Impatto della terapia anticoagulante orale in pazienti ricoverati per patologia cerebrovascolare.

La terapia anticoagulante orale costituisce il trattamento di prima scelta nella prevenzione dell’ictus cardioembolico con particolare riferimento alla fibrillazione atriale che determina circa il 25% degli eventi ischemici cerebrali. Tuttavia tale terapia è di provata efficacia solo se vengono mantenuti corretti livelli di anticoagulazione (valori di INR compresi tra 2 e 3) in quanto al di sotto di questo range permane il rischio di ictus cardioembolico mentre per valori superiori incrementa il rischio emorragico. La difficoltà a mantenere costante nel tempo il range terapeutico degli anticoagulanti orali è dovuta a scarsa compliance e a numerose interferenze alimentari e farmacologiche con una possibile ricaduta negativa in termini di efficacia. Lo scopo di questo studio è stato di valutare in pazienti con malattia cerebrovascolare acuta l’impatto della prevenzione con anticoagulanti orali sul tipo di evento cerebrovascolare (ischemico ed emorragico) e sul sottotipo eziopatogenetico dell’ischemia (cardioembolico, lacunare, aterosclerosi dei grossi vasi). A questo scopo sono stati valutati in modo retrospettivo 144 pazienti consecutivi (80 maschi e 64 femmine; età media±DS=77,5±3,9 anni; range 47-88 anni) in trattamento anticoagulante orale ricoverati presso la Clinica Neurologica dell’Università di Pisa dal Gennaio 2004 al Gennaio 2009 per malattia cerebrovascolare acuta (ictus ischemico, attacco ischemico transitorio, ictus emorragico parenchimale, emorragia subaracnoidea). Al momento del ricovero è stata effettuata TC cranio per diagnosticare il tipo di evento (ischemico o emorragico) ed è stato valutato il livello di anticoagulazione attraverso il dosaggio plasmatico di INR. In tutti i casi di ischemia cerebrale è stata effettuata la classificazione del sottotipo eziopatogenetico (cardioembolia, aterosclerosi dei grossi vasi, malattia dei piccoli vasi). La maggior parte dei pazienti (85%) presentava un evento di natura ischemica e il 15% un evento di natura emorragica. Il gruppo dei pazienti ischemici con INR<2 aveva una eziopatogenesi di tipo cardioembolico nel 69,7% dei casi, mentre il gruppo con INR≥2 aveva un’eziopatogenesi da malattia dei piccoli vasi (lacunare) nel 53,6% dei casi e cardioembolica solo nel 32,1% dei casi. Il gruppo di pazienti emorragici presentava valori di INR<2 nel 55% dei casi e di INR≥2 nel 45% dei casi. Alcuni fattori di rischio emorragico come l’ipertensione arteriosa e la leucoaraiosi valutata alla TC cranio sono stati riscontrati in tutti i casi emorragici con INR≥2. Con i limiti legati al carattere retrospettivo di questo studio, i risultati ottenuti tendono a confermare l’efficacia della terapia anticoagulante orale nella prevenzione di eventi ischemici cerebrali di natura cardioembolica quando viene rispettato il range terapeutico, tuttavia tale trattamento non risulta altrettanto efficace quando l’eziopatogenesi è dovuta a malattia dei piccoli vasi (lacunare). Per quanto riguarda invece il rischio di ictus emorragico questo appare essere solo in parte associato all’entità dell’anticoagulazione verosimilmente per il ruolo che svolge nell’aumentare tale rischio l’elevata frequenza di ipertensione arteriosa e leucoaraiosi

Measurement of a urinary marker (8-hydroxydeoxy-guanosine, 8-OHdG) of DNA oxidative stress in epidemiological surveys: a pilot study

Background: 8-Hydroxydeoxyguanosine (8-OHdG) is a commonly used marker of DNA oxidative stress in epidemiological studies. The aim of this study was to establish whether the urinary concentration of 8-OHdG varies during the first part of the day, when clinical tests are usually performed, and whether it can therefore be measured without bias in spot urine samples. Material and methods: Spot urine samples were collected using a convenience sample. A linear mixed-effects model for repeated measurements was used to analyze 8-OHdG levels. Results: A significant increasing trend in time in the 8-OHdG concentration was found among smokers, but not in the case of nonsmokers. Conclusions: In epidemiological studies on oxidative stress, all participants should collect their early morning urine specimens – before their first cigarette if they are smokers – to gather information on individual background oxidation levels

Focused ultrasound to diagnose HIV-associated tuberculosis (FASH) in the extremely resource-limited setting of South Sudan: a cross-sectional study

Our cross-sectional study aimed at evaluating the diagnostic performance of Focused Assessment with Sonography for HIV-associated tuberculosis (FASH) to detect extrapulmonary tuberculosis in extremely resource-limited settings, with visceral leishmaniasis as a differential diagnosis with overlapping sonographic feature

Determining Breast Implant Prevalence. A Population Study of Italian Chest Radiographs

Background Current breast implant prevalence within the general population remains elusive. An accurate prevalence is critical to serve as the denominator for any assessment of breast implant-related complication. The purpose of this manuscript is to assess this prevalence in women aged 20-70 years in Italy.Materials and Methods Eight reviewers, demonstrating a mean sensitivity of 87.0% and specificity of 97.0%, were recruited for retrospective identification of implants on chest radiographs from a tertiary academic hospital in a major urban setting. Three final reviewers were selected, and they assessed all eligible chest radiographs collected between January and December 2019. The hospital-based population was compared to epidemiological data at a local, regional and national level to demonstrate homogeneity of age structures using the phi correlation coefficient.Results We identified 3,448 chest X-rays which yielded 140 implants, with an overall prevalence of 4.1% for women aged 20-70. Implants were bilateral in 76% of cases and unilateral in 24%. They were placed cosmetically in 47.1% cases and used for reconstruction in 52.9% cases. Phi correlation coefficient found no differences across hospital-based, local, regional and national populations.Conclusion A validated method was performed to estimate implant prevalence from an academic hospital in a major urban setting at 4.1% and was used to estimate national prevalence in Italy. The implications of this epidemiologic study may reach across national borders for improved understanding of breast implant epidemiology and in predicting the total number of patients within a given population that may be affected by device complications

Seroprevalence of hepatitis B and hepatitis C among blood donors in Sierra Leone: A multi-year retrospective study

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Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes

Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors--and how this cross talk influences physiological processes--is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein-mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein-mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors

Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B.

Background & aims In chronic HBV infection, mitochondrial functions and proteostasis are dysregulated in exhausted HBV-specific CD8 T cells. To better characterise the potential involvement of deregulated protein degradation mechanisms in T cell exhaustion, we analysed lysosome-mediated autophagy in HBV-specific CD8 T cells. Bioactive compounds able to simultaneously target both mitochondrial functions and proteostasis were tested to identify optimal combination strategies to reconstitute efficient antiviral CD8 T cell responses in patients with chronic HBV infection. Methods Lysosome-mediated degradation pathways were analysed by flow cytometry in virus-specific CD8 T cells from patients with chronic HBV infection. Mitochondrial function, intracellular proteostasis, and cytokine production were evaluated in HBV-peptide-stimulated T cell cultures, in the presence or absence of the polyphenols resveratrol (RSV) and oleuropein (OLE) and their metabolites, either alone or in combination with other bioactive compounds. Results HBV-specific CD8 T cells from patients with CHB showed impaired autophagic flux. RSV and OLE elicited a significant improvement in mitochondrial, proteostasis and antiviral functions in CD8 T cells. Cytokine production was also enhanced by synthetic metabolites, which correspond to those generated by RSV and OLE metabolism in vivo, suggesting that these polyphenols may also display an effect after transformation in vivo. Moreover, polyphenolic compounds improved the T cell revitalising effect of mitochondria-targeted antioxidants and of programmed cell death protein 1/programmed cell death ligand 1 blockade. Conclusions Simultaneously targeting multiple altered intracellular pathways with the combination of mitochondria-targeted antioxidants and natural polyphenols may represent a promising immune reconstitution strategy for the treatment of chronic HBV infection. Lay summary In chronic hepatitis B, antiviral T lymphocytes are deeply impaired, with many altered intracellular functions. In vitro exposure to polyphenols, such as resveratrol and oleuropein, can correct some of the deregulated intracellular pathways and improve antiviral T cell function. This effect can be further strengthened by the association of polyphenols with antioxidant compounds in a significant proportion of patients. Thus, the combination of antioxidants and natural polyphenols represents a promising strategy for chronic hepatitis B therapy