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PurposeTo investigate the prevalence, incidence and characteristics of bacterial infections and their impact on outcome in critically ill patients infected with COVID-19. MethodsWe conducted a prospective observational study in eight Italian ICUs from February to May 2020; data were collected through an interactive electronic database. Kaplan–Meier analysis (limit product method) was used to identify the occurrence of infections and risk of acquisition.ResultsDuring the study period 248 patients were recruited in the eight participating ICUs. Ninety (36.3%) patients developed at least one episode of secondary infection. An ICU length of stay between 7 and 14 days was characterized by a higher occurrence of infectious complications, with ventilator-associated pneumonia being the most frequent. At least one course of antibiotic therapy was given to 161 (64.9%) patients. Overall ICU and hospital mortality were 33.9% and 42.9%, respectively. Patients developing bacteremia had a higher risk of ICU mortality [45.9% vs. 31.6%, odds ratio 1.8 (95% CI 0.9–3.7), p = 0.069] and hospital mortality [56.8% vs. 40.3%, odds ratio 1.9 (95% CI 1.1–3.9), p = 0.04].ConclusionIn critically ill patients infected with COVID-19 the incidence of bacterial infections is high and associated with worse outcomes. Regular microbiological surveillance and strict infection control measures are mandated.

Up to 40–60% of patients undergoing coronary angiography because of angina and/or evidence of inducible ischaemia on non-invasive stress testing are diagnosed with ischaemia and non-obstructive coronary artery disease (INOCA). The pathogenesis of this condition is primarily attributed to two mechanisms: coronary microvascular dysfunction (CMD) and coronary vasospasm. Notably, ischaemic heart disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Insulin resistance (IR), affecting 10–25% of the general adult population, plays a major role in the pathophysiology of T2DM, but can precede diabetes by years. IR is recognised as a major cardiovascular risk factor, involved in endothelial dysfunction and inflammation, two key processes leading to CMD and vasomotor dysfunction. Hyperinsulinaemia, dysglycaemia, and oxidative stress contribute to this complex relationship, yet the connection between IR, CMD and coronary vasospasm remains incompletely defined. Moreover, IR may represent a target for tailored therapies aimed at improving microvascular function and alleviating symptom burden. Although a few studies have investigated this relationship, the molecular mechanisms by which multiple pathways lead to different INOCA endotypes remain incompletely defined. The aim of this review is to summarise current evidence linking IR, CMD and coronary vasospasm, with emphasis on pathophysiological mechanisms and diagnostic approaches, and to highlight future research directions in this clinical setting. Graphical abstract

Botulinum neurotoxins (BoNTs) produced by Clostridia species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. The most know typical clinical syndrome of botulism refers to the foodborne form. All different forms are characterized by the same symptoms, caused by toxin-induced neuromuscular paralysis. The diagnosis of botulism is essentially clinical, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is mandatory to confirm the clinical suspicion in relation to regulatory agencies, to identify the BoNTs involved and the source of intoxication. The laboratory diagnosis of foodborne botulism is based on the detection of BoNTs in clinical specimens/food samples and the isolation of BoNT from stools. Foodborne botulism intoxication is often underdiagnosed; the initial symptoms can be confused with more common clinical conditions (i.e., stroke, myasthenia gravis, Guillain–Barré syndrome—Miller–Fisher variant, Eaton–Lambert syndrome, tick paralysis and shellfish or tetrodotoxin poisoning). The treatment includes procedures for decontamination, antidote administration and, when required, support of respiratory function; few differences are related to the different way of exposure.

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.

Objectives To evaluate whether ERAS is feasible and beneficial in elderly patients undergoing VATS lobectomy for lung cancer. Methods From February 2016 to March 2019, 182 patients were included into a 17-items ERAS pathway. Patients were divided into two groups according to age: Group A (< 75 years) 138 patients and Group B (≥ 75 years) 44 patients. End points were: length of stay (LoS), 30-day morbidity, 90-day mortality, 30-day re-admittance rate, and ERAS–score (number of ERAS objectives achieved). Results Elderly patients had significantly more chronic renal failure ( p  = 0.039) and a worse pulmonary function. Mean FEV1% was 101.6% (± 21.0% SD) and 90.8% (± 19.1% SD) and mean FEV1/FVC was 0.75 (± 0.10 SD) and 0.68 (± 0.12 SD) for group A and B, respectively ( p  = 0.02 and p  = 0.01). Median LoS was longer in Group B (6 days) than in Group A (5 days; p  = 0.006). Morbidity was higher for elderly patients (A 32.6% vs B 56.8%; p  = 0.007), major complication rates were similar ( p  = 0.782). No post-operative mortality was observed, re-admittance rates were similar (A 7.8% vs B 11.5%; p  = 0.548). Mean ERAS-scores were 13.8 (± 1.83 SD) for Group A and 13.4 (± 1.98 SD) for Group B ( p  = 0.240). Multivariable analysis showed previous major surgery ( p  = 0.028), COPD ( p  = 0.027), history of arrhythmic disease ( p  = 0.015), post-operative complications ( p  < 0.001), and ERAS-score ( p  < 0.001) as independent predictive factors of LoS, age did not significantly influence LoS. Conclusions Elderly patients adhere to an ERAS protocol similarly to younger ones. ERAS pathway in VATS lobectomy patients seems to be beneficial regardless the age.

In the last decades, increasing evidence has revealed that a large number of channel protein and ion pumps exhibit impaired expression in cancers. This dysregulation is responsible for high proliferative rates as well as migration and invasiveness, reflected in the recently coined term oncochannelopathies. In glioblastoma (GBM), the most invasive and aggressive primary brain tumor, GBM cells modify their ionic equilibrium in order to change their volume as a necessary step prior to migration. This mechanism involves increased expression of BK channels and downregulation of the normally widespread Kir4.1 channels, as noted in GBM biopsies from patients. Despite a large body of work implicating BK channels in migration in response to an artificial intracellular calcium rise, little is known about how this channel acts in GBM cells at resting membrane potential (RMP), as compared to other channels that are constitutively open, such as Kir4.1. In this review we propose that a residual fraction of functionally active Kir4.1 channels mediates a small, but continuous, efflux of potassium at the more depolarized RMP of GBM cells. In addition, coinciding with transient membrane deformation and the intracellular rise in calcium concentration, brief activity of BK channels can induce massive and rapid cytosolic water loss that reduces cell volume (cell shrinkage), a necessary step for migration within the brain parenchyma.

Background In response to the COVID-19 health emergency, mass media widely spread guidelines to stop the virus transmission, leading to an excessive and unaware use of detergents and disinfectants. In Italy and in other countries this tendency caused a significant increase of exposures to these products in 2020. Evaluating data collected by the Italian Pavia Poison Centre (PPC), this study intends to examine the relationship between the COVID-19 lockdown and the variations of exposures to specific product categories possibly associated to the containment measures implemented. Simultaneously, this work shows the effectiveness of the European Product Categorisation System (EuPCS) in surveillance activities of dangerous chemicals. Methods Exposure cases managed by the PPC during March–May 2020 (lockdown) and during the same months of 2017–2018-2019 were compared. Differences in categorical variables were tested with the Chi-square test. The level of significance was set at Alpha = .05. The study included all EuPCS groups but specifically focused on cleaners, detergents, biocides and cosmetics. Results During the lockdown, calls from private citizens showed a highly significant increase (+ 11.5%, p  < .001) and occupational exposures decreased (− 11.7%, p  = .011). Among Cleaners, exposures to Bleaches slightly increased while Drain cleaning products went through a significant reduction (− 13.9%, p  = .035). A highly significant increase of exposures to Disinfectants was observed (+ 7.7%, p  = .007), particularly to those for surfaces (+ 6.8%, p  = .039). Regarding Cosmetics, both handwashing soaps and gel products significantly increased (respectively: + 25.0, p  = .016 and + 9.7%, p  = .028). Among children 1–5 years, the statistical significance is reached with exposures to Dishwashing detergents (+ 13.1%, p  = .032), handwashing soaps (+ 28.6%, p  = .014) and handwashing gel products (+ 16.8%, p  = .010). Contrarily, Liquid Laundry Detergent Capsules decreased in a highly significant manner (− 25%; p  = .001). The general severity of exposures showed a highly significant decrease (Moderate: − 10.1%, p  = .0002). Conclusions This study investigated the relationship between the COVID-19 lockdown and the variations of exposures to some product categories related to the containment measures. The results obtained support any action to be taken by Competent Authorities to implement measures for a safer use of cleaners/disinfectants. This paper shows the benefit in applying the EuPCS to categorize products according to their intended use, though an extension of this system to products not covered by CLP Regulation may be a further advantage.

In experimental conditions alveolar fluid clearance is controlled by alveolar β2-adrenergic receptors. We hypothesized that if this occurs in humans, then non-selective β-blockers should reduce the membrane diffusing capacity (DM), an index of lung interstitial fluid homeostasis. Moreover, we wondered whether this effect is potentiated by saline solution infusion, an intervention expected to cause interstitial lung edema. Since fluid retention within the lungs might trigger excessive ventilation during exercise, we also hypothesized that after the β2-blockade ventilation increased in excess to CO2 output and this was further enhanced by interstitial edema. 22 healthy males took part in the study. On day 1, spirometry, lung diffusion for carbon monoxide (DLCO) including its subcomponents DM and capillary volume (VCap), and cardiopulmonary exercise test were performed. On day 2, these tests were repeated after rapid 25 ml/kg saline infusion. Then, in random order 11 subjects were assigned to oral treatment with Carvedilol (CARV) and 11 to Bisoprolol (BISOPR). When heart rate fell at least by 10 beats·min(-1), the tests were repeated before (day 3) and after saline infusion (day 4). CARV but not BISOPR, decreased DM (-13 ± 7%, p = 0.001) and increased VCap (+20 ± 22%, p = 0.016) and VE/VCO2 slope (+12 ± 8%, p<0.01). These changes further increased after saline: -18 ± 13% for DM (p<0.01), +44 ± 28% for VCap (p<0.001), and +20 ± 10% for VE/VCO2 slope (p<0.001). These findings support the hypothesis that in humans in vivo the β2-alveolar receptors contribute to control alveolar fluid clearance and that interstitial lung fluid may trigger exercise hyperventilation.

Bioactive metabolites isolated from medicinal mushrooms (MM) used as supportive treatment in conventional oncology have recently gained interest. Acting as anticancer agents, they interfere with tumor cells and microenvironment (TME), disturbing cancer development/progression. Nonetheless, their action mechanisms still need to be elucidated. Recently, using a 4T1 triple-negative mouse BC model, we demonstrated that supplementation with Micotherapy U-Care, a MM blend, produced a striking reduction of lung metastases density/number, paralleled by decreased inflammation and oxidative stress both in TME and metastases, together with QoL amelioration. We hypothesized that these effects could be due to either a direct anticancer effect and/or to a secondary/indirect impact of Micotherapy U-Care on systemic inflammation/immunomodulation. To address this question, we presently focused on apoptosis/proliferation, investigating specific molecules, i.e., PARP1, p53, BAX, Bcl2, and PCNA, whose critical role in BC is well recognized. We revealed that Micotherapy U-Care is effective to influence balance between cell death and proliferation, which appeared strictly interconnected and inversely related (p53/Bax vs. Bcl2/PARP1/PCNA expression trends). MM blend displayed a direct effect, with different efficacy extent on cancer cells and TME, forcing tumor cells to apoptosis. Yet again, this study supports the potential of MM extracts, as adjuvant supplement in the TNBC management.

Glioblastoma (GBM) is the most common tumor of the central nervous system. Current therapies, often associated with severe side effects, are inefficacious to contrast the GBM relapsing forms. In trying to overcome these drawbacks, ( OC -6-44)-acetatodiamminedichlorido(2-(2-propynyl)octanoato)platinum(IV), also called Pt(IV)Ac-POA, has been recently synthesized. This new prodrug bearing as axial ligand (2-propynyl)octanoic acid (POA), a histone deacetylase inhibitor, has a higher activity due to (i) its high cellular accumulation by virtue of its high lipophilicity and (ii) the inhibition of histone deacetylase, which leads to the increased exposure of nuclear DNA, permitting higher platination and promoting cancer cell death. In the present study, we investigated the effects induced by Pt(IV)Ac-POA and its potential antitumor activity in human U251 glioblastoma cell line using a battery of complementary techniques, i.e., flow cytometry, immunocytochemistry, TEM, and Western blotting analyses. In addition, the synergistic effect of Pt(IV)Ac-POA associated with the innovative oncological hadrontherapy with carbon ions was investigated, with the aim to identify the most efficient anticancer treatment combination. Our in vitro data demonstrated that Pt(IV)Ac-POA is able to induce cell death, through different pathways, at concentrations lower than those tested for other platinum analogs. In particular, an enduring Pt(IV)Ac-POA antitumor effect, persisting in long-term treatment, was demonstrated. Interestingly, this effect was further amplified by the combined exposure to carbon ion radiation. In conclusion, Pt(IV)Ac-POA represents a promising prodrug to be incorporated into the treatment regimen for GBM. Moreover, the synergistic efficacy of the combined protocol using chemotherapeutic Pt(IV)Ac-POA followed by carbon ion radiation may represent a promising approach, which may overcome some typical limitations of conventional therapeutic protocols for GBM treatment.