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When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar Po2 and the calculated arterial Po2. The end-tidal Po2 is measured using a rapid gas analyzer, and the arterial Po2 is derived from pulse oximetry after allowing for the effect of the Pco2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal Po2 and Pco2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial Po2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley’s criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same Pco2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal Po2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar Po2, but that it is easier to obtain.

The oxygen deficit (OD) is the difference between the end-tidal alveolar Po2 and the calculated Po2 of arterial blood based on measured oxygen saturation that acts as a proxy for the alveolar-arterial Po2 difference. Previous work has shown that the alveolar gas meter (AGM100) can measure pulmonary gas exchange, via the OD, in patients with a history of lung disease and in normal subjects breathing 12.5% O2. The present study measured how the OD varied at different values of inspired O2. Healthy subjects were split by age (young 22–31; n = 23; older 42–90; n = 13). Across all inspired O2 levels (12.5, 15, 17.5, and 21%), the OD was higher in the older cohort 10.6 ± 1.0 mmHg compared with the young −0.4 ± 0.6 mmHg ( P < 0.0001, using repeated measures ANOVA), the difference being significant at all O2 levels (all P < 0.0001). The OD difference between age groups and its variance was greater at higher O2 values (age × O2 interaction; P = 0.002). The decrease in OD with lower values of inspired O2 in both cohorts is consistent with the increased accuracy of the calculated arterial Po2 based on the O2-Hb dissociation curve and with the expected decrease in the alveolar-arterial Po2 difference due to a lower arterial saturation. The persisting higher OD seen in older subjects, irrespective of the inspired O2, shows that the measurement of OD remains sensitive to mild gas exchange impairment, even when breathing 21% O2.

BACKGROUND: Left-hemisphere brain damage commonly affects patients’ abilities to produce and comprehend syntactic structures, a condition typically referred to as “agrammatism”. The neural correlates of agrammatism remain disputed in the literature, and distributed areas have been implicated as important predictors of performance, e.g. Broca’s area, anterior temporal areas and temporo-parietal areas. OBJECTIVE AND HYPOTHESIS: We examined the association between damage to specific language-related regions of interest and impaired syntactic processing in acute aphasia. We hypothesized that damage to the posterior middle temporal gyrus, and not Broca’s area, would predict syntactic processing abilities. METHOD: 104 individuals with acute aphasia (

Purpose The brain-derived neurotrophic factor (BDNF) gene has been shown to be important for synaptic plasticity in animal models. Human research has suggested that BDNF genotype may influence stroke recovery. Some studies have suggested a genotype-specific motor-related brain activation in stroke recovery. However, recovery from aphasia in relation to BDNF genotype and language-related brain activation has received limited attention. We aimed to explore functional brain activation by BDNF genotype in individuals with chronic aphasia. Consistent with findings in healthy individuals and individuals with poststroke motor impairment, we hypothesized that, among individuals with aphasia, the presence of the Met allele of the BDNF gene is associated with reduced functional brain activation compared to noncarriers of the Met allele. Method Eighty-seven individuals with chronic stroke-induced aphasia performed a naming task during functional magnetic resonance imaging scanning and submitted blood or saliva samples for BDNF genotyping. The mean number of activated voxels was compared between groups, and group-based activation maps were directly compared. Neuropsychological testing was conducted to compare language impairment between BDNF genotype groups. The Western Aphasia Battery Aphasia Quotient ( Kertesz, 2007 ) was included as a covariate in all analyses. Results While lesion size was comparable between groups, the amount of activation, quantified as the number of activated voxels, was significantly greater in noncarriers of the Met allele (whole brain: 98,500 vs. 28,630, p < .001; left hemisphere only: 37,209 vs. 7,000, p < .001; right hemisphere only: 74,830 vs. 30,630, p < .001). This difference was most strongly expressed in the right hemisphere posterior temporal area, pre- and postcentral gyrus, and frontal lobe, extending into the white matter. Correspondingly, the atypical BDNF genotype group was found to have significantly less severe aphasia (Western Aphasia Battery Aphasia Quotient of 64.2 vs. 54.3, p = .033) and performed better on a naming task (Philadelphia Naming Test [ Roach, Schwartz, Martin, Grewal, & Brecher, 1996 ] score of 74.7 vs. 52.8, p = .047). A region of interest analysis of intensity of activation revealed no group differences, and a direct comparison of average activation maps across groups similarly yielded null results. Conclusion BDNF genotype mediates cortical brain activation in individuals with chronic aphasia. Correspondingly, individuals carrying the Met allele present with more severe aphasia compared to noncarriers. These findings warrant further study into the effects of BDNF genotype in aphasia. Supplemental Material https://doi.org/10.23641/asha.10073147 Presentation Video https://doi.org/10.23641/asha.10257581

To assess the safety and effectiveness of Schlemm canal stenting for reducing intraocular pressure (IOP) in combination with cataract surgery in the United States cohort of the HORIZON study.Twenty-six clinical sites in the U.S.Prospective clinical trial.Eyes with mild to moderate primary open-angle glaucoma (POAG) on 1 to 4 medications, significant cataract, and an unmedicated diurnal IOP between 22 mm Hg and 34 mm Hg after medication washout were randomized 2:1 to receive the Hydrus microstent or no further treatment after successful cataract surgery. Patients were followed for 24 months. Medication washout and diurnal IOP measurements were repeated at 12 months and 24 months.Two hundred nineteen eyes were randomized to microstent implantation and 112 patients to phacoemulsification only. At 24 months, the diurnal IOP was reduced by 20.0% or more in a greater proportion of eyes in the microstent group (78.5% versus 54.5%; P .001). The mean change in the number of medications was -1.2 ± 0.9 (SD) in the microstent group and -0.8 ± 1.1 in the phaco-only group (P .001), and 78.5% of eyes and 39.2% of eyes, respectively, were medication free (difference 38.8%; P .001).Implantation of a Schlemm canal microstent after phacoemulsification significantly reduced diurnal IOP and medication use compared with phacoemulsification only in patients with mild to moderately severe POAG. The combination procedure was equivalent to cataract surgery alone in terms of visual acuity outcomes and the rate of adverse ocular events.

Intraductal biliary stones can result in significant acute and long-term complications. When patients' anatomy precludes more traditional management, the interventional radiologist may be called upon to provide well-established techniques for percutaneous biliary drainage and stone removal. This can be particularly challenging when the patient has excessively mobile, impacted, large or multiple stones. Percutaneous biliary endoscopy with adjunct interventional techniques can successfully treat these patients avoiding the patient dreaded "tube for life" scenario. Direct percutaneous visualization of the biliary tree can also diagnose and provide symptomatic relief for stone-mimicking pathologic conditions such as biliary tumors. This article will review the role, technique, and considerations for percutaneous biliary endoscopy and adjunct interventions in patients with isolated and complex, biliary stone disease and stone-mimicking pathologies.

Background. A fraction of stroke survivors with chronic aphasia experience declines in language abilities over time, but the reason for this remains unclear. Objective. To evaluate the effect of leukoaraiosis on baseline aphasia severity and long-term changes in aphasia severity. This study directly compares the predictive capacity of leukoaraiosis severity to that of lesion damage, a factor known to account for a substantial proportion of variance in the degree of language impairment and recovery. Methods. Using a longitudinal database of behavioral and neuroimaging data from 35 individuals in the chronic stage of recovery after a single-event left-hemisphere stroke (9 females, mean stroke age = 55.8 ± 9.1 years, mean months poststroke at initial evaluation = 36.3 ± 40.8), we examined 2 lines of inquiry: (1) to what extent does leukoaraiosis severity at initial evaluation predict aphasia severity and (2) to what extent does leukoaraiosis severity at initial evaluation predict longitudinal change in aphasia severity. Participants underwent high-resolution magnetic resonance imaging for the purpose of lesion volume analysis and leukoaraiosis severity rating. Biographical information was also considered. Results. Lesion volume and time poststroke at initial assessment best predicted initial aphasia severity (adjusted R2= 0.37). Leukoaraiosis severity and initial aphasia severity significantly predicted decline in language abilities at follow-up, accounting for approximately one-third of the variance (adjusted R2= 0.33). More severe leukoaraiosis was associated with a 4.3 odds increase of decline. Conclusions. Leukoaraiosis is a significant risk factor for declining language abilities in aphasia and should be considered for better identification of individuals at risk for long-term decline, which can guide clinical decision making.

The fundamental distinction of grammatical deficits in aphasia, agrammatism and paragrammatism, was made over a century ago. However, the extent to which the agrammatism/paragrammatism distinction exists independently of differences in speech fluency has not clearly been investigated. Despite much research on agrammatism, the lesion correlates of paragrammatism are essentially unknown. Lesion-symptom mapping was used to investigate the degree to which the lesion correlates of agrammatism and paragrammatism overlap or dissociate. Four expert raters assessed videos of 53 right-handed patients with aphasia following chronic left hemisphere stroke retelling the Cinderella story. Consensus discussion determined each subject’s classification with respect to grammatical deficits as Agrammatic, Paragrammatic, Both, or No Grammatical Deficit. Each subject’s lesion was manually drawn on a high-resolution MRI and warped to standard space for group analyses. Lesion-symptom mapping analyses were performed in NiiStat including lesion volume as a covariate. Secondary analyses included speech rate (words per minute) as an additional covariate. Region of interest analyses identified a double dissociation between these syndromes: damage to Broca’s area was significantly associated with agrammatism, p = 0.001 (but not paragrammatism, p = 0.930), while damage to the left posterior superior and middle temporal gyri was significantly associated with paragrammatism, p < 0.001 (but not agrammatism, p = 0.873). The same results obtained when regressing out the effect of speech rate, and non-overlapping lesion distributions between the syndromes were confirmed by uncorrected whole brain analyses. Our results support a fundamental distinction between agrammatism and paragrammatism.

Objective To compare cataract surgery with implantation of a Schlemm canal microstent with cataract surgery alone for the reduction of intraocular pressure (IOP) and medication use after 24 months. Design Prospective, multicenter, single-masked, randomized controlled trial. Participants Subjects with concomitant primary open-angle glaucoma (POAG), visually significant cataract, and washed-out modified diurnal IOP (MDIOP) between 22 and 34 mmHg. Methods Subjects were randomized 2:1 to receive a single Hydrus Microstent (Ivantis, Inc, Irvine, CA) in the Schlemm canal or no stent after uncomplicated phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months postoperatively. Medication washout and MDIOP measurement were repeated at 12 and 24 months. Main Outcome Measures The primary and secondary effectiveness end points were the proportion of subjects demonstrating a 20% or greater reduction in unmedicated MDIOP and change in mean MDIOP from baseline at 24 months, respectively. Hypotensive medication use was tracked throughout the course of follow-up. Safety measures included the frequency of surgical complications and adverse events. Results A total of 369 eyes were randomized after phacoemulsification to Hydrus Microstent (HMS) and 187 to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by ≥20% in 77.3% of HMS group eyes and in 57.8% of NMS group eyes (difference = 19.5%, 95% confidence interval [CI] 11.2%–27.8%, P Conclusions This 24-month multicenter randomized controlled trial demonstrated superior reduction in MDIOP and medication use among subjects with mild-to-moderate POAG who received a Schlemm canal microstent combined with phacoemulsification compared with phacoemulsification alone.

OBJECTIVE To determine whether cell-free DNA (cfDNA) was detectable in CSF samples from dogs, whether CSF sample volume impacted CSF cfDNA concentration measurement, and whether CSF cfDNA concentration was associated with CNS disease category or CSF RBC count (RBCC), nucleated cell count (NCC), or protein concentration, which could aid in the diagnosis of neurologic diseases in dogs. SAMPLE 80 CSF samples collected from dogs with (n = 60) and without (20) clinical neurologic disease between February 2017 and May 2018. PROCEDURES Results for CSF RBCC, NCC, protein concentration, and cfDNA concentration were compared across CSF groups established on the basis of whether they were obtained from dogs with (case groups) or without (control group) clinical signs of neurologic disease In addition, 5 paired CSF samples representing large (3.0-mL) and small (0.5-mL) volumes, were used to evaluate whether sample volume impacted measurement of CSF cfDNA concentration. RESULTS cfDNA was detected in 76 of the 80 (95%) CSF samples used to evaluate parameters across disease categories and in all 5 of the paired samples used to evaluate whether sample volume impacted cfDNA quantification. There were no substantial differences in cfDNA concentrations identified between groups (on the basis of disease category or sample volume), and the CSF cfDNA concentration did not meaningfully correlate with CSF RBCC, NCC, or protein concentration. CONCLUSIONS AND CLINICAL RELEVANCE Although results indicated that the CSF cfDNA concentration could not be used to differentiate between categories of neurologic disease in dogs of the the present study, further investigation is warranted regarding the use of CSF analysis, including sequencing specific cfDNA mutations, for diagnosing and monitoring neurologic disease in dogs.

Background Several studies, including a randomized controlled trial by our group, support applying anodal tDCS (A-tDCS) to the left hemisphere during behavioral aphasia treatment to improve outcomes. A clear mechanism explaining A-tDCS's efficacy has not been established, but modulation of neuroplasticity may be involved. Objective/hypothesis The brain-derived neurotrophic factor (BDNF) gene influences neuroplasticity and may modulate the effects of tDCS. Utilizing data from our recently completed trial, we conducted a planned test of whether aphasia treatment outcome is influenced by interaction between A-tDCS and a single-nucleotide polymorphism of the BDNF gene, rs6265. Methods Seventy-four individuals with chronic stroke-induced aphasia completed 15 language therapy sessions and were randomized to receive 1 mA A-tDCS or sham tDCS (S-tDCS) to the intact left temporoparietal region for the first 20 min of each session. BDNF genotype was available for 67 participants: 37 participants had the typical val/val genotype. The remaining 30 participants had atypical BDNF genotype (Met allele carriers). The primary outcome factor was improvement in object naming at 1 week after treatment completion. Maintenance of treatment effects was evaluated at 4 and 24 weeks. Results An interaction was revealed between tDCS condition and genotype for treatment-related naming improvement (F = 4.97, p = 0.03). Participants with val/val genotype who received A-tDCS showed greater response to aphasia treatment than val/val participants who received S-tDCS, as well as the Met allele carriers, regardless of tDCS condition. Conclusion Individuals with the val/val BDNF genotype are more likely to benefit from A-tDCS during aphasia treatment.

ZusammenfassungMechanische Kräfte sind essenziell, um die Funktionen von Geweben, wie dem Knochen, aufrechtzuerhalten. Die Wichtigkeit der Muskulatur und deren einwirkende Kräfte auf den Knochen für die Skelettentwicklung sind seit langem bekannt. Das Konzept der funktionellen Muskel-Knochen-Einheit empfiehlt die konsequente Überprüfung der Muskulatur, um primäre von sekundären Skeletterkrankungen zu unterscheiden. Beide haben ein erhöhtes Frakturrisiko gemeinsam, welches es gilt, durch rehabilitative Maßnahmen zu minimieren. Effektive Rehabilitationskonzepte mit Schwerpunkt der Mobilität sollten die Zusammenhänge der Inaktivität und neuromuskulären Kommunikation berücksichtigen. Das multimodale Rehabilitationsprogramm „Auf die Beine“ für Kinder und Jugendliche mit Bewegungsstörungen ist translational aus Modellen zur funktionellen Muskel-Knochen-Einheit entstanden und es konnte eine positive Entwicklung der Mobilität bei Kindern und Jugendlichen mit Störungen der Mobilität nach Teilnahme festgestellt werden.

ZusammenfassungPrimäre Erkrankungen des Skelettsystems (z. B. Osteogenesis imperfecta, idiopathische, juvenile Osteoporose) sind im Kindesalter selten. Frakturen dagegen treten häfig auf. Zunehmend sind Erkrankungen, welche sekundär mit einer erhöhten Frakturneigung einhergehen, wie zum Beispiel chronische, entzündliche und immobilisierende Erkrankungen. Die Aufgabe des Kinderarztes ist es, Kinder mit primären Knochenerkrankungen zu erkennen, sowie gegebenenfalls ein sekundär erhöhtes Frakturrisiko bei schweren und chronischen Grunderkrankungen nachzuweisen, um es adäquat therapieren zu können.Die Knochendichte beziehungsweise die Knochenmasse sind Surrogatparameter für die Knochengesundheit in diesen Situationen. Wir stellen im vorliegenden Text Begrifflichkeiten und physikalische Grundlagen der Knochendichtemessung vor, sowie die verschiedenen, in der Pädiatrie gebräuchlichen technischen Methoden zur Messung. Die Goldstandardmethode ist die Dual-energy X-ray absorptiometry (DXA)-Untersuchung. Für diese Methode stellen wir die Besonderheiten bei der Indikationsstellung und der Interpretation der Ergebnisse vor. Abschließend fassen wir die konkreten Empfehlungen der internationalen Gesellschaft für klinische Densitometrie zusammen.

ZusammenfassungFrakturen treten im Kindes- und Jugendalter bei vielen Kindern auf und sind meist durch adäquate Traumata verursacht. Sie können jedoch auch im Zusammenhang mit einer Kindesmisshandlung oder als Zeichen einer systemischen Skeletterkrankung beobachtet werden. Die diagnostischen Schritte umfassen neben Anamnese und klinischer Untersuchung, bildgebende Verfahren, Laboruntersuchungen und Knochendichtemessungen. In der Kinder- und Jugendmedizin ist bei allen diesen Methoden auf die Verwendung von alters- und größenkorrelierten Normwerten zu achten. Hierdurch können primäre und sekundäre Osteoporosen sowie Mineralisierungs- Synthese- und Abbaustörungen voneinander getrennt werden. Im Falle angeborener Erkrankungen können genetische Untersuchungen zur Diagnosesicherung beitragen. Eine sichere Diagnosestellung ist erforderlich, um eine kostenbewusste Diagnostik durchzuführen und letzten Endes eine zielgerichtete Therapie initiieren zu können.

ZusammenfassungDie Diagnose und Therapie seltener Erkrankungen im Kindes- und Jugendalter nimmt zunehmend einen großen Stellenwert in der pädiatrischen Praxis ein. Die hohe Anzahl seltener Erkrankungen mit jeweils nur einzelnen Betroffenen stellt eine besondere Herausforderung an die alltäglichen Versorgungsstrukturen dar. Durch die detaillierte Entschlüsselung der jeweiligen genetischen und pathophysiologischen Grundlage vieler der monogenetisch bedingten seltenen Erkrankungen ist es jedoch in den letzten Jahren gelungen, gezielte Therapieansätze zu entwickeln, welche derzeit in der klinischen Erprobung sind. Aktuell werden Studien im Kindes- und Jugendalter bei Patienten mit Achondroplasie, Osteogenesis imperfecta, Hypophosphatasie, hypophosphatämischer Rachitis und Fibrodysplasia ossificans progressiva durchgeführt. Die zugrunde liegenden genetischen Veränderungen, deren pathophysiologische Auswirkungen bis hin zum translationalen Therapieansatz werden in dieser Übersichtsarbeit schematisch dargestellt.

To determine if hepatic venous pressure gradient (HVPG) correlates with advanced hepatic fibrosis, as a complement to transjugular (transvenous) core needle liver biopsy. After institutional review board approval, a retrospective review was conducted on 340 patients who underwent transjugular (transvenous) core needle liver biopsy with concurrent pressure measurements between 6/1/2007 and 6/1/2013. Spearman correlation and linear regression were performed. A receiver operating characteristic (ROC) curve was created and sensitivity, specificity, predictive values and likelihood ratios were calculated. Indications included hepatitis C, abnormal liver function tests, non-alcoholic steatohepatitis, autoimmune hepatitis, and cirrhosis, among others. Biopsies showed stage 1 or 2 fibrosis in 15.6% each, stage 3 fibrosis in 21.6%, stage 4 fibrosis in 40.7%, and no fibrosis in 6.5%. Mean HVPG was 6.5 mm Hg (SD 5.0) with a range of 0–26 mm Hg. Spearman correlation coefficient for association between HVPG and fibrosis stage was 0.561 (p

Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using only age- and height-adjusted bone mineral content (BMC) and areal bone mineral density (aBMD). When applying the functional muscle-bone unit diagnostic algorithm (FMBU-A), the prevalence of positive results decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP. The prevalence of bone health deficits in children with cerebral palsy (CP) might be overestimated because age- and height-adjusted reference percentiles for bone mineral content (BMC) and areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry (DXA) do not consider reduced muscle activity. The aim of this study was to compare the prevalence of positive DXA-based indicators for bone health deficits in children with CP to the prevalence of positive findings after applying a functional muscle-bone unit diagnostic algorithm (FMBU-A) considering reduced muscle activity. The present study was a monocentric retrospective analysis of 297 whole body DXA scans of children with CP. The prevalence of positive results of age- and height-adjusted BMC and aBMD defined as BMC and aBMD below the P3 percentile and of the FMBU-A was calculated. In children with CP, the prevalence of positive results of age-adjusted BMC were 33.3% and of aBMD 50.8%. Height-adjusted results for BMC and aBMD were positive in 16.8 and 36.0% of cases. The prevalence of positive results applying the FMBU-A regarding BMC and aBMD were significantly (p

We sought to determine the underlying pathophysiology relating white matter hyperintensities to chronic aphasia severity. We hypothesized that: (i) white matter hyperintensities are associated with damage to fibres of any length, but to a higher percentage of long-range compared to mid- and short-range intracerebral white matter fibres; and (ii) the number of long-range fibres mediates the relationship between white matter hyperintensities and chronic post-stroke aphasia severity. We measured the severity of periventricular and deep white matter hyperintensities and calculated the number and percentages of short-, mid- and long-range white matter fibres in 48 individuals with chronic post-stroke aphasia. Correlation and mediation analyses were performed to assess the relationship between white matter hyperintensities, connectome fibre-length measures and aphasia severity as measured with the aphasia quotient of the Western Aphasia Battery-Revised (WAB-AQ). We found that more severe periventricular and deep white matter hyperintensities correlated with a lower proportion of long-range fibres (r = −0.423, P = 0.003 and r = −0.315, P = 0.029, respectively), counterbalanced by a higher proportion of short-range fibres (r = 0.427, P = 0.002 and r = 0.285, P = 0.050, respectively). More severe periventricular white matter hyperintensities also correlated with a lower proportion of mid-range fibres (r = −0.334, P = 0.020), while deep white matter hyperintensities did not correlate with mid-range fibres (r = −0.169, P = 0.250). Mediation analyses revealed: (i) a significant total effect of periventricular white matter hyperintensities on WAB-AQ (standardized beta = −0.348, P = 0.008); (ii) a non-significant direct effect of periventricular white matter hyperintensities on WAB-AQ (P > 0.05); (iii) significant indirect effects of more severe periventricular white matter hyperintensities on worse aphasia severity mediated in parallel by fewer long-range fibres (effect = −6.23, bootstrapping: standard error = 2.64, 95%CI: −11.82 to −1.56) and more short-range fibres (effect = 4.50, bootstrapping: standard error = 2.59, 95%CI: 0.16 to 10.29). We conclude that small vessel brain disease seems to affect chronic aphasia severity through a change of the proportions of long- and short-range fibres. This observation provides insight into the pathophysiology of small vessel brain disease, and its relationship with brain health and chronic aphasia severity.

Introduction Percutaneous mechanical circulatory support devices are increasingly used in acute cardiogenic shock (CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the full support Impella 5 and 5.5 as a short- term left ventricular device (LVAD) and to identify preoperative predictors of short -term mortality. Methods Data of patients in CS (n=51) treated with the Impella 5 (n=48) and 5.5 (n=3) devices at our institution were collected retrospectively. The primary endpoint was 30-day all-cause mortality. Clinical follow up including adverse events was analyzed. Results Mean age was 58.2±12.1 years; 80.4% were male. 13 patients had BMI >30 kg/m2. CS was caused by acute myocardial infarction (n=14), decompensated chronic heart failure (n=29), postcardiotomy syndrom and acute myocarditis (n=4 each). Before implantation, median Intermacs profile was 1 (range 1–3) and 31 patients (61%) were on respiratory support. In 49 patients the axillary artery was used for vascular access (n=4 left and n=45 right) employing a 10mm dacron graft tunneled through the skin, in one patient left femoral artery and ascending aorta, respectively. Median support time was 14 days. In 12 cases the pump was removed for myocardial recovery. In 15 patients a continuous flow permanent LVAD was implanted. Bleeding (n=9), thromboembolic event (n=5), pump dislodgement (n=7) requiring revision occurred during support. Seven patients developed ventricular arrhythmia requiring flow reduction. In 5 cases the pump was explanted for hemolysis, in 2 other patients pump exchange was performed. The overall 30-day survival was 53% (95% CI: 38.8–67.1%). Penalized multivariable logistic regression analysis identified preoperative elevated lactate (p=0.027) and CK-MB (p=0.022) as predictors for 30- day mortality. On the basis of these data, a nomogram to estimate 30d-mortality after Impella implantation was created. Conclusion Stabilization of patients suffering from CS employing temporary full support Impella LVAD is feasible and results in acceptable survival. Preoperative degree of shock and myocardial damage predict the short-term mortality. Effect of full support Impella LVAD in earlier stages of shock may prevent irreversible end organ damage.

Background Our previous study showed sub-epicardial longitudinal strain (EpiLS) was an independent prognostic factor for worse outcome in regular treated hypertension but not global longitudinal strain (GLS) and sub-endocardial longitudinal strain (EndLS). Increased blood pressure variability (BPV) has been found associated with target organ damage in hypertension. However, effects of BPV on layer-specific longitudinal strain have not been well studied. Purpose The aim of this study was to investigate the effects of different blood pressure parameters on layer-specific longitudinal strain in hypertension. Methods This study included 95 patients (57 men, age 65 ± 12 years) with uncomplicated hypertension who have been regularly treated for more than 1 year. Speckle tracking echocardiography was used for measurement of longitudinal deformation from 3 apical views of left ventricle. GLS was measured by automated function imaging (AFI). We further divided into sub-endocardial and sub-epicardial myocardium and measured their longitudinal strain by manual click-and-draw method and averaged from 3 apical views. Blood pressure parameters included office systolic blood pressure (SBP), office diastolic blood pressure (DBP), central SBP and DBP by tonometry, average 24-hour SBP and DBP, and BPV parameters by ambulatory blood pressure monitor. BPV parameters included standard deviation of daytime SBP (DSSD), standard deviation of nighttime SBP (NSSD), standard deviation of daytime DBP (DDSD), and standard deviation of nighttime DBP (NDSD). Results We divided subjects into low and high group according to median level of each strain. No blood pressure parameters were different between low and high EndLS group except week difference in NDSD (9.0 ± 3.4 vs. 7.8 ± 2.0 mmHg, p = 0.051). NSSD (11.2 ± 4.6 vs. 9.3 ± 2.9 mmHg, p = 0.027) and NDSD (9.1 ± 3.4 vs. 7.7 ± 2.0 mmHg, p = 0.031) were significant increased in low GLS group but not other parameters. DDSD (10.3 ± 3.0 vs. 9.0 ± 2.5 mmHg, p = 0.034), NSSD (11.4 ± 4.4 vs. 9.1 ± 3.1 mmHg, p = 0.006), and NDSD (9.2 ± 3.2 vs. 7.6 ± 2.2 mmHg, p = 0.012) were significantly increased in low EpiLS group. Conclusions Only BPV parameters were associated with decreased longitudinal strain in hypertension. Effects of BPV were majorly noted in EpiLS.

White matter hyperintensities (WMH) are linked to poor brain health, cardiovascular risk factors, cognitive decline, and stroke. The cumulative effect of microangiopathic changes and perivascular lipohyalinosis is commonly associated with white matter changes in the brain. However, the pathomechanism linking small vessel disease, white matter network disruption, cognitive decline, and stroke recovery is not well understood. We hypothesized that WMH are associated with loss of long range cortical connections, and subsequent disorganization of the optimal topological structure of white matter networks leading to poor post-stroke aphasia recovery. Using post-processing methods of diffusion tensor imaging optimized for lesioned brains, we reconstructed the individual structural whole-brain connectome from 49 right handed participants with a single left hemisphere ischemic stroke (age 59.9±12.5). All participants underwent language assessment using the Western Aphasia Battery (mean 58.9±22.76). WMHs were determined in the right hemisphere aphasia using the Fazekas scale. We assessed the density of each subject’s right hemisphere connectome, and then calculated the Euclidean distance between each pair of node centroids in each connectome. All fibers with lengths above the 3 rd quartile (75% and above) were designated long range. We further quantified the white matter topological network organization using Newman’s modularity algorithm. We found that participants with high a Fazekas score (especially PWMH) had lower connectome density (r = -0.41, p = 0.003), and more severe aphasia (r = -0.42, p = 0.002). Participants with lower right hemisphere density also had more severe aphasia (r = 0.5, p < 10 -3 ). Furthermore, loss of long range cortical connections was associated with the fragmentation of the right hemisphere network topology quantified by the optimal modularity score (r = 0.76, p < 10 -9 ). Loss of long range fiber connections related to higher WMH, and was associated with deviations from the optimal topological architecture that signifies a healthy brain. We postulate a mechanism by which brain health is lost – via loss of energy demanding long range fibers resulting in the disorganization of residual brain networks.

Alveolar capillary dysplasia (ACD) is a rare neonatal lung disease characterized anatomically by a defective and hypoplastic development of pulmonary alveoli leading to persistent pulmonary hypertension (PPHN) and finally lethal respiratory failure. It is often associated with congenital left heart obstruction. Given the fatal prognosis an early diagnosis is important. However, due to the fast onset of PPHN in neonates and lack of pathognomonic signs for its cause, safe and fast detection of ACD is challenging. Therefore, following the exclusion of cardiac and common pulmonary causes, lung biopsy becomes essential for diagnosis.We hereby report a case of ACD with atrial septal defect type one and hypoplastic aortic arch with an ante-mortem diagnosis and discuss the current state of medicine in relation to ACD.

Aims The European ‘Step-by-Step’ algorithm (Gomez et al) has been shown to be superior in the management of febrile infants compared with the Rochester and Lab-Score criteria, especially identifying low risk patients. If we applied the ‘Step-by-Step’ algorithm retrospectively to an audit could we identify areas to improve our capability and confidence of recognising low risk patients, including the use Procalcintonin (PCT). Methods An audit over 6 months from November 2016 to April 2017 at Evelina Children’s Hospital Paediatric Emergency Department recorded the investigation and management of all infants aged 1–3 months who had a fever recorded at triage or a history of fever recorded in nursing triage. We excluded patients less than 4 weeks old as fever in the neonatal period is treated as high risk. Results Sixteen infants aged 1–3 months presented with a fever (only two with a fever >24 hours), thirteen were admitted and given intravenous antibiotics, the average length of admission was twenty-eight hours. Only one had a CRP >20, two had leukocytouria and none had a raised WCC or neutrophil count. Forty-two infants aged 1–3 months were triaged with a history of fever, nineteen were admitted for intravenous antibiotics, the average length of admission was fifteen hours. Two had a rise in CRP, three showed leukocytouria and two showed raised neutrophils. No cases of isolated bacterial pathogen in blood or CSF were identified in either group. Using the ‘Step-by-Step’ approach seven (54%) with fever and six (32%) with a history of fever who were admitted and treated could be identified as low risk. The most reliable identification for high risk is clinical appearance. Conclusion The ‘Step-by-Step’ approach is a valuable and a more applicable tool than previous methods in the management of febrile infants. This approach shows we can improve our method of identification of low risk patients in infants aged 1–3 months that present with fever, possibly reducing admissions. PCT could also be a further useful step in identifying low risk patients. Reference . Gomez, et al. Validation of the ‘step-by-step’ approach in management of young febrile infants. Paediatrics2016;138. doi:10.1542/ped.2015-4381

Self-delivered speech therapy provides an opportunity for individualised dosage as a complement to the speech-therapy regime in the long-term rehabilitation pathway. Few apps for speech therapy have been subject to clinical trials, especially on a self-delivered platform. In a crossover design study, the Comprehensive Aphasia Test (CAT) and Cookie Theft Picture Description (CTPD) were used to measure untrained improvement in a group of chronic expressive aphasic patients after using a speech therapy app. A pilot study (n = 3) and crossover design (n = 7) comparing the therapy app with a non-language mind-game were conducted. Patients self-selected their training on the app, with a recommended use of 20 minutes per day. There was significant post-therapy improvement on the CAT and CTPD but no significant improvement after the mind-game intervention, suggesting there were language-specific effects following use of the therapy app. Improvements on the CTPD, a functional measurement of speech, suggest that a therapy app can produce practical, important changes in speech. The improvements post-therapy were not due to type of language category trained or amount of training on the app, but an inverse relationship with severity at baseline and post-therapy improvement was shown. This study suggests that self-delivered therapy via an app is beneficial for chronic expressive aphasia.

Efference copy is a cognitive mechanism argued to be critical for initiating and monitoring speech: however, the extent to which breakdown of efference copy mechanisms impact speech production is unclear. This study examined the best mechanistic predictors of non-fluent speech among 88 stroke survivors. Objective speech fluency measures were subjected to a principal component analysis (PCA). The primary PCA factor was then entered into a multiple stepwise linear regression analysis as the dependent variable, with a set of independent mechanistic variables. Participants' ability to mimic audio-visual speech ("speech entrainment response") was the best independent predictor of non-fluent speech. We suggest that this "speech entrainment" factor reflects integrity of internal monitoring (i.e., efference copy) of speech production, which affects speech initiation and maintenance. Results support models of normal speech production and suggest that therapy focused on speech initiation and maintenance may improve speech fluency for individuals with chronic non-fluent aphasia post stroke.

Aim To investigate the demographic characteristics, care pathways, and clinical and service outcomes of people who present to ambulance services with a psychiatric or self-harm emergency Methods We conducted a retrospective cohort study of patients attended by the Scottish Ambulance Service in 2011 with ambulance clinician attendance codes relating to ‘psychiatric emergency’ or ‘self-harm’. Patients resident in Scotland and>=16 years on first contact were included. We used NHS Scotland’s Unscheduled Care Data Mart (1) to link data from: – the ambulance service; emergency departments (ED); general and psychiatric inpatient hospital admissions episodes; and death records. Results There were 9014 calls from 6802 people. Slightly more males (n=4708, 52%) than females (n=4306, 48%) were attended. Most were discharged from ED with no known follow-up (n=4566; 51%). Some were left at home (n=1003 attendances, 11%). Almost half of the people (n=3238, 48%) made at least one repeat call. People who self-discharge from ED were more likely to have another ambulance attendance for psychiatric emergency/self-harm within the same year (Pearson chi square=5.24, p=0.02). Two hundred and seventy-nine (4%) people died within the study period, 97 (35%) were recorded as suicide. Ethical approval (NRES 15/EM/0260) and other data approvals were received. Conclusion While linked data analysis may not identify all relevant cases, it provides important information to guide the development and evaluation of evidence-based interventions. Ambulance service and ED are missing opportunities to improve outcomes for people who experience a psychiatric emergency or who self-harm. New interventions could lead to decreases in the number of suicides, episodes of self-harm and levels of patient distress; and ambulance and ED service use. Reference Information Services Division (NHS Scotland) (2016) Unscheduled Care Datamart Background Paper. Accessible at http://www.isdscotland.org/Health-Topics/Emergency-Care/Patient-Pathways/unscheduledcare_background.pdf Accessed on 13/01/17 Conflict of interest None declared. Funding Scottish Government, Chief Scientists Office

Rheumatic diseases in childhood and adolescence can lead to secondary osteoporosis based on various pathophysiologies. The underlying disease, medication and immobility resulting in a reduced osteoanabolic stimulus contribute to the development of a fragile skeletal system. For diagnostic purposes dual-energy X-ray absorptiometry (DXA) is the most frequently used technology. For interpretation of the areal bone mineral density, age and gender matched reference data have to be used. Particularly in the pediatric field, body height must additionally be taken into consideration. Further techniques which can provide detailed information are peripheral quantitative computed tomography and high resolution magnetic resonance imaging. Nowadays, skeletal assessments have to be interpreted in the context of the muscular system. The concept of the functional muscle-bone unit is widely accepted and uses the muscles as the dominating factor. In a second step the adaptation of the skeletal system to the applied muscle force is evaluated. This allows a differentiation between primary and secondary skeletal diseases depending on the ratio of muscles to bone. Therapeutic options for secondary osteoporosis include reduction of the causative medication, treatment of the underlying disease, antiresorptive treatment with bisphosphonates and different programs to activate the muscles. A multimodal interval rehabilitation program including alternating side vibration shows positive effects on mobility, muscle function and bone mass in children and adolescents.

Ziel der Rehabilitation von Patienten mit Zerebralparese (CP) ist es, durch Masnahmen wie Physiotherapie die motorischen Funktionen zu verbessern. Das Angebot ist gros, die Evidenz fur die einzelnen Behandlungskonzepte jedoch trotz mehrerer Studien nicht zufriedenstellend. „Auf die Beine“, das Kolner Modell der Intervallrehabilitation, kombiniert kurze intensive stationare Phasen mit 6 Monaten hauslichem Training unter Verwendung der seitenalternierenden Ganzkorpervibration. Die Ergebnisse der motorischen Fahigkeiten nach der aktiven Phase und nach weiteren 6 Monaten Follow-up werden vorgestellt. Die motorischen Fahigkeiten wurden mit dem Gross Motor Function Measure (GMFM) gemessen. Die Auswertung der Daten von 356 Patienten erfolgte mithilfe des GMFM-66-Gesamtscores nach 6 (aktive Phase) und 12 Monaten (6-Monate-Follow-up) bzw. der Zieldimensionen des GMFM-88 nach 6 Monaten. Die Patienten zeigten nach Abschluss des Trainings einen verbesserten GMFM-66-Gesamtscore um 2,9 Punkte (Mittelwert 3,4; p

Background Few data describe the natural history of Charcot neuroarthropathy treated with a total contact plaster cast (TCC). Methods A 5 year retrospective analysis of 50 patients presenting with an acute CN, Assessing time to clinical resolution into appropriate footwear and assessing if initial immobilisation device influenced resolution time. Results During the study period 42 patients (84%) of patients went into remission, 2 died during their treatment, 4 had major amputations, in 2 patients treatment was ongoing. 36 patients were treated with combination offloading devices, 6 were treated with one modality only. Median time to resolution for patients initially treated with a TCC was not significantly shorter than for those treated with a removable below knee boot. 34.9% required re-casting due to clinical deterioration in the removable device. Conclusions More precise measures of resolution of CN are needed to assess the impact of initial treatment modality on time to resolution.

PurposeRelatively preserved inner speech alongside poor overt speech has been documented in some persons with aphasia (PWA), but the relationship of overt speech with inner speech is still largely unclear, as few studies have directly investigated these factors. The present study investigates the relationship of relatively preserved inner speech in aphasia with selected measures of language and cognition.MethodThirty-eight persons with chronic aphasia (27 men, 11 women; average age 64.53 ± 13.29 years, time since stroke 8–111 months) were classified as having relatively preserved inner and overt speech (n= 21), relatively preserved inner speech with poor overt speech (n= 8), or not classified due to insufficient measurements of inner and/or overt speech (n= 9). Inner speech scores (by group) were correlated with selected measures of language and cognition from the Comprehensive Aphasia Test (Swinburn, Porter, & Al, 2004).ResultsThe group with poor overt speech showed a significant relationship of inner speech with overt naming (r= .95,p< .01) and with mean length of utterance produced during a written picture description (r= .96,p< .01). Correlations between inner speech and language and cognition factors were not significant for the group with relatively good overt speech.ConclusionsAs in previous research, we show that relatively preserved inner speech is found alongside otherwise severe production deficits in PWA. PWA with poor overt speech may rely more on preserved inner speech for overt picture naming (perhaps due to shared resources with verbal working memory) and for written picture description (perhaps due to reliance on inner speech due to perceived task difficulty). Assessments of inner speech may be useful as a standard component of aphasia screening, and therapy focused on improving and using inner speech may prove clinically worthwhile.Supplemental Materialshttps://doi.org/10.23641/asha.5303542

SUMMARY Memory impairment in patients with Alzheimer’s disease (AD) may be treated with cholinesterase inhibitors. Attention, alertness, initiative and memory (indirectly) may be treated with memantine. In addition to pharmacologic treatments, nonpharmacologic treatments, including external systems and devices, participation in social activities and exercise, as well as the use of habits, pictures and strategies, improve memory. We believe that although memory loss cannot be halted, both pharmacologic and nonpharmacologic treatments may help to improve AD patients’ memory and allow them to continue independent activities. Patients with mild cognitive impairment due to AD may be treated with nonpharmacologic therapies and with off-label cholinesterase inhibitors.

e15629Background: Obesity is a known risk factor for the development of colorectal cancer (CRC) and has long been associated with increased mortality of CRC. However, recent studies have shown that...

1. Adenylyl cyclase VI (ACVI) is one of the most abundantly expressed beta adrenergic receptor (betaAR)-coupled cyclases responsible for cyclic AMP (cAMP) production within the mammalian myocardium. We investigated the role of ACVI in the regulation of cardiomyocyte contractility and whether it is functionally coupled with beta(1) adrenergic receptor (beta(1)AR). 2. Recombinant adenoviruses were generated for ACVI and for antisense to ACVI (AS). Adult rat ventricular myocytes were transfected with ACVI virus, AS or both (SAS). Adenovirus for green fluorescent protein (GFP) served as control. Myocyte contraction amplitudes (% shortening) and relaxation times (R50) were analysed. ACVI function was determined using cAMP assays. 3. ACVI-transfected cells demonstrated a strong 139 kDa ACVI protein band compared to controls. ACVI myocytes had higher steady-state intracellular cAMP levels than GFP myocytes when unstimulated (GFP vs ACVI=6.60+/-0.98 vs 14.2+/-2.1 fmol cAMP/viable cell, n=4, P

This article outlines the role of botulinum toxin as an adjunct to physiotherapy in spasticity management. It stresses the need for a multi-disciplinary approach in order to maximize the potential for a successful outcome. Criteria for effective use of botulinum toxin are discussed, and the importance of constant evaluation through outcome measures is emphasized.

BACKGROUND: The study compared the efficacy of oral iron combined with intravenous iron supplementation to that of oral iron supplementation alone in increasing the preoperative production of hemoglobin (Hb) in autologous blood donors with normal iron stores. STUDY DESIGN AND METHODS:One hundred eight iron-replete patients who were scheduled for donation of 3 units of autologous blood at weekly intervals were randomly assigned to receive, in a double-blind fashion, no iron supplementation (placebo, Group 1), oral iron supplementation (285.6 mg of elemental iron/day, Group 2), or oral iron plus intravenous iron supplementation (285.6 mg of elemental iron/day orally plus 102.5 mg of elemental iron/week intravenously, Group 3). The amount of Hb produced during the 21-day study period was determined by the total amount of Hb donated minus the change in the amount of circulating Hb between the first donation (Day 0) and the poststudy examination (Day 21). RESULTS:Hb production did not differ significantly in the two iron-supplemented groups (oral iron, 85 +/− 36 g; oral plus intravenous iron, 74 +/− 43 g). The patients in the oral iron group produced a significantly greater amount of Hb than those in the placebo group (85 +/− 36 g vs. 52 +/− 41 g, p < 0.01). CONCLUSION: Oral iron supplementation increased the production of Hb in autologous blood donors more than placebo did. Additional intravenous iron did not lead to a further increase in preoperative Hb production.

OBJECTIVE: To investigate the regulation of expression of the angiogenic cytokine vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA), in order to determine whether new blood vessel formation could be a potential therapeutic target in RA. METHODS: Dissociated RA synovial membrane cells were cultured in the presence of cytokine inhibitors, or under hypoxic conditions. Serum VEGF levels were serially measured in RA patients enrolled in clinical trials of anti-tumor necrosis factor alpha (anti-TNFalpha) monoclonal antibody treatment. RESULTS: Combined neutralization of TNFalpha and interleukin-1 (IL-1) in RA synovial membrane cultures reduced VEGF release by 45% (P < 0.05 versus control), although blockade of either TNFalpha or IL-1 activities alone resulted in only small inhibitory effects. In addition, release of VEGF from RA synovial membrane cells was selectively up-regulated by hypoxia. Serum VEGF levels were significantly elevated in RA patients relative to control subjects, and correlated with disease activity. Treatment of RA patients with anti-TNFalpha significantly decreased serum VEGF, and this effect was enhanced by cotreatment with methotrexate. CONCLUSION: Inhibition of TNFalpha and IL-1 activity in vivo could reduce the drive to new blood vessel formation, and hence pannus mass, adding to other therapeutic effects of anti-TNFalpha therapy in RA.

The effects of two food-related chemicals (sodium saccharin and linoleic acid) on the levels of Her2/neu and p53 mRNA in a non-cancerous human breast epithelial cell line (HBL-100) were tested in comparison with the effects of the known tumor promoter phorbol 12-myristate 13-acetate (TPA). Treatments were made both with and without prior treatment with two well-known tumor initiators, N-nitroso-N-methylurea (NMU) or 7,12-dimethylbenz[a]anthracene (DMBA). The effects in general were small, the greatest being increases of 46-67% in Her2/neu mRNA levels in response to treatments with TPA or sodium saccharin following NMU treatments. These results demonstrate that sodium saccharin following NMU treatments might be involved in transcriptional regulation of Her2/neu in HBL-100 cells and suggest that its effects may not be limited to urinary bladder.

Fourteen patients with Helicobacter pylori infection were treated with omeprazole capsules 20 mg and amoxycillin capsules 1000 mg twice daily for 14 days and 14 patients with omeprazole capsules 20 mg and placebo twice daily for 14 days. Samples from saliva, dental plaque and faeces and biopsies from antrum and corpus were analysed in order to determine the ecological changes in the normal microflora. Several microorganisms were affected by both treatment regimens. Two patients were colonised with enterobacteria in the oral cavity and stomach during the omeprazole plus amoxycillin treatment. A general increase in the number of microorganisms from gastric mucosa was observed in both treatment groups. A selection of resistant enterobacteria and an increase in beta-lactamase production was observed in the faecal samples during the omeprazole plus amoxycillin treatment. Eradication of H. pylori in the omeprazole-amoxycillin group was 50% and in the omeprazole placebo group 0% four weeks after treatment. No viable H. pylori were cultivated in the saliva, dental plaque or faecal samples. Treatment with omeprazole 20 mg and amoxycillin 1000 mg twice daily for 14 days altered the normal microflora in the oral, gastric and intestinal tract and antibiotic resistant microorganisms increased in numbers in the intestinal microflora.

BackgroundThe perinatal or early life environment may influence the development of mental illness in adulthood. It is not clear how, or when, any such influences might be mediated. Foetal exposure to maternal stress in the intrauterine environment has been suggested as a possible mediator of foetal origins of mental illness but the postnatal environment may also be of importance. This study aimed to test the foetal origins hypothesis by using retrograde and antegrade interbirth intervals (time to mother's most recent and next deliveries respectively) as proxy measures of antenatal and postnatal maternal stress.MethodLinked datasets of the Scottish Morbidity Record (SMR) were used to identify a birth cohort. Where applicable, the dates of each mother's most recent previous and/or next subsequent delivery were noted, allowing birth intervals to be calculated. The cohort was followed up into young adulthood, using self-harm, substance misuse, psychotic disorder and affective disorder as outcome measures. Data were analysed using Cox regression.ResultsNo significant relationship was observed between affective disorders and interbirth interval, neither retrograde nor antegrade. Short (72-month) retrograde intervals were associated with increased risk of self-harm and substance misuse.ConclusionsThe data do not provide evidence for the foetal origins of mental disorders but, in the cases of psychotic disorders, and of self-harm, suggest that the early postnatal rather than the antenatal environment may be of greater importance.