/transcription factor coactivator involved in the transcriptional regulation of lipogenesis, displays protective effects against NAFLD/NASH progression. In this review, we focus on the implication of lipogenesis and triglycerides synthesis on the development of non-alcoholic fatty liver diseases and discuss the involvement of these pathways in the protective role of PGC-1β toward these hepatic manifestations.

Purpose: The role of pancreatectomy with en bloc venous resection and the prognostic impact of pathological venous invasion are still debated. The authors analyzed perioperative, survival results, and prognostic factors of pancreatectomy with en bloc portal (PV) or superior mesenteric vein (SMV) resection for borderline resectable pancreatic carcinoma, focusing on predictive factors of histological venous invasion and its prognostic role., Methods: A multicenter database of 406 patients submitted to pancreatectomy with en bloc SMV and/or PV resection for pancreatic adenocarcinoma was analyzed retrospectively. Univariate and multivariate analysis of factors related to histological venous invasion were performed using logistic regression model. Prognostic factors were analyzed with log-rank test and multivariate proportional hazard regression analysis., Results: Complications occurred in 51.9 % of patients and postoperative death in 7.1 %. Histological invasion of the resected vein was confirmed in 56.7 % of specimens. Five-year survival was 24.4 % with median survival of 24 months. Vein invasion at preoperative computed tomography (CT), N status, number of metastatic lymph nodes, preoperative serum albumin were related to pathological venous invasion at univariate analysis, and vein invasion at CT was independently related to venous invasion at multivariate analysis. Use of preoperative biliary drain was significantly associated with postoperative complications. Multivariate proportional hazard regression analysis demonstrated a significant correlation between overall survival and histological venous invasion and administration of adjuvant therapy., Conclusions: This study identifies predictive factors of pathological venous invasion and prognostic factors for overall survival, including pathological venous invasion, which may help with patients' selection for different treatment protocols.

Purpose: Diabetic osteopathy is an upcoming complication of diabetes characterized by osteoporosis, increased risk for bone fractures and alterations in bone metabolism. Osteocalcin (OC) is a bone-specific protein produced by osteoblasts involved in the regulation of glucose and energy metabolism. The aim of this study is to determine whether OC serum levels are correlated with metabolic control in adult subjects with type one diabetes mellitus (T1DM)., Methods: A cross-sectional study was conducted on 93 subjects (51 men) with mean age, disease duration and body mass index (BMI) of 39.9 ± 12.3, 17.2 ± 12.6 years and 24.5 ± 3.4 kg/m(2), respectively. Blood samples were drawn to measure levels of hemoglobin A1c (HbA1c), OC, 25-OH vitamin D and PTH., Results: Significant inverse correlations were found between OC and HbA1c (r = -0.295, P = 0.004) and between OC and BMI (r = -0.218, P = 0.037). These correlations were confirmed also among men in the analyses by gender [HbA1c vs OC: r = -0.363, P = 0.009; BMI vs OC: r = -0.291, P = 0.043], and similar but nonsignificant trends were confirmed among women. A significant difference in mean OC was also found between the lowest and the highest HbA1c tertile (22.3 ± 10.0 vs 16.9 ± 8.0 ng/mL, P = 0.025)., Conclusions: These data show that in T1DM of long duration, OC serum levels are inversely associated with HbA1c and BMI, supporting the hypothesis that a poor glycemic control can affect osteoblast function.

The role of apoptosis in the persistence of hepatitis C virus (HCV) infection is controversial. Moreover, conflicting data on the modulation of this process by HCV proteins have been provided. We evaluated the susceptibility of peripheral lymphocytes from patients with chronic hepatitis C to apoptosis both spontaneous and after incubation with a chimeric Cucumber mosaic virus (CMV) carrying 180 copies of the synthetic R9 mimotope obtained from more than 200 hypervariable region-1 sequences of HCV. Resting T lymphocytes were found to be sensitized to apoptosis as a result of chronic HCV infection. The plant virus-derived vector R9-CMV displayed a strong pro-apoptotic effect associated with activation of both caspase-8 and -9, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. A parallel R9-CMV-mediated activation of endoplasmic reticulum-stress was suggested by the significant induction of BiP/GRP78, GADD153 and caspase-12. These data contribute to define the complex HCV/host interaction, and open new prospects for developing a plant-derived antigen-presenting system to strengthen host defences against persistent pathogens.

The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

Background: Adipose tissue has been suggested to influence bone density and metabolism through the effect of some adipokines. However, whether adiponectin and visfatin may correlate with bone metabolism is still unclear., Aim: The aim of this study was to investigate the relationship of adiponectin and visfatin with bone density in patients with metabolic syndrome (MS)., Subjects: We enroled 72 consecutive patients with MS (25 males, 47 females; mean age 58.14±11 yr) and 40 control subjects., Methods: Plasma adiponectin and visfatin levels were measured. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) at the level of lumbar spine L2-L4 (BMD L2-L4) and femoral neck (BMD-Fn)., Results: MS patients had higher plasma visfatin and lower adiponectin levels than controls, (p<0.01 for both). Adiponectin was negatively correlated with BMD-Fn and BMD L2-L4 (r=-0.20, r=-0.24, respectively; p<0.05 for both) whereas plasma visfatin levels were positively correlated to BMD L2-L4 only in men (r=0.44; p<0.05)., Conclusions: Our study shows that adiponectin and visfatin are oppositely associated with BMD. Although the mechanisms behind these correlations are unclear, a modulation of bone metabolism by these adipokines can be suggested.

Background and Aim: Dendritic cell (DC) dysfunction has been suggested to play a role in the weak antiviral T-cell responsiveness observed during the course of chronic hepatitis C virus (HCV) infection. This study was undertaken to evaluate whether changes in DC functions might be related to a different therapeutic outcome in HCV-infected patients., Methods: Peripheral blood DCs (PBDCs) or monocyte-derived DCs (MoDCs) were obtained from chronic HCV-infected patients, sustained virologic responders (SVR) or non-responders (NR) to interferon/ribavirin therapy, and from healthy controls (HC). The frequency of BDCA-1+, BDCA-3+ or CD16+ myeloid DCs (mDCs) and BDCA-2+ plasmacytoid DCs (pDCs), as well as the expression of the costimulatory molecule CD86 in each PBDC subset, were evaluated by flow cytometry. MoDCs from single individuals were stimulated with TLR2, TLR3, TLR4, and TLR7 ligands and analyzed for CD86, CD83, CD40, CD80, and CD209 expression. Finally, mitogen-activated protein kinase (MAPK) phosphorylation of TLR7-triggered MoDCs was assessed by Western blotting., Results: NR exhibited a reduced percentage of BDCA-1+ mDCs, as well as lower levels of CD86+ cells, in both BDCA-1+ mDCs and pDCs as compared to SVR and HC. Furthermore, MoDCs from NR displayed a defective CD86 and CD83 increase and ERK1/2 or p38-MAPK phosphorylation upon TLR7-cell triggering., Conclusions: Our data suggest that a TLR7-dependent impairment of costimulatory molecule expression caused by HCV persistence may affect DC activity in NR patients.