SIRT2 deficiency modulates macrophage polarization and susceptibility to experimental colitis

BACKGROUND SIRT2 belongs to a highly conserved family of NAD+-dependent deacylases, consisting of seven members (SIRT1-SIRT7), which vary in subcellular localizations and have substrates ranging from histones to transcription factors and enzymes. Recently SIRT2 was revealed to play an important role in inflammation, directly binding, deacetylating, and inhibiting the p65 subunit of NF-κB. METHODS A Sirt2 deficient mouse line (Sirt2-/-) was generated by deleting exons 5-7, encoding part of the SIRT2 deacetylase domain, by homologous recombination. Age- and sex-matched Sirt2-/- and Sirt2+/+ littermate mice were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility. RESULTS Sirt2-/- mice displayed more severe clinical and histological manifestations after DSS colitis compared to wild type littermates. Notably, under basal condition, Sirt2 deficiency does not affect the basal phenotype and intestinal morphology Sirt2 deficiency, however, affects macrophage polarization, creating a pro-inflammatory milieu in the immune cells compartment. CONCLUSION These data confirm a protective role for SIRT2 against the development of inflammatory processes, pointing out a potential role for this sirtuin as a suppressor of colitis. In fact, SIRT2 deletion promotes inflammatory responses by increasing NF-κB acetylation and by reducing the M2-associated anti-inflammatory pathway. Finally, we speculate that the activation of SIRT2 may be a potential approach for the treatment of inflammatory bowel disease.

ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax.

Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research.The European Respiratory Society's Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence.Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach.In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required.

Dynamic changes of intramural hematoma in patients with acute spontaneous internal carotid artery dissection.

BACKGROUND We prospectively investigated temporal and spatial evolution of intramural hematomas in patients with acute spontaneous internal carotid artery dissection using repeated magnetic resonance imaging over six-months. AIM The aim of the present study was to assess dynamic changes of intramural hematoma in patients with acute spontaneous internal carotid artery dissection at multiple follow-up time-points with T1w, PD/T2w, and magnetic resonance angiography. METHODS We performed serial multiparametric magnetic resonance imaging in 10 patients with spontaneous internal carotid artery dissection on admission, at days 1, 3, 7-14 and at months 1·5, 3, and 6. We calculated the volume and extension of the hyperintense intramural hematoma using T1w and PD/T2w fat suppressed sequences and assessed the degree of stenosis due to the hematoma using magnetic resonance angiography. RESULTS Mean interval from symptom onset to first magnetic resonance imaging was two-days (SD 2·7). Two patients presented with ischemic stroke, three with transient ischemic attacks, and five with pain and local symptoms only. Nine patients had a transient increase of the intramural hematoma volume, mainly up to day 10 after symptom onset. Fifty percent had a transient increase in the degree of the internal carotid artery stenosis on MRA, one resulting in a temporary occlusion. Lesions older than one-week were predominantly characterized by a shift from iso- to hyperintese signal on T2w images. At three-month follow-up, intramural hematoma was no longer detectable in 80% of patients and had completely resolved in all patients after six-months. CONCLUSIONS Spatial and temporal dynamics of intramural hematomas after spontaneous internal carotid artery dissection showed an early volume increase with concomitant progression of the internal carotid artery stenosis in 5 of 10 patients. Although spontaneous internal carotid artery dissection overall carries a good prognosis with spontaneous hematoma resorption in all our patients, early follow-up imaging may be considered, especially in case of new clinical symptoms.

Management of spontaneous intracranial hypotension - Transorbital ultrasound as discriminator.

OBJECTIVE Spontaneous intracranial hypotension (SIH) is most commonly caused by cerebrospinal fluid (CSF) leakage. Therefore, we hypothesised that patients with orthostatic headache (OH) would show decreased optic nerve sheath diameter (ONSD) during changes from supine to upright position. METHODS Transorbital B-mode ultrasound was performed employing a high-frequency transducer for ONSD measurements in the supine and upright positions. Absolute values and changes of ONSD from supine to upright were assessed. Ultrasound was performed in 39 SIH patients, 18 with OH and 21 without OH, and in 39 age-matched control subjects. The control group comprised 20 patients admitted for back surgery without headache or any orthostatic symptoms, and 19 healthy controls. RESULTS In supine position, mean ONSD (±SD) was similar in patients with (5.38±0.91 mm) or without OH (5.48±0.89 mm; p=0.921). However, in upright position, mean ONSD was different between patients with (4.84±0.99 mm) and without OH (5.53±0.99 mm; p=0.044). Furthermore, the change in ONSD from supine to upright position was significantly greater in SIH patients with OH (-0.53±0.34 mm) than in SIH patients without OH (0.05±0.41 mm; p≤0.001) or in control subjects (0.01±0.38 mm; p≤0.001; area under the curve: 0.874 in receiver operating characteristics analysis). CONCLUSIONS Symptomatic patients with SIH showed a significant decrease of ONSD, as assessed by ultrasound, when changing from the supine to the upright position. Ultrasound assessment of the ONSD in two positions may be a novel, non-invasive tool for the diagnosis and follow-up of SIH and for elucidating the pathophysiology of SIH.