Sirtuin 6 Protects Against Oxidative Stress and Vascular Dysfunction in Mice.

Objective: Sirtuin deacetylases are major regulators of organismal aging, and while depletion of sirtuin 6 (SIRT6) in mice results in a profound progeroid phenotype, the role of SIRT6 in the regulation of vasomotor function is unknown. Thus, our objective was to test the hypothesis that reductions in SIRT6 elicit endothelial dysfunction in young, genetically altered mice. Results and Approach: We used young (3 month old), littermate-matched, SIRT6 wild-type (WT), and SIRT6 heterozygous (HET) mice. SIRT6 expression (qRT-PCR) was reduced by 50% in HET mice. Carotid vessel responses to acetylcholine, sodium nitroprusside, U46619, and serotonin were examined in isolated organ chamber baths. Relaxation in response to acetylcholine (ACH) was impaired in HET mice compared to littermate-matched WT controls (67 ± 3% versus 76 ± 3%, respectively; p < 0.05), while responses to sodium nitroprusside were unchanged. Short-term incubation of carotid rings with the NAD(P)H oxidase inhibitor, apocynin, significantly improved in vessels from HET mice but not their WT littermates. Peak tension generated in response to either U46619 or serotonin was significantly blunted in HET mice compared to their WT littermates. Conclusion: These data suggest that SIRT6 is a key regulator of vasomotor function in conduit vessels. More specifically, we propose that SIRT6 serves as a tonic suppressor of NAD(P)H oxidase expression and activation, as inhibition of NAD(P)H oxidase improved endothelial function in SIRT6 haploinsufficient mice. Collectively, SIRT6 activation and/or histone acetyltransferase inhibition may be useful therapeutic approaches to reduce endothelial dysfunction and combat age-associated cardiovascular disease.

Quantitative pupillometry for the monitoring of intracranial hypertension in patients with severe traumatic brain injury.

BACKGROUND: Elevated intracranial pressure (ICP) is frequent after traumatic brain injury (TBI) and may cause abnormal pupillary reactivity, which in turn is associated with a worse prognosis. Using automated infrared pupillometry, we examined the relationship between the Neurological Pupil index (NPi) and invasive ICP in patients with severe TBI. METHODS: This was an observational cohort of consecutive subjects with severe TBI (Glasgow Coma Scale [GCS] < 9 with abnormal lesions on head CT) who underwent parenchymal ICP monitoring and repeated NPi assessment with the NPi-200® pupillometer. We examined NPi trends over time (four consecutive measurements over intervals of 6 h) prior to sustained elevated ICP > 20 mmHg. We further analyzed the relationship of cumulative abnormal NPi burden (%NPi values < 3 during total ICP monitoring time) with intracranial hypertension (ICHT)-categorized as refractory (ICHT-r; requiring surgical decompression) vs. non-refractory (ICHT-nr; responsive to medical therapy)-and with the 6-month Glasgow Outcome Score (GOS). RESULTS: A total of 54 patients were studied (mean age 54 ± 21 years, 74% with focal injuries on CT), of whom 32 (59%) had ICHT. Among subjects with ICHT, episodes of sustained elevated ICP (n = 43, 172 matched ICP-NPi samples; baseline ICP [T- 6 h] 14 ± 5 mmHg vs. ICPmax [T0 h] 30 ± 9 mmHg) were associated with a concomitant decrease of the NPi (baseline 4.2 ± 0.5 vs. 2.8 ± 1.6, p < 0.0001 ANOVA for repeated measures). Abnormal NPi values were more frequent in patients with ICHT-r (n = 17; 38 [3-96]% of monitored time vs. 1 [0-9]% in patients with ICHT-nr [n = 15] and 0.5 [0-10]% in those without ICHT [n = 22]; p = 0.007) and were associated with an unfavorable 6-month outcome (15 [1-80]% in GOS 1-3 vs. 0 [0-7]% in GOS 4-5 patients; p = 0.002). CONCLUSIONS: In a selected cohort of severe TBI patients with abnormal head CT lesions and predominantly focal cerebral injury, elevated ICP episodes correlated with a concomitant decrease of NPi. Sustained abnormal NPi was in turn associated with a more complicated ICP course and worse outcome.

[The « Osler ¼ group : a new opportunity to think about « becoming a physician ¼]. / Le groupe « Osler ¼ : une nouvelle opportunité pour réfléchir sur le « devenir médecin ¼.

Issues of professionalism and professional identity formation, particularly amongst young doctors, have been the object of increasing attention. This is explained in part by the evolution of the hospital environment (specialization, shorter stays), as well as by the prevalence of physician burnout and suicide. In this context, the CHUV implemented a pilot project within the department of internal medicine aiming to support its residents in the construction of their professional identity. The Osler group convened 10 residents led by an attending physician and a senior resident from the internal medicine department as well as an attending physician of the liaison psychiatry department. The experience has been a success, with residents describing clear benefits of the group.

Les enjeux de professionnalisme et d'identité professionnelle chez les médecins font l'objet d'un intérêt croissant, en raison des évolutions du milieu hospitalier (spécialisation, raccourcissement de la durée de séjour) ainsi que de phénomènes comme le burn-out ou le suicide. C'est dans ce contexte que le CHUV a mis en place un projet pilote dans le Service de médecine interne (SMI) pour soutenir les médecins assistants dans la construction de leur identité professionnelle, valoriser la transmission de l'expérience clinique et leur offrir un espace de parole et d'échange. Le groupe « Osler ¼ a ainsi réuni dix assistants pour des rencontres animées par un médecin cadre et une cheffe de clinique du SMI, ainsi qu'un médecin cadre du Service de psychiatrie de liaison. L'expérience a été un succès, les assistants exprimant clairement les bienfaits du groupe, notamment quant à leur rapport au métier.

HeartMate 3 implantation via left antero-lateral thoracotomy to avoid resternotomy in high risk patients.

Left ventricular assist devices (LVADs) are currently the best alternative to cardiac transplantation for patients with end-stage heart failure (HF) as a bridge to transplant or to decision, or as destination therapy. Full median sternotomy or minimally invasive techniques are the more standard approaches used at present.  LVADs are usually implanted between the left ventricle apex and the ascending aorta. An implantation through a left thoracotomy with an outflow graft connected to the descending aorta is much less performed nowadays due to the longer times to extubation, higher incidence of postoperative pain, and poorer hemodynamics in the ascending aorta, which may lead to thrombosis. However, some patients present a prohibitive risk for a medial approach. Also, many patients with a VAD will require future transplantation, and avoiding a sternotomy or crossing the mediastinum with the outflow graft can reduce the risks of the subsequent procedure in these patients. Various options for implantation may be used. Our described approach consists of implanting the left VAD (LVAD) via a left lateral thoracotomy and anastomosing the outflow graft to the descending aorta.

Too Hot to Handle: A Case Report of Extreme Pyrexia After MDMA Ingestion.

Hyperpyrexia is a well-documented adverse effect of 3,4-methylenedioxymethamphetamine (MDMA) and is associated with a poor prognosis. There are currently limited published records of patients surviving a pyrexia of or greater than 43°C after MDMA intake. Rapid cooling and multiorgan support in an intensive care setting may offer patients the best chance of recovery. We present the case of a 16-year-old male who was admitted to our tertiary, adult intensive care unit (ICU) for unrecordable pyrexia (>43°C) after reported ecstasy intake. The patient went on to develop severe multiorgan failure and profound disseminated intravascular coagulopathy. Initial patient management focused on rapid cooling using an endovascular cooling catheter and rigorous monitoring and treatment of autonomic symptoms, followed by subsequent surgical therapy (fasciotomy) and multiorgan support. The patient eventually achieved a good clinical outcome after 4 weeks of management in the ICU, and was discharged well to his local hospital. Despite multiple end-organ dysfunctions and often severely poor prognosis, survival after severe hyperpyrexia induced by MDMA intake is possible with proper management and organ support in an appropriate intensive care environment.