Risk factors for COVID-19 associated pulmonary aspergillosis and outcomes in patients with acute respiratory failure in a respiratory sub-intensive care unit.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients. MATERIALS AND METHODS: This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients. RESULTS: Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155-314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12-31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75-4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12-4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19-5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47-5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20-26.92), p = 0.035]. No differences were observed in hematological cohort. CONCLUSION: CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia.

The Impact of Alcohol Consumption and Oral Microbiota on Upper Aerodigestive Tract Carcinomas: A Pilot Study.

Alcohol consumption is associated with oxidative stress and an increased risk of carcinoma of the upper aero-digestive tract (UADT). Recently, it has been found that some microorganisms in the human oral cavity may locally metabolize ethanol, forming acetaldehyde, a carcinogenic metabolite of alcohol. In a cohort of patients first visited for UADT cancers, we estimated their alcohol consumption by measuring Ethyl Glucuronide/EtG (a long-lasting metabolite of ethanol) in the hair and carbohydrate-deficient transferrin/CDT (short-term index of alcohol intake) in the serum. Moreover, we analyzed, by culture-based methods, the presence of Neisseria subflava, Streptococcus mitis, Candida albicans, and glabrata (microorganisms generating acetaldehyde) in the oral cavity. According to the EtG values, we correlated drinking alcohol with endogenous oxidative stress and the investigated microorganism's presence. We found that 55% of heavy drinkers presented microorganisms generating acetaldehyde locally. Moreover, we found that the presence of oral acetaldehyde-producing bacteria correlates with increased oxidative stress compared to patients without such bacteria. As for the study of alcohol dehydrogenase gene polymorphisms (the enzyme that transforms alcohol to acetaldehyde), we found that only the "CGTCGTCCC" haplotype was more frequent in the general population than in carcinoma patients. This pilot study suggests the importance of estimating alcohol consumption (EtG), the presence of bacteria producing acetaldehyde, and oxidative stress as risk factors for the onset of oral carcinomas.

The effect of the electromagnetic field on metabolic-active bacterial biofilm experimentallyinduced on titanium dental implants.

Microbial biofilm is of paramount importance in the development of mucositis or peri-implantitis in patients with dental implants. This study was designed to investigate whether an electromagnetic field at high frequency waves directly applied on 33 titanium implants could remove experimentally-induced Enterococcus faecalis bacterial biofilm. A specially designed device (X-IMPLANT) was used to generate the electromagnetic field, with output power of 8 W, supply frequency (action/pause) 3/2s, and an output frequency of 625±5% kHz in plastic devices containing the biofilm-covered implants immersed in sterile saline. The bacterial biofilm on both treated and untreated control implants was quantitatively measured by phenol red-based Bio-Timer-Assay reagent. The kinetic analysis of the curves showed that the electrical treatment generated by the X-IMPLANT device completely removed the bacterial biofilm after 30 minutes of treatment (p<0.01). Elimination of the biofilm was also confirmed by chromatic observation in the macro-method. Our data seem to indicate that the procedure could be considered for clinical application in peri-implantitis to counteract bacterial biofilm on dental implants.

Extra Virgin Olive Oil-Based Green Formulations With Promising Antimicrobial Activity Against Drug-Resistant Isolates.

Extra virgin olive oil (EVOO) from Olea europaea L. drupes, a cornerstone in the Mediterranean diet, is well known for its nutritional and health properties, especially for prevention of cardiovascular diseases and metabolic disorders. Traditionally, beneficial health effects have been largely attributed to the high concentration of monounsaturated fatty acids, and in recent years, these have also been related to other components including oleacein and oleocanthal. Here, we evaluated, for the first time, the antimicrobial activity of different green extra virgin olive oil-based formulations in natural deep eutectic solvents (NaDESs) emerging as powerful and biocompatible solvents. Specifically, the antimicrobial activity of the EVOO extract, as well as purified oleocanthal and oleacein in two NaDESs (choline/glycerol and choline/propylene glycol), against several drug-resistant clinical isolates and standard microbial strains has been evaluated. The main result was the inhibitory activity of the EVOO extract in choline/glycerol as well as oleacein in choline/propylene glycol toward drug-resistant Gram-positive and -negative strains. Specifically, the EVOO extract in choline/glycerol showed the highest antibacterial activity against several clinical strains of Staphylococcus aureus, whereas oleacein in choline/propylene glycol was the most effective toward various clinical strains of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In addition, all the formulations tested were effective against Candida spp. In conclusion, our results suggest EVOO-based formulations in NaDESs as an interesting strategy that may help in reducing the risk of development of drug resistance. Under this perspective, the usage of NaDESs for the preparation of new antimicrobial formulations may represent a promising approach.

Exposure to b-LED Light While Exerting Antimicrobial Activity on Gram-Negative and -Positive Bacteria Promotes Transient EMT-like Changes and Growth Arrest in Keratinocytes.

While blue LED (b-LED) light is increasingly being studied for its cytotoxic activity towards bacteria in therapy of skin-related infections, its effects on eukaryotic cells plasticity are less well characterized. Moreover, since different protocols are often used, comparing the effect of b-LED towards both microorganisms and epithelial surfaces may be difficult. The aim of this study was to analyze, in the same experimental setting, both the bactericidal activity and the effects on human keratinocytes. Exposure to b-LED induced an intense cytocidal activity against Gram-positive (i.e, Staphylococcus aureus) and Gram-negative (i.e., Pseudomonas aeruginosa) bacteria associated with catheter-related infections. Treatment with b-LED of a human keratinocyte cell line induced a transient cell cycle arrest. At the molecular level, exposure to b-LED induced a transient downregulation of Cyclin D1 and an upregulation of p21, but not signs of apoptosis. Interestingly, a transient induction of phosphor-histone γ-H2Ax, which is associated with genotoxic damages, was observed. At the same time, keratinocytes underwent a transient epithelial to mesenchymal transition (EMT)-like phenotype, characterized by E-cadherin downregulation and SNAIL/SLUG induction. As a functional readout of EMT induction, a scratch assay was performed. Surprisingly, b-LED treatment provoked a delay in the scratch closure. In conclusion, we demonstrated that b-LED microbicidal activity is associated with complex responses in keratinocytes that certainly deserve further analysis.

Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents.

Head and neck cancer (HNC) concerns more than 890,000 patients worldwide annually and is associated with the advanced stage at presentation and heavy outcomes. Alcohol drinking, together with tobacco smoking, and human papillomavirus infection are the main recognized risk factors. The tumorigenesis of HNC represents an intricate sequential process that implicates a gradual acquisition of genetic and epigenetics alterations targeting crucial pathways regulating cell growth, motility, and stromal interactions. Tumor microenvironment and growth factors also play a major role in HNC. Alcohol toxicity is caused both directly by ethanol and indirectly by its metabolic products, with the involvement of the oral microbiota and oxidative stress; alcohol might enhance the exposure of epithelial cells to carcinogens, causing epigenetic modifications, DNA damage, and inaccurate DNA repair with the formation of DNA adducts. Long-term markers of alcohol consumption, especially those detected in the hair, may provide crucial information on the real alcohol drinking of HNC patients. Strategies for prevention could include food supplements as polyphenols, and alkylating drugs as therapy that play a key role in HNC management. Indeed, polyphenols throughout their antioxidant and anti-inflammatory actions may counteract or limit the toxic effect of alcohol whereas alkylating agents inhibiting cancer cells' growth could reduce the carcinogenic damage induced by alcohol. Despite the established association between alcohol and HNC, a concerning pattern of alcohol consumption in survivors of HNC has been shown. It is of primary importance to increase the awareness of cancer risks associated with alcohol consumption, both in oncologic patients and the general population, to provide advice for reducing HNC prevalence and complications.

Candida parapsilosis osteomyelitis following dog bite: a case report and review of the literature.

Candida osteomyelitis is uncommon, especially after dog bites. We describe a case of a 63-year-old man without significant comorbidities presenting progressing swelling of the distal interphalangeal joint (DIJ) of right index finger following a dog bite. Despite empiric antibiotic therapy and local medications, there were no clinical signs of improvement. Clinical examination revealed fistula with purulent drainage on the volar region. Even though laboratory data showed inflammatory markers on range, magnetic resonance imaging (MRI) demonstrated signs of osteomyelitis. The patient was taken to exploration and debridement of the bite wound. Culture of the bone biopsy showed growth of Candida parapsilosis. Therefore, the patient was diagnosed with isolated fungal osteomyelitis and was initiated on fluconazole therapy. The treatment was effective and all symptoms were resolved in 8 weeks after the surgery. There were no signs of recurrence after 20 months of follow-up. The patient had no cosmetic abnormalities or sequelae. Concurrently with the description of the case report a review of the literature was provided. According to the authors, there are three main etiopathogenesis for this infection. The first pathogenic mechanism is direct inoculation into the deep tissues through the dog bite. The second hypothesis is direct translocation of the pathogen from the skin to the deep tissue and to the bone. The last mode of transmission is hematogenous dissemination. Fungal osteomyelitis are really rare conditions, especially after dog bites, but nevertheless it should be considered as a possible diagnosis when there is no response to antibiotics.

Disinfection of Root Canals with Laser-Activated Irrigation, Photoactivated Disinfection, and Combined Laser Techniques: An Ex Vivo Preliminary Study.

Objective: This study aimed to evaluate the efficacy of laser-activated irrigation using photon-induced photoacoustic streaming (PIPS®) and photoactivated disinfection (PAD) techniques and their combination to improve penetration and activation of toluidine blue in the endodontic space of teeth experimentally infected with Enterococcus faecalis. Materials and methods: Twenty-seven extracted single-root teeth were instrumented, sterilized, and infected with E. faecalis and divided into seven groups of three teeth each: Group A [sodium hypochlorite (NaClO) 5% hand irrigation], Group B [NaClO 5% hand irrigation+ethylenediaminetetraacetic acid (EDTA)+NaClO 5% activated by PIPS], Group C (EDTA+NaClO 5% activated by PIPS), Group D (toluidine blue activated by PAD), Group E (toluidine blue activated by PIPS and PAD), Group F (NaClO 5% hand irrigation+toluidine blue activated by PAD), and Group G (NaClO 5% hand irrigation+toluidine blue activated by PIPS and PAD). Finally, positive and negative group controls were prepared. The presence of biofilms after the treatments was assessed by the BioTimer assay. PIPS was performed with an Er:YAG laser (2940 nm, LightWalker, Fotona® d.o.o., Slovenia) at 20 mJ, 15 Hz, 0.3 W, and 50-µs pulse duration. PAD was performed with a 635 nm diode laser (Smart M, Lasotronix®, Poland) at 400 mW in continuous wave (CW). Results: When NaClO was used, significant decontamination (p ≤ 0.05) was obtained in all experimental groups with respect to the positive control, other than Group G. Irrigation with EDTA+NaClO activated by PIPS produced a higher level of decontamination than Group A (p ≤ 0.05). Significant results in reducing biofilm load compared with the control and Group A were observed when NaClO was coupled with toluidine blue activated by PAD (p ≤ 0.05). Conclusions: Disinfection of root canals can be obtained using a combination of different irrigants, photosensitizers, and activation protocols. EDTA+NaClO using the PIPS protocol and toluidine blue activated by PAD (both preceded by NaClO irrigation) can be considered effective tools. The possibility of replacing NaClO with toluidine blue, whatever the method of activation, should be further investigated.

Protective features of monoclonal antibodies to Escherichia coli during experimental infection of mice with homologous and heterologous serotypes of E. coli.

Murine monoclonal antibodies (MAbs) MT1F and ARM1-4, recognising proteins on the surface of untreated Escherichia coli O6:K-, protected 100% of mice challenged intraperitoneally with 2 x LD50 of the same strain. MAb MT1F protected 70% of animals challenged with 2 x LD50 of E. coli O111:B4, whereas ARM1-4 gave complete protection. Lower survival was observed in mice given either MAb and challenged with E. coli O128:K-, with values ranging from 30 to 42%. However, the protection afforded against E. coli O111:B4 and E. coli O128:K- was significantly improved when the mice were pre-treated with a mixture of the two MAbs. Control mice, pre-treated with unrelated ascitic fluid and challenged with any of the E. coli serotypes, showed 100% mortality and organ histological lesions resembling those of the early stages of septic shock. The mice had high levels of circulating endotoxin and tumour necrosis factor-alpha (TNF-alpha) at 90 min after challenge. In contrast, mice treated with MAbs and surviving the infection displayed moderate histological lesions, enhanced bacterial clearance and lower serum levels of TNF-alpha, despite circulating endotoxin levels that were higher than in the control group. Protection by the MAbs was probably due to the prevention of the bacterial spread to organs and of the cascade of events leading to septic shock. This occurred in spite of the presence of high levels of circulating endotoxin.