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Abstract In response to gradual nanoindentation, the surface of muscovite mica deforms by sudden stochastic nanometer-scale displacement bursts. Here, the statistics of these displacement events are interpreted using a statistical model previously used to model earthquakes to understand how chemically reactive environments alter the surface properties of this material. We show that the statistics of nanoindentation displacement bursts in muscovite mica are tuned by chemomechanical weakening in a manner similar to how the statistics of model events are tuned by a mechanical weakening parameter that describes how easily system-spanning cracks can be nucleated. Because the predictions of this model are independent of any surface defects or structural details, these results suggest this simple model can be universally used to describe chemomechanical weakening in many systems prone to slip avalanches on a wide range of spatio-temporal scales.

For decades, materials scientists have relied on the process-structure–property paradigm to guide investigations into material behaviors. Traditional studies often examine a limited number of process-structure–property variables, striving to elucidate mechanisms governing material response. However, this approach is time consuming and can limit exploration, as well as the discovery of process-structure–property relations in novel materials. In this paper, we combined combinatorial sputter deposition and multi-modal high-throughput materials characterization with feedforward neural networks to establish high-dimensional process-structure–property relations in Pt-Au alloys, yielding nanocrystalline alloys with high hardness and low resistivity relevant to electrical contact switch applications. We mapped three indicators of process conditions (composition and two atomic deposition characteristics) onto four indicators of material structure (X-ray diffraction, film thickness, density, and surface roughness) and two indicators of material properties (hardness and resistivity), resulting in 784 unique combinations evaluated over a 13-dimensional space. The neural networks predicted Pt-Au alloys with 18–24 at.% Au, when deposited at specific conditions, to have a nanoindentation hardness up to 7.2 GPa. This high hardness value, comparable to some steels, represents a 3-fold improvement in hardness over “hard gold”, a commonly used electrical contact alloy, while maintaining requisite electrical conductivity. The neural network models provide an avenue to identify expected process windows capable of maximizing material performance.

This work investigated non-standard HIP cycles for PBF-L Ti-6Al-4V and characterized microstructure and tensile properties to compare between material that originated from the same build. For 920°C, faster cooling rates (100°C/min, 2000°C/min) were found to promote bi-lamellar α microstructure, while the 2000°C/min cooling rate improved the strength. For HIP with lower temperature (800°C, 200 MPa), coarsening was minimized resulting in strength improvement. The slow cooling rate (12°C/min) showed the highest strength as faster rates increased the amount of orthorhombic martensite (α″). For HIP with higher temperature (1050°C), the as-built crystallographic texture was reduced and equiaxed prior-β grain morphology resulted, leading to more isotropic tensile properties. However, the cooling rate (2000°C/min) was not enough to prevent formation of grain boundary α, which reduced strength and elongation. Machine learning was carried out on the dataset via Principal Component Analysis (PCA) to reduce the dimensionality of the parameters and microstructural features.

Background: In patient with a complete or near-complete clinical response after neoadjuvant treatment for locally advanced rectal cancer, the organ-sparing approach [watch & wait (W&W) or local excision (LE)] is a possible alternative to major rectal resection. Although, in case of local recurrence or regrowth, after these treatments, a total mesorectal excision (TME) can be operated. Method: In this retrospective study, we selected 120 patients with locally advanced rectal cancer (LARC) who had a complete or near-complete clinical response after neoadjuvant treatment, from June 2011 to June 2021. Among them, 41 patients were managed by W&W approach, whereas 79 patients were managed by LE. Twenty-three patients underwent salvage TME for an unfavorable histology after LE (11 patients) or a local recurrence/regrowth (seven patients in LE group – five patients in W&W group), with a median follow-up of 42 months. Results: Following salvage TME, no patients died within 30 days; serious adverse events occurred in four patients; 8 (34.8%) patients had a definitive stoma; 8 (34.8%) patients undergone to major surgery for unfavorable histology after LE – a complete response was confirmed. Conclusion: Notably active surveillance after rectal sparing allows prompt identifying signs of regrowth or relapse leading to a radical TME. Rectal sparing is a possible strategy for LARC patients although an active surveillance is necessary.

BackgroundThe molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status.MethodsAnonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I-III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated.ResultsA total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively).ConclusionPatients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers.

Desde el sometimiento de las campañas militares de 1878-1885, la población originaria (mapuche-tehuelche) del norte de la Patagonia sufrió la reubicación forzosa, la desestructuración de las unidades sociopolíticas y familiares, el borramiento de la identidad de cientos de menores y la declamación de la extinción del mundo cultural y social indígena. A partir de este proceso genocida, la agencia de individuos y colectivos indígenas fue condicionada en el marco de la construcción de una nueva sociedad que se definía “sin indios”. En adelante, esto se constituyó en un condicionante de sus posibilidades de acceder a la tierra, como así también en un principio de estigmatización y diferenciación social. En este artículo se aborda una instancia particular de la agencia de esta población: la Asociación Nacional de Aborígenes. Esta organización se destacó por su autoreconocimiento como aborigen y por su estructura supracomunitaria, transterritorial y nacional. La Asociación militó en un período clave durante el cual definió una estrategia política que defendía al productor indígena, alentó procesos de comunalización y de articulación de la agencia de los pueblos originarios con otros actores políticos, tanto en el norte de la Patagonia como en el contexto nacional.

BackgroundImpairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (

Abstract Background Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as “oligo-metastatic disease” (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. Methods The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. Discussion Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. Trial registration ClinicalTrials.gov ID NCT05806151.

El trabajo aborda los cambios y continuidades que se desplegaron en relación con el enrolamiento indígena antes, durante y con posterioridad a las campañas de conquista de Pampa y Norpatagonia entre 1878 y 1885. Se enfoca en las transformaciones producidas en los reconocimientos de las unidades sociopolíticas indígenas, los modos de negociación, la percepción y evaluación de los resultados por parte de su agencia. Se analizan los condicionamientos a dicha agencia en el contexto post-conquista y las distintas formas de incorporación al mercado de trabajo. A partir de documentación de archivo, de testimonios recogidos por la etnografía del período y de la bibliografía especializada se abordan los procesos de militarización indígena y su incidencia en la conformación de nuevas comunidades en Norpatagonia.

Due to its tunable bandgap, anisotropic behavior, and superior thermoelectric properties, device applications using layered tellurene (Te) are becoming more attractive. Here, we report a thinning technique for exfoliated tellurene nanosheets using thermal annealing in an oxygen environment. We characterize different thinning parameters, including temperature and annealing time. Based on our measurements, we show that controlled layer thinning occurs in the narrow temperature range of 325–350 °C. We also show a reliable method to form β-tellurene oxide (β-TeO2), which is an emerging wide bandgap semiconductor with promising electronic and optoelectronic properties. This wide bandgap semiconductor exhibits a broad photoluminescence (PL) spectrum with multiple peaks covering the range of 1.76–2.08 eV. This PL emission, coupled with Raman spectra, is strong evidence of the formation of 2D β-TeO2. We discuss the results obtained and the mechanisms of Te thinning and β-TeO2 formation at different temperature regimes. We also discuss the optical bandgap of β-TeO2 and show the existence of pronounced excitonic effects evident by the large exciton binding energy in this 2D β-TeO2 system that reach 1.54–1.62 eV for bulk and monolayer, respectively. Our work can be utilized to have better control over the Te nanosheet thickness. It also sheds light on the formation of well-controlled β-TeO2 layered semiconductors for electronic and optoelectronic applications.

Introduction: Growing evidence supports extracorporeal cardiopulmonary resuscitation (ECPR) for refractory out-of-hospital cardiac arrest (OHCA) patients, especially in experienced centres. We present characteristics, treatments, and outcomes of patients treated with ECPR in a high-volume cardiac arrest centre in the metropolitan area of Milan, Italy and determine prognostic factors. Methods: Refractory OHCA patients treated with ECPR between 2013 and 2022 at IRCCS San Raffaele Scientific Institute in Milan had survival and neurological outcome assessed at hospital discharge. Results: Out of 307 consecutive OHCA patients treated with ECPR (95% witnessed, 66% shockable, low-flow 70 [IQR 58–81] minutes), 17% survived and 9.4% had favourable neurological outcome. Survival and favourable neurological outcome increased to 51% (OR = 8.7; 95% CI, 4.3–18) and 28% (OR = 6.3; 95% CI, 2.8–14) when initial rhythm was shockable and low-flow (time between CPR initiation and ROSC or ECMO flow) ≤60 minutes and decreased to 9.5% and 6.3% when low-flow exceeded 60 minutes (72% of patients). At multivariable analysis, shockable rhythm (aOR for survival = 2.39; 95% CI, 1.04–5.48), shorter low-flow (aOR = 0.95; 95% CI, 0.94–0.97), intermittent ROSC (aOR = 2.5; 95% CI, 1.2–5.6), and signs of life (aOR = 3.7; 95% CI, 1.5–8.7) were associated with better outcomes. Survival reached 10% after treating 104 patients (p for trend

ImportanceThe incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.ObservationsWithin the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and relevanceThe clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

ImportanceThe incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.ObservationsWithin the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and relevanceThe clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

In this letter, we demonstrated stable nanoscale fracture in single-crystal silicon using an in-situ wedge-loaded double cantilever beam (DCB) specimen. The fracture toughness KIC was calculated directly from instrumented measurement of force and displacement via finite element analysis with frictional corrections. Measurements on multiple test specimens were used to show KIC = 0.72 ± 0.07 MPa m1/2 on {111} planes and observe the crack-growth resistance curve in

Abstract Pre-operative delirium may cause delay in surgical intervention in older patients hospitalized for hip fracture. Also it has been associated with higher risk of post-surgical complications and worst functional outcomes. Aim of this retrospective cohort study was to evaluate whether the multidimensional prognostic index (MPI) at hospital admission was associated with pre-operative delirium in older individuals with hip fracture who are deemed to require surgical intervention. Consecutive older patients (≥ 65 years) with hip fracture underwent a comprehensive geriatric assessment to calculate the MPI at hospital admission. According to previously established cut-offs, MPI was expressed in three grades, i.e. MPI-1 (low-risk), MPI-2 (moderate-risk) and MPI-3 (high risk of mortality). Pre-operative delirium was assessed using the four ‘A’s Test. Out of 244 older patients who underwent surgery for hip fracture, 104 subjects (43%) received a diagnosis of delirium. Overall, the incidence of delirium before surgery was significantly higher in patients with more severe MPI score at admission. Higher MPI grade (MPI-3) was independently associated with higher risk of pre-operative delirium (OR 2.45, CI 1.21–4.96). Therefore, the MPI at hospital admission might help in early identification of older patients with hip fracture at risk for pre-operative delirium.

Approximately 13 million tons of foundry sand (FS), a waste from the metallurgic industry, are produced worldwide annually. Although several applications for this waste have been reported, there is a lack of research regarding its application in energy production, such as the hydrogen evolution reaction (HER). Due to several metal oxides commonly present in this waste, like iron oxides, FS may have great potential for HER. Simple carbon-paste electrodes comprised of graphite and FS were prepared and tested for HER. FS, after thermal treatment, showed an onset potential near +0.39 V vs Reversible Hydrogen Electrode and a current density of approximately 16 mA cm ^‒2 at ‒0.9 V. HER geometric rate, turnover number (TON), and faradaic efficiency were 1.77 μ mol h ^‒1 cm ^‒2 , 3126, and 43.4%, respectively. Those are reasonable values compared to the ones reported in the literature, showing the potential of this waste for the manufacturing of low-cost electrodes.

Objective:. To evaluate the influence of enhanced recovery pathway (ERP) on patient-reported outcome measures (PROMs) and return to intended oncologic therapy (RIOT) after colorectal surgery. Background:. ERP improves early outcomes after colorectal surgery; however, little is known about its influence on PROMs and on RIOT. Methods:. Prospective multicenter enrollment of patients who underwent colorectal resection with anastomosis was performed, recording variables related to patient-, institution-, procedure-level data, adherence to the ERP, and outcomes. The primary endpoints were PROMs (administered before surgery, at discharge, and 6 to 8 weeks after surgery) and RIOT after surgery for malignancy, defined as the intended oncologic treatment according to national guidelines and disease stage, administered within 8 weeks from the index operation, evaluated through multivariate regression models. Results:. The study included 4529 patients, analyzed for PROMs, 1467 of which were analyzed for RIOT. Compared to their baseline preoperative values, all PROMs showed significant worsening at discharge and improvement at late evaluation. PROMs values at discharge and 6 to 8 weeks after surgery, adjusted through a generalized mixed regression model according to preoperative status and other variables, showed no association with ERP adherence rates. RIOT rates (overall 54.5%) were independently lower by aged > 69 years, ASA Class III, open surgery, and presence of major morbidity; conversely, they were independently higher after surgery performed in an institutional ERP center and by ERP adherence rates > median (69.2%). Conclusions:. Adherence to the ERP had no effect on PROMs, whereas it independently influenced RIOT rates after surgery for colorectal cancer.

BackgroundMini-invasive surgery (MIS), ERAS, and preoperative nutritional screening are currently used to reduce complications and the length of hospital stay (LOS); however, inter-variable correlations have seldom been explored. This research aimed to define inter-variable correlations in a large series of patients with gastrointestinal cancer and their impact on outcomes.MethodsPatients with consecutive cancer who underwent radical gastrointestinal surgery between 2019 and 2020 were analyzed. Age, BMI, comorbidities, ERAS, nutritional screening, and MIS were evaluated to determine their impact on 30-day complications and LOS. Inter-variable correlations were measured, and a latent variable was computed to define the patients' performance status using nutritional screening and comorbidity. Analyses were conducted using structural equation modeling (SEM).ResultsOf the 1,968 eligible patients, 1,648 were analyzed. Univariable analyses documented the benefit of nutritional screening for LOS and MIS and ERAS (≥7 items) for LOS and complications; conversely, being male and comorbidities correlated with complications, while increased age and BMI correlated with worse outcomes. SEM analysis revealed that (a) the latent variable is explained by the use of nutritional screening (p0·004); (b) the variables were correlated (age–comorbidity, ERAS–MIS, and ERAS–nutritional screening, p < 0·001); and (c) their impact on the outcomes was based on direct effects (complications: sex, p0·001), indirect effects (LOS: MIS-ERAS-nutritional screening, p < 0·001; complications: MIS-ERAS, p0·001), and regression-based effects (LOS: ERAS, MIS, p < 0·001, nutritional screening, p0·021; complications: ERAS, MIS, p < 0·001, sex, p0·001). Finally, LOS and complications were correlated (p < 0·001).ConclusionEnhanced recovery after surgery (ERAS), MIS, and nutritional screening are beneficial in surgical oncology; however, the inter-variable correlation is reliable, underlying the importance of the multidisciplinary approach.

BackgroundMetastatic colorectal cancer is one of the most common causes of cancer death worldwide. RAS and BRAF mutational analyses are strongly recommended before beginning chemotherapy in the metastatic setting for their predictive role for the efficacy of anti-EGFR monoclonal antibodies. In most of cases, mutational status coincides between primary tumor and metastases. In RAS and BRAF wild-type patients treated with anti-EGFRs, after an induction treatment period, recent evidence supports the role of a maintenance treatment with fluoropyrimidines and anti-EGFRs. However, skin toxicity is the most described and limiting side-effect of maintenance. Moreover, it is described that the continuous administration of these monoclonal antibodies leads to an acquired resistance to anti-EGFRs, with subsequent treatment failure. Intermittent strategy with chemotherapy plus anti-EGFR may help maintain treatment efficacy, delaying resistance.Case presentationIn this case report, we describe the case of a RAS-BRAF wild-type elderly patient undergoing first-line chemotherapy with FOLFOX + panitumumab, reporting response of disease on all metastatic sites except for a node. This node, surgically removed, revealed host BRAF V600 mutant clones. After surgery, patient continued chemotherapy with a stop-and-go strategy continuing to benefit from the same drugs after 4 years since diagnosis, and continuing to achieve response when on treatment, avoiding unacceptable anti-EGFR toxicity. This patient, still alive after 6 years since the diagnosis, represents the case of a good synergy between molecular profiling of disease, surgery, and intermittent treatment.

Abstract Background Arterial Tortuosity Syndrome (ATS) is a rare autosomal recessive disorder characterized by elongated and tortuous arteries. Although ATS showed a significant clinical and pathophysiological overlap with other syndromes involving connective tissues, only few cases of cerebrovascular events related to this syndrome have been described so far. Case presentation We report the case of a 33-years-old male diagnosed with ATS since childhood, that experienced three sudden episodes of expressive aphasia and right hemiparesis with spontaneous resolution. He was treated with recombinant tissue plasminogen activator (r-TPA) at a dosage of 0.9 mg/kg with a complete recovery. Brain Magnetic Resonance Imaging (MRI) showed the absence of acute ischemic lesions and the patient was diagnosed with recurrent transient ischemic attacks (TIA). Intracranial and supra-aortic trunks Magnetic Resonance Angiography (MRA) and Angio-CT scan of the thoracic and abdominal aorta showed marked vessel tortuosity without stenosis. To our knowledge, this is the first reported case of an ATS patient with TIA in young age that was treated with intravenous thrombolysis with recombinant plasminogen activator. Conclusion Our report strengthens the relationship between ATS and juvenile cerebrovascular events, suggesting that an extensive study of body vessels in order to detect potential stenoses or occlusions in these cases is needed. The greater predisposition to cerebrovascular events in ATS could benefit from a more aggressive primary and secondary prevention therapy.

PurposeIn metastatic colorectal cancer (mCRC) patients (pts), treatment strategies integrating liver resection with induction chemotherapy offer better 5-year survival rates than chemotherapy alone. However, liver resection is a complex and costly procedure, and recurrence occurs in almost 2/3rds of pts, suggesting the need to identify those at higher risk. The aim of this work was to evaluate whether the integration of plasma metabolomics and lipidomics combined with the multiplex analysis of a large panel of plasma cytokines can be used to predict the risk of relapse and other patient outcomes after liver surgery, beyond or in combination with clinical morphovolumetric criteria.Experimental designPeripheral blood metabolomics and lipidomics were performed by 600 MHz NMR spectroscopy on plasma from 30 unresectable mCRC pts treated with bevacizumab plus oxaliplatin-based regimens within the Obelics trial (NCT01718873) and subdivided into responder (R) and non-R (NR) according to 1-year disease-free survival (DFS): ≥ 1-year (R, n = 12) and < 1-year (NR, n = 18). A large panel of cytokines, chemokines, and growth factors was evaluated on the same plasma using Luminex xMAP-based multiplex bead-based immunoassay technology. A multiple biomarkers model was built using a support vector machine (SVM) classifier.ResultsSparse partial least squares discriminant analysis (sPLS-DA) and loading plots obtained by analyzing metabolomics profiles of samples collected at the time of response evaluation when resectability was established showed significantly different levels of metabolites between the two groups. Two metabolites, 3-hydroxybutyrate and histidine, significantly predicted DFS and overall survival. Lipidomics analysis confirmed clear differences between the R and NR pts, indicating a statistically significant increase in lipids (cholesterol, triglycerides and phospholipids) in NR pts, reflecting a nonspecific inflammatory response. Indeed, a significant increase in proinflammatory cytokines was demonstrated in NR pts plasma. Finally, a multiple biomarkers model based on the combination of presurgery plasma levels of 3-hydroxybutyrate, cholesterol, phospholipids, triglycerides and IL-6 was able to correctly classify patients by their DFS with good accuracy.ConclusionOverall, this exploratory study suggests the potential of these combined biomarker approaches to predict outcomes in mCRC patients who are candidates for liver metastasis resection after induction treatment for defining personalized management and treatment strategies.

We previously described three patients affected by metastatic colorectal cancer (mCRC) who experienced spontaneous tumour shrinkage during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thereafter, the patients were closely monitored and no systemic treatments were applied. Here, we report follow-up clinical information about these patients as well as genetic characterization of their primary tumours through the TruSigt™Oncology 500 Next Generation Sequencing test targeting 523 cancer-relevant genes. An Illumina NovaSeq 6000 platform was used to perform sequencing. Time-to-progression was 23 and 2 months, respectively, in Patients 2 and 3 while it was not reached in Patient 1. Patients 1 and 2 had the greatest anti-SARS-CoV-2 IgG titres. Assessment of genetic landscapes evidenced common mutation in BARD1 gene (p.Val507Met) in Patients 1 and 2. Although our report is descriptive in its nature, we suggest that complex and unexplored interactions between genetic background and components of the immune response to SARS-CoV-2 infection could be responsible of unexpected rare mCRC shrinkage.

Francesco Gossetti,1 Nikolaus Zuegel,2 Pasquale Giordano,3 Rupert Pullan,4 Jochen Schuld,5 Paolo Delrio,6 Marco Montorsi,7 Olivier van Kerschaver,8 Jean Lemaitre,9 Ben Griffiths,10 Linda D’Amore1 1Department of Abdominal Wall Surgery, University Hospital (C/O Instituto Clinica Chirugica II), Rome, Italy; 2Visceral Surgery, Centre Hospitalier Emile Mayrisch, Esch-sur-Alzette, Luxembourg; 3Department of Colorectal Surgery, Whipps Cross University Hospital, Leytonstone, UK; 4Colorectal Surgery, Torbay Hospital, Torquay, UK; 5Clinic for General and Visceral Surgery, Universitätsklinikum des Saarlandes, Homburg, Germany; 6Department of Abdominal Oncology, Istituto Nazionale Tumori, Napoli, Italy; 7General Surgery, Humanitas University and IRCCS Humanitas Research Hospital, Milano, Italy; 8General Surgery, Algemeen Ziekenhuis Sint LUCAS, Gent, Belgium; 9Thoracic Surgery, CHU Ambroise Pare, Mons, Belgium; 10Colorectal Surgery, Royal Victoria Infirmary, Newcastle Upon Tyne, UKCorrespondence: Francesco GossettiDepartment of Abdominal Wall Surgery, University Hospital (C/O Instituto Clinica Chirurgica II), Policlinico Umberto I, Rome, 00162, ItalyEmail gossetti@tiscali.itPurpose: Despite the advancements in the reinforcement and closure techniques available, complex abdominal wall reconstruction (CAWR) remains a challenging surgical undertaking with considerable risk of postoperative complications. Biological meshes were developed that may help to complement standard closure techniques and offer an alternative to synthetic meshes, which carry significant risks with their use in complex cases.Patients and Methods: A total of 114 patients underwent surgical treatment for CAWR with a Permacol™ (a biologic surgical implant). The study objective was to evaluate the short-term (6 months), mid-term (12– 24 months), and long-term (36 months) clinical outcomes (through 36 months) associated with the use of a biologic surgical implant in these cases.Results: The cumulative hernia recurrence rate was 18.7% (17/91) at 24 months and 22.4% (19/85) at 36 months. Twelve (14.1%) subjects required reoperation for hernia repair within 36 months for repair of recurrent hernias. Between 6- and 36-months post-surgery, patients reported improvement in their Carolina comfort scale (CSS) measures of severity of pain, sensation of mesh, and movement limitations.Conclusion: A biologic surgical implant can provide long-term benefit to complex abdominal wall repairs in patients staged grade III according to the Ventral Hernia Working Group (VHWG).Keywords: Permacol, biologic surgical implant, complex abdominal wall repair