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Background Physiologically regulated insulin secretion and euglycemia are achievable in type 1 diabetes (T1D) by islet or pancreas transplantation. However, pancreas transplant alone (PTA) remains a debated approach, with uncertainties on its relative benefits and risks. We determined the actual long-term (10 years) efficacy and safety of PTA in carefully characterized T1D subjects. Methods This is a single-centre, cohort study in 66 consecutive T1D subjects who received a PTA between April 2001 and December 2007, and were then all followed until 10 years since transplant. Main features evaluated were patient survival, pancreas graft function, C-peptide levels, glycemic parameters, and the function of the native kidneys. Results Ten-year actual patient survival was 92.4%. Optimal (insulin-independence) or good (minimal insulin requirement) graft function was observed in 57.4 and 3.2% of patients, respectively. Six (9.0%) patients developed stage 5 or 4 chronic kidney disease. In the remaining individuals bearing a successful PTA, eGFR decline per year was -2.29±2.69 ml/min/1.73m. Reduction of eGFR at 1 year post-PTA was higher in those with pre-PTA hyperfiltration and higher HbA1c concentrations; eGFR changes afterwards significantly correlated with diabetes duration. In recipients with normoglycemia at 10 years, 74% of normo- or micro-albuminuric subjects pre-PTA remained stable, and 26% progressed towards a worse stage; conversely, in 62.5% of the macro-albuminuric individuals albuminuria severity regressed. Conclusions These long-term effects of PTA on patient survival, graft function and the native kidneys support PTA as a suitable approach to treat diabetes in selected T1D patients.

Sex-related differences have been shown to deeply affect health-related aspects of patients. However, the lack of gender-specific analysis makes it difficult to advance personalized medicine in terms of a gender-based approach. The aim of the present study was to describe gender-specific features of patients diagnosed with heart failure (HF), with a focus on the clinical presentation. Data were collected from a properly designed database and referred to an Italian hospital. Patients aged ≥18 years with a primary or secondary diagnosis of HF between 1 January 2012 and 31 December 2016 were included, and their demographic and clinical characteristics were analyzed according to gender. Of the 719 HF patients included, 317 (44.1%) were male and 402 (55.9%) were female. Women tended to be older compared to men (82.4±8.8 years and 77.1±10.6 years, respectively). As for clinical presentation, 62.1% of female and 38.3% of male patients had preserved ejection fraction, and 56.1% of men and 58.2% of women suffered from atrial fibrillation. The left atrium was partially compromised in 62.4% of male and 63% of female patients, while right atrium dysfunction tended to be more frequent in male patients compared to female patients (29.1% and 25.5%, respectively). In conclusion, gender-specific features of a cohort of HF patients from a clinical setting were accurately described.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368, Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888, Funder: Pisa University Hospital, Pisa, Italy, Funder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514, The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Objective. To provide estimates of patients with rheumatoid arthritis (RA) eligible for biotechnological therapy and to evaluate their healthcare costs. Method. An observational analysis was performed based on data-linkage between administrative databases of selected Italian Regional/Local healthcare departments. Data were then re-proportioned to the Italian population. Patients with RA diagnosis defined by discharge diagnosis and/or exemption code during 01/01/2013- 31/12/2017 were included. The criteria applied to evaluate the elegibility for biotechnological therapy were: 1) methotrexate (MTX)-treatment failure ≥6 months and start of a different conventional-synthetic diseasemodifying antirheumatic drugs (csDMARD); 2) corticosteroid ≥6 months with dosage ≥7.5 mg/die; 3) MTX-contraindication (therapy or hospitalization for renal damage/interstizial lung disease/hepatic failure). Mean annual costs per patient included drugs, hospitalizations, outpatient services. Results. Data re-proportioned to the Italian population estimated 318,328 RA patients: 43,361 with, 274,967 without biotechnological agents. Among the latter, 26,487(9.6%) patients met ≥1 criteria applied for eligibility: 1,896 had MTX-treatment failure and started another csDMARD; 15,833 received corticosteroid ≥7.5 mg/die; 7,788 had MTX-contraindication. Regarding patients fulfilling two criteria, 107 had MTX-treatment failure followed by another csDMARDs and corticosteroid ≥7.5 mg/die, 53 were treated with another csDMARDs after MTX-treatment failure and also presented MTX-contraindication, 810 had corticosteroid ≥7.5 mg/die and MTX-contraindication. Mean total annual costs for patients estimated eligible for biotechnological therapy was € 3,132, of which € 177 related to drugs indicated for RA and € 2,955 related to other direct costs. Conclusions. According to our estimates, around 10% RA patients not currently treated with biotechnological agents are eligible for such therapies, highlighting a trend of under-use in clinical practice for RA management.

Background and importance Novel treatment approaches for the management of severe refractory asthma include monoclonal antibodies (Mabs). Aim and objectives The study aimed to estimate the number of the most suitable patients with severe uncontrolled asthma who are eligible for new Mabs therapy and related costs in the Veneto region (Italy). Material and methods The regional administrative database was retrospectively analysed to identify specific eligibility and assessment criteria. All patients aged ≥6 years with an exemption code for asthma (007) (level 1 patients (L1)) between 1 January 2011 and 31 December 2016 were screened. The following parameters were considered in succession: spirometry (codes: 89.37, 89.38)–(level 2 patients (L2)); inhaled corticosteroids (ICS) in combination with long acting beta adenoreceptor agonists (LABA) and/or theophylline (ATC: R03DA04), and/or antileucotriene (ATC: R03DC), and/or anticholinergics (ATC: R03BB)–(level 3 patients (L3)); high dose ICS therapy (ATC: R03BA, R03AK)–(level 4 patients (L4)); adherence to each medication–(level 5 patients (L5)); asthma hospitalisation (ICD9: 493) or treatment with systemic corticosteroids (ATC: H02)–(level 6 patients (L6)). For each patient level, the mean annual healthcare costs per patient, based on total resource consumption, were assessed. Results For a total of 4.6 million beneficiaries, aged ≥6 years, 103 138 (2.2%) patients were screened (L1). Spirometry tests were prescribed in 28 611 patients (27.7%) (L2), of whom 13 432 (46.9%) had a prescription for ICS with LABA or other agents (L3). In 5782 (43%) patients treated with previous combinations, high dose ICS therapy was prescribed (L4), and of them, 3307 (57.2%) were treatment adherent (L5) and 1136 (35.2%) had a hospital admission for asthma or treatment with systemic corticosteroids (L6). For this last level of patients, centres specialising in Mabs prescription evaluated eligibility. Total costs of the illness according to disease progression were €1279.6 for L1, €1567.7 for L2, €2045.3 for L3, €2524.2 for L4, €3233.2 for L5 and €4326.2 for L6; overall asthma related treatment and hospitalisation costs were €274.2 for L1, €400.1 for L2, €598.5 for L3, €784.3 for L4, €1118.4 for L5 and €1449.9 for L5. Conclusion and relevance This analysis allowed estimation of the number of asthma patients eligible for Mabs therapy in the Veneto region. Our findings on healthcare costs highlighted that the average cost per patient increased by severity level. Post marketing, it will be possible to assess the appropriateness of Mabs prescriptions through indicators such as over- and under-use. References and/or acknowledgements No conflict of interest.

Background The European Medicines Agency has recently approved rivaroxaban for the prevention of atherothrombotic events in patients with coronary artery disease (CAD) and peripheral arterial disease (PAD). Purpose The present study aimed at analysing the prevalence of CAD and PAD among the health-assisted population and to estimate the pharmaceutical expenditure. Material and methods Data have been obtained by retrospectively analysing a regional healthcare database between 1 January 2017 and 31 December 2017. We included adult patients (≥18 years) with a diagnosis of CAD (at least one prescription of nitrates and/or CAD diagnosis at hospital discharge) and a diagnosis of PAD (at least one prescription of antiplatelet drugs with concomitant prescription of anti-hypertensive agents or lipid-lowering agents and/or PAD diagnosis at hospital discharge). Patients were characterised over the period 2009–2016 for comorbidities (diabetes mellitus, heart failure, chronic kidney disease, cardiovascular event), during 2016 for drug use. Treatment adherence was calculated using the Medication Possession Ratio. Results More than 4.9 million health-assisted participants, 8.8% (430,254, mean age 74.2 years) received a diagnosis of CAD or PAD (41.2% PAD, 30.4% CAD, 28.4% both). Forty-two per cent (180,551) of patients had at least one comorbidity. Most frequently prescribed cardiovascular agents were anti-hypertensives (85%), antiplatelet drugs (58.7%), lipid-lowering drugs (53%) and anticoagulants (17.2%). Among patients treated with antiplatelet drugs, 36.2% were adherent to treatment. Considering the actual price of rivaroxaban, the pharmaceutical expenditure for one-year treatment in the considered region resulted at €266 million (€38 million is the current pharmaceutical expenditure for new anticoagulant therapies for 2018). Applying this analysis for patient sub-groups, the estimation was €191 million for patients with CAD or PAD, €75 million for patients with both and €112 million for those with at least one comorbidity. Considering patients adherent to antiplatelet treatment, the estimation was €58 million. Conclusion Nearly one out of ten health-assisted subjects had CAD and PAD diagnosis, in accordance with that already published for the national population. Pharmaceutical costs’ estimations represent the maximal costs as they did not consider the possible reduction in drug prices negotiated by the National Medicines Agency, considering the significant market increase and redeemability limitations. References and/or acknowledgements No conflict of interest.

Background:Ankylosing spondylitis (AS) is a chronic rheumatologic condition requiring lifelong treatments. To date, few real-world studies on AS patients in Italy are reported.Objectives:Aims of the study were to evaluate treatment patterns and to analyse pharmacoutilization on patients affected by AS in a real-world setting of Italian clinical practice.Methods:This observational study was based on administrative databases of a pool of Italian settings. A retrospective cross-sectional analysis was performed for years 2015-2017 to evaluate AS-diagnosed patients and, among them, to estimate percentage of treated and untreated ones. Patients were included if having a hospitalization discharge diagnosis at any level of AS (ICD-9-CM: 720.0) or exemption code for AS (054.720.0). Index date (ID) was date in which patients met one of the inclusion criteria. Patients with a prescription for drugs indicated for AS [non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs) - targeted synthetic (tsDMARDs) and biological (bDMARDs)] at ID were defined “treated”. Patients without such drug prescriptions at ID were considered “untreated”. To analyse treatment patterns of b/tsDMARDs-treated patients a longitudinal cohort study was conducted considering as inclusion periods the year 2014 and a period from 01/07/2016 to 30/06/2017. ID was date of first b/tsDMARDs prescription during inclusion period. Follow-up (F-up) lasted one year after ID. The interruption of treatment was defined as the absence of prescriptions in the last 3 months of F-up.Results:For cross-sectional-cohort: AS-diagnosed patients were 4,824 in 2015, 5,357 in 2016, 5,894 in 2017. In all years analysed, about 50% of patients were male. Mean age±SD ranged from 51.5±13.7 (2015) to 52.4±14.0 (2017). Untreated patients were 33.6% (2015), 35.1% (2016) and 37.9% (2017), while patients in therapy with b/tsDMARDs were 22.7% (2015), 22.3% (2016) and22.2% (2017). The remaining percentage of patients were treated with csDMARDs/NSAIDS: 43.7% (2015), 42.6% (2016), 39.9% (2017)). In 2015 and 2016 all b/tsDMARDs-treated patients were in therapy with anti-TFN agents, while the advent of IL-inhibitors was observed starting from 2017 (8.2% b/tsDMARDs-treated patients with IL-inhibitors). For longitudinal-cohort: in 2014, 310 patients had a b/tsDMARDs prescription and during 1-year F-up 11.9% of them interrupted the treatment after a mean time ±SD of 83.3±66.9 days. Of the 183 patients who had a prescription of b/tsDMARDs at ID during 2016-2017, 22.4% had a treatment interruption after a mean time±SD of 134.4±86.1 days during F-up.Conclusion:This real-world study provided insights on AS treatment patterns. Preliminary results showed that approximately one third of AS patients are untreated and about one in five are treated with b/tsDMARDs. Despite the improvement in treatment duration observed from 2014 to 2016/17, still 22.4% of b/tsDMARDs-treated patients interrupted therapy in the most recent cohort. A larger sample size is needed to confirm results.Disclosure of Interests:Valentina Perrone: None declared, Serena Losi Shareholder of: minor stockholder at Eli Lilly, Employee of: Employed by Eli Lilly, Erica Filippi Shareholder of: minor stockholder at Eli Lilly, Employee of: Employed by Eli Lilly, Silvia Antonelli Shareholder of: minor stockholder at Eli Lilly, Employee of: Employed by Eli Lilly, Massimo Giovannitti Shareholder of: minor stockholder at Eli Lilly, Employee of: Employed by Eli Lilly, Elisa Giacomini: None declared, Diego Sangiorgi: None declared, Luca Degli Esposti: None declared

No data are available on the learning curve in robotic distal pancreatectomy (RADP). The learning curve in RADP was assessed in 55 consecutive patients using the cumulative sum method, based on operative time. Data were extracted from a prospectively maintained database and analyzed retrospectively considering all events occurring within 90 days of surgery. No operation was converted to laparoscopic or open surgery and no patient died. Post-operative complications occurred in 34 patients (61.8%), being of Clavien-Dindo grade I-II in 32 patients (58.1%), including pancreatic fistula in 29 patients (52.7%). No grade C pancreatic fistula occurred. Four patients received blood transfusions (7.2%), three were readmitted (5.4%) and one required repeat surgery (1.8%). Based on the reduction of operative times (421.1 ± 20.5 vs 248.9 ± 9.3 min; p < 0.0001), completion of the learning curve was achieved after ten operations. Operative time of the first 10 operations was associated with a positive slope (0.47 + 1.78* case number; R (2) 0.97; p < 0.0001*), while that of the following 45 procedures showed a negative slope (23.52 - 0.39* case number; R (2) 0.97; p < 0.0001*). After completion of the learning curve, more patients had a malignant histology (0 vs 35.6%; p = 0.002), accounting for both higher lymph node yields (11.1 ± 12.2 vs 20.9 ± 18.5) (p = 0.04) and lower rate of spleen preservation (90 vs 55.6%) (p = 0.04). RADP was safely feasible in selected patients and the learning curve was completed after ten operations. Improvement in clinical outcome was not demonstrated, probably because of the limited occurrence of outcome comparators.

Minimally invasive surgical procedures have revolutionized the world of surgery in the past decades. While laparoscopy, the first minimally invasive surgical technique to be developed, is widely used and has been addressed by several guidelines and recommendations, the implementation of robotic-assisted surgery is still hindered by the lack of consensus documents that support healthcare professionals in the management of this novel surgical procedure. Here we summarize the available evidence and provide expert opinion aimed at improving the implementation and resolution of issues derived from robotic abdominal surgery procedures. A joint task force of Italian surgeons, anesthesiologists and clinical epidemiologists reviewed the available evidence on robotic abdominal surgery. Recommendations were graded according to the strength of evidence. Statements and recommendations are provided for general issues regarding robotic abdominal surgery, operating theatre organization, preoperative patient assessment and preparation, intraoperative management, and postoperative procedures and discharge. The consensus document provides evidence-based recommendations and expert statements aimed at improving the implementation and management of robotic abdominal surgery.

The first successful kidney transplantation between identical twins, performed in Boston in 1954, opened the clinical transplant era. Ever since, kidney transplantation has become one of the milestones of the recent history of medicine, whilst saving millions of lives. Although the nature of this extraordinary accomplishment is multifactorial, the successful outcome of a renal transplant begins with an impeccable surgery. This chapter will illustrate the state of the art of kidney transplant surgery in the recipient.

Pancreas transplantation is the only therapy that can restore insulin independence in beta-cell penic diabetic recipients. Because of the need for life-long immunosuppression and the intial surgical risk associated with the transplant procedure, Pancreas transplantation is a therapeutic option only in selected diabetic patients. Based on renal function, three main populations of diabetic recipients of a pancreas transplant can be identified: uremic patients, posturemic patients (following successful kidney transplantation), and non-uremic patients. Uremic patients are best treated by simultaneous kidney-pancreas transplantation with grafts obtained from the same deceased donor. Posturemic patients can receive a pancreas after kidney transplantation, if the previous renal graft has a good functional reserve. Non-uremic patients can receive a pancreas alone transplant if their diabetes is poorly controlled, despite optimal insulin therapy, suffer from unawareness hypoglycemia events and/or develop progressive chronic complications of diabetes. The results of pancreas transplantation have improved over the years and are currently not inferior to those of renal transplantation in non-diabetic recipients. A functioning pancreatic graft can prolong the life of diabetic recipients, improves their quality of life, and can halt, or reverse, the progression of chronic complications of diabetes. Unfortunately, because of ageing of donor population and lack of timely referral of potential recipients, the annual volume of pancreas transplants is declining. Considering that the results of pancreas transplantation depend on center volume, and that adequate center volume is required also for training of newer generations of transplant physcians and surgeons, centralization of pancreas transplantation activity should be considered.

To assess if exposure to videogames, musical instrument playing, or both influence the psychomotor skills level, assessed by a virtual reality simulator for robot-assisted surgery (RAS).A cohort of 57 medical students were recruited: playing musical instruments (group 1), videogames (group 2), both (group 3), and no activity (group 4); all students executed four exercises on a virtual simulator for RAS.Subjects from group 3 achieved the best performances on overall score: 527.09 ± 130.54 vs. 493.73 ± 108.88 (group 2), 472.72 ± 85.31 (group 1), and 403.13 ± 99.83 (group 4). Statistically significant differences (p .05) between group 3 and group 4 were found for overall score (p = .009) and for time of completion (p = .044). As regards experience with the piano, subjects from group 3 outperformed those from group 1 on overall score (496.98 ± 122.71 vs. 470.25 ± 92.31), but without statistically significant difference (p = .646).The present study suggests that the level of psychomotor skills in subjects exposed to both musical instrument playing and videogames is higher than that in those practicing either one alone. The effect of videogames appears negligible in individuals playing the piano.

Robotic assistance improves surgical dexterity in minimally invasive operations, especially when fine dissection and multiple sutures are required. As such, robotic assistance could be rewarding in the setting of robotic pancreatoduodenectomy (RPD). RPD was implemented at a high volume center with preemptive experience in advanced laparoscopy. Indications, surgical technique, and results of RPD are discussed against the background of current literature. RPD was performed in 112 consecutive patients. Conversion to open surgery was required in three patients, despite nine required segmental resection and reconstruction of the superior mesenteric/portal vein. No patient was converted to laparoscopy. A pancreato-jejunostomy was created in 106 patients (94.6 %), using either a duct-to-mucosa (n = 82; 73.2 %) or an invaginating (n = 24; 21.4 %) technique. Pancreato-gastrostomy was performed in one patient, the pancreatic duct was occluded in two patients, and a pancreatico-cutaneous fistula was created in three patients. Mean operative time was 526.3 ± 102.4 in the entire cohort and reduced significantly over the course of time. Experience was also associated with reduced rates of delayed gastric emptying and increased proportion of malignant tumor histology. Ninety day mortality was 3.6 %. Postoperative complications occurred in 83 patients (74.1 %) with a median comprehensive complication index of 20.9 (0–30.8). Clinically relevant pancreatic fistula occurred in 19.6 % of the patients. No grade C pancreatic fistula was noted in the last 72 consecutive patients. RPD is safely feasible in selected patients. Implementation of RPD requires sound experience with open pancreatoduodenectomy and advanced laparoscopic procedures, as well as specific training with the robotic platform.

Recent findings from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study showed that long-term improved glycemic control in patients with type 1 diabetes with normal renal function and normoalbuminuria can delay development of impaired renal function by at least 6.5 years, although the reduction in the relative risk of end-stage renal disease (ESRD) was not significant. The unanswered question is: can improvement of glycemic control delay the onset of ESRD in patients with established diabetic nephropathy? In this context, pancreas transplantation (PATx) can be considered the most effective intervention to restore normoglycemia. Can this aggressive/experimental intervention be applied to arrest/retard renal function decline? To answer this question, this review summarizes the relevant findings from observational studies conducted in cohorts of patients, followed up for 4 to 15 years, who underwent PATx. These noncontrolled studies provided positive answers to the earlier question, principally concerning a significant decrease in albumin excretion levels. However, current drugs used to prevent rejection could impair renal function, principally in recipients with low pretransplant estimated glomerular filtration rate (ie,60 mL/min). Unfortunately, all these studies had shortcuts that qualify interpretation of the findings. First, it is unclear how much initial estimated glomerular filtration rate loss results from nephrotoxic effect of antirejection drugs, and how much results from improved glycemia and its impact on the reduction of hyperfiltration. Second, the study designs did not consider the wide variation in rates of renal function loss observed in patients with established nephropathy (ie, one third are nonprogressors, one third are slow progressors, and one third are rapid progressors). Third, all studies were observational in nature and clinical trials are needed to properly evaluate the effectiveness of normalization of hyperglycemia through PATx on postponing the onset of ESRD in type 1 diabetes.