37 research outputs found
Un raro caso di flogosi granulomatosa non necrotizzante in paziente sieropositivo
Si presenta il caso di un paziente di 54 anni HIV-positivo in terapia antiretrovirale dal 1996, giunto alla nostra osservazione nel 2011 per la comparsa di maculo-papule eritematose degli arti superiori. Il paziente ha contratto negli ultimi 20 anni diverse infezioni opportunistiche, epatite A, B, D e C ed ha sviluppato un’invalidante polineuropatia sensitivo-motoria di tipo assonale. L’esame istologico delle lesioni cutanee ha evidenziato una flogosi granulomatosa non necrotizzante di tipo interstiziale. Dopo un inefficace trattamento con steroidi topici si è osservata una trasformazione del quadro clinico con marcata estensione delle lesioni maculo-papulari a tutto l’ambito cutaneo con risparmio del volto e con comparsa di noduli deturpanti dei gomiti. Nel sospetto di una grave patologia sistemica con interessamento cutaneo, sono stati eseguiti accertamenti strumentali, valutazioni multidisciplinari ed una biopsia di una delle lesioni nodulari che ha portato a diagnosticare un raro quadro di flogosi granulomatosa non necrotizzante del derma superficiale e profondo con aspetti peculiari. È stato quindi iniziato trattamento con idrossiclorochina e successivamente con metotrexato, quest’ultimo sospeso dopo 1 mese per la comparsa di importanti effetti collaterali, da cui il paziente non ha tratto alcun beneficio. Attualmente è in corso di valutazione terapia con farmaco biologico anti-TNF alfa
Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign
Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come
Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy
BackgroundConsolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented.MethodsA total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy.ResultsPreclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027).ConclusionMulti-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation
Event reconstruction for KM3NeT/ORCA using convolutional neural networks
The KM3NeT research infrastructure is currently under construction at two
locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino
detector off the French coast will instrument several megatons of seawater with
photosensors. Its main objective is the determination of the neutrino mass
ordering. This work aims at demonstrating the general applicability of deep
convolutional neural networks to neutrino telescopes, using simulated datasets
for the KM3NeT/ORCA detector as an example. To this end, the networks are
employed to achieve reconstruction and classification tasks that constitute an
alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT
Letter of Intent. They are used to infer event reconstruction estimates for the
energy, the direction, and the interaction point of incident neutrinos. The
spatial distribution of Cherenkov light generated by charged particles induced
in neutrino interactions is classified as shower- or track-like, and the main
background processes associated with the detection of atmospheric neutrinos are
recognized. Performance comparisons to machine-learning classification and
maximum-likelihood reconstruction algorithms previously developed for
KM3NeT/ORCA are provided. It is shown that this application of deep
convolutional neural networks to simulated datasets for a large-volume neutrino
telescope yields competitive reconstruction results and performance
improvements with respect to classical approaches
Event reconstruction for KM3NeT/ORCA using convolutional neural networks
The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino de tector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower-or track-like, and the main background processes associated with the detection of atmospheric neutrinos are
recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance
improvements with respect to classical approaches
Propofol and α2-Agonists Attenuate Microglia Activation and Restore Mitochondrial Function in an In Vitro Model of Microglia Hypoxia/Reoxygenation
Cerebrovascular ischemia is a common clinical disease encompassing a series of complex pathophysiological processes in which oxidative stress plays a major role. The present study aimed to evaluate the effects of Dexmedetomidine, Clonidine, and Propofol in a model of hypoxia/reoxygenation injury. Microglial cells were exposed to 1%hypoxia for 3 h and reoxygenated for 3 h, and oxidative stress was measured by ROS formation and the expression of inflammatory process genes. Mitochondrial dysfunction was assessed by membrane potential maintenance and the levels of various metabolites involved in energetic metabolism. The results showed that Propofol and α2-agonists attenuate the formation of ROS during hypoxia and after reoxygenation. Furthermore, the α2-agonists treatment restored membrane potential to values comparable to the normoxic control and were both more effective than Propofol. At the same time, Propofol, but not α2-agonists, reduces proliferation (Untreated Hypoxia = 1.16 ± 0.2, Untreated 3 h Reoxygenation = 1.28 ± 0.01 vs. Propofol hypoxia = 1.01 ± 0.01 vs. Propofol 3 h Reoxygenation = 1.12 ± 0.03) and microglial migration. Interestingly, all of the treatments reduced inflammatory gene and protein expressions and restored energy metabolism following hypoxia/reoxygenation (ATP content in hypoxia/reoxygenation 3 h: Untreated = 3.11 ± 0.8 vs. Propofol = 7.03 ± 0.4 vs. Dexmedetomidine = 5.44 ± 0.8 vs. Clonidine = 7.70 ± 0.1), showing that the drugs resulted in a different neuroprotective profile. In conclusion, our results may provide clinically relevant insights for neuroprotective strategies in intensive care units
(+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload
Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an in vitro model. Methods: HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles. Results: Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways. Conclusion: In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD
Autoalgometry: An Important Tool for Pressure Pain Threshold Evaluation
The term "pain threshold" refers to the measurement of the intensity of a physical stimulus that evokes pain. To estimate the pain threshold, a mechanical or electrical stimulus with increasing intensity is usually applied until the subject under evaluation refers to a pain sensation. This study aims to evaluate the autoalgometric pain threshold as a perfect technique to determine the effects of stimulation rate in relation to both gender and the site of stimulation. In this experimental model, pressure algometry was applied: the subject under evaluation pushed a finger against a small round metal tip, producing and at the same time controlling the intensity of the noxious stimulus. Through autoalgometry, the stimulus intensity was recorded over time, measuring the force change rate applied and studying the subject's behavior on approaching pain. This test was performed with 50 healthy volunteers on two days, applying a fast or slow rate of stimulation. The results described demonstrate that there is a positive correlation between the pressure increase rate and the pressure threshold evaluation. In light of these findings, autoalgometry can be proposed as an objective measure of pressure pain threshold for clinical and research use
Risk of surgical site infections following hip and knee arthroplasty. Results of the ischia-gisio study
Introduzione. L'infezione del sito chirurgico (SSI) è una delle principali complicanze a seguito dell'inserimento della protesi dell'anca o del ginocchio. Lo scopo del presente studio era di descrivere i tassi di SSI e i fattori di rischio associati durante le procedure di protesi dell'anca e del ginocchio negli ospedali italiani.
Metodi. Gli ospedali italiani sono stati invitati a unirsi al progetto ISChIA (Infezioni del sito chirurgico in chirurgia di artroplastica) e hanno partecipato allo studio su base volontaria. La sorveglianza SSI è stata eseguita in base al protocollo SSI di collegamento ospedaliero per il controllo delle infezioni attraverso la sorveglianza (HELICS). La popolazione dello studio era composta da tutti i pazienti che avevano avuto una protesi protesica del ginocchio o dell'anca tra marzo 2010 e febbraio 2011. Sono state incluse solo operazioni elettive.
Risultati. Sono stati inclusi un totale di 14 ospedali e 1285 procedure chirurgiche. L'incidenza cumulativa di SSI è stata di 1,3 per 100 anca e 2,4 per 100 interventi chirurgici al ginocchio; una tendenza positiva significativa delle incidenze SSI è stata osservata con l'aumento dell'indice di rischio SSI. Nell'analisi multivariata, considerando le procedure dell'anca, il singolo fattore di rischio indipendente associato alla SSI era la lunghezza dell'operazione (RR: 4,54; IC al 95%: 1,06-19,48). Per le procedure al ginocchio, non è stato identificato alcun fattore di rischio significativo.
Conclusioni. Nel presente studio, l'incidenza cumulativa SSI era nell'intervallo di dati europei. Tuttavia, è necessario un numero maggiore di operazioni per stimare meglio le tariffe SSI. È già stata condotta una seconda edizione del progetto ISChIA e i risultati dei due sondaggi forniranno nuove conoscenze per approfondire le nostre conoscenze per il controllo delle infezioni.Background. Surgical Site Infection (SSI) is one of the major complications following insertion of hip or knee prosthesis. The aim of the present study was to describe rates of SSIs and associated risk factors during hip and knee prosthesis procedures in Italian hospitals.
Methods. Italian hospitals were invited to join the ISChIA (Surgical Site Infections in Arthroplasty Surgery) project and participated in the study on a voluntary basis. SSI surveillance was performed according to the Hospitals in Europe Link for Infection Control through Surveillance (HELICS)-SSI protocol. The study population consisted of all patients who had a prosthetic knee or hip joint replacement between March 2010 and February 2011. Only elective operations were included.
Results. A total of 14 hospitals and 1285 surgical procedures were included. SSI cumulative incidence was 1.3 per 100 hip and 2.4 per 100 knee surgical procedures; a significant positive trend of SSI incidences was observed with increasing SSI risk index. In multivariate analysis, considering hip procedures, the single independent risk factor associated to SSI was operation length (RR: 4.54; 95%CI: 1.06-19.48). For knee procedures, no significant risk factor was identified.
Conclusions. In the present study, SSI cumulative incidence was in the range of European data. However, a larger number of operations is needed to better estimate SSI rates. A second edition of the ISChIA project has been already conducted and results of the two surveys will provide new insight to further our knowledge for infection control
Risk of surgical site infections following hip and knee arthroplasty. Results of the ischia-gisio study
Introduzione. L'infezione del sito chirurgico (SSI) è una delle principali complicanze a seguito dell'inserimento della protesi dell'anca o del ginocchio. Lo scopo del presente studio era di descrivere i tassi di SSI e i fattori di rischio associati durante le procedure di protesi dell'anca e del ginocchio negli ospedali italiani.
Metodi. Gli ospedali italiani sono stati invitati a unirsi al progetto ISChIA (Infezioni del sito chirurgico in chirurgia di artroplastica) e hanno partecipato allo studio su base volontaria. La sorveglianza SSI è stata eseguita in base al protocollo SSI di collegamento ospedaliero per il controllo delle infezioni attraverso la sorveglianza (HELICS). La popolazione dello studio era composta da tutti i pazienti che avevano avuto una protesi protesica del ginocchio o dell'anca tra marzo 2010 e febbraio 2011. Sono state incluse solo operazioni elettive.
Risultati. Sono stati inclusi un totale di 14 ospedali e 1285 procedure chirurgiche. L'incidenza cumulativa di SSI è stata di 1,3 per 100 anca e 2,4 per 100 interventi chirurgici al ginocchio; una tendenza positiva significativa delle incidenze SSI è stata osservata con l'aumento dell'indice di rischio SSI. Nell'analisi multivariata, considerando le procedure dell'anca, il singolo fattore di rischio indipendente associato alla SSI era la lunghezza dell'operazione (RR: 4,54; IC al 95%: 1,06-19,48). Per le procedure al ginocchio, non è stato identificato alcun fattore di rischio significativo.
Conclusioni. Nel presente studio, l'incidenza cumulativa SSI era nell'intervallo di dati europei. Tuttavia, è necessario un numero maggiore di operazioni per stimare meglio le tariffe SSI. È già stata condotta una seconda edizione del progetto ISChIA e i risultati dei due sondaggi forniranno nuove conoscenze per approfondire le nostre conoscenze per il controllo delle infezioni.Background. Surgical Site Infection (SSI) is one of the major complications following insertion of hip or knee prosthesis. The aim of the present study was to describe rates of SSIs and associated risk factors during hip and knee prosthesis procedures in Italian hospitals.
Methods. Italian hospitals were invited to join the ISChIA (Surgical Site Infections in Arthroplasty Surgery) project and participated in the study on a voluntary basis. SSI surveillance was performed according to the Hospitals in Europe Link for Infection Control through Surveillance (HELICS)-SSI protocol. The study population consisted of all patients who had a prosthetic knee or hip joint replacement between March 2010 and February 2011. Only elective operations were included.
Results. A total of 14 hospitals and 1285 surgical procedures were included. SSI cumulative incidence was 1.3 per 100 hip and 2.4 per 100 knee surgical procedures; a significant positive trend of SSI incidences was observed with increasing SSI risk index. In multivariate analysis, considering hip procedures, the single independent risk factor associated to SSI was operation length (RR: 4.54; 95%CI: 1.06-19.48). For knee procedures, no significant risk factor was identified.
Conclusions. In the present study, SSI cumulative incidence was in the range of European data. However, a larger number of operations is needed to better estimate SSI rates. A second edition of the ISChIA project has been already conducted and results of the two surveys will provide new insight to further our knowledge for infection control