Simondon reconsidered : An interview with Nathalie Simondon

Nel presente contributo proponiamo un’intervista a Nathalie Simondon, responsabile dell’edizione dell’opera di Gilbert Simondon, al fine di fare luce sui temi di ecologia, enciclopedismo, transdisciplinarità e umanismo nella produzione filosofica di Gilbert Simondon.In this paper we propose an interview with Nathalie Simondon, responsible for the edition of Gilbert Simondon’s work, in order to shed a light on the topics of ecology, encyclopedism, transdisciplinarity and humanism in Gilbert Simondon’s philosophical production

Prognostic value of H-index in patients surgically treated for squamous cell carcinoma of the larynx.

OBJECTIVE: Recently, a novel host-related index, the Host-index (H-index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host-related indexes This study aimed to investigate the prognostic performance of the H-index using pretreatment blood tests in patients receiving up-front surgery for SCC of the larynx. METHODS: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H-index. Their association with disease-free survival (DFS) and overall survival (OS) was measured. RESULTS: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37-96] years; 191 [82.7%] men). The median follow-up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04-1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07-2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21-3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24-4.40) and OS (aHR for death = 2.67; 95% CI: 1.51-4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H-index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65-4.79) and death (2.22; 95% CI: 1.26-3.89). CONCLUSION: In conclusion, the present study confirms the prognostic value of pretreatment H-index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. LEVEL OF EVIDENCE: III

Sequelae in adults at 12 months after mild-to-moderate coronavirus disease 2019 (COVID-19).

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can cause a wide array of symptoms ranging from mild to severe or fatal forms of coronavirus disease 2019 (COVID-19). Furthermore, it has been observed that in a proportion of patients a variable range of symptoms may persist for a long time. An increasing number of studies have been focused on long COVID, but they have mainly been concentrated on previously hospitalized severe COVID-19 patients reporting symptoms up to 6-months after illness. The main aim of this study was to evaluate the prevalence of COVID-related symptoms 12-months after the onset of mild-to-moderate disease

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Oral ondansetron versus domperidone for acute gastroenteritis in pediatric emergency departments: Multicenter double blind randomized controlled trial

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Diritto, economia e giustizia. Da Pindaro a Amartya Sen

Spostandosi dal campo dell’economia a quello della filosofia etica e del diritto, Amartya Sen ha recentemente pubblicato una trattazione di ampio respiro, pur se non del tutto sistematica, sulla presenza o l’assenza della giustizia nel mondo (The Idea of Justice, 2009, ora anche in italiano). Negli ultimi decenni era risultata dominante la costruzione di John Rawls, che Sen respinge come "trascendentale", perseguendo invece l’obiettivo - non tanto pragmatico quanto ideologico (in netta contrapposizione anche ai liberisti Dworkin e Nozick) - di una giustizia da realizzare caso per caso con la rimozione di ogni singola ingiustizia sociale dovuta essenzialmente alle discriminazioni ed agli squilibri tra società avanzate e paesi emarginati, troppo stridenti nel quadro della globalizzazione. Ne risulta complessivamente quella che si potrebbe definire non tanto un’idea di giustizia quanto una "teoria dell’ingiustizia". Il presente articolo rappresenta un’ampia integrazione di alcuni passaggi ripresi dal volume Diritto, economia e forse giustizia (2010).

COVID-19-Related Quantitative and Qualitative Olfactory and Gustatory Dysfunction: Long-Term Prevalence and Recovery Rate

Introduction: No studies have reported data on 2-year prevalence and recovery rates of self-reported COVID-19-related quantitative and qualitative olfactory and gustatory dysfunction. The aim of the present study was to estimate the 2-year prevalence and recovery rate of self-reported COVID-19-related olfactory and gustatory dysfunction in a cohort of patients with antecedent mild-to-moderate disease. Methods: This is a prospective observational study, measuring the prevalence of altered sense of smell or taste at follow-up and their variation from baseline, on adult patients consecutively assessed at Trieste University Hospital, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction during March 2020. Results: Overall, 174 (68.8%), 53 (20.9%), and 36 (14.2%) of 253 responders reported an altered sense of smell or taste (SNOT-22 >0) at baseline, 12 months, and 24 months, respectively. Among the 174 patients who have complained a COVID-19-associated olfactory or gustatory dysfunction at baseline, 138 (79.3%) reported complete resolution of smell or taste impairment with 17 subjects (9.8%) recovering after more than 1 year after the initial infection, 33 (19.0%) reported a decrease in the severity, and only 3 (1.7%) reported that the symptom was unchanged at the 24-month interview. Twenty subjects (7.9%) complained of at least one qualitative long-term symptom. Conclusion: Two years after the infection, most patients experience a favourable evolution of COVID-19-related olfactory or gustatory dysfunction. A late recovery was observed in 10% of subjects

Spatial rotational orientation ability in standing children with cerebral palsy

This study quantified perception and reorientation ability after passive horizontal rotations in thirteen children with cerebral palsy (CP). They stood barefoot on a platform in front of a fixed reference point (static posture task, SPT) and were then blindfolded and passively rotated with six velocity profiles (maximum angular velocity: 57 degrees/s; rotation amplitudes: +/- 90 degrees, +/- 180 degrees and +/- 360 degrees). After the perturbation, the blindfolded children were asked to point to the fixed reference point with their preferred hand (pointing task, PT) and to step back to the initial position on the stationary platform (reorientation task, RT). In order to gain further insight into rotational attitude, the results were comparatively examined with body segment rotations determined using standardized gait analysis (gait task, GT). The kinematic evaluations were conducted using an optoelectronic system: for SPT, PT and RT we confined the analysis, in the horizontal plane, to the head and upper pointing arm of the subject and to the platform; for GT a full body analysis was performed. When CP children were passively rotated towards their more affected side, they overestimated the imposed angle in PT but under-reproduced it in RT. A higher variability emerged in left-hemiplegic children, confirming that the spatial disorganization is predominantly related to right brain lesion. Patients tended to rotate in GT towards the more affected side while in RT they showed an opposite trend. (C) 2012 Elsevier B.V. All rights reserved

Prevalence and prognostic impact of retropharyngeal lymph nodes metastases in oropharyngeal squamous cell carcinoma: Meta-analysis of published literature.

BACKGROUND: This systematic review and meta-analysis aims to estimate the prevalence and prognostic impact of retropharyngeal lymph node metastases (RLNMs) in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: This meta-analysis was conducted according to PRISMA guidelines. INCLUSION CRITERIA: studies with more than 20 patients reporting the prevalence or prognostic impact of RLNMs in OPSCC. Whenever available, data on HPV status and subsites were extracted. RESULTS: Twenty-two articles were included. The overall prevalence of RLNMs in OPSCC was 13%, with no significant differences depending on HPV status. The highest prevalence was observed for posterior pharyngeal wall SCC (24%), followed by soft palate (17%), palatine tonsil (15%), and base of tongue (8%). RLNMs were associated with a significantly higher risk of death (HR:2.54;IC95%1.89-3.41) and progression (HR:2.44;IC95%1.80-3.30). CONCLUSIONS: The prevalence of RLNMs in OPSCC was 13%, being higher in tumors of the posterior pharyngeal wall. RLNMs were associated with unfavorable outcomes