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Abstract Background Prophylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure. The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score ≥ 3), and, secondarily, POPF grade B/C. Methods/design Binational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score ≥ 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality. Discussion PANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente et al., 2007; Bassi et al., 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., 2016; Pratt et al., 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., 2022; Asbun and Stauffer, 2011).

The Molise and Apulia subsurface exploration has found clastic calcareous layers at the top of the Mesozoic—Miocene carbonate sequence and within the Middle Pliocene turbidites. The first are the result of Karst—fissures and crushing on the structural highs and mass flows at the base of fault slopes. Within the turbidites a biocalcarenitic horizon IS an electric good marker which proves an event of a shelf build up. It corresponds to the Middle Pliocene gap widely developed in the Apennines.

The paper analyses the efficacy of digital platforms for deliberative and participatory democracy in enhancing democracy. After examining the concepts of deliberative and participatory democracy (§IA), particularly their meaning from a legal standpoint and their relation to representative and direct democracy (§IB), the study introduces the broader concept of ‘digital democratic innovations’ (§IC) and adopts a classification framework (§II). Then, the current legal framework of e-participation in Italy, Germany, France, and the EU is analysed (§III). This comparative analysis sets the stage for a detailed examination of five digital platforms operating at both local and national levels, which serve as case studies. Through a systematic evaluation of the key features of these platforms, the paper classifies those platforms according to the classification framework (§IVA-E). It also assesses the quality of citizen participation facilitated by each digital democratic innovation exploring two indicators: the meaningfulness of participation and the extent of digital deliberation (§IVF). In drawing conclusions, the paper also suggests potential avenues for further legal research into digitised civic participation (§V).

The actuator line method (ALM) is increasingly being preferred to the ubiquitous blade element momentum (BEM) approach in several applications related to wind turbine simulation, thanks to the higher level of fidelity required by the design and analysis of modern machines. Its capability to resolve blade tip vortices and their effect on the blade load profile is, however, still unsatisfactory, especially when compared to other medium-fidelity methodologies such as the lifting line theory (LLT). Despite the numerical strategies proposed so far to overcome this limitation, the reason for such behavior is still unclear. To investigate this aspect, the present study uses the ALM tool developed by the authors for the ANSYS® Fluent® solver (v. 20.2) to simulate a NACA0018 finite wing for different pitch angles. Three different test cases were considered: high-fidelity blade-resolved computational fluid dynamics (CFD) simulations (to be used as a benchmark), standard ALM, and ALM with the spanwise force distribution coming from blade-resolved data (frozen ALM). The last option was included to isolate the effect of force projection, using three different smearing functions. For the postprocessing of the results, two different techniques were applied: the LineAverage sampling of the local angle of attack along the blade and state-of-the-art vortex identification methods (VIMs) to outline the blade vortex system. The analysis showed that the ALM can account for tip effects without the need for additional corrections, provided that the correct angle of attack sampling and force projection strategies are adopted.

ABSTRACTWe present the characterization of geohazard-related features of the Ligurian Sea with the map of its physiographic domains (1:250,000 scale) and five maps (1:100,000 scale) of the morphological and morpho-bathymetric elements. These were realized in the framework of the MaGIC (Marine Geohazard along Italian Coasts) project, promoted by the Italian Civil Protection Department. The characterization of submarine geohazards along continental margins, together with mapping of marine geological features are critical for the management of coastal risks. Multibeam bathymetric data combined with high-resolution 2D reflection seismic data, allowed to identify and map the main tectono-sedimentary features related to mass movements along the Ligurian continental margin. A dense grid of seismic profiles allowed to improve the comprehension of the margin structure as well as its recent tectonic activity providing new insights concerning mass wasting processes and active tectonics relationships to plan further, focalized investigations in areas of maximum risk.

Summary: Background: Metastatic retroperitoneal lymph node dissection (LND) for nodal recurrence is applied for a variety of cancers, such as urological, gynaecological and rectal cancer. Precise localisation and resection of these lymph nodes (LNs) during surgery can be challenging, especially after previous radiotherapy or surgery. The objective of this study was to assess the added value of surgical navigation for targeted LND in the retroperitoneum. Methods: We performed an open-label randomised, controlled, phase 3 trial at the Netherlands Cancer Institute, Amsterdam. Eligible participants were over 18 years of age, scheduled for targeted retroperitoneal LND by laparotomy, with removal of one or more suspected (targeted) LN(s) as assessed by diagnostic imaging. Patients were randomised (1:1) between conventional LND and LND using surgical navigation, by means of a minimisation method stratified for tumour origin (urological, colorectal and other). For the surgical navigation, a digital 3D model of the patients' anatomy was created from diagnostic CT scans, including delineation of the targeted LN(s). The 3D model was linked to the patients’ position in the operation room. Using an electromagnetic tracking system, with a sterile tracked pointer, the actual position of the pointer was shown in the 3D model, enabling the surgeon to localize the targeted LN(s). The primary outcome of the study was the percentage of successful procedures. Success was defined as no residual target LN(s) visible on postoperative CT imaging. This study was registered with ClinicalTrials.gov, NCT05867095. Findings: From January 2017 to December 2020, 69 participants were included in the study, 35 (51%) in the conventional arm and 34 (49%) in the navigation arm. Four patients were not evaluable and excluded from further analysis; three in the conventional arm (patients withdraw from study participation), one in the navigation arm (discontinued surgery, misclassified diagnosis). According to intention-to-treat analysis, 50% (16/32) of the surgical procedures was successful in the conventional arm, versus 85% (28/33) in the surgical navigation arm (one-tailed p = 0.0028, 90% CI: 14%–56%). Using the Clavien-Dindo classification, the overall complication rate was comparable between the conventional arm and the navigation arm. Surgeons judged the surgical navigation setup as valuable, the median preference score to use surgical navigation was 3.7 (3.3–4.0) (scale 1–5), and the median system usability score was 75 (70–85) (scale 0–100). Interpretation: Surgical navigation allows for significantly better localisation and removal of target LN(s) in the retroperitoneum. Funding: This research was supported by the KWF-Alpe d'HuZes (NKI 2014-6596) and by an institutional grant of The Dutch Cancer Society and of the Dutch Ministry of Health, Welfare and Sport.

IntroductionAmong girls assessed for pubertal precocity, pelvic ultrasound (pUS) may represent a pivotal tool to predict the time expected to elapse between sonographic assessment and the onset of menarche (TUS-M). Accordingly, the present analysis is meant to define the statistical relationship between sonographic parameters and TUS-M, in order to identify the most reliable predictor of the timing of menarche.MethodsRetrospective, multicenter analysis. Girls assessed for sexual precocity and showing sonographic and clinical findings consistent with pubertal onset upon referral were considered eligible. Patients treated with GnRH analogues were excluded and only those who had subsequently achieved complete and spontaneous pubertal attainment and for whom the exact date of menarche was available were included. Overall, we enrolled 184 girls from five tertiary care Italian Centers.ResultsThe time elapsed (months) between baseline endocrine assessment and spontaneous achievement of menarche showed a negative statistically significant correlation (p

Gas evolution and flow patterns inside an alkaline electrolyzer cell strongly affect efficiency, although such effects have not been explored in detail to date. The present study aims to critically analyze the dependence of cell performance on the multiphase flow phenomena, defining some key metrics for its assessment using CFD. Six performance indicators, involving gas accumulation, bubble coverage, and flow uniformity, are applied to a 3D CFD model of an alkaline cathodic cell, and possible optimizations of the cell geometry are evaluated. The results demonstrate the complexity of defining the optimal indicator, which strictly depends on the case study and on the analysis at hand. For the cell analyzed herein, the parameters linked to the electrode volume fraction were indicated as the most influential on the cell efficiency, allowing us to define the best geometry case during the optimization. Furthermore, a sensitivity analysis was conducted, which showed that higher mass flow rates are generally preferable as they are linked to higher bubble removal. Higher current densities, allowing enhanced gas production, are instead associated with slightly lower efficiencies and stronger nonuniformity of the electrolyte flow inside the cell.

Anti T-lymphocyte globulin (ATLG) is used in hematopoietic stem cell transplantation (HSCT) to prevent graft-versus-host disease (GvHD) and graft failure. To date, insight in ATLG pharmacokinetics and -dynamics (PK/PD) is limited, and population PK (POPPK) models are lacking. In this prospective study, we describe ATLG POPPK using NONMEM® and the impact of ATLG exposure on clinical outcome and immune reconstitution in a homogeneous cohort of pediatric acute lymphoblastic leukemia (ALL) patients transplanted with a matched unrelated donor and receiving uniform ATLG dosing. Based on 121 patients and 812 samples for POPPK analysis, a two-compartmental model with parallel linear and non-linear clearance and bodyweight as covariate, best described the ATLG concentrationtime data. The level of ATLG exposure (day active ATLG day 16 8.2%, p

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.

In children with acute myeloid leukemia (AML) who lack an HLA identical sibling, the donor can be replaced with an HLA matched unrelated donor (MUD) or a haploidentical donor (haplo). We compared outcomes of patients