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Background Sarcopenia is a condition characterized by decreased skeletal muscle mass due to physiological ageing or to a concomitant disease such as neoplasia. In cancer patients, a low lean body mass is suggested to be a negative prognostic factor for survival and for the development of dose-limiting chemotherapy toxicities irrespective of disease stage. Aim To evaluate the prognostic role of sarcopenia in patients with metastatic colorectal cancer (mCRC) undergoing first-line chemotherapy. Methods Our retrospective analysis included 56 mCRC patients who received first-line chemotherapy from 2014 to 2017 at the Medical Oncology Unit of our hospital. Computerized scans were performed before starting chemotherapy and at the first disease reassessment. Sarcopenia was assessed using the skeletal mass index = muscle area in cm2/(height in m2) calculated at the L3 vertebra. Overall survival and objective response rate were evaluated. Toxicities were analyzed during the first four cycles of therapy and graded according to Common Terminology Criteria for Adverse Events version 4.0. A loss of skeletal muscle mass ≥ 5% was considered indicative of deterioration in muscle condition. Results Median age was 67 years and 35.7% of patients were ≥ 70 years old. Fourteen patients (25%) were sarcopenic at baseline computed tomography (CT) scan (7/33 men; 7/23 women); 5/14 sarcopenic patients were ≥ 70 years old. Median follow-up was 26.8 mo (3.8-66.8 mo) and median overall survival was 27.2 mo (95%CI: 23.3-37.3). Sarcopenia was not correlated to overall survival (P = 0.362), to higher toxicities reported during the first 4 cycles of chemotherapy (P = 1.0) or to response to treatment (P = 0.221). At the first disease reassessment, a skeletal muscle loss (SML) ≥ 5% was found in 17 patients (30.3%) 3 of whom were already sarcopenic at baseline CT scan, while 7 patients became sarcopenic. SML was not correlated to overall survival (P = 0.961). No statistically significant correlation was found between baseline sarcopenia and age (P = 1.0), body mass index (P = 0.728), stage at diagnosis (P = 0.355) or neutrophil/lymphocyte ratio (P = 0.751). Conclusion Neither baseline sarcopenia nor SML affected survival. In addition, baseline sarcopenia was not related to worse treatment toxicity. However, these results must be interpreted with caution due to the limited sample size.

Background Immunosuppression induced by anticancer therapy in a COVID-19-positive asymptomatic patient with cancer may have a devastating effect and, eventually, be lethal. To identify asymptomatic cases among patients receiving active cancer treatment, the Federico II University Hospital in Naples performs rapid serological tests in addition to hospital standard clinical triage for COVID-19 infection. Methods From 6 to 17 April 2020, all candidates for chemotherapy, radiotherapy or target/immunotherapy, if negative at the standard clinical triage on the day scheduled for anticancer treatment, received a rapid serological test on peripheral blood for COVID-19 IgM and IgG detection. In case of COVID-19 IgM and/or IgG positivity, patients underwent a real-time PCR (RT-PCR) SARS-CoV-2 test to confirm infection, and active cancer treatment was delayed. Results Overall 466 patients, negative for COVID-19 symptoms, underwent serological testing in addition to standard clinical triage. The average age was 61 years (range 25–88 years). Most patients (190, 40.8%) had breast cancer, and chemotherapy with or without immunotherapy was administered in 323 (69.3%) patients. Overall 433 (92.9%) patients were IgG-negative and IgM-negative, and 33 (7.1%) were IgM-positive and/or IgG-positive. Among the latter patients, 18 (3.9%), 11 (2.4%) and 4 (0.9%) were IgM-negative/IgG-positive, IgM-positive/IgG-negative and IgM-positive/IgG-positive, respectively. All 33 patients with a positive serological test, tested negative for RT-PCR SARS-CoV-2 test. No patient in our cohort developed symptoms suggestive of active COVID-19 infection. Conclusion Rapid serological testing at hospital admission failed to detect active asymptomatic COVID-19 infection. Moreover, it entailed additional economic and human resources, delayed therapy administrationand increased hospital accesses.

The proportion of patients with metastatic colorectal cancer (mCRC) receiving second or further lines of treatment has not been widely studied. To shed light on this issue, we retrospectively analysed the treatments administered for metastatic disease, and investigated prognostic factors after a diagnosis of metastases, in a consecutive cohort of mCRC patients. Three hundred forty-six mCRC patients were enrolled: 173 were stage II or III (metachronous group), and 173 stage IV (synchronous group) at diagnosis. Survival was calculated between the date of metastatic disease and the date of death or last follow-up. Patients with synchronous lesions more frequently had multiple disease sites, peritoneal carcinomatosis and massive liver deposits, whereas significantly more patients with metachronous lesions developed lung metastases as the sole disease site. 97.4% patients received at least one, 62.4% two, 41.9% three and 23.7% four treatment lines. Patients with metachronous metastases more frequently underwent surgery of metastases in first-line treatment (48.5 versus 24.8%), and more of them were progression-free at the time of the analysis (44 versus 34.9%). At univariate analysis, age > 70 years, multiple disease sites and peritoneal carcinomatosis were associated with significantly decreased survival, whereas surgery of metastases and isolated lung metastases predicted better survival. At multivariate analysis, only peritoneal carcinomatosis and surgery of metastases independently affected survival. The percentage of patients who received an active treatment decreased going from first- to fourth-line treatment. However, the proportion of patients who received efficacious treatment in advanced line remained high. Surgery of metastases was the most important prognostic factors.

A mathematical model and simulation of airborne particle collisions with a 38 m, 1.5 MW horizontal axis wind turbine blade are presented. Two types of particles were analyzed, namely insects and sand grains. Computations were performed using a two-dimensional inviscid flowfield solver coupled with a particle position code. Three locations along the blade were considered and characterized by airfoils of the DU series. The insect simulations estimated the residual debris thickness on the blade, while sand simulations computed the surface erosion rate. Results show that the impact locations along the blade depend on angle of attack, freestream velocity, airfoil shape, and particle mass. Particles were found to collide primarily at the leading edge. The volume of insect debris per unit span was maximum at r/ R = 0.75. The erosion rate due to sand was maximum on the low pressure side of the blade. An erosion rate approximately ten times higher was observed at r/ R = 0.75, as compared with the section at r/ R = 0.35. Near the leading edge, large angles of impact occurred and erosion rate had a minimum, while it reached maximum values slightly downstream where the impact angle was more skewed.

BackgroundAnalysis of K- and N-RAS mutations is mandatory before planning treatment of metastatic colorectal cancer, because only RAS wild-type (WT) patients can benefit from treatment with anti-EGFR monoclonal antibodies (cetuximab and panitumumab).Case reportHere we report the case of a 69-year-old male patient affected by metastatic sigmoid cancer. He underwent left hemicolectomy, and histology diagnosed a well-differentiated, pT4, node-positive adenocarcinoma; KRAS analysis performed with direct sequencing identified a mutation in exon 2 of the KRAS gene (GGT->GTT). After first-line chemotherapy with FOLFOX6 plus bevacizumab, the patient underwent surgical resection of residual liver metastases. Histology showed metastatic deposits from colic adenocarcinoma with extensive coagulative necrosis. Mutational analysis of the KRAS gene was also performed on liver metastases by pyrosequencing assay, and no mutation was identified. Due to the discordant results (GGT->GTT exon 2 KRAS mutation in the primary tumor, and KRAS-WT in the liver metastases), mutational analysis on liver metastasis was repeated using next-generation sequencing and enriching the sample in tumor cells by manual microdissection; the same type of mutation of the primary tumor (GGT->GTT exon 2 KRAS gene) was confirmed.ConclusionsAccurate tissue sampling and adequately sensitive assays are essential to correctly identify colorectal cancer patients who can be treated with an anti-EGFR monoclonal antibody.

Uterine leiomyoma is a benign smooth muscle tumor characterized by a high incidence in women of reproductive age. The aetiology of this tumor is still unknown but established risk factors include high levels of female hormones, family history, African ancestry, early age of menarche and obesity. Here, to identify proteomic features associated with this tumor type, we performed a liquid cromatography-mass spectrometry (LC-MS/MS) analysis of uterine myomas. The identified proteins were subjected to a gene ontology analysis to generate biological functions, molecular processes, and protein networks that were relevant to the uploaded dataset. Pathway-based analysis was an effective approach to investigate the molecular mechanisms underlying the disease and to create biological hypotheses about regulation of our proteins including the identification of upstream regulators and main protein nodes. Moreover, proteomic and in silico data were combined with immunohistochemistry and western blotting to identify a group of proteins representative of some selected pathways, with a dysregulated expression in in myoma, pseudocapsule, and normal myometrium samples. Based on these results, we confirmed the over-expression of extracellular matrix components, and estrogen and progesterone receptors in uterine myomas, and proposed biological networks, canonical pathways and functions that may be relevant to the pathophysiology of this tumor.

A time-marching code for predicting the evolving shape of wind turbine airfoils subject to erosion is discussed. The erosive damage to the blade surface was represented by sand grains colliding with the blade leading edge. The erosion rate was computed on the airfoil, and the damage depth was evaluated at each location. It was found that the locations of maximum erosion rate did not necessarily overlap with the locations of maximum eroded depth on the blade surface. In particular, the maximum damage depth was found very near the leading edge, and the results are in good agreement with photographic evidence. Three main phases were identified through the blade lifespan: an upper core breach, a lower core breach, and a leading edge core breach. A parametric study was performed in order to determine the most relevant drivers of the blade lifespan. In particular, the sand grain diameter was found to be the most significant driver, and the lifespan of the blade decreases parabolically as the grain diameter increases. Both the blade lift coefficient and the turbine hub height showed a direct relationship with blade lifespan. Large lift coefficients and large turbine hub heights are beneficial to increasing blade lifespan. It was also found that modern, large wind turbines are affected consistently less by sand erosion than small wind turbines. Such an effect is due to the increased influence of the blade flowfield toward a deviation of the incoming particles when large blade chord lengths are involved. Finally, a survey of various airfoil geometries allowed to identify the shape of the leading edge along with the airfoil aft camber as the primary drivers of blade section lifespan. The survey was performed by using the NREL S-airfoil family along with the tip-region airfoil DU 96-W-180. It was found that bulbous and round leading edges, coupled with moderately aft-cambered airfoils allowed for the longest blade lifespans, since they reduce the blade upper suction peak and offer steeper impact angles to the particles.

Rationale: Paraneoplastic limbic encephalitis (PLE) is one of the most common causes of neurologic paraneoplastic syndromes, with unclear pathogenesis. While several reports published in the last decades showed the occurrence of PLE in a variety of cancers, only a few cases have been associated with colon cancer. Patient concerns: In February 2017, a 54-year-old man with clinical history of radically resected colon cancer started first line chemotherapy with FOLFOXIRI plus bevacizumab, after radiological diagnosis of multiple liver and bone metastases. During the third cycle of treatment, the patient developed psychomotor agitation and hallucinations followed by severe consciousness level reduction and cognitive impairment. Diagnoses: Magnetic resonance imaging showed hyperintense signals in both hippocampal areas, insula and right cingulate gyrus on fluid attenuated inversion recovery, diffusion weighted imaging, and T2-weighted images, highly suggestive of limbic encephalitis. Other causes (brain metastases, toxicity of chemotherapeutic agents, and infections) were excluded. Interventions: Empirical immunosuppressive treatment (high-dose immunoglobulins and corticosteroids) was administered and chemotherapy was resumed. Outcomes: A slowly progressive improvement in neurological condition has been observed, even though radiological signs of limbic encephalitis are still evident. Lessons: The present case highlights the complex diagnostic process of PLE, and the lack of a standard treatment. Moreover, the absence of correlation between PLE and tumor progression or tumor burden, and the opportunity of treating underlying neoplasm is discussed.

An optimization of wind turbine airfoils subject to particle erosion is investigated. The erosive damage to the surface was represented by sand grains colliding with the blade leading edge. The optimization was performed by using a genetic algorithm approach (GA). A newly-written GA code was coupled with a two-dimensional inviscid flowfield solver (XFOIL) and with a particle dynamics code (BugFoil). The chosen scheme of the GA was based on random tournament selection. Each geometry was evaluated through a figure of merit that represented the airfoil fitness to damage and to aerodynamic performance when the airfoil is damaged. Multiple approaches to the optimization were taken. The initial step of this study involved optimization through geometry perturbations of the leading edge by means of Bezier curves. It was found that the leading edge shape modifications of existing airfoils increase the fitness of the airfoils subject to erosion. The second approach involved a crossover of existing airfoil geometries along with leading edge shape mutations, in order to expand the design space. The fitness of such airfoils was improved with respect to the first approach. However, for both these approaches the airfoil aerodynamic performance was disregarded, as they were intended to give insight on the optimal airfoil shapes. The final step of the study made use of an inverse airfoil design method (PROFOIL) to widen the design space even further. In this approach the aerodynamic performance of the airfoil was evaluated, and the GA became a two-objective optimization process (maximum lift-to-drag ratio, and erosive figure of merit). It was observed that bulbous upper leading edges, and slanted, flat lower leading edges allowed for best erosion performance. Moreover, it was seen that the airfoils with a positive camber required a smaller angle of attack to operate at the same lift coefficient, hence reducing the erosive damage experienced for sand grain impacts. The airfoils obtained from the inverse design GA algorithm were characterized by a lift-to-drag ratio greater than 310 for a Reynolds number of 5.84×106.