Automated Phasor Segmentation of Fluorescence Lifetime Imaging Data for Discriminating Pigments and Binders Used in Artworks

The non-invasive analysis of fluorescence from binders and pigments employed in mixtures in artworks is a major challenge in cultural heritage science due to the broad overlapping emission of different fluorescent species causing difficulties in the data interpretation. To improve the specificity of fluorescence measurements, we went beyond steady-state fluorescence measurements by resolving the fluorescence decay dynamics of the emitting species through time-resolved fluorescence imaging (TRFI). In particular, we acquired the fluorescence decay features of different pigments and binders using a portable and compact fibre-based imaging setup. Fluorescence time-resolved data were analysed using the phasor method followed by a Gaussian mixture model (GMM) to automatically identify the populations of fluorescent species within the fluorescence decay maps. Our results demonstrate that this approach allows distinguishing different binders when mixed with the same pigment as well as discriminating different pigments dispersed in a common binder. The results obtained could establish a framework for the analysis of a broader range of pigments and binders to be then extended to several other materials used in art production. The obtained results, together with the compactness and portability of the instrument, pave the way for future in situ applications of the technology on paintings

Routine extra-hepatic bile duct resection in gallbladder cancer patients without bile duct infiltration. A systematic review

The optimal treatment for advanced gallbladder cancer, in particular T2 stage cancer, is unclear. The use of "radical cholecystectomy" or more extended procedures with extra-hepatic bile duct resection are matter of debate. Due to the lack of consensus regarding the oncological significance of routine extra-hepatic bile duct (EBD) resection for gallbladder carcinoma, we decided to perform a systematic review investigating the real benefit of this procedure focusing on the primary outcomes of overall survival and disease-free survival. METHODS: A systematic literature search was performed using PubMed, EMBASE, Scopus and the Cochrane Library Central according to the PRISMA statement guidelines for conducting and reporting systematic reviews. Multiple primary and secondary outcomes were analyzed. RESULTS: The selected articles included 424 patients who underwent routine EBD resection without bile duct infiltration. Only two papers discussed the number of dissected lymph nodes during EBD resection for gallbladder carcinoma. Four of the seven included papers reported on tumor involvement in lymph nodes at rates ranging between 39% and 83%. All of the studies included in this systematic review reported on results of overall survival. In general, 5-years OS rate of the EBD-resected patients was not significantly different than that of the EBD-preservation group, while the mobility was significantly higher in the EBD resection group. CONCLUSIONS: Routine EBD resection in gallbladder cancer patients without bile duct infiltration is not associated with improved overall survival, improved lymph-node harvesting or with minor recurrence rate, but it is associated with higher morbidity rates. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved

In-Depth Analysis of Egg-Tempera Paint Layers by Multiphoton Excitation Fluorescence Microscopy

© 2020 by the authors.The non-invasive depth-resolved imaging of pictorial layers in paintings by means of linear optical techniques represents a challenge in the field of Cultural Heritage (CH). The presence of opaque and/or highly-scattering materials may obstruct the penetration of the radiation probe, thus impeding the visualization of the stratigraphy of paintings. Nonlinear Optical Microscopy (NLOM), which makes use of tightly-focused femtosecond pulsed lasers as illumination sources, is an emerging technique for the analysis of painted objects enabling micrometric three-dimensional (3D) resolution with good penetration capability in semi-transparent materials. In this work, we evaluated the potential of NLOM, specifically in the modality of Multi-Photon Excitation Fluorescence (MPEF), to probe the stratigraphy of egg-tempera mock-up paintings. A multi-analytical non-invasive approach, involving ultraviolet-visible-near infrared (UV-Vis-NIR) Fiber Optics Reflectance Spectroscopy, Vis-NIR photoluminescence, and Laser Induced Fluorescence, yielded key-information for the characterization of the constituting materials and for the interpretation of the nonlinear results. Furthermore, the use of three nonlinear optical systems allowed evaluation of the response of the analyzed paints to different excitation wavelengths and photon doses, which proved useful for the definition of the most suitable measurement conditions. The micrometric thickness of the paint layers, which was not measurable by means of Optical Coherence Tomography (OCT), was instead assessed by MPEF, thus demonstrating the effectiveness of this nonlinear modality in probing highly-scattering media, while ensuring the minimal photochemical disturbance to the examined materials.This research was funded by the European H2020 IPERION CH Project (Integrated Platform for the European Research Infrastructure ON Cultural Heritage (GA 654028, WP6); Spanish State Research Agency (AEI) and European Regional Development (FEDER) through Project CTQ2016-75880-P-AEI/FEDER, UE; and TOP Heritage-CM (S2018/NMT-4372) from the Community of Madrid and with the support of Plataforma Temática Interdisciplinar of CSIC “Patrimonio Abierto: Investigación y Sociedad” (PTI-PAIS).Peer reviewe

Drug-drug interactions (DDIs) in elderly patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib within the multicenter prospective trial ZEBRA/Meet-URO 9

Background: The oral tyrosine kinase inhibitor Cabozantinib (CABO) is frequently used to treat patients with metastatic RCC. Polypharmacy is common in elderly pts, thus several drug-drug interactions (DDIs) with cabozantinib may ensue. Methods: ZEBRA /MEET-URO 9 was a prospective, real world trial enrolling pts ≥ 70 years with mRRC treated with CABO at 13 Italian Oncology Centers. All concomitants drugs administered to pts were collected and categorized according to active principles and indication. DDIs were identified through a dedicated software (Lexicomp), scientific databases (Sider4.1) and published articles. Results: we enrolled 104 pts, median age 75.8 years (range 70.2-87.4 yrs). Overall, 91.4% of the cohort was treated at a reduced dose either upfront or due to side effects. Pts took a median of 6 concomitant drugs (IQR: 4-9), for a total of 131 active principles. Software analysis identified 4 DDIs (warfarin, apixaban, diltiazem and furosemide); whereas scientific reports allowed us to identify 15 additional DDIs involving metoprolol, nebivolol, olmesartan, amiloride, simvastatin, rosuvastatin, polyenoic omega-3 fatty acids, loperamide, metoclopramide, metformin, dutasteride, dexamethasone, prednisone, cetirizine and doxazosin. Seventy pts with potential DDIs experienced a trend for higher rate of grade 3-4 adverse events compared to other pts, although difference was not statistically significant (48.7% v 23.5 %, p=0.485). The table summarizes the main DDIs and suggestions to avoid or mitigate their effects Conclusions: the risk of DDIs was not negligible in our cohort of elderly mRCC pts treated with CABO, although the frequent dose reductions of CABO probably confounded their impact on toxicities. Unremitting attention to concomitant medications in the elderly is thus warranted

Cabozantinib in the elderly with metastatic renal cell carcinoma undergoing geriatric G8 screening test: A prospective multicenter observational study (ZEBRA/MEET-URO 9)

Background: Cabozantinib (CABO) is an oral tyrosine kinase inhibitor registered for the treatment of metastatic renal cell carcinoma (mRCC) for the first or subsequent lines. Tolerability in real world elderly patients is poorly documented. G8 is a short test for vulnerability gaining increased interest as a screening tool for trials in geriatric oncology. Methods: ZEBRA/MEET-URO 9 was a prospective multicenter study of safety and activity of CABO administered to pts ≥70 years with mRCC, either in the first or subsequent lines of treatment, until progression or unacceptable toxicity. All pts underwent G8 score at baseline, with a cut-off for vulnerability of 14 or below. Data on tolerability and activity were collected prospectively after signature of informed consent. Results: A total of 104 pts started CABO at 13 Italian Centers, 38,5% as first line. Median age was 75.8 yrs (range 70.2-87.4 yrs, 26 pts ≥80 yrs), 73.1% males. IMDC score was good 19.2%, intermediate 53.9%, poor 26.9%. Primary tumor had been removed in 82.7% of pts, histology was clear cell 78.8%, papillary 8.7%, chromophobe 5.8%, unclassified 6.7%. G8 score was ≤14 in 65.4% of pts. Up-front dose reduction of CABO was more frequent in pts with low G8 score (79.4 vs 41.7%, p=0.003), but eventually the majority of pts (91.4%) underwent dose reductions of CABO. After a median treatment of 6.4 months (0.5-26.1 months), 38.4% of pts developed G3-4 toxicities, 22.1% interrupted treatment due to adverse events, 2.8% (3 pts) died due to cardiovascular or thromboembolic events. Median PFS was 7.6 months (95% CI=5.8-12.6 months) in first line, 10.0 months (5.8-15.6) in second or further lines, median OS was 20.1 months (11.1-not reached) and 15.6 months (12.5-not reached), respectively. G8 score ≤14 did not correlate with rate of temporary interruptions >7 days, hospitalization, incidence of G3-5 toxicities, as well as with PFS. Pts with G8 score ≤14 had a trend for reduced OS, but difference was not statistically significant both in the first and further lines of treatment. Conclusions: Screening G8 test was positive in more than a half of pts, underlying the need for detailed geriatric assessment and increased clinical monitoring of such patients. A G8 score ≤14 correlated with up-front dose reduction of CABO but not with G3-5 toxicities probably due to the high rates of dose reductions in the whole cohort. Correlation between low G8 score and OS could not be demonstrated in this population

Surgical management of haemorrhoids: an Italian survey of over 32 000 patients over 17 years

Aim: The management of haemorrhoids has changed significantly in the last two decades as a result of new insights into their pathophysiology and the availability of new surgical devices. The aim of this survey was to evaluate changes in the management of haemorrhoids in Italy over the last 17 years. Method: An electronic database which recorded details of management relating to the severity of haemorrhoids between 2000 and 2016 was obtained from 18 of 34 colorectal surgeons who were invited to participate. Results: A total of 32 458 patients were treated for haemorrhoids by 18 expert coloproctologists during a 17-year period. Patients were classified as Grade II (7542, 23.2%), Grade III(15 360, 47.3%) and Grade IV (9556, 29.4%). Grade II haemorrhoids were treated with rubber band ligation in over 90% of the cases, and patients with Grade IV had a Milligan–Morgan (MM) haemorrhoidectomy in over 90% of the cases. In Grade III, the use of stapled haemorrhoidopexy progressively decreased from 30% to 35% (between 2000 and 2007) to 5% of the cases. Meanwhile, commencing from 2006 the use of Doppler-guided haemorrhoid artery ligation (DGHAL) with mucopexy increased progressively from 6% to 24%. Over the years, the percentage of MM haemorrhoidectomy remained consistent at between 65% and 70% of the cases. Conclusion: Relevant changes in the surgical choice of haemorrhoid treatment have occurred in Italy over the last 17 years. MM haemorrhoidectomy remains the most frequently performed procedure for Grade III haemorrhoids. Stapled haemorrhoidopexy has become much less popular in contrast to DGHAL with mucopexy which is being performed much more frequently

Effective Rapid Diagnosis of Bacterial and Fungal Bloodstream Infections by T2 Magnetic Resonance Technology in the Pediatric Population

Children are prone to bloodstream infections (BSIs), the rapid and accurate diagnosis of which is an unmet clinical need. The T2MR technology is a direct molecular assay for identification of BSI pathogens, which can help to overcome the limits of blood culture (BC) such as diagnostic accuracy, blood volumes required, and turnaround time. We analyzed results obtained with the T2Bacteria (648) and T2Candida (106) panels in pediatric patients of the Bambino Gesu Children's Hospital between May 2018 and September 2020 in order to evaluate the performance of the T2Dx instrument with respect to BC. T2Bacteria and T2Candida panels showed 84.2% and 100% sensitivity with 85.9% and 94.1% specificity, respectively. The sensitivity and specificity of the T2Bacteria panel increased to 94.9% and 98.7%, respectively, when BC was negative but other laboratory data supported the molecular result. T2Bacteria sensitivity was 100% with blood volumes <2 mL in neonates and infants. T2Bacteria and T2Candida provided definitive microorganism identification in a mean time of 4.4 and 3.7 h, respectively, versus 65.7 and 125.5 h for BCs (P < 0.001). T2 panels rapidly and accurately enable a diagnosis of a pediatric BSI, even in children under 1 year of age and for very small blood volumes. These findings support their clinical use in life-threatening pediatric infections, where the time to diagnosis is of utmost importance, in order to improve survival and minimize the long-term sequalae of sepsis. The T2 technology could be further developed to include more bacteria and fungi species that are involved in the etiology of sepsis

Long-term outcome of COVID-19 patients treated with helmet noninvasive ventilation vs. high-flow nasal oxygen: a randomized trial

Abstract Background Long-term outcomes of patients treated with helmet noninvasive ventilation (NIV) are unknown: safety concerns regarding the risk of patient self-inflicted lung injury and delayed intubation exist when NIV is applied in hypoxemic patients. We assessed the 6-month outcome of patients who received helmet NIV or high-flow nasal oxygen for COVID-19 hypoxemic respiratory failure. Methods In this prespecified analysis of a randomized trial of helmet NIV versus high-flow nasal oxygen (HENIVOT), clinical status, physical performance (6-min-walking-test and 30-s chair stand test), respiratory function and quality of life (EuroQoL five dimensions five levels questionnaire, EuroQoL VAS, SF36 and Post-Traumatic Stress Disorder Checklist for the DSM) were evaluated 6 months after the enrollment. Results Among 80 patients who were alive, 71 (89%) completed the follow-up: 35 had received helmet NIV, 36 high-flow oxygen. There was no inter-group difference in any item concerning vital signs (N = 4), physical performance (N = 18), respiratory function (N = 27), quality of life (N = 21) and laboratory tests (N = 15). Arthralgia was significantly lower in the helmet group (16% vs. 55%, p = 0.002). Fifty-two percent of patients in helmet group vs. 63% of patients in high-flow group had diffusing capacity of the lungs for carbon monoxide < 80% of predicted (p = 0.44); 13% vs. 22% had forced vital capacity < 80% of predicted (p = 0.51). Both groups reported similar degree of pain (p = 0.81) and anxiety (p = 0.81) at the EQ-5D-5L test; the EQ-VAS score was similar in the two groups (p = 0.27). Compared to patients who successfully avoided invasive mechanical ventilation (54/71, 76%), intubated patients (17/71, 24%) had significantly worse pulmonary function (median diffusing capacity of the lungs for carbon monoxide 66% [Interquartile range: 47–77] of predicted vs. 80% [71–88], p = 0.005) and decreased quality of life (EQ-VAS: 70 [53–70] vs. 80 [70–83], p = 0.01). Conclusions In patients with COVID-19 hypoxemic respiratory failure, treatment with helmet NIV or high-flow oxygen yielded similar quality of life and functional outcome at 6 months. The need for invasive mechanical ventilation was associated with worse outcomes. These data indicate that helmet NIV, as applied in the HENIVOT trial, can be safely used in hypoxemic patients. Trial registration Registered on clinicaltrials.gov NCT04502576 on August 6, 202

Long-term outcome of COVID-19 patients treated with helmet noninvasive ventilation vs. high-flow nasal oxygen: a randomized trial

BackgroundLong-term outcomes of patients treated with helmet noninvasive ventilation (NIV) are unknown: safety concerns regarding the risk of patient self-inflicted lung injury and delayed intubation exist when NIV is applied in hypoxemic patients. We assessed the 6-month outcome of patients who received helmet NIV or high-flow nasal oxygen for COVID-19 hypoxemic respiratory failure.MethodsIn this prespecified analysis of a randomized trial of helmet NIV versus high-flow nasal oxygen (HENIVOT), clinical status, physical performance (6-min-walking-test and 30-s chair stand test), respiratory function and quality of life (EuroQoL five dimensions five levels questionnaire, EuroQoL VAS, SF36 and Post-Traumatic Stress Disorder Checklist for the DSM) were evaluated 6 months after the enrollment.ResultsAmong 80 patients who were alive, 71 (89%) completed the follow-up: 35 had received helmet NIV, 36 high-flow oxygen. There was no inter-group difference in any item concerning vital signs (N = 4), physical performance (N = 18), respiratory function (N = 27), quality of life (N = 21) and laboratory tests (N = 15). Arthralgia was significantly lower in the helmet group (16% vs. 55%, p = 0.002). Fifty-two percent of patients in helmet group vs. 63% of patients in high-flow group had diffusing capacity of the lungs for carbon monoxide &lt; 80% of predicted (p = 0.44); 13% vs. 22% had forced vital capacity &lt; 80% of predicted (p = 0.51). Both groups reported similar degree of pain (p = 0.81) and anxiety (p = 0.81) at the EQ-5D-5L test; the EQ-VAS score was similar in the two groups (p = 0.27). Compared to patients who successfully avoided invasive mechanical ventilation (54/71, 76%), intubated patients (17/71, 24%) had significantly worse pulmonary function (median diffusing capacity of the lungs for carbon monoxide 66% [Interquartile range: 47-77] of predicted vs. 80% [71-88], p = 0.005) and decreased quality of life (EQ-VAS: 70 [53-70] vs. 80 [70-83], p = 0.01).ConclusionsIn patients with COVID-19 hypoxemic respiratory failure, treatment with helmet NIV or high-flow oxygen yielded similar quality of life and functional outcome at 6 months. The need for invasive mechanical ventilation was associated with worse outcomes. These data indicate that helmet NIV, as applied in the HENIVOT trial, can be safely used in hypoxemic patients.Trial registration Registered on clinicaltrials.gov NCT04502576 on August 6, 202

STUDIO OSSERVAZIONALE SULL’INTEGRAZIONE CON LICOPENE BIOLOGICO NELLA DEGENERAZIONE MACULARE LEGATA ALL’ETÀ (DMLE): CARATTERISTICHE IN CONDIZIONI BASALI DEI PAZIENTI.

Nel mondo la degenerazione maculare legata all’età (DMLE) è la principale causa di grave riduzione della vista (1). Negli USA questa malattia è responsabile di più del 54% dei casi di perdita della vista nella popolazione bianca (2). Studi epidemiologici indicano che più di 1 milione di Americani è affetto dalla forma neovascolare (vedi oltre) e 970 mila sono colpiti dalla forma atrofica (vedi oltre). Una recente revisione della letteratura ha mostrato che in Europa globalmente la prevalenza della DMLE nei soggetti di età compresa tra 65-75 anni varia dal 9 al 25%. Francia e Germania sono i paesi con più elevata prevalenza, rispettivamente 40% e 39%, mentre nel Regno Unito la prevalenza è del 3,5%. In Italia si stima che 1 milione di persone presenti segni di DMLE; ogni anno si registrano 20 mila nuovi casi della forma neovascolare che colpisce l’1% degli ultra 50enni, il 14% degli ultra 75enni e il 30% degli ultra 85enni. La cecità si manifesta in età avanzata: più dell’80% di quelli che ne sono affetti diventano ciechi dopo i 70 anni. La DMLE è due volte più frequente nelle donne rispetto agli uomini. L’esatta patogenesi di questa affezione rimane incerta; si tratta di una malattia multifattoriale legata all'interazione di fattori genetici e ambientali. Tra questi spicca il fumo di sigaretta. Quest’ultimo agirebbe attraverso lo stress ossidativo che è considerato uno dei principali meccanismi che influenzano l’insorgenza della DMLE. La DMLE può presentarsi in due forme: la secca (non essudativa o atrofica) e la umida (essudativa o neovascolare). • La forma secca è caratterizzata dalla comparsa nella macula delle drusen: si tratta di escrescenze di materiale colloide (lipidi, fosfolipidi, collagene) che si accumulano nella membrana di Bruch sottostante all’epitelio pigmentato retinico. Le drusen ostacolano l’ossigenazione e determinano la degenerazione dei fotorecettori, con atrofia e graduale riduzione dell’acuità. È stato evidenziato che più di 8 milioni di Americani hanno almeno una voluminosa drusen in un occhio e che in 3,6 milioni di questi sono presenti drusen bilaterali Di notevole rilevanza è il fatto che la forma secca può evolvere nella più grave forma umida. • La forma umida si manifesta con essudazione ed emorragie maculari, generate dalla neoangiogenesi coroidale, che determinano una rapida perdita della vista. La terapia standard della DMLE neovascolare è rappresentata dall’iniezione intravitreale di un farmaco anti-VEGF. Per prevenire e contrastare l’angiogenesi a livello oculare è necessario identificare molecole angiostatiche che siano dotate di scarsa o nulla tossicità e con via di somministrazione che sia la più semplice possibile. Studi molto recenti hanno dimostrato che il licopene, oltre a essere un potente antiossidante, possiede anche una spiccata attività antiangiogenica. Sahin et al., utilizzando cellule endoteliali umane, hanno infatti evidenziato che il licopene riduce in vitro, in modo dose-dipendente, la loro proliferazione, la loro migrazione e la formazione di neocapillari. L’inibizione dell’angiogenesi è stata confermata da altri studi in cui è stato osservato che questo effetto è la conseguenza di differenti meccanismi: • attività anti-VEGF; • azione anti TNF-α (pro-angiogenesi); • up-regolazione della IL-12 e dell’IFN-γ (citochine antiangiogenesi); • inibizione della MMP-2 (proteasi proangiogenesi) tramite l’attenuazione del VEGFR2. È stato sottolineato che il licopene esercita il suo effetto antiangiogenico a concentrazioni che possono essere raggiunte anche in vivo, ma, a causa della variabilità degli individui e del contenuto di licopene dei pomodori, non è ancora possibile indicare la quantità di questi ortaggi necessaria al raggiungimento dello scopo. È da tempo noto tuttavia che i livelli di licopene sono più bassi nei pazienti con DMLE e solo da poco è stato osservato che esiste una correlazione inversa tra livelli plasmatici di carotenoidi e presenza di questa grave malattia oculare e che ciò è particolarmente rilevante per il licopene che è risultato essere il solo carotenoide in grado di proteggere significativamente sia nei confronti della forma iniziale, sia ancor di più nei confronti della forma essudativa