Social Determinants of Health among Older Adults with Dementia in Urban and Rural Areas.

BACKGROUND: Social determinants of health (SDOH) may influence health in people living with dementia. Little is known about SDOH differences in urban compared to rural dwelling people living with dementia. OBJECTIVES: To explore urban-rural differences in SDOH in people living with mild cognitive impairment (MCI) and dementia. DESIGN: Descriptive study. SETTING/PARTICIPANTS: People ≥55 years with MCI or dementia empaneled to Community Internal Medicine at Mayo Clinic (Rochester, MN, USA) who completed SDOH questions between June 1, 2019 and June 30, 2021 were included. MEASUREMENTS: SDOH questions addressed education, depression, alcohol use, financial strain, food insecurity, physical activity, social connections, stress and transportation. SDOH data were compared by location based on Rural-Urban Commuting Areas Codes. RESULTS: Of 3552 persons with MCI (n=1495) or dementia (n=2057), 62% lived in urban areas, 19% in large rural, 10% in small rural and 9% in isolated areas. Approximately 60% were physically inactive, 20% socially isolated and 30% had stress concerns. Rural patients experienced greater financial strain (p=0.003). CONCLUSION: Social isolation, stress and physical inactivity are common in people living with MCI and dementia across urban and rural areas. Targeted interventions to improve physical and psychosocial health could have great impact in this population.

Implementing a cirrhosis order set in a tertiary healthcare system: a theory-informed formative evaluation.

BACKGROUND: Standardized order sets are a means of increasing adherence to clinical practice guidelines and improving the quality of patient care. Implementation of novel quality improvement initiatives like order sets can be challenging. Before the COVID-19 pandemic, we conducted a formative evaluation to understand healthcare providers' perspectives on implementing clinical changes and the individual, collective and organizational contextual factors that might impact implementation at eight hospital sites in Alberta, Canada. METHODS: We utilized concepts from the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT) to understand the context, past implementation experiences, and perceptions of the cirrhosis order set. Eight focus groups were held with healthcare professionals caring for patients with cirrhosis. Data were coded deductively using relevant constructs of NPT and CFIR. A total of 54 healthcare professionals, including physicians, nurses, nurse practitioners, social workers and pharmacists and a physiotherapist, participated in the focus groups. RESULTS: Key findings revealed that participants recognized the value of the cirrhosis order set and its potential to improve the quality of care. Participants highlighted potential implementation challenges, including multiple competing quality improvement initiatives, feelings of burnout, lack of communication between healthcare provider groups, and a lack of dedicated resources to support implementation. CONCLUSIONS: Implementing a complex improvement initiative across clinician groups and acute care sites presents challenges. This work yielded insights into the significant influence of past implementation of similar interventions and highlighted the importance of communication between clinician groups and resources to support implementation. However, by using multiple theoretical lenses to illuminate what and how contextual and social processes will influence uptake, we can better anticipate challenges during the implementation process.

Gravid status is not associated with postoperative nausea and vomiting: a matched case-control study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common and unpleasant complication of general anesthesia. There are well-known risk factors that predispose a patient to develop PONV. While studies exist that explore PONV incidence in gravid and non-gravid women separately, limited studies exist to compare the two cohorts to identify if pregnancy is associated with increased risk for PONV or differences in PONV prophylaxis and treatment. METHODS: This is a retrospective case-control cohort study, with 1:2 matching based on age, year of surgery, and surgical procedure. Electronic medical records were abstracted for demographic information, predisposing risk factors, prophylactic antiemetics, PONV documentation, rescue antiemetics, PACU stay, and length of hospitalization. Analyses of risk factors for PONV were performed using logistic and multinomial logistic regression analyses. RESULTS: 237 gravid women who underwent non-obstetric procedures with general anesthesia were identified and matched with 474 non-gravid women. PONV complicated the course of 51 (21.5%) gravid and 72 (15.2%) non-gravid women. The number of prophylactic antiemetics was fewer among gravid (median 2 [1, 2]) than non-gravid (3 [2, 3]) women (P < 0.001). No association was found between gravid status and risk for PONV (adjusted odds ratio 1.35 [95%CI 0.84, 2.17], P = 0.222). Gravid women had longer hospital lengths of stay (P < 0.001), despite having shorter surgical duration (P = 0.015). CONCLUSIONS: The risk for PONV is similar between gravid and similarly aged women. However, anesthesiologists administer fewer prophylactic antiemetics to gravid women during non-obstetric surgery.

Mouse models of NADK2 deficiency analyzed for metabolic and gene expression changes to elucidate pathophysiology.

NADK2 encodes the mitochondrial form of nicotinamide adenine dinucleotide (NAD) kinase, which phosphorylates NAD. Rare recessive mutations in human NADK2 are associated with a syndromic neurological mitochondrial disease that includes metabolic changes, such as hyperlysinemia and 2,4 dienoyl CoA reductase (DECR) deficiency. However, the full pathophysiology resulting from NADK2 deficiency is not known. Here, we describe two chemically induced mouse mutations in Nadk2-S326L and S330P-which cause severe neuromuscular disease and shorten lifespan. The S330P allele was characterized in detail and shown to have marked denervation of neuromuscular junctions by 5 weeks of age and muscle atrophy by 11 weeks of age. Cerebellar Purkinje cells also showed progressive degeneration in this model. Transcriptome profiling on brain and muscle was performed at early and late disease stages. In addition, metabolomic profiling was performed on the brain, muscle, liver and spinal cord at the same ages and on plasma at 5 weeks. Combined transcriptomic and metabolomic analyses identified hyperlysinemia, DECR deficiency and generalized metabolic dysfunction in Nadk2 mutant mice, indicating relevance to the human disease. We compared findings from the Nadk model to equivalent RNA sequencing and metabolomic datasets from a mouse model of infantile neuroaxonal dystrophy, caused by recessive mutations in Pla2g6. This enabled us to identify disrupted biological processes that are common between these mouse models of neurological disease, as well as those processes that are gene-specific. These findings improve our understanding of the pathophysiology of neuromuscular diseases and describe mouse models that will be useful for future preclinical studies.

Efficiency of different flows for apneic oxygenation when using high flow nasal oxygen application - a technical simulation.

BACKGROUND: Preoxygenation and application of apneic oxygenation are standard to prevent patients from desaturation e.g. during emergency intubation. The time before desaturation occurs can be prolonged by applying high flow oxygen into the airway. Aim of this study was to scientifically assess the flow that is necessary to avoid nitrogen entering the airway of a manikin model during application of pure oxygen via high flow nasal oxygen. METHODS: We measured oxygen content over a 20-min observation period for each method in a preoxygenated test lung applied to a human manikin, allowing either room air entering the airway in control group, or applying pure oxygen via high flow nasal oxygen at flows of 10, 20, 40, 60 and 80 L/min via nasal cannula in the other groups. Our formal hypothesis was that there would be no difference in oxygen fraction decrease between the groups. RESULTS: Oxygen content in the test lung dropped from 97 ± 1% at baseline in all groups to 43 ± 1% in the control group (p < 0.001 compared to all other groups), to 92 ± 1% in the 10 L/min group, 92 ± 1% in the 20 L/min group, 90 ± 1% in the 40 L/min group, 89 ± 0% in the 60 L/min group and 87 ± 0% in the 80 L/min group. Apart from comparisons 10 l/ min vs. 20 L/min group (p = .715) and 10/L/min vs. 40 L/min group (p = .018), p was < 0.009 for all other comparisons. CONCLUSIONS: Simulating apneic oxygenation in a preoxygenated manikin connected to a test lung over 20 min by applying high flow nasal oxygen resulted in the highest oxygen content at a flow of 10 L/min; higher flows resulted in slightly decreased oxygen percentages in the test lung.

Deformed wing virus variant shift from 2010 to 2016 in managed and feral UK honey bee colonies.

Deformed wing virus (DWV) has been linked to the global decline of honey bees. DWV exists as three master variants (DWV-A, DWV-B, and DWV-C), each with differing outcomes for the honey bee host. Research in the USA showed a shift from DWV-A to DWV-B between 2010 to 2016 in honey bee colonies. Likewise, in the UK, a small study in 2007 found only DWV-A, whereas in 2016, DWV-B was the most prevalent variant. This suggests a shift from DWV-A to DWV-B might have occurred in the UK between 2007 and 2016. To investigate this further, data from samples collected in 2009/10 (n = 46) were compared to existing data from 2016 (n = 42). These samples also allowed a comparison of DWV variants between Varroa-untreated (feral) and Varroa-treated (managed) colonies. The results revealed that, in the UK, DWV-A was far more prevalent in 2009/10 (87%) than in 2016 (43%). In contrast, DWV-B was less prevalent in 2009/10 (76%) than in 2016 (93%). Regardless if colonies had been treated for Varroa (managed) or not (feral), the same trend from DWV-A to DWV-B occurred. Overall, the results reveal a decrease in DWV-A and an increase in DWV-B in UK colonies.

Oxygenation laryngoscope vs. nasal standard and nasal high flow oxygenation in a technical simulation of apnoeic oxygenation.

BACKGROUND: Failed airway management is the major contributor for anaesthesia-related morbidity and mortality. Cannot-intubate-cannot-ventilate scenarios are the most critical emergency in airway management, and belong to the worst imaginable scenarios in an anaesthetist's life. In such situations, apnoeic oxygenation might be useful to avoid hypoxaemia. Anaesthesia guidelines recommend careful preoxygenation and application of high flow oxygen in difficult intubation scenarios to prevent episodes of deoxygenation. In this study, we evaluated the decrease in oxygen concentration in a model when using different strategies of oxygenation: using a special oxygenation laryngoscope, nasal oxygen, nasal high flow oxygen, and control. METHODS: In this experimental study we compared no oxygen application as a control, standard pure oxygen application of 10 l·min- 1 via nasal cannula, high flow 90% oxygen application at 20 l·min- 1 using a special nasal high flow device, and pure oxygen application via our oxygenation laryngoscope at 10 l·min- 1. We preoxygenated a simulation lung to 97% oxygen concentration and connected this to the trachea of a manikin model simulating apnoeic oxygenation. Decrease in oxygen concentration in the simulation lung was measured continuously for 20 min. RESULTS: Oxygen concentration in the simulation lung dropped from 97 ± 1% at baseline to 40 ± 1% in the no oxygen group, to 80 ± 1% in the standard nasal oxygen group, and to 73 ± 2% in the high flow nasal oxygenation group. However, it remained at 96 ± 0% in the oxygenation laryngoscope group (p < 0.001 between all groups). CONCLUSIONS: In this technical simulation, oxygenation via oxygenation laryngoscope was more effective than standard oxygen insufflation via nasal cannula, which was more effective than nasal high flow insufflation of 90% oxygen.

Experience and expectations of patients on weight loss: The Learning Health System Network Experience.

OBJECTIVE: Weight perception and degree of confidence in achieving healthy lifestyle can be determinants of engagement in obesity interventions. This study explored patients' perceived need for weight loss and the degree of self-confidence in ability to lose weight and sought to identify factors associated with patients' self-confidence in ability to lose weight. METHODS: The authors analysed data from a survey mailed to primary care patients within five sites of the Learning Health Systems Network that explored participants' prior experience with weight management. RESULTS: Among the 2,263 participants who completed the survey section on 'Patients' Experience with Weight Management', perceived need to lose 51 lb or more was statistically significant among those with class III obesity compared with other body mass index (BMI) groups (p value < 0.001). Reported desire to lose weight was also significantly higher among those with the highest BMI than those who were overweight (p value < 0.001). However, this same group had the lowest belief in ability to lose weight (p value < 0.001). In a multiple regression analysis, female gender, higher BMI and need to lose >10 lb were each independently associated with less belief in being able to lose weight. CONCLUSIONS: Patients had varying perceptions on weight loss; those with category III obesity had the highest desire to lose weight but had the least confidence in ability to lose weight. Higher BMI, female gender and need to lose >10 lb were associated with decreased self-confidence in ability to lose weight.

Agitation in adults in the post-anaesthesia care unit after general anaesthesia.

BACKGROUND: Agitation after general anaesthesia can lead to self-harm, violence against staff, and increased resource utilisation. We aimed to assess patient and procedural characteristics associated with this complication in adults. METHODS: We identified cases of agitation (Richmond Agitation-Sedation Scale score +3 or +4, or administration of haloperidol) in patients after general anaesthesia in the PACU from July 1, 2010 to September 30, 2016. The cases were matched 1:1 with control patients without agitation by age, sex, and procedure. Potential clinical associations were assessed with a multivariable analysis. RESULTS: We identified agitation in 510 patients [incidence: 2.5 cases/1000 patients; 95% confidence interval (CI): 2.3-2.7]. Variables associated with agitation were substance misuse [odds ratio (OR): 6.77; 95% CI: 1.23-37.2; P=0.03], cognitive impairment (OR: 4.66; 95% CI: 1.79-12.1; P=0.002), obesity (OR: 2.49; 95% CI: 1.66-3.73; P<0.001), psychiatric problems (OR: 2.05; 95% CI: 1.32-3.19; P=0.002), fall risk (OR: 1.66; 95% CI: 1.02-2.70; P=0.04), postoperative presence of a tracheal tube (OR: 16.6; 95% CI: 7.25-38.2; P<0.001), urine catheter (OR: 7.25; 95% CI: 4.31-12.2; P<0.001), nasogastric tube (OR: 4.06; 95% CI: 1.51-10.9; P=0.006), or chest tube (OR: 3.46; 95% CI: 1.07-11.2; P=0.006). Compared with control patients, more agitated patients had postoperative delirium (16.1% vs 6.3%; P<0.001) and pulmonary complications (9.8% vs 4.7%; P=0.002). CONCLUSIONS: Agitation after general anaesthesia was associated with postoperative indwelling catheters, tracheal intubation and patient features suggestive of pre-existing mental health problems. Anticipation of high-risk patients could allow allocation of staffing resources to provide a safe environment for anaesthetic recovery.

Association between exposure to anaesthesia and surgery and long-term cognitive trajectories in older adults: report from the Mayo Clinic Study of Aging.

BACKGROUND: The link between exposure to general anaesthesia and surgery (exposure) and cognitive decline in older adults is debated. We hypothesised that it is associated with cognitive decline. METHODS: We analysed the longitudinal cognitive function trajectory in a cohort of older adults. Models assessed the rate of change in cognition over time, and its association with exposure to anaesthesia and surgery. Analyses assessed whether exposure in the 20 yr before enrolment is associated with cognitive decline when compared with those unexposed, and whether post-enrolment exposure is associated with a change in cognition in those unexposed before enrolment. RESULTS: We included 1819 subjects with median (25th and 75th percentiles) follow-up of 5.1 (2.7-7.6) yr and 4 (3-6) cognitive assessments. Exposure in the previous 20 yr was associated with a greater negative slope compared with not exposed (slope: -0.077 vs -0.059; difference: -0.018; 95% confidence interval: -0.032, -0.003; P=0.015). Post-enrolment exposure in those previously unexposed was associated with a change in slope after exposure (slope: -0.100 vs -0.059 for post-exposure vs pre-exposure, respectively; difference: -0.041; 95% confidence interval: -0.074, -0.008; P=0.016). Cognitive impairment could be attributed to declines in memory and attention/executive cognitive domains. CONCLUSIONS: In older adults, exposure to general anaesthesia and surgery was associated with a subtle decline in cognitive z-scores. For an individual with no prior exposure and with exposure after enrolment, the decline in cognitive function over a 5 yr period after the exposure would be 0.2 standard deviations more than the expected decline as a result of ageing. This small cognitive decline could be meaningful for individuals with already low baseline cognition.

Pattern of perioperative gabapentinoid use and risk for postoperative naloxone administration.

BACKGROUND: Single preoperative gabapentinoid (gabapentin and pregabalin) administration has been associated with respiratory depression during Phase I anaesthesia recovery. In this study, we assess for associations between chronic (home) use and perioperative administration (preoperative and postoperative) of gabapentinoids, and risk for severe over-sedation or respiratory depression as inferred from the use of naloxone. METHODS: From 2011 to 2016, we identified patients undergoing general anaesthesia discharged to standard postoperative wards and administered naloxone within 48 h of surgery in a single centre. These patients were 2:1 matched on age, sex, and type of procedure. Patient and perioperative characteristics were abstracted and compared to assess for risk for naloxone administration. RESULTS: We identified 128 patients that received naloxone after operation [odds ratio 1.2; 95% confidence interval (CI) 1.0, 1.4 per 1000 general anaesthetics]. Patients on chronic or postoperative gabapentinoid therapy were at significantly higher risk for receiving naloxone after operation. Multivariable analysis detected significant interactions between chronic and postoperative use of gabapentinoids, where continuation of chronic gabapentinoid medications into the postoperative period was associated with an increased rate of naloxone administration (6.30, 95% CI 2.4, 16.7; P=0.001). Obstructive sleep apnoea (P=0.005) and preoperative disability (P=0.003) were also associated with an increased risk for postoperative naloxone administration. Patients who received naloxone had longer hospital stays and higher rates of postoperative delirium. CONCLUSIONS: Continuation of chronic gabapentinoid medications into the postoperative period is associated with the increased use of naloxone to reverse over-sedation or respiratory depression. Such patients requiring this therapy warrant high levels of postoperative monitoring.

Students' perceptions of STEM learning after participating in a summer informal learning experience.

BACKGROUND: Informal learning environments increase students' interest in STEM (e.g., Mohr-Schroeder et al. School Sci Math 114: 291-301, 2014) and increase the chances a student will pursue a STEM career (Kitchen et al. Sci Educ 102: 529-547, 2018). The purpose of this study was to examine the impact of an informal STEM summer learning experience on student participants, to gain in-depth perspectives about how they felt this experience prepared them for their in-school mathematics and science classes as well as how it influenced their perception of STEM learning. Students' attitudes and perceptions toward STEM are affected by their motivation, experience, and self-efficacy (Brown et al. J STEM Educ Innov Res 17: 27, 2016). The academic and social experiences students' have are also important. Traditionally, formal learning is taught in a solitary form (Martin Science Education 88: S71-S82, 2004), while, informal learning is brimming with chances to connect and intermingle with peers (Denson et al. J STEM Educ: Innovations and Research 16: 11, 2015). RESULTS: We used a naturalistic inquiry, phenomenological approach to examine students' perceptions of STEM while participating in a summer informal learning experience. Data came from students at the summer informal STEM learning experiences at three diverse institutions across the USA. Data were collected from reflection forms and interviews which were designed to explore students' "lived experiences" (Van Manen 1990, p. 9) and how those experiences influenced their STEM learning. As we used a situative lens to examine the research question of how participation in an informal learning environment influences students' perceptions of STEM learning, three prominent themes emerged from the data. The informal learning environment (a) provided context and purpose to formal learning, (b) provided students opportunity and access, and (c) extended STEM content learning and student engagement. CONCLUSIONS: By using authentic STEM workplaces, the STEM summer learning experience fostered a learning environment that extended and deepened STEM content learning while providing opportunity and access to content, settings, and materials that most middle level students otherwise would not have access to. Students also acknowledged the access they received to hands-on activities in authentic STEM settings and the opportunities they received to interact with STEM professionals were important components of the summer informal learning experience.

Postoperative delirium in elderly patients is associated with subsequent cognitive impairment.

BACKGROUND: We examined the risk for postoperative delirium (POD) in patients with mild cognitive impairment (MCI) or dementia, and the association between POD and subsequent development of MCI or dementia in cognitively normal elderly patients. METHODS: Patients ≥65 yr of age enrolled in the Mayo Clinic Study of Aging who were exposed to any type of anaesthesia from 2004 to 2014 were included. Cognitive status was evaluated before and after surgery by neuropsychological testing and clinical assessment, and was defined as normal or MCI/dementia. Postoperative delirium was detected with the Confusion Assessment Method for the intensive care unit. Logistic regression analyses were performed. RESULTS: Among 2014 surgical patients, 74 (3.7%) developed POD. Before surgery, 1667 participants were cognitively normal, and 347 met MCI/dementia criteria. The frequency of POD was higher in patients with pre-existing MCI/dementia compared with no MCI/dementia {8.7 vs 2.6%; odds ratio (OR) 2.53, [95% confidence interval (CI) 1.52-4.21]; P <0.001}. Postoperative delirium was associated with lower education [OR, 3.40 (95% CI, 1.60-7.40); P =0.002 for those with <12 vs ≥16 yr of schooling]. Of the 1667 patients cognitively normal at their most recent assessment, 1152 returned for postoperative evaluation, and 109 (9.5%) met MCI/dementia criteria. The frequency of MCI/dementia at the first postoperative evaluation was higher in patients who experienced POD compared with those who did not [33.3 vs 9.0%; adjusted OR, 3.00 (95% CI, 1.12-8.05); P =0.029]. CONCLUSIONS: Mild cognitive impairment or dementia is a risk for POD. Elderly patients who have not been diagnosed with MCI or dementia but experience POD are more likely to be diagnosed subsequently with MCI or dementia.

["Kids Save Lives"-resuscitation training for schoolchildren : Systematic review]. / "Kids Save Lives" ­ Wiederbelebungstrainings für Schulkinder : Systematische Übersichtsarbeit.

BACKGROUND: Even in western developed countries, the probability of survival after out-of-hospital cardiac arrest (OHCA) is only 6-10%. In order to improve survival after OHCA, early initiation of cardiopulmonary resuscitation (CPR) by laypersons is essential. Introduction of CPR training in schoolchildren seems to be effective to increase lay-CPR rates. OBJECTIVE: The objective of the present investigation was to elucidate educational aspects of teaching schoolchildren in CPR and to summarize campaigns related to a comprehensive establishment of lay-CPR worldwide. MATERIALS AND METHODS: A literature research in PubMed was performed, the cutoff date was 27 February 2017. Overall, 192 abstracts were analyzed; 51 articles were considered relevant and included in the manuscript. An additional keyword research in Google revealed >230,000 entries, and 20 of those were included in the present manuscript. RESULTS: A minimum age of 12-13 years is required to achieve a comparable quality of CPR to adult basic life support (BLS). Key issues are (i) the correct detection of a cardiac arrest, (ii) a correctly performed call for help, (iii) thoracic compressions and (iv) if applicable, the initiation of adequate mouth-to-mouth ventilation. Practical training showed a significantly higher CPR quality compared to theoretical training only or to the use of instruction or online videos only. Worldwide implementation of a 2-h BLS training per year in children from the age of 12 or younger is recommended by the "Kids Save Lives"- statement since 2015. In Germany, implementation at the level of the federal states has progressed to different degrees.

A negative view of menopause: does the type of symptom matter?

OBJECTIVES: To assess the association between the type of symptom and women's self-reported view of menopause. METHODS: The study was conducted at Mayo Clinic, Rochester MN, between January 2006 and October 2014. Women aged 40-64 were included. Data from 1420 women were analyzed in a cross-sectional design. The Menopause Health Questionnaire was used for symptom assessment. Odds ratios (ORs) and population attributable risk (PAR) (OR × percent frequency) were calculated for each symptom. Logistic regression analyses were performed with the view of menopause as the dependent variable. RESULTS: Anxiety (2.34), depressed mood (2.24), irritability (2.22), vaginal itching (2.27), crying spells (2.1) and breast tenderness (2.08) were associated with highest odds of having a negative view of menopause. Highest PAR (population impact) symptoms were anxiety (22.27), weight gain (20.66), fatigue (20.28) and irritability (19.41). Hot flushes and night sweats, although common, were not associated with a negative view of menopause (OR 1.3 and 1.16; PAR 3.85 and 4.42, respectively). CONCLUSION: Mood symptoms, vaginal itching, weight gain, breast tenderness and fatigue, although less common than hot flushes, were noted to have greater association with a negative view of menopause. Specifically addressing these symptoms during menopausal consultation may improve patient satisfaction and outcomes.

Differential Gene Expression in Coiled versus Flow-Diverter-Treated Aneurysms: RNA Sequencing Analysis in a Rabbit Aneurysm Model.

BACKGROUND AND PURPOSE: The biologic mechanisms leading to aneurysm healing or rare complications such as delayed aneurysm ruptures after flow-diverter placement remain poorly understood. We used RNA sequencing following implantation of coils or flow diverters in elastase aneurysms in rabbits to identify genes and pathways of potential interest. MATERIALS AND METHODS: Aneurysms were treated with coils (n = 5) or flow diverters (n = 4) or were left untreated for controls (n = 6). Messenger RNA was isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed by using RNA-sequencing technology and were analyzed by using the Ingenuity Pathway Analysis tool. RESULTS: With RNA sequencing for coiled versus untreated aneurysms, 464/9990 genes (4.6%) were differentially expressed (58 down-regulated, 406 up-regulated). When we compared flow-diverter versus untreated aneurysms, 177/10,041 (1.8%) genes were differentially expressed (8 down-regulated, 169 up-regulated). When we compared flow-diverter versus coiled aneurysms, 13/9982 (0.13%) genes were differentially expressed (8 down-regulated, 5 up-regulated). Keratin 8 was overexpressed in flow diverters versus coils. This molecule may potentially play a critical role in delayed ruptures due to plasmin production. We identified overregulation of apelin in flow diverters, supporting the preponderance of endothelialization, whereas we found overexpression of molecules implicated in wound healing (dectin 1 and hedgehog interacting protein) for coiled aneurysms. Furthermore, we identified metallopeptidases 1, 12, and 13 as overexpressed in coiled versus untreated aneurysms. CONCLUSIONS: We observed different physiopathologic responses after endovascular treatment with various devices. Flow diverters promote endothelialization but express molecules that could potentially explain the rare delayed ruptures. Coils promote wound healing and express genes potentially implicated in the recurrence of coiled aneurysms.

Preclinical Testing of a Novel Thin Film Nitinol Flow-Diversion Stent in a Rabbit Elastase Aneurysm Model.

BACKGROUND AND PURPOSE: Thin film nitinol can be processed to produce a thin microporous sheet with a low percentage of metal coverage (<20%) and high pore attenuation (∼70 pores/mm(2)) for flow diversion. We present in vivo results from the treatment of experimental rabbit aneurysms by using a thin film nitinol-based flow-diversion device. MATERIALS AND METHODS: Nineteen aneurysms in the rabbit elastase aneurysm model were treated with a single thin film nitinol flow diverter. Devices were also placed over 17 lumbar arteries to model perianeurysmal branch arteries of the intracranial circulation. Angiography was performed at 2 weeks (n = 7), 1 month (n = 8), and 3 months (n = 4) immediately before sacrifice. Aneurysm occlusion was graded on a 3-point scale (grade I, complete occlusion; grade II, near-complete occlusion; grade III, incomplete occlusion). Toluidine blue staining was used for histologic evaluation. En face CD31 immunofluorescent staining was performed to quantify neck endothelialization. RESULTS: Markedly reduced intra-aneurysmal flow was observed on angiography immediately after device placement in all aneurysms. Grade I or II occlusion was noted in 4 (57%) aneurysms at 2-week, in 6 (75%) aneurysms at 4-week, and in 3 (75%) aneurysms at 12-week follow-up. All 17 lumbar arteries were patent. CD31 staining showed that 75% ± 16% of the aneurysm neck region was endothelialized. Histopathology demonstrated incorporation of the thin film nitinol flow diverter into the vessel wall and no evidence of excessive neointimal hyperplasia. CONCLUSIONS: In this rabbit model, the thin film nitinol flow diverter achieved high rates of aneurysm occlusion and promoted tissue in-growth and aneurysm neck healing, even early after implantation.

The distribution of basal water between Antarctic subglacial lakes from radar sounding.

Antarctica's subglacial lakes have two end member geophysical expressions: as hydraulically flat, radar reflective regions highlighted in ice surface topography and radar sounding profiles ('definite lakes'), and as localized sites of elevation change identified from repeat elevation observations ('active lakes') that are often found in fast flowing ice streams or enhanced ice flow tributaries. While 'definite lakes' can be identified readily by high bed reflectivity in radar sounding, the identification and characterization of less distinct subglacial lakes and water systems with radar sounding are complicated by variable radio-wave attenuation in the overlying ice. When relying on repeat elevation observations, the relatively short times series and biased distribution of elevation observations, along with the episodic nature of 'active lake' outflow and replenishment, limit our understanding of how water flows under the ice sheet. Using recently developed methods for quantifying the radar scattering behaviour of the basal interface of the ice, we can avoid the problem of attenuation, and observe the plumbing of the subglacial landscape. In West Antarctica's Ross Sea Embayment, we confirm that extensive distributed water systems underlie these ice streams. Distributed water sheets are upstream in the onset regions of fast flow, while canal systems underly downstream regions of fast flow. In East Antarctica, we use specularity analysis to recover substantial hydraulic connectivity extending beyond previous knowledge, connecting the lakes already delineated by traditional radar sounding or surface elevation transients.

Retrospective Derivation and Validation of an Automated Electronic Search Algorithm to Identify Post Operative Cardiovascular and Thromboembolic Complications.

BACKGROUND: With increasing numbers of hospitals adopting electronic medical records, electronic search algorithms for identifying postoperative complications can be invaluable tools to expedite data abstraction and clinical research to improve patient outcomes. OBJECTIVES: To derive and validate an electronic search algorithm to identify postoperative thromboembolic and cardiovascular complications such as deep venous thrombosis, pulmonary embolism, or myocardial infarction within 30 days of total hip or knee arthroplasty. METHODS: A total of 34 517 patients undergoing total hip or knee arthroplasty between January 1, 1996 and December 31, 2013 were identified. Using a derivation cohort of 418 patients, several iterations of a free-text electronic search were developed and refined for each complication. Subsequently, the automated search algorithm was validated on an independent cohort of 2 857 patients, and the sensitivity and specificities were compared to the results of manual chart review. RESULTS: In the final derivation subset, the automated search algorithm achieved a sensitivity of 91% and specificity of 85% for deep vein thrombosis, a sensitivity of 96% and specificity of 100% for pulmonary embolism, and a sensitivity of 100% and specificity of 95% for myocardial infarction. When applied to the validation cohort, the search algorithm achieved a sensitivity of 97% and specificity of 99% for deep vein thrombosis, a sensitivity of 97% and specificity of 100% for pulmonary embolism, and a sensitivity of 100% and specificity of 99% for myocardial infarction. CONCLUSIONS: The derivation and validation of an electronic search strategy can accelerate the data abstraction process for research, quality improvement, and enhancement of patient care, while maintaining superb reliability compared to manual review.

Modifications in integrin expression and extracellular matrix composition in children with biliary atresia.

BACKGROUND: The aetiology of biliary atresia (BA) is still unresolved. The study's aim was to investigate the distribution of extracellular matrix proteins and cellular adhesion molecules in children with BA compared to other cholestatic liver disease (CLD) and normal liver architecture (NLA). PATIENTS: Liver biopsies were obtained from children with BA (n=13), CLD (n=6) and NLA (n=8). METHOD: We systematically analysed ultra thin frozen sections from the liver hilum stained with 25 monoclonal antibodies for cellular characterisation, extracellular matrix proteins and adhesion molecules. RESULTS: 2 changes were specifically found in BA: laminin beta1 was reduced in children with BA vs. NLA and CLD. Conversely, integrin alpha 3 was increased in BA vs. NLA and CLD (p<0.05). Furthermore, we detected changes in a similar pattern for both BA and CLD vs. NLA: in BA and CLD perlecan was increased. On the contrary, integrin beta1 and entactin were decreased vs. NLA (p<0.05). DISCUSSION: Extracellular matrix proteins and adhesion molecules mediate cellular polarity and integrity, development of tubular structures, and proliferation. Therefore, our findings can be important for the understanding of the genesis of BA. CONCLUSION: The composition of extracellular matrix proteins and adhesion molecules in children with BA differs from NLA and other CLD in distribution of laminin beta1 and integrin alpha 3, which may have implications for genetic, immunologic and environmental associations in BA.