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ObjectiveThe impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists’ sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence.DesignWe defined the ‘rate of advanced adenoma on the target population’ (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50–69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50–74 year old subjects and the cumulative AA-TAP.ResultsIn 2016, the AA-TAP at a national level was 105×100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149×100 000) and the South and Islands (36×100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013–2014 and those in 2003–2004 (p=0.009).ConclusionThe AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.

Background Data on analgesic effects of breast/formula milk sucking while receiving routine childhood immunizations are available only in early infancy, have rarely been compared in the same study, and are not accompanied by information on mothers’ satisfaction/acceptance. Here we aimed to compare the analgesic effect of both methods vs. held-only controls up to 1 year of age, and verify mothers’ satisfaction. Methods Two to 12 months children subjected to vaccine were allocated into three groups: breastfed, formula-fed, and held-only controls. A video recording was performed to analyze pain parameters: crying latency/duration and specific scales [FLACC (Face, Legs, Activity, Cry, and Consolability), NIPS (Neonatal Infant Pain Scale)]. After the procedure, mothers filled in a satisfaction questionnaire. Results One-hundred and sixty-two children were recruited: 54 breastfed, 35 formula fed, and 73 controls. Breastfed showed the longest crying latency, and together with formula fed, had the shortest duration and lowest pain scores. Most mothers appreciated not only the respective feeding-mediated pain mitigation method used, but also the simply-holding procedure. In all cases, they felt reassured, with an unexpected frequent underestimation of their child’s pain during the shot. Conclusions The analgesic effect of breastfeeding during vaccination extends also to children >6 months old, and is obtained by formula too. Embracing the child may help to reassure mothers. Impact We confirmed the analgesic effect of breastfeeding during the vaccination procedures in early infancy. We show for the first time that this effect is extended also to children up to 1 year of age, and it may be obtained by formula feeding as well. Most mothers appreciated pain mitigation not only through feeding, but also the simply-holding procedure. In all cases, mothers felt reassured, with an unexpected frequent underestimation of their child’ pain during the shot. The promotion of these easily feasible and well-accepted strategies should be further encouraged within health professionals during vaccination procedures.

PurposeGastropleural and gastrobronchial fistulas (GPF/GBFs) are serious but rare complications after bariatric surgery whose management is not consensual. The aim was to establish a cohort and evaluate different clinical presentations and therapeutic options.Materials and MethodsA multicenter and retrospective study analyzing GPF/GBFs after bariatric surgery in France between 2007 and 2018, via a questionnaire sent to digestive and thoracic surgery departments.ResultsThe study included 24 patients from 9 surgical departments after initial bariatric surgery (21 sleeve gastrectomies; 3 gastric bypass) for morbid obesity (mean BMI = 42 ± 8 kg/m2). The GPF/GBFs occurred, on average, 124 days after bariatric surgery, complicating an initial post-operative gastric fistula (POGF) in 66% of cases. Endoscopic digestive treatment was performed in 79% of cases (n = 19) associated in 25% of cases (n = 6) with thoracic endoscopy. Surgical treatment was performed in 83% of cases (n = 20): thoracic surgery (n = 5), digestive surgery (n = 8), and combined surgery (n = 7). No patient died. Overall morbidity was 42%. The overall success rate of the initial and secondary strategies was 58.5% and 90%, respectively. The average healing time was approximately 7 months. Patients who had undergone thoracic surgery (n = 12) had more initial management failures (n = 9/12) than patients who had not (n = 3/12), p = 0.001.ConclusionComplex and life-threatening fistulas that are revealed late require a multidisciplinary strategy. Thoracic surgery should be reserved once the abdominal leak heals; otherwise, it is associated with a higher risk of failure.

Plasma growth differentiation factor-15 (GDF-15) levels increase with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) but the underlying mechanism remains poorly defined. Using male mouse models of obesity and MASLD, and biopsies from carefully-characterized patients regarding obesity, type 2 diabetes (T2D) and MASLD status, we identify adipose tissue (AT) as the key source of GDF-15 at onset of obesity and T2D, followed by liver during the progression towards metabolic dysfunction-associated steatohepatitis (MASH). Obesity and T2D increase GDF15 expression in AT through the accumulation of macrophages, which are the main immune cells expressing GDF15 . Inactivation of Gdf15 in macrophages reduces plasma GDF-15 concentrations and exacerbates obesity in mice. During MASH development, Gdf15 expression additionally increases in hepatocytes through stress-induced TFEB and DDIT3 signaling. Together, these results demonstrate a dual contribution of AT and liver to GDF-15 production in metabolic diseases and identify potential therapeutic targets to raise endogenous GDF-15 levels. GDF-15 is a cytokine regulating food intake and a potential therapeutic target for treating obesity. Here, the authors show that macrophage infiltration in adipose tissue increases GDF-15 during obesity and type 2 diabetes, and hepatocyte stress further increases its levels when developing MASH.

Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity. The identified clusters were applied across three independent MASLD cohorts with liver biopsy (totaling 1,099 participants), and in the UK Biobank to assess the incidence of chronic liver disease, cardiovascular disease and type 2 diabetes. Results unveiled two distinct types of MASLD associated with steatohepatitis on histology and liver imaging. The first cluster, liver-specific, was genetically linked and showed rapid progression of chronic liver disease but limited risk of cardiovascular disease. The second cluster, cardiometabolic, was primarily associated with dysglycemia and high levels of triglycerides, leading to a similar incidence of chronic liver disease but a higher risk of cardiovascular disease and type 2 diabetes. Analyses of samples from 831 individuals with available liver transcriptomics and 1,322 with available plasma metabolomics highlighted that these two types of MASLD exhibited distinct liver transcriptomic profiles and plasma metabolomic signatures, respectively. In conclusion, these data provide preliminary evidence of the existence of two distinct types of clinically relevant MASLD with similar liver phenotypes at baseline, but each with specific underlying biological profiles and different clinical trajectories, suggesting the need for tailored therapeutic strategies. Partitioning clustering based on clinical variables applied to multiple patient cohorts identifies two subtypes of metabolic dysfunction-associated steatotic liver disease with different associations to hepatic and cardiovascular outcomes.

Since 2007, single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has been proposed as an alternative to Roux-en-Y gastric bypass (RYGB) in the treatment of obesity. We conducted a multicentre randomised trial, with the hypothesis that SADI-S could be more effective than RYGB at 2-year follow-up. This multicentre, open-label, individually randomised superiority trial was conducted in France; patients were recruited from 22 bariatric institutions, mostly public academic hospitals. Key inclusion criteria were patients with a BMI ≥40 kg/m2 or ≥35 kg/m2 with obesity-related comorbidities (type 2 diabetes, hypertension, dyslipidaemia, sleep apnoea, or osteoarthrosis), and a candidate for SADI-S or RYGB gastric bypass as a primary surgery or after a sleeve gastrectomy. Main key exclusions included previous bariatric surgery (other than sleeve gastrectomy), inflammatory bowel disease, type 1 diabetes, and untreated Helicobacter pylori infection. Participants were randomly assigned (1:1) to SADI-S or RYGB, stratified by centre, failure of sleeve gastrectomy, and presence of type 2 diabetes. The primary endpoint was percentage excess weight loss (%EWL) at 2 years (%EWL=[(weight at 2 years – initial weight)/(initial weight – ideal weight)] × 100). The study is registered with ClinicalTrials.gov, NCT03610256 and is completed. Between Nov 8, 2018, and Sept 29, 2021, a total of 381 patients were randomly assigned (intention-to-treat population) and included in the primary analysis (SADI-S: 190, RYGB: 191). Mean age was 44·4 years (SD 10·64), mean BMI was 46·2 kg/m2 (6·40), 265 (70%) were female, and 79 (21%) had a primary sleeve gastrectomy. 43 (12%) of 370 participants were lost to follow-up. At 2 years, the mean %EWL was statistically significantly higher in the SADI-S group compared with the RYGB group (–76·0% [SD 26·7] vs –68·1% [28·7], confirming the superiority of SADI-S (mean difference –6·72% [95% CI –12·64 to –0·80], p=0·026). The primary outcome was missing for 78 (20%) of 381 participants, with 46 (59%) of 78 participants in the SADI-S group and 32 (41%) of 78 in the RYGB group, p=0·09. The number of serious adverse events related to the surgical technique in the safety population, including all operated patients, was 40 in the SADI-S group including three anastomotic leaks and eight severe diarrhoea compared with 35 in the RYGB group including five internal hernia and five severe abdominal pain cases of which two required diagnostic laparoscopy. SADI-S showed superior weight loss compared with RYGB at 2 years, with a similar safety profile. French Ministry of Health (Direction Générale de l'offre de Soin – DGOS).

Steel porous materials are multifunctional lightweight materials with a great potential in several applications. Their properties are strongly influenced by type, dimension and distribution of pores. Selective laser melting (SLM) is one of the most important additive manufacturing technologies, which allows to properly control the main parameters that affect the behavior of manufactured porous materials. The purpose of this study is to simulate the room temperature compression behavior of steel specimens with large spherical pores built via SLM. Such a construction is a highly innovative manufacturing concept. The numerical simulation covers the whole deformation range undergone by specimens that is up to 80% nominal strain. In this regard, three finite element models of the specimens subjected to uniaxial compression are developed including different levels of detail. The Hollomon model is selected as the constitutive model given in input to the FE simulations. Although experimental tests highlight a highly nonlinear behavior entailing plastic collapse of porous samples, numerical simulations can accurately reproduce experimental results. Modeling issues that may contribute to limit the computational cost of simulations yet preserving good level of accuracy of FE results also are discussed in the article.

Aviation emissions impact surface air quality at multiple scales-from near-airport pollution peaks associated with airport landing and take off (LTO) emissions, to intercontinental pollution attributable to aircraft cruise emissions. Previous studies have quantified aviation's air quality impacts around a specific airport, in a specific region, or at the global scale. However, no study has assessed the air quality and human health impacts of aviation, capturing effects on all aforementioned scales. This study uses a multi-scale modeling approach to quantify and monetize the air quality impact of civil aviation emissions, approximating effects of aircraft plume dynamics-related local dispersion (∼1 km), near-airport dispersion (∼10 km), regional (∼1000 km) and global (∼10 000 km) scale chemistry and transport. We use concentration-response functions to estimate premature deaths due to population exposure to aviation-attributable PM2.5 and ozone, finding that aviation emissions cause ∼16 000 (90% CI: 8300-24 000) premature deaths per year. Of these, LTO emissions contribute a quarter. Our estimate shows that premature deaths due to long-term exposure to aviation-attributable PM2.5 and O3 lead to costs of ∼$21 bn per year. We compare these costs to other societal costs of aviation and find that they are on the same order of magnitude as global aviation-attributable climate costs, and one order of magnitude larger than aviation-attributable accident and noise costs.

The paper investigates the fabrication of Selective Laser Melting (SLM) titanium alloy Ti6Al4V micro-lattice structures for the production of lightweight components. Specifically, the pillar textile unit cell is used as base lattice structure and alternative lattice topologies including reinforcing vertical bars are also considered. Detailed characterizations of dimensional accuracy, surface roughness, and micro-hardness are performed. In addition, compression tests are carried out in order to evaluate the mechanical strength and the energy absorbed per unit mass of the lattice truss specimens made by SLM. The built structures have a relative density ranging between 0.2234 and 0.5822. An optimization procedure is implemented via the method of Taguchi to identify the optimal geometric configuration which maximizes peak strength and energy absorbed per unit mass.