•This review describes an integrated and multidisciplinary approach for the “early” diagnosis of Alzheimer's disease (AD).•An overview of epidemiology, genetic risk factors, and different biomarkers ...of AD is provided.•Latest findings suggest EEG rhythms analysis as a valid screening tool to predict AD conversion.
Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to prodromal stages of AD. Thus, the identification of markers of conversion from prodromal form to clinically AD may be crucial for developing strategies of early interventions. The current available markers, including volumetric magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebral spinal fluid (CSF) analysis are expensive, poorly available in community health facilities, and relatively invasive. Taking into account its low cost, widespread availability and non-invasiveness, electroencephalography (EEG) would represent a candidate for tracking the prodromal phases of cognitive decline in routine clinical settings eventually in combination with other markers. In this scenario, the present paper provides an overview of epidemiology, genetic risk factors, neuropsychological, fluid and neuroimaging biomarkers in AD and describes the potential role of EEG in AD investigation, trying in particular to point out whether advanced analysis of EEG rhythms exploring brain function has sufficient specificity/sensitivity/accuracy for the early diagnosis of AD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Multivariate analysis was used to identify the variables affecting the performance of pilot-scale activated sludge (AS) reactors treating old leachate from a landfill and from domestic wastewater. ...Raw leachate was pre-treated using air stripping to partially remove the total ammoniacal nitrogen (TAN). The control AS reactor (AS-0%) was loaded only with domestic wastewater, whereas the other reactor was loaded with mixtures containing leachate at volumetric ratios of 2 and 5%. The best removal efficiencies were obtained for a ratio of 2%, as follows: 70 ± 4% for total suspended solids (TSS), 70 ± 3% for soluble chemical oxygen demand (SCOD), 70 ± 4% for dissolved organic carbon (DOC), and 51 ± 9% for the leachate slowly biodegradable organic matter (SBOM). Fourier transform infrared (FTIR) spectroscopic analysis confirmed that most of the SBOM was removed by partial biodegradation rather than dilution or adsorption of organics in the sludge. Nitrification was approximately 80% in the AS-0% and AS-2% reactors. No significant accumulation of heavy metals was observed for any of the tested volumetric ratios. Principal component analysis (PCA) and partial least squares (PLS) indicated that the data dimension could be reduced and that TAN, SCOD, DOC and nitrification efficiency were the main variables that affected the performance of the AS reactors.
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•Among the tested volumetric leachate ratios, a ratio of 2% was optimal.•Leachate was mostly (51%) biodegraded by aerobic microorganisms.•Up to 1.60 mg L−1 free ammonia did not inhibit nitrification.•The activated sludge reactors efficiently eliminated heavy metals.•Variables affecting the co-treatment were identified by multivariate analysis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii in patients hospitalized in intensive care units for coronavirus disease-2019 is an important and ...challenging superinfection.•Considering the poor lung penetration of most antibiotics, the choice of the best antibiotic regimen for treatment of VAP is still being debated.•Data from this study showed a possible benefit deriving from the use of cefiderocol and its association with fosfomycin compared with a colistin-based regimen.•This real-life study in patients with bacteraemic VAP provides useful suggestions for clinicians about the management of this difficult-to-treat infection.
Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated.
This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model.
During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis.
This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The 97% of dementia patients develops fluctuant neuropsychiatric symptoms often related to under-diagnosed and unrelieved pain. Up to 80% severe demented nursing home residents experiences chronic ...pain due to age-related comorbidities. Patients lacking self-report skills risk not to be appropriately treated for pain. Mobilization–Observation–Behavior–Intensity–Dementia (MOBID2) is the sole pain scale to consider the frequent co-occurrence of musculoskeletal and visceral pain and to unravel concealed pain through active guided movements. Accordingly, the Italian real-world setting can benefit from its translation and validation. This clinical study provides a translated, adapted and validated version of the MOBID2, the Italian I-MOBID2. The translation, adaptation and validation of the scale for non-verbal, severe demented patients was conducted according to current guidelines in a cohort of 11 patients over 65 with mini-mental state examination ≤ 12. The I-MOBID2 proves: good face and scale content validity index (0.89); reliable internal consistency (Cronbach’s α = 0.751); good to excellent inter-rater (Intraclass correlation coefficient, and test-retest (ICC = 0.902) reliability. The construct validity is high (Rho = 0.748 p < 0.05 for 11 patients, Spearman rank order correlation of the overall pain intensity score with the maximum item score of I-MOBID2 Part 1; rho=0.895 p < 0.01 for 11 patients, for the overall pain intensity score with the maximum item score of I-MOBID2 Part 2) and a good rate of inter-rater and test-retest agreement was demonstrated by Cohen’s K = 0.744. The average execution time is of 5.8 min, thus making I-MOBID2 a useful tool suitable also for future development in community setting with administration by caregivers.
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•Impaired communication during dementia hampers pain evaluation.•Unrelieved pain may trigger agitation.•The control with potentially harmful antipsychotics claims therapeutic innovation.•Analgesia is a demonstrated priority in neuropsychiatric symptoms (NPS) management.•I-MOBID2 validation is necessary to improve pain and NPS therapy in Italian context.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•SABR provides high rates of local control to lung oligometastases.•Local control of colorectal lung metastases seems lower compared to other tumors.•We identified predictive factors of SABR response ...and polymetastases development.•Predictive factors of local control are BED ≥125 Gy and lesion diameter ≤20 mm.•Having lesion >20 mm and 4–5 metastases predicted for a polymetastatic evolution.
Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD).
The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC).
Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100–124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10–20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11–0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2–3 or 4–5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035).
The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite the great interest paid to protein components in colostrum, fat also plays an important role in the supply of essential nutrients to provide energy, increase metabolism, and protect the ...newborn calf against microbial infections. This work aimed to elucidate levels of different fat components in colostrum, in particular fatty acid (FA), triglyceride (TG), cholesterol, and phospholipid contents. Colostrum samples from primiparous and multiparous (3–5 lactations) Holstein dams, fed the same ration indoors, were collected on the first 5d after parturition, analyzed, and compared with milk samples from the same cows collected at 5mo of lactation. Fat content during the first 5d of milking did not vary. However, the proportion of short-chain saturated FA increased and that of long-chain FA decreased. The concentration of n-3 FA was higher on the first day of calving than on the other days, with clear differences in the number and type of n-3 FA. Conjugated linoleic isomers and trans FA slowly increased from d 1 to 5, reaching a maximum at 5mo of lactation. Changes in the distribution profile of TG were observed as lactation progressed, with a shift from a prevalence of high-carbon-number TG (C48–50) on d 1 to a bimodal distribution (maxima at C38 and C50) on d 5, characteristic of mid-lactation milk. Cholesterol content was high in the first hours after calving and rapidly decreased within 48h. Colostrum sampled on d 1 also had a high content of phospholipids. Phosphatidylethanolamine and sphingomyelin were, respectively, lower and higher in the first 5d than in mid-lactation milk. The influence of lactation number on colostrum fat composition was also considered and significant results were obtained for all FA groups (except for polyunsaturated and n-6 FA) and TG content.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Resistive Plate Chamber detectors are largely used in current High Energy Physics experiments, typically operated in avalanche mode with large fractions of Tetrafluoroethane (C2H2F4), a gas recently ...banned by the European Union due to its high Global Warming Potential (GWP). An intense R&D activity is ongoing to improve RPC technology in view of future HEP applications. In the last few years the RPC EcoGas@GIF++ Collaboration has been putting in place a joint effort between the ALICE, ATLAS, CMS, LHCb/SHiP and EP-DT Communities to investigate the performance of present and future RPC generations with eco-friendly gas mixtures. Detectors with different layout and electronics have been operated with ecological gas mixtures, with and without irradiation at the CERN Gamma Irradiation Facility (GIF++). Results of these performance studies together with plans for an aging test campaign are discussed in this article.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line ...treatment with androgen receptor-targeted therapy (ARTT).
Patients and methods
Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan–Meier method, univariate and multivariate analysis (MVA) were performed.
Results
Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio HR 3.66,
p
= 0.009; HR 3.03,
p
= 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23,
p
= 0.017; HR 0.19,
p
= 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39,
p
= 0.026; HR 2.79,
p
= 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity.
Conclusion
Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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