Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Background & aims: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. Methods: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. Results: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. Conclusions: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.publishedVersionPeer reviewe

The natural emergence of asymmetric tree-shaped pathways for cooling of a non-uniformly heated domain

Here, we show that the peak temperature on a non-uniformly heated domain can be decreased by embedding a high-conductivity insert in it. The trunk of the high-conductivity insert is in contact with a heat sink. The heat is generated non-uniformly throughout the domain or concentrated in a square spot of length scale 0.1 L0, where L0 is the length scale of the non-uniformly heated domain. Peak and average temperatures are affected by the volume fraction of the high-conductivity material and by the shape of the high-conductivity pathways. This paper uncovers how varying the shape of the symmetric and asymmetric high-conductivity trees affects the overall thermal conductance of the heat generating domain. The tree-shaped high-conductivity inserts tend to grow toward where the heat generation is concentrated in order to minimize the peak temperature, i.e., in order to minimize the resistances to the heat flow. This behaviour of high-conductivity trees is alike with the root growth of the plants and trees. They also tend to grow towards sunlight, and their roots tend to grow towards water and nutrients. This paper uncovers the similarity between biological trees and high-conductivity trees, which is that trees should grow asymmetrically when the boundary conditions are non-uniform. We show here even though all the trees have the same objectives (minimum flow resistance), their shape should not be the same because of the variation in boundary conditions. To sum up, this paper shows that there is a high-conductivity tree design corresponding to minimum peak temperature with fixed constraints and conditions. This result is in accord with the constructal law which states that there should be an optimal design for a given set of conditions and constraints, and this design should be morphed in order to ensure minimum flow resistances as conditions and constraints change.Scientific and Technological Research Council of Turkey (114M592

Evaluation of the Wear-Resistant Plate Performance on Different Locations Over the Flow Path of a Large-Sized Heavy-Duty Centrifugal Fan

In industrial applications as chemical plants, cement factories, and glassmakers, large-sized centrifugal fans are commonly used for dust-laden flow processing. In many cases, the contamination is due to solid particles which are responsible for fouling and erosion issues. Erosion induces the reduction of mechanical resistance and at the same time, the modification of the geometry and the surface characteristics of the internal flow path. The process works according to the characteristics of the erodent particles, such as dimension and hardness which have to be coupled with the mechanical characteristics of the substrate, like hardness and roughness level. In addition to this, the intensity of the erosion depends on the dynamic characteristics of particles, especially velocity and impact angle. For these reasons, erosion-related issues are difficult to be predicted and reduced. In the attempt of preserving the structural integrity of the internal walls, wear-resistant plates are positioned where the impacting contaminants are supposed to be more detrimental. In the present work, a combined experimental and numerical approach is proposed to evaluate the proper set up of wear-resistance plates over the flow path of a large-sized centrifugal fan. The results show how different regions (rotating and stationary walls) are subjected to different impact behavior and for this reason, the design of the position of the wear-resistant plate is not straightforward. Suggestions related to the reduction of the erosion intensity are reported, highlighting the possibility to design the best compromise between erosion, performance, and costs

A strategy for the robust forecasting of gas turbine health subjected to fouling

Fouling represents a major problem for Gas Turbines (GTs) in both heavy-duty and aero-propulsion applications. Solid particles entering the engine can stick to the internal surfaces and form deposits. Components' lifetime and performance can dramatically vary as a consequence of this phenomenon. These effects impact the whole engine in terms of residual life, operating stability, and maintenance costs. In the High-Pressure Turbine (HPT), in particular, the high temperatures soft the particles and promote their adhesion, especially in the short term. Unfortunately, predicting the GT response to this detrimental issue is still an open problem for scientists. Furthermore, the stochastic variations of the components operating conditions increase the uncertainty of the forecasting results. In this work, a strategy to predict the effects of turbine fouling on the whole engine is proposed. A stationary Gas Path Analysis (GPA) has been performed for this scope to predict the GT health parameters. Their alteration as a consequence of fouling has been evaluated by scaling the turbine map. The scaling factor has been found by performing Computational Fluid Dynamic (CFD) simulations of a HPT nozzle with particle injection. Being its operating conditions strongly uncertain, a stochastic analysis has been conducted. The uncertainty sources considered are the circumferential hot core location and the turbulence level at the inlet. The study enables to build of confidence intervals on the GT health parameters predictions and represents a step forward towards a robust forecasting tool

Off-line washing effectiveness on a multistage axial compressor

The interaction between gas turbines and airborne particles determines detrimental effects on the performance, efficiency, and reliability of the power unit. When it is possible, the interaction is reduced by the use of inlet separators and filtration systems. In an aero engine, these barriers are difficult to implement, and only bigger particles (usually greater than 10 μm) are separated from the airflow. Small units, especially those equips helicopters, are usually affected by fouling issues, especially when the aircraft is employed in harsh environments such as firefighting and rescue activities. To recover this contamination, the unit is washed after the mission by ground operations to restore the unit performance by removing the deposits. This operation occurs during a sub-idle unit operation, and the washing process has to be effective when the engine operates in this off-design condition. In this paper, the evaluation of the washing performance during a sub-idle unit operation is carried out. The compressor unit is a multistage axial compressor that equips the Allison 250-C18 engine. The washing operation was performed by water, and a sensitivity analysis is carried out to discover the capability of water droplets to remove the contaminants. The experimental analysis involves the contamination of the unit by micro-sized soot particles and a washing operation by micro-sized water droplets. These experimental results are compared to numerical simulations to discover the effects of the washing operation on a small power unit during sub-idle operating conditions. The off-design regime imposes a specific evaluation of the proper setup of the washing strategy: flow separations involve wider regions in the compressor unit, and the removal capability is strongly related to the droplet path through the stages. The results show how in the off-design washing operation, the droplet diameter has greater importance than the water flow rate for reducing the deposits over the compressor stages

Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine

Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. We aim systematically promote this intervention with all Lynch syndrome carriers

Clinical profile and mortality of Sars-Cov-2 infection in cancer patients across two pandemic time periods (Feb 2020-Sep 2020; Sep 2020-May 2021) in the Veneto Oncology Network: The ROVID study

Introduction: We analyzed a cohort of patients with cancer and Sars-Cov-2 infec- tion from the Veneto Oncology Network registry across two pandemic time periods. Materials and methods: 761 patients with cancer and SARS-CoV-2 infection were included. Results: 198 patients were diagnosed during the first pandemic time period (TP1; February 2020 September 2020), 494 during TP2 before the vaccination campaign (TP2/pre-vaccination; September 2020-21 February 2021) and 69 in TP2/post-vaccination (22 February 2021-15 May 2021). TP2 vs TP1 patients were younger (p Z 0.004), showed more frequently a good perfor- mance status (p < 0.001) and <2 comorbidities (p Z 0.002), were more likely to be on active anticancer therapy (p Z 0.006). Significantly fewer patients in TP2 (3-4%) vs TP1 (22%) had an in-hospital potential source of infection (p < 0.001). TP2 patients were more frequently asymptomatic (p Z 0.003). Significantly fewer patients from TP2 were hospitalized (p < 0.001) or admitted to intensive care unit (p Z 0.006). All-cause mortality decreased from 30.3% in TP1, to 8.9% and 8.7% in the two TP2 periods (p < 0.001), reflected by a significant reduction in Sars-Cov-2-related mortality (15.2%, 7.5% and 5.8% in the three consecutive time periods, p Z 0.004). Conclusions: Differences in clinical characteristics and features of Sars-Cov-2 infection be- tween TP1 and TP2 reflect the effects of protective measures and increased testing capacity. The lower mortality in TP2 is in line with a less frail population. However, the vast majority of death events in TP2 were related to COVID-19, reinforcing the priority to protect cancer patients

Quality standards for the management of bronchiectasis in Italy:a national audit

Although historically considered a neglected disease, bronchiectasis has become a disease of renewed interest over recent decades in light of an increase in prevalence and a substantial burden on healthcare systems. In 2010, the British Thoracic Society (BTS) published guidelines on the management of bronchiectasis in adults, along with specific quality standards. To date, these represent the only quality standards available in Europe. These have been tested over a number of years in the UK with progressive improvements in the standard of care. No national guidelines are available in Italy and no indications on which guideline should be followed have been given by the Italian Society of Respiratory Medicine (SIP). There are limited published data on the quality of bronchiectasis care in Europe outside of the UK. The BTS standards have not been tested in continental Europe or in Italy, where information on characteristics and management of bronchiectasis patients are lacking