Macrophages, cells belonging to the innate immune system, present a high plasticity grade, being able to change their phenotype in response to environmental stimuli. They play central roles during ...development, homeostatic tissue processes, tissue repair, and immunity. Furthermore, it is recognized that macrophages are involved in chronic inflammation and that they play central roles in inflammatory diseases and cancer. Due to their large involvement in the pathogenesis of several types of human diseases, macrophages are considered to be relevant therapeutic targets. Nanotechnology-based systems have attracted a lot of attention in this field, gaining a pivotal role as useful moieties to target macrophages in diseased tissues. Among the different approaches that can target macrophages, the most radical is represented by their depletion, commonly obtained by means of clodronate-containing liposomal formulations and/or depleting antibodies. These strategies have produced encouraging results in experimental mouse models. In this review, we focus on macrophage targeting, based on the results so far obtained in preclinical models of inflammatory diseases and cancer. Pros and cons of these therapeutic interventions will be highlighted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal ...degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of retinitis pigmentosa. Electrophysiological and behavioural analyses reveal a prosthesis-dependent recovery of light sensitivity and visual acuity that persists up to 6-10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the ...effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited.
This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint.
We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria.
Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus responsible for the pandemic disease in the last year, is able to affect the central nervous system (CNS). Compared ...with its well‐known pulmonary tropism and respiratory complications, little has been studied about SARS‐CoV‐2 neurotropism and pathogenesis of its neurological manifestations, but also about postmortem histopathological findings in the CNS of patients who died from COVID‐19 (coronavirus disease 2019). We present a systematic review, carried out according to the Preferred Reporting Items for Systematic Review standards, of the neuropathological features of COVID‐19. We found 21 scientific papers, the majority of which refer to postmortem examinations; the total amount of cases is 197. Hypoxic changes are the most frequently reported alteration of brain tissue, followed by ischemic and hemorrhagic lesions and reactive astrogliosis and microgliosis. These findings do not seem to be specific to SARS‐CoV‐2 infection, they are more likely because of systemic inflammation and coagulopathy caused by COVID‐19. More studies are needed to confirm this hypothesis and to detect other possible alterations of neural tissue. Brain examination of patients dead from COVID‐19 should be included in a protocol of standardized criteria to perform autopsies on these subjects.
SARS‐CoV‐2, the new coronavirus responsible for the pandemic disease in the last year, is able to affect the Central Nervous System. However, little has been studied about SARS‐CoV‐2 neurotropism and neuropathogenesis. We present a systematic review of the neuropathological features of COVID‐19. Hypoxic changes, ischemic and hemorrhagic lesions, reactive astrogliosis, and microgliosis are the brain alterations mainly described in the literature. These findings do not seem to be specific to SARS‐CoV‐2 infection, they are more likely due to systemic inflammation and coagulopathy caused by COVID‐19.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims Circulating microRNAs (miRNAs) may represent a novel class of biomarkers; therefore, we examined whether acute myocardial infarction (MI) modulates miRNAs plasma levels in humans and mice. ...Methods and results Healthy donors (n = 17) and patients (n = 33) with acute ST-segment elevation MI (STEMI) were evaluated. In one cohort (n = 25), the first plasma sample was obtained 517 ± 309 min after the onset of MI symptoms and after coronary reperfusion with percutaneous coronary intervention (PCI); miR-1, -133a, -133b, and -499-5p were ∼15- to 140-fold control, whereas miR-122 and -375 were ∼87–90% lower than control; 5 days later, miR-1, -133a, -133b, -499-5p, and -375 were back to baseline, whereas miR-122 remained lower than control through Day 30. In additional patients (n = 8; four treated with thrombolysis and four with PCI), miRNAs and troponin I (TnI) were quantified simultaneously starting 156 ± 72 min after the onset of symptoms and at different times thereafter. Peak miR-1, -133a, and -133b expression and TnI level occurred at a similar time, whereas miR-499-5p exhibited a slower time course. In mice, miRNAs plasma levels and TnI were measured 15 min after coronary ligation and at different times thereafter. The behaviour of miR-1, -133a, -133b, and -499-5p was similar to STEMI patients; further, reciprocal changes in the expression levels of these miRNAs were found in cardiac tissue 3–6 h after coronary ligation. In contrast, miR-122 and -375 exhibited minor changes and no significant modulation. In mice with acute hind-limb ischaemia, there was no increase in the plasma level of the above miRNAs. Conclusion Acute MI up-regulated miR-1, -133a, -133b, and -499-5p plasma levels, both in humans and mice, whereas miR-122 and -375 were lower than control only in STEMI patients. These miRNAs represent novel biomarkers of cardiac damage.
What is a “good” result after transcatheter mitral repair? Impact of 2+ residual mitral regurgitation Buzzatti, Nicola, MD; De Bonis, Michele, MD; Denti, Paolo, MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
2016, January 2016, 2016-Jan, 2016-01-00, 20160101, Volume:
151, Issue:
1
Journal Article
Peer reviewed
Open access
Abstract Objective The study objective was to assess the impact on follow-up outcomes of residual mitral regurgitation 2+ in comparison with ≤1+ after MitraClip (Abbott Vascular Inc, Santa Clara, ...Calif) repair. Methods We compared the outcomes of mitral regurgitation 2+ and mitral regurgitation ≤1+ groups among a population of 223 consecutive patients with acute residual mitral regurgitation ≤2+ who underwent MitraClip implantation at San Raffaele Scientific Institute (Milan, Italy) between October 2008 and December 2014. Results Residual mitral regurgitation 2+ was found in 64 patients (28.7%). Overall actuarial survival was 63.1% ± 4.4% at 48 months. Cumulative incidence functions of cardiac death in patients with mitral regurgitation 2+ was significantly higher (Gray test P < .001) compared with the mitral regurgitation ≤1+ group. The adjusted hazard ratio was 5.28 (95% confidence interval, 2.41-11.56, P < .001). Cumulative incidence function of mitral regurgitation ≥3+ recurrence in patients with residual mitral regurgitation ≤1+ and mitral regurgitation 2+ at 48 months was 13.3% ± 3.8% and 45.2% ± 6.8%, respectively (Gray test P < .001). Multivariate model showed that mitral regurgitation 2+ was the only factor associated with the development of mitral regurgitation ≥3+ at follow-up (adjusted hazard ratio, 6.71; 95% confidence interval, 3.48-12.90; P < .001). Mitral regurgitation cause was not associated with cardiac death and recurrence of mitral regurgitation ≥3+ at follow-up. No relationship between New York Heart Association class and follow-up time after MitraClip implant was found (odds ratio, 1.07; 95% confidence interval, 0.98-1.15; P = .11), and factors related to postoperative New York Heart Association also included residual mitral regurgitation 2+ ( P = .07). Conclusions Residual 2+ mitral regurgitation after MitraClip implantation was associated with worse follow-up outcomes compared with ≤1+ mitral regurgitation, including survival, symptom relief, and mitral regurgitation recurrence. Better efficacy should be pursued by transcatheter mitral repair technologies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was ...Lombardy, with the first reported case on 20 February 2020.
San Raffaele Scientific Institute - a large tertiary hospital and research centre in Milan, Italy - was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy.
In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces.
All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs.
Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
X-ray binary systems consist of a companion star and a compact object in close orbit. Thanks to their copious X-ray emission, these objects have been studied in detail using X-ray ...spectroscopy and timing. The inclination of these systems is a major uncertainty in the determination of the mass of the compact object using optical spectroscopic methods. In this paper, we present a new method to constrain the inclination of X-ray binaries, which is based on the modeling of the polarization of X-rays photons produced by a compact source and scattered off the companion star. We describe our method and explore the potential of this technique in the specific case of the low-mass X-ray binary GS 1826−238 observed by the Imaging X-ray Polarimetry Explorer observatory.
Prosenescence therapy has recently emerged as a novel therapeutic approach for treating cancer. However, this concept is challenged by conflicting evidence showing that the senescence-associated ...secretory phenotype (SASP) of senescent tumor cells can have pro- as well as antitumorigenic effects. Herein, we report that, in Pten-null senescent tumors, activation of the Jak2/Stat3 pathway establishes an immunosuppressive tumor microenvironment that contributes to tumor growth and chemoresistance. Activation of the Jak2/Stat3 pathway in Pten-null tumors is sustained by the downregulation of the protein tyrosine phosphatase PTPN11/SHP2, providing evidence for the existence of a novel PTEN/SHP2 axis. Importantly, treatment with docetaxel in combination with a JAK2 inhibitor reprograms the SASP and improves the efficacy of docetaxel-induced senescence by triggering a strong antitumor immune response in Pten-null tumors. Altogether, these data demonstrate that immune surveillance of senescent tumor cells can be suppressed in specific genetic backgrounds but also evoked by pharmacological treatments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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