Safety profile and outcome after ultrasound-guided suprainguinal fascia iliaca catheters for hip fracture: a single-centre propensity-matched historical cohort study.

PURPOSE: Peripheral nerve blocks improve analgesia following hip fracture; however, there are little published data on safety and outcomes of continuous regional anesthetic techniques. Our institution offers pre- and perioperative, anesthesiologist-delivered ultrasound-guided suprainguinal fascia iliaca catheters (FICs) to patients with hip fracture. We aimed to document the safety profile of this technique and establish whether there are any significant clinical benefits in outcomes measured by the UK National Hip Fracture Database. METHODS: We performed a single-centre historical cohort study of 2,187 patients admitted to our institution with hip fracture over a 5.75-year period. Of these, 915 were treated with FIC and 1,272 received standard care (single-shot block). To control for baseline differences between these two cohorts, we used propensity score matching and exact matching, resulting in two well-matched groups of 728 patients treated with an FIC and standard care. RESULTS: No serious complications were observed as a result of an FIC. Unplanned removal occurred in 146/852 (17.1%) patients with documented data. No differences in 30-day mortality, pressure ulcer rates, or hospital length of stay were observed between the matched groups. The percentage of patients who were discharged to their usual residence was 79.3% in the FIC cohort vs 75.1% in the standard care cohort (difference, 4.2%; 95% confidence interval, -0.1 to 8.4; P = 0.06). DISCUSSION: Our single-centre propensity-matched historical cohort study suggests that ultrasound-guided suprainguinal fascia iliaca catheterization is a safe technique for patients with hip fracture and that our service is deliverable and sustainable within the UK's National Health Service. This study did not show statistically significant differences in outcomes between patients treated with FIC and standard care. An adequately powered multicentre randomized controlled trial comparing these approaches is warranted.

RéSUMé: OBJECTIF: Les blocs nerveux périphériques améliorent l'analgésie après une fracture de la hanche; cependant, il existe peu de données publiées sur l'innocuité et les devenirs des techniques d'anesthésie régionale continue. Notre établissement propose des cathéters iliofasciaux suprainguinaux échoguidés pré- et périopératoires aux patients souffrant d'une fracture de la hanche. Notre objectif était de documenter le profil d'innocuité de cette technique et de déterminer s'il existe des avantages cliniques significatifs au niveau des devenirs tels que mesurés par la Base de données nationale sur les fractures de la hanche du Royaume-Uni. MéTHODE: Nous avons réalisé une étude de cohorte historique monocentrique portant sur 2187 patients admis dans notre établissement avec une fracture de la hanche sur une période de 5,75 ans. De ce nombre, 915 ont été traités avec un cathéter iliofascial et 1272 ont reçu des soins standard (bloc à injection unique). Pour tenir compte des différences initiales entre ces deux cohortes, nous avons utilisé l'appariement par score de propension et l'appariement exact, ce qui a donné deux groupes bien appariés de 728 patients chaque, les patients étant traités par cathéter ilio-fascial ou soins standard. RéSULTATS: Aucune complication grave n'a été observée à la suite de l'utilisation d'un cathéter iliofascial. Un retrait imprévu est survenu chez 146/852 (17,1 %) patients dont les données ont été documentées. Aucune différence dans la mortalité à 30 jours, les taux d'escarres ou la durée de séjour à l'hôpital n'a été observée entre les groupes appariés. Le pourcentage de patients qui ont reçu leur congé à leur résidence habituelle était de 79,3 % dans la cohorte cathéter iliofascial vs 75,1 % dans la cohorte de soins standard (différence, 4,2 %; intervalle de confiance à 95 %, -0,1 à 8,4; P = 0,06). DISCUSSION: Notre étude de cohorte historique monocentrique et appariée par propension suggère que le cathétérisme iliofascial suprainguinal échoguidé est une technique sécuritaire pour les patients atteints de fracture de la hanche et que notre service est utilisable et durable au sein du National Health Service du Royaume-Uni. Cette étude n'a pas montré de différences statistiquement significatives dans les devenirs entre les patients traités par cathéter iliofascial ou par soins standard. Une étude randomisée contrôlée multicentrique suffisamment puissante comparant ces approches est justifiée.

Deficits in executive function and suppression of default mode network in obesity.

BACKGROUND: Although nutritional and metabolic factors are well established in obesity, neurocognitive determinants are less understood. Using data from the Human Connectome Project, this study concurrently investigated neurocognitive performance, neural activation during a working memory task, and cortical brain morphometry in relation to obesity in a group of young adults, 22-35 years old. METHODS: Using a case-control design, obese individuals (n = 243, body mass index [BMI] ≥ 30 kg/m2) were compared to a control group of lean BMI individuals (n = 469, BMI = 18-24.9 kg/m2). Performance tests comprised a battery of behavioral neurocognitive assessments. Neural activity was measured as blood-oxygenation-level-dependent (BOLD) activity during an N-Back task using functional magnetic resonance imaging (fMRI). Cortical morphometry included indices of volume, thickness, and surface area. RESULTS: Relative to the control group, the obese group exhibited significantly worse performance in terms of the National Institutes of Health Toolkit (NIH) 9-Hole Peg Board, Penn Working Memory Test, Delay Discounting, Penn Progressive Matrices, NIH Picture Vocabulary Test, Dimensional Change Card Sort Test and the in-scanner N-Back working memory test (FDR-corrected ps<0.05; ds = 0.231-0.405). The obese group also exhibited significantly greater BOLD activation in N-Back task-negative regions, including the ventromedial prefrontal cortex, posterior cingulate, and right precentral gyrus (FDR-corrected ps<0.05). Supplemental functional connectivity analyses provided evidence that the implicated regions were part of the default mode network. Significant differences in morphometry were present in the medial orbitofrontal cortex, rostral anterior cingulate cortex, inferior and superior parietal gyri, and temporal pole (FDR-corrected p<0.001). A data-driven integrative model classified 73.8% of participants correctly. CONCLUSIONS AND RELEVANCE: This multimodal investigation suggests diverse aspects of neurocognition are associated with obesity, particularly implicating deficits in executive function and ineffective suppression of the default mode network.

T1-Mapping and Outcome in Nonischemic Cardiomyopathy: All-Cause Mortality and Heart Failure.

OBJECTIVES: The study sought to examine prognostic relevance of T1 mapping parameters (based on a T1 mapping method) in nonischemic dilated cardiomyopathy (NIDCM) and compare them with conventional markers of adverse outcome. BACKGROUND: NIDCM is a recognized cause of poor clinical outcome. NIDCM is characterized by intrinsic myocardial remodeling due to complex pathophysiological processes affecting myocardium diffusely. Lack of accurate and noninvasive characterization of diffuse myocardial disease limits recognition of early cardiomyopathy and effective clinical management in NIDCM. Cardiac magnetic resonance (CMR) supports detection of diffuse myocardial disease by T1 mapping. METHODS: This is a prospective observational multicenter longitudinal study in 637 consecutive patients with dilated NIDCM (mean age 50 years [interquartile range: 37 to 76 years]; 395 males [62%]) undergoing CMR with T1 mapping and late gadolinium enhancement (LGE) at 1.5-T and 3.0-T. The primary endpoint was all-cause mortality. A composite of heart failure (HF) mortality and hospitalization was a secondary endpoint. RESULTS: During a median follow-up period of 22 months (interquartile range: 19 to 25 months), we observed a total of 28 deaths (22 cardiac) and 68 composite HF events. T1 mapping indices (native T1 and extracellular volume fraction), as well as the presence and extent of LGE, were predictive of all-cause mortality and HF endpoint (p < 0.001 for all). In multivariable analyses, native T1 was the sole independent predictor of all-cause and HF composite endpoints (hazard ratio: 1.1; 95% confidence interval: 1.06 to 1.15; hazard ratio: 1.1; 95% confidence interval: 1.05 to 1.1; p < 0.001 for both), followed by the models including the extent of LGE and right ventricular ejection fraction, respectively. CONCLUSIONS: Noninvasive measures of diffuse myocardial disease by T1 mapping are significantly predictive of all-cause mortality and HF events in NIDCM. We provide a basis for a novel algorithm of risk stratification in NIDCM using a complementary assessment of diffuse and regional disease by T1 mapping and LGE, respectively.

Validity of the Postoperative Morbidity Survey after abdominal aortic aneurysm repair-a prospective observational study.

BACKGROUND: Currently, there is no standardised tool used to capture morbidity following abdominal aortic aneurysm (AAA) repair. The aim of this prospective observational study was to validate the Postoperative Morbidity Survey (POMS) according to its two guiding principles: to only capture morbidity substantial enough to delay discharge from hospital and to be a rapid, simple screening tool. METHODS: A total of 64 adult patients undergoing elective infrarenal AAA repair participated in the study. Following surgery, the POMS was recorded daily, by trained research staff with the clinical teams blinded, until hospital discharge or death. We modelled the data using Cox regression, accounting for the competing risk of death, with POMS as a binary time-dependent (repeated measures) internal covariate. For each day for each patient, 'discharged' (yes/no) was the event, with the elapsed number of days post-surgery as the time variable. We derived the hazard ratio for any POMS morbidity (score 1-9) vs. no morbidity (zero), adjusted for type of repair (endovascular versus open), age and aneurysm size. RESULTS: The hazard ratio for alive discharge with any POMS-recorded morbidity versus no morbidity was 0.130 (95 % confidence interval 0.070 to 0.243). The median time-to-discharge was 13 days after recording any POMS morbidity vs. 2 days after scoring zero for POMS morbidity. Compliance with POMS completion was 99.5 %. CONCLUSIONS: The POMS is a valid tool for capturing short-term postoperative morbidity following elective infrarenal AAA repair that is substantial enough to delay discharge from hospital. Daily POMS measurement is recommended to fully capture morbidity and allow robust analysis. The survey could be a valuable outcome measure for use in quality improvement programmes and future research.

Dynamic regulation of Oct1 during mitosis by phosphorylation and ubiquitination.

BACKGROUND: Transcription factor Oct1 regulates multiple cellular processes. It is known to be phosphorylated during the cell cycle and by stress, however the upstream kinases and downstream consequences are not well understood. One of these modified forms, phosphorylated at S335, lacks the ability to bind DNA. Other modification states besides phosphorylation have not been described. METHODOLOGY/PRINCIPAL FINDINGS: We show that Oct1 is phosphorylated at S335 in the Oct1 DNA binding domain during M-phase by the NIMA-related kinase Nek6. Phospho-Oct1 is also ubiquitinated. Phosphorylation excludes Oct1 from mitotic chromatin. Instead, Oct1(pS335) concentrates at centrosomes, mitotic spindle poles, kinetochores and the midbody. Oct1 siRNA knockdown diminishes the signal at these locations. Both Oct1 ablation and overexpression result in abnormal mitoses. S335 is important for the overexpression phenotype, implicating this residue in mitotic regulation. Oct1 depletion causes defects in spindle morphogenesis in Xenopus egg extracts, establishing a mitosis-specific function of Oct1. Oct1 colocalizes with lamin B1 at the spindle poles and midbody. At the midbody, both proteins are mutually required to correctly localize the other. We show that phospho-Oct1 is modified late in mitosis by non-canonical K11-linked polyubiquitin chains. Ubiquitination requires the anaphase-promoting complex, and we further show that the anaphase-promoting complex large subunit APC1 and Oct1(pS335) interact. CONCLUSIONS/SIGNIFICANCE: These findings reveal mechanistic coupling between Oct1 phosphorylation and ubquitination during mitotic progression, and a role for Oct1 in mitosis.