Advanced lung cancer inflammation index and its prognostic value in HPV-negative head and neck squamous cell carcinoma: a multicentre study

Purpose: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. Methods: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). Results: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51–6.90 for PFS and HR 3.41, CI 1.47–7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31–4.51 for PFS and HR = 2.40, 95% CI: 1.19–4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23–5.10 for PFS and HR = 2.60, 95% CI: 1.19–5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01–13.73) and death (HR = 5.68, 95% CI: 1.92–16.79) than low ALI and low PNI considered alone. Conclusions: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC

Cogeneration: An option to facilitate load following in Small Modular Reactors

Nuclear Power Plants (NPPs) have been historically deployed to cover the base-load of the electricity demand. Nowadays some NPPs might perform daily load cycling operation (i.e. load following) between 50% and 100% of their rated power. With respect to the insertion of control rods or comparable action to reduce the nuclear power generation, a more efficient alternative might be the “Load Following by Cogeneration”, i.e. diverting the excess of power, respect to the electricity demand, to an auxiliary system. A suitable cogeneration system needs: 1. To have a demand of electricity and/or heat in the region of 500 MWe–1.5 GWt; 2. To meet a significant market demand; 3. To have access to adequate input to process; 4. To be flexible: cogeneration might operate at full load during the night when the request of electricity is low, and be turned off during the daytime. From the economic standpoint, it is essential that the investment in the auxiliary system is profitable. This paper provides a techno-economic assessment of systems potentially suitable for coupling with a NPP for load following. The results show that district heating, desalination and hydrogen might be technically and economically feasible

Investigating heart-specific toxicity of amyloidogenic immunoglobulin light chains: A lesson from C. elegans

Abnormalities in protein folding are involved in many localized and systemic diseases, all of which are characterized by insoluble amyloid formation and deposition. In immunoglobulin light chain (LC) amyloidosis, the most frequent systemic form of amyloidosis, the amyloid involvement of the heart dictates the prognosis and the elucidation of the mechanism of heart targeting and toxicity is essential for designing and testing new effective treatments. To this end, the availability of an appropriate animal model is crucial. We recently described the use of C. elegans as an innovative experimental system to investigate in vivo the pathogenic effects of monoclonal LC. This idea stems from the knowledge that the worm's pharynx is an "ancestral heart" with the additional ability to recognize stressor compounds. The feeding of worms with LC purified from patients suffering from cardiomyopathy, selectively and permanently impaired the pharyngeal function. This irreversible damage resulted in time, in a significant reduction in the lifespan of worms. We also reported that the ability of LC to generate reactive oxygen species was associated with their toxic effects and was counteracted by anti-oxidant compounds. This new nematode-based assay represents a promising model for elucidating the heart-specific toxicity of LC and for a rapid screening of new therapeutic strategies

Advanced lung cancer inflammation index and its prognostic value in HPV-negative head and neck squamous cell carcinoma: a multicentre study.

Funder: Università degli Studi di TriestePURPOSE: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. METHODS: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). RESULTS: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI  2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone. CONCLUSIONS: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC

Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis

none25Amyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem motor neuron disease for which currently there is no effective treatment. There is an urgent need to identify biomarkers to tackle the disease's complexity and help in early diagnosis, prognosis, and therapy. Extracellular vesicles (EVs) are nanostructures released by any cell type into body fluids. Their biophysical and biochemical characteristics vary with the parent cell's physiological and pathological state and make them an attractive source of multidimensional data for patient classification and stratification.nonePasetto, Laura; Callegaro, Stefano; Corbelli, Alessandro; Fiordaliso, Fabio; Ferrara, Deborah; Brunelli, Laura; Sestito, Giovanna; Pastorelli, Roberta; Bianchi, Elisa; Cretich, Marina; Chiari, Marcella; Potrich, Cristina; Moglia, Cristina; Corbo, Massimo; Sorarù, Gianni; Lunetta, Christian; Calvo, Andrea; Chiò, Adriano; Mora, Gabriele; Pennuto, Maria; Quattrone, Alessandro; Rinaldi, Francesco; D'Agostino, Vito Giuseppe; Basso, Manuela; Bonetto, ValentinaPasetto, Laura; Callegaro, Stefano; Corbelli, Alessandro; Fiordaliso, Fabio; Ferrara, Deborah; Brunelli, Laura; Sestito, Giovanna; Pastorelli, Roberta; Bianchi, Elisa; Cretich, Marina; Chiari, Marcella; Potrich, Cristina; Moglia, Cristina; Corbo, Massimo; Sorarù, Gianni; Lunetta, Christian; Calvo, Andrea; Chiò, Adriano; Mora, Gabriele; Pennuto, Maria; Quattrone, Alessandro; Rinaldi, Francesco; D'Agostino, Vito Giuseppe; Basso, Manuela; Bonetto, Valentin

The risk of recurrence in surgically treated head and neck squamous cell carcinomas: a conditional probability approach

Background Over 50% of patients with head-and-neck squamous cell carcinoma (HNSCC) experience locoregional recurrence, which is associated with poor outcome. In the course of follow-up for patients surviving primary surgery for HNSCC, one might ask: What is the probability of recurrence in one year considering that the cancer has not yet recurred to date? Materials and methods To answer this question, 979 patients surgically treated for HNSCC (i.e. cancer of the oral cavity, oropharynx, hypopharynx or larynx) between March 2004 and June 2018 were enrolled in a multicenter retrospective cohort study, followed up for death and recurrence over a 5 year period. The conditional probability of recurrence in 12 months - i.e. the probability of recurrence in the next 12 months given that, to date, the patient has not recurred - was derived from the cumulative incidence function (Aalen-Johansen method). Results Overall, the probability of recurrence was the highest during the first (17.3%) and the second years (9.6%) after surgery, declining thereafter to less than 5.0% a year thereafter. The probability of recurrence was significantly higher for stage III-IV HNSCCs than for stage I-II HNSCCs in the first year after surgery (20.4% versus 10.0%; p < 0.01), but not thereafter. This difference was most pronounced for oral cavity cancers. No significant differences were observed across different tumor sites. Conclusion This dynamic evaluation of recurrence risk in patients surgically treated for HNSCC provides helpful and clinically meaningful information, which can be useful to patients in planning their future life, and to clinicians in tailoring post-treatment surveillance according to a more personalized risk stratification