Citations

Abstract Background The advancement of knowledge about control of antibiotic resistance depends on the rigorous evaluation of alternative intervention strategies. The STAR*ICU trial examined the effects of active surveillance and expanded barrier precautions on acquisition of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) in intensive care units. We report a reanalyses of the STAR*ICU trial using a Bayesian transmission modeling framework. Methods The data included admission and discharge times and surveillance test times and results. Markov chain Monte Carlo stochastic integration was used to estimate the transmission rate, importation, false negativity, and clearance separately for MRSA and VRE. The primary outcome was the intervention effect, which when less than (or greater than) zero, indicated a decreased (or increased) transmission rate attributable to the intervention. Results The transmission rate increased in both arms from pre- to postintervention (by 20% and 26% for MRSA and VRE). The estimated intervention effect was 0.00 (95% confidence interval [CI], −0.57 to 0.56) for MRSA and 0.05 (95% CI, −0.39 to 0.48) for VRE. Compared with MRSA, VRE had a higher transmission rate (preintervention, 0.0069 vs 0.0039; postintervention, 0.0087 vs 0.0046), higher importation probability (0.22 vs 0.17), and a lower clearance rate per colonized patient-day (0.016 vs 0.035). Conclusions Transmission rates in the 2 treatment arms were statistically indistinguishable from the pre- to postintervention phase, consistent with the original analysis of the STAR*ICU trial. Our statistical framework was able to disentangle transmission from importation and account for imperfect testing. Epidemiological differences between VRE and MRSA were revealed.

Gliosarcoma is an uncommon variant of glioblastoma, which commonly demonstrates dural attachment. However, skull base invasion is rarely seen with this entity. Herein, we report a 44-year-old female patient diagnosed with primary intracranial gliosarcoma extensively invading the skull base and muscles of mastication. She presented to our institution with a three-month history of difficult right jaw opening and retro-orbital pressure and one week of severe right-sided postauricular headache. Head CT demonstrated a 6 cm mass with marked bony erosion. Brain MRI at a one-week interval more clearly characterized tumor extension through the right orbit and muscles of mastication, with overall growth to 7 cm and worsening midline shift. The patient underwent a right frontotemporal craniotomy for gross total resection. Pathology confirmed the diagnosis of gliosarcoma, IDH-wildtype (WHO grade IV). Her postoperative course was uneventful and she was discharged at preoperative neurologic baseline. To our knowledge, this is the third reported case of a primary intracranial gliosarcoma with direct invasion of skull base, brain parenchyma, and extracranial compartment. However, this is the first report case of primary GS invading the surrounding musculature and orbit. This case report highlights the rapid aggressiveness of gliosarcomas and further a prior undescribed radiographic and anatomic finding of skull base invasion with this entity.

AbstractIntroductionWe hypothesized that common Alzheimer's disease (AD)‐associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression.MethodsExpression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis.ResultsA variant within a DNase hypersensitive site 5′ of TREM2, rs9357347‐C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta‐analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni‐corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively).DiscussionOur findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome‐wide association study meta‐analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD.

Abstract The prognosis of the antineutrophil cytoplasmic antibody associated vasculitides (AAV), microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA), has been fundamentally improved over the last five decades by the use of glucocorticoids and immunosuppressants, turning them from consistently fatal diseases into chronic conditions. The long-term course is now largely determined by the frequency of disease flares and by accruing damage caused by disease activity and treatment-related comorbidities. This review summarizes the evidence derived from clinical trials performed during the last 30 years and the remaining clinical unmet needs that new studies aim to address. In MPA and GPA, ongoing studies assess (i) different strategies to reduce cumulative glucocorticoid doses currently used for induction and maintenance of remission, (ii) the efficacy of new drugs and (iii) the optimal duration of immunosuppression and the use of biomarkers to individualize therapy. Prospective randomized trials also target disease-associated cardiovascular risk and infections. The first prospective controlled trials specifically designed for EGPA have recently been launched and could lead to new therapeutic options for patients diagnosed with this rare disease. This is an exciting time for researchers in the field of AAV, and for patients as collaborative efforts raise the hope of developing new therapies and more individualized approaches to the management of the diseases, maximizing efficacy while minimizing treatment toxicities.

SummaryBackgroundSubtotal or total colectomy or proctocolectomy with permanent ileostomy (TC‐PI) may be a treatment option for medically refractory colonic Crohn's disease (CD).AimTo perform a systematic review and meta‐analysis to evaluate the rate, risk factors and outcomes of CD recurrence after TC‐PI.MethodsIn a systematic review ending 31 March 2016, we identified 18 cohort studies (1438 adults) who underwent TC‐PI for colonic CD (median follow‐up, 7.4 years; interquartile range, 5.3–9.0). We estimated pooled rates [with 95% confidence interval (CI)] of clinical and surgical recurrence, and risk factors for disease recurrence.ResultsOn meta‐analysis, the risk of clinical recurrence after TC‐PI was 28.0% (95% CI, 21.7–35.3; 14 studies, 260/1004 patients), with a 5 and 10‐year median cumulative rate of 23.5% (range, 7–35) and 40% (range, 11–60) respectively. The risk of surgical recurrence was 16.0% (95% CI, 11.1–22.7; 10 studies; 183/1092 patients), with a 5 and 10‐year median cumulative rate of 10% (range, 3–29) and 18.5% (range, 14–34) respectively. The risk of clinical and surgical recurrence in patients without ileal disease at baseline was 11.5% (95% CI, 7.7–16.8) and 10.4% (95% CI, 4.5–22.5) respectively. History of ileal disease was associated with 3.2 times higher risk of disease recurrence (RR, 3.2; 95% CI, 1.8–5.6). Other inconsistent risk factors for disease recurrence were penetrating disease and young age at disease onset.ConclusionsSmall bowel clinical recurrence occurs in about 28% of patients after total colectomy with permanent ileostomy for colonic Crohn's disease. Disease recurrence risk is 3.2 times higher in patients with history of ileal disease, and continued medical therapy may be advisable in this population. In patients without ileal inflammation at surgery, continued endoscopic surveillance may identify asymptomatic disease recurrence to guide therapy.