Microbial shifts in the aging mouse gut

YesBackground: The changes that occur in the microbiome of aging individuals are unclear, especially in light of the imperfect correlation of frailty with age. Studies in older human subjects have reported subtle effects, but these results may be confounded by other variables that often change with age such as diet and place of residence. To test these associations in a more controlled model system, we examined the relationship between age, frailty, and the gut microbiome of female C57BL/6 J mice. Results: The frailty index, which is based on the evaluation of 31 clinical signs of deterioration in mice, showed a near-perfect correlation with age. We observed a statistically significant relationship between age and the taxonomic composition of the corresponding microbiome. Consistent with previous human studies, the Rikenellaceae family, which includes the Alistipes genus, was the most significantly overrepresented taxon within middle-aged and older mice. The functional profile of the mouse gut microbiome also varied with host age and frailty. Bacterial-encoded functions that were underrepresented in older mice included cobalamin (B12) and biotin (B7) biosynthesis, and bacterial SOS genes associated with DNA repair. Conversely, creatine degradation, associated with muscle wasting, was overrepresented within the gut microbiomes of the older mice, as were bacterial-encoded β-glucuronidases, which can influence drug-induced epithelial cell toxicity. Older mice also showed an overabundance of monosaccharide utilization genes relative to di-, oligo-, and polysaccharide utilization genes, which may have a substantial impact on gut homeostasis. Conclusion: We have identified taxonomic and functional patterns that correlate with age and frailty in the mouse microbiome. Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty. Future work with larger cohorts of mice will aim to separate the effects of age and frailty, and other factors.This work was supported by the Canadian Institutes of Health Research (CIHR) through an Emerging Team Grant to RGB, CIHR Operating Grants to Langille et al. Microbiome 2014, 2:50 Page 10 of 12 http://www.microbiomejournal.com/content/2/1/50 SEH (MOP 126018) and RAR (MOP 93718), and a CIHR Fellowship to MGIL. Infrastructure was supported by the Canada Foundation for Innovation through a grant to RGB. RGB also acknowledges the support of the Canada Research Chairs program

Efficacy of rituximab on seizure control and cognitive symptoms in leucine-rich, glioma-inactivated 1 (LGI1) limbic encephalitis: a high-density electroencephalography case study

LGI1 encephalitis is an autoimmune disorder characterized by cognitive symptoms and seizures, which rarely respond to common antiepileptic drugs (AEDs). Rituximab (RTX) is a CD-20-depleting monoclonal antibody which has been used for the treatment of LGI1 encephalitis, however, its efficacy remains controversial. A 54-year-old woman came to our attention due to memory loss and gambling. Brain MRI revealed areas of bilateral hippocampal hyperintensity and LGI1 antibodies were found in both serum and cerebrospinal fluid. Immunotherapy with steroids was started, followed by intravenous immunoglobulins with partial improvement. The patient developed multiple generalized tonic-clonic seizures. She was then administered intravenous rituximab with significant improvement for both cognitive symptoms and seizure control. High-density EEG was recorded before treatment, seven days after the first dose and seven days after the second dose. Topoplot and power spectrum analysis were performed for each recording. Interictal epileptiform discharges, as well as theta power bands, were significantly reduced after each dose, while topoplot analysis showed reduced spreading over posterior and frontal electrodes for interictal epileptiform discharges of temporal origin. Our experience indicates that rituximab is a valid treatment for LGI1 encephalitis, demonstrating efficacy for both cognitive symptoms and seizure control. High-density EEG could represent a novel, safe and reproducible method to study epileptogenesis in autoimmune limbic encephalitis

Single-Center Experience and Preliminary Results of Intravascular Ultrasound in Endovascular Aneurysm Repair

Background: Intravascular ultrasound (IVUS) has been introduced as diagnostic adjunct to provide new insights into the diagnosis and therapy of vascular disease. Herein, we compared the outcomes of conventional endovascular aneurysm repair (EVAR) and EVAR with IVUS in patients presenting with infrarenal abdominal aortic aneurysm using a propensity-matched cohort. Methods: From May 2013 to August 2017, 221 patients were retrospectively analyzed. Of that, 122 patients were eligible for inclusion and underwent propensity score matching. Perioperative mortality and morbidity, renal function impairment, endoleak incidence, mean contrast medium usage, operative time, radiation exposure (including fluoroscopy time, dose-area product [DAP], and digital subtraction angiography [DSA] runs), survival, and freedom from reintervention were the outcomes measured. Results: After matching, 52 patients were included, 26 in the conventional EVAR group and 26 in the EVAR with IVUS group. No perioperative mortality or type I/III endoleak were registered. One perioperative lymphatic fistula and one iliac limb occlusion were observed. In the EVAR with IVUS group, a significant reduction of contrast medium (92 [vs. 51 \ub1 17] vs. 51 [20\u201368] mL; P = 0.003) and radiation exposure including fluoroscopy time (12 [9\u201316] vs. 20 [12\u201325] min; P = 0.001), DAP (15 [9\u201321] vs. 32 [16\u201344] G*cm 2 ; P = 0.002), and DSA runs (2 [1\u20133] vs. 3 [2\u20134]; P = 0.04) was reported. No differences were observed in terms of glomerular filtration rate (86 [45\u2013121] vs. 90 [38\u2013117] mL/min; P = 0.14) and operation time (176 [124\u2013210] vs. 179 [120\u2013210]; P = 0.48). Survival at 36 months was 93% for standard EVAR and 92% for EVAR with IVUS (P = 0.845). Freedom from reintervention at 36 months was 85.5% in both the groups (P = 0.834). Conclusions: In this preliminary experience, the use of IVUS during EVAR was feasible with no registered postoperative complications. A significant reduction of contrast medium usage and radiation exposure was observed with the use of IVUS. The IVUS is an adjunctive tool to consider in the vascular surgeon armamentarium, especially in centers where advanced radiological tools of imaging fusion are not available

Managing Peripheral Artery Disease in Diabetic Patients: A Questionnaire Survey from Vascular Centers of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS)

Background: The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded on October 1, 2018, to enhance cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic arteriopathy has been selected as the very first topic to be investigated by the federation. Methods: MeFAVS members were asked to reply to a questionnaire on the management of diabetic ischemic foot. Results were collected and analyzed statistically. The questionnaire consisted of 15 multiple choice answers regarding diabetic foot (DF) diagnosis and treatment. The questionnaire was submitted to 21 centers on April 20, 2019. Results: Response rate was 62%. The survey revealed that vascular surgeons, diabetologists, and wound care nurses made-up the core of the diabetic teams present in 76.9%, 69.3%, and 92.3% of the centers, respectively. Diabetic teams were most often led by vascular surgeons (53.8%) and diabetologists (42.2%), but only in 7.9% of cases by nurses. Duplex ultrasonography and computed tomographic angiography were the most commonly available tools used to assess diabetic peripheral arterial disease (PAD). Surgical wound care was undertaken by vascular surgeons in the majority of cases, and only in 46.2% of the cases to orthopedic or plastic surgeons, while nonsurgical wound care was handled by specialized nurses (76.6%) and diabetologists (53.8%). First-line revascularization was preferred over conservative treatment (61.5% vs 53.8%) and endovascular strategy (45.3%) over open (33.7%) or hybrid (21.0%) surgery. Vascular surgeons and interventional radiologists were found to be the most common performers of endovascular revascularization (92.3% and 53.8%, respectively). Amputations had an overall rate of 16.6% (range 4\u201330%) and a mean reintervention rate of 22.5%, and were usually performed by vascular surgeons for both minor and major interventions (84.6%) followed by orthopedic surgeons (15.4% minor and 30.8% major). The availability of a DF clinic (84.6%) and endovascular (53.8%) and open surgery (46.2%) capabilities were considered fundamental to reduce amputation rates. Conclusions: Especially since the introduction and spreading of new endovascular techniques for the treatment of DF, it is a common consensus amongst vascular surgeons that a standardized approach to the discipline is necessary in order to improve outcomes such as amputation-free survival and mortality and it is with this perspective and purpose that transnational cooperation amongst vascular professionals and residents in training are aiming for greater proficiency in endovascular and open surgery

AEGIS/AD-6 status report

AEGIS / AD-6 status report 200