Continuous-flow left ventricular assist devices (LVAD) have emerged as the standard of care for advanced heart failure patients requiring long-term mechanical circulatory support. Evidence-based ...clinical management of LVAD-supported patients is becoming increasingly important for optimizing outcomes. In this state-of-art review, we propose key elements in managing patients supported with the new continuous-flow LVADs. Although most of the presented information is largely based on investigator experience during the 1,300-patient HeartMate II clinical trial, many of the discussed principles can be applied to other emerging devices as well. Patient selection, pre-operative preparation, and the timing of LVAD implant are some of the most important elements critical to successful circulatory support and are principles universal to all devices. In addition, proper nutrition management and avoidance of infectious complications can significantly affect morbidity and mortality during LVAD support. Optimizing intraoperative and peri-operative care, and the monitoring and treatment of other organ system dysfunction as it relates to LVAD support, are discussed. A multidisciplinary heart failure team must be organized and charged with providing comprehensive care from initial referral until support is terminated. Preparing for hospital discharge requires detailed education for the patient and family or friends, with provisions for emergencies and routine care. Implantation techniques, troubleshooting device problems, and algorithms for outpatient management, including the diagnosis and treatment of related problems associated with the HeartMate II, are discussed as an example of a specific continuous-flow LVAD. Ongoing trials with other continuous-flow devices may produce additional information in the future for improving clinical management of patients with these devices.
Objective To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or ...chronic lung disease in extremely low birth weight infants. Study design Evaluation of infants at 18-22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index and the Psychomotor Developmental Index. NDI was defined as moderate or severe cerebral palsy, Mental Developmental Index or Psychomotor Developmental Index <70, blindness, or hearing impairment. Results Death or NDI at 18-22 months corrected age was similar in the dexamethasone and placebo groups (65% vs 66%, P = .99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50% vs 41%, P = .42 for weight less than 10th percentile); 49% of infants in the placebo group received treatment with corticosteroid compared with 32% in the dexamethasone group ( P = .02). Conclusion The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.
To describe the predisposing pathology and clinical features of all incident cases of rhegmatogenous retinal detachment (RRD) recruited in Scotland during a 2-year period.
Prospective surveillance ...study of incident cases of RRD.
All incident cases of RRD recruited as part of the Scottish Retinal Detachment Study.
During a 2-year period, we coordinated a comprehensive system in which every case of primary RRD presenting to 1 of 6 vitreoretinal surgical sites in Scotland was examined and approached for study inclusion.
Rhegmatogenous retinal detachment incidence, predisposing features, and clinical characteristics.
A total of 1202 cases were recruited. Detailed clinical information was available on 1130 (94%) of cases. By causative break, the proportions of RRD were horseshoe tear (HST) associated with posterior vitreous detachment (PVD) in 86.2%, giant retinal tear (GRT) and PVD in 1.3%, non-PVD round hole (RH) in 4.9%, retinal dialysis in 5.9%, and retinoschisis RRD in 1.6%. One in 10 cases reported significant ocular trauma. One in 5 cases were pseudophakic. Round hole RRD more frequently presented with multiple retinal breaks compared with HST RRD (67.8% vs. 48.7%; P = 0.003). In PVD-associated RRD, 56.1% (95% confidence interval CI, 53.8-58.3) of breaks were identified in the superotemporal retina. In non-PVD RRD, 54.6% (95% CI, 47.9-61.1) of breaks were inferotemporal, followed by superotemporal in 34.9% (95% CI, 28.7-41.5). Lattice degeneration was present in 18.7% of affected eyes and more common in RH RRD (35.7%) than in HST RRD (19.3%) (P = 0.003). Seven percent reported an affected first-degree relative, and these cases were significantly more myopic than nonfamilial cases.
More than 85% of RRD cases are associated with PVD and related tractional tears. Non-PVD RH RRD occurred in younger and more myopic individuals. The majority of cases are caused by more than 1 retinal break, and the macula is affected in more than 50% at presentation. Ocular trauma, previous cataract surgery, family history, and lattice degeneration are important predisposing features.
Mouse laser-induced choroidal neovascularization (mouse LCNV) recapitulates the “wet” form of human age-related macular degeneration (AMD). Vascular cell adhesion molecule-1 (VCAM-1) is a known ...inflammatory biomarker, and it increases in the choroidal neovascular tissues characteristic of this experimental model. We have designed and constructed gold nanoparticles (AuNPs) functionalized with hairpin-DNA that incorporates an antisense sequence complementary to VCAM-1 mRNA (AS-VCAM-1 hAuNPs) and tested them as optical imaging probes. The 3′ end of the hairpin is coupled to a near-infrared fluorophore that is quenched by the AuNP surface via Förster resonance energy transfer (FRET). Hybridization of the antisense sequence to VCAM-1 mRNA displaces the fluorophore away from the AuNP surface, inducing fluorescent activity. In vitro testing showed that hAuNPs hybridize to an exogenous complementary oligonucleotide within a pH range of 4.5–7.4, and that they are stable at reduced pH. LCNV mice received tail-vein injections of AS-VCAM-1 hAuNPs. Hyperspectral imaging revealed the delivery of AS-VCAM-1 hAuNPs to excised choroidal tissues. Fluorescent images of CNV lesions were obtained, presumably in response to the hybridization of AS-hAuNPs to LCNV-induced VCAM-1 mRNA. This is the first demonstration of systemic delivery of hAuNPs to ocular tissues to facilitate mRNA imaging of any target.
Women in poor urban neighborhoods have high rates of stress and allergic diseases, but whether stress or stress correlates such as depression promote inflammatory and type 2 cytokine responses is ...unknown.
To examine associations among external stressors, perceived stress, depression, and peripheral blood mononuclear cell cytokine responses of mothers enrolled in the Urban Environment and Childhood Asthma Study and test the hypothesis that stress would be positively associated with type 2 and selected proinflammatory (tumor necrosis factor-α and interleukin-8) responses.
Questionnaire data from mothers living in 4 inner cities included information about external stress, stress perception, and depression. The external stress domains (interpersonal problems, housing, and neighborhood stress) were combined into a Composite Stressor score. Peripheral blood mononuclear cells were stimulated ex vivo and cytokine responses to innate, adaptive, and polyclonal immune stimuli were compared with stress and depression scores for 469 of the 606 study participants.
There were no significant positive associations between Composite Stressor scores, perceived stress, or depression scores and proinflammatory or type 2 cytokine responses, and these findings were not modified by allergy or asthma status. There were some modest associations with individual stressors and cytokine responses, but no consistent relations were noted. Depression was associated with decreased responses to some stimuli, particularly dust mite.
Composite measurements of stressors, perceived stress, or depression were not positively related to proinflammatory or type 2 cytokine responses in these young urban women. These data do not support the hypothesis that these factors promote cytokine responses associated with allergy.
ClinicalTrials.gov, identifier NCT00114881.
Evidence for the light-by-light scattering process, γγ→γγ, in ultraperipheral PbPb collisions at a centre-of-mass energy per nucleon pair of 5.02TeV is reported. The analysis is conducted using a ...data sample corresponding to an integrated luminosity of 390μb−1 recorded by the CMS experiment at the LHC. Light-by-light scattering processes are selected in events with two photons exclusively produced, each with transverse energy ETγ>2GeV, pseudorapidity |ηγ|<2.4, diphoton invariant mass mγγ>5GeV, diphoton transverse momentum pTγγ<1GeV, and diphoton acoplanarity below 0.01. After all selection criteria are applied, 14 events are observed, compared to expectations of 9.0±0.9(theo) events for the signal and 4.0±1.2(stat) for the background processes. The excess observed in data relative to the background-only expectation corresponds to a significance of 3.7 standard deviations, and has properties consistent with those expected for the light-by-light scattering signal. The measured fiducial light-by-light scattering cross section, σfid(γγ→γγ)=120±46(stat)±28(syst)±12(theo)nb, is consistent with the standard model prediction. The mγγ distribution is used to set new exclusion limits on the production of pseudoscalar axion-like particles, via the ▪ process, in the mass range ▪.
Imaging plays an essential role in identifying intracranial injury in patients with traumatic brain injury (TBI). The goals of imaging include (1) detecting injuries that may require immediate ...surgical or procedural intervention, (2) detecting injuries that may benefit from early medical therapy or vigilant neurologic supervision, and (3) determining the prognosis of patients to tailor rehabilitative therapy or help with family counseling and discharge planning. In this article, the authors perform a review of the evidence on the utility of various imaging techniques in patients presenting with TBI to provide guidance for evidence-based, clinical imaging protocols. The intent of this article is to suggest practical imaging recommendations for patients presenting with TBI across different practice settings and to simultaneously provide the rationale and background evidence supporting their use. These recommendations should ultimately assist referring physicians faced with the task of ordering appropriate imaging tests in particular patients with TBI for whom they are providing care. These recommendations should also help radiologists advise their clinical colleagues on appropriate imaging utilization for patients with TBI.
To assess the differences in rod-mediated dark adaptation (RMDA) between different grades of age-related macular degeneration (AMD) severity using an OCT-based criterion compared with those of AMD ...severity using the Beckman color fundus photography (CFP)-based classification and to assess the association between the presence of subretinal drusenoid deposits (SDDs) and RMDA at different grades of AMD severity using an OCT-based classification.
Cross-sectional study.
Participants from the Northern Ireland Sensory Ageing study (Queen’s University Belfast).
Complete RMDA (rod-intercept time RIT) data, CFP, and spectral-domain OCT images were extracted. Participants were stratified into 4 Beckman groups (omitting late-stage AMD) and 3 OCT-based groups. The presence and stage of SDDs were identified using OCT.
Rod-intercept time data (age-corrected).
Data from 459 participants (median interquartile range age, 65 59–71 years) were stratified by both the classifications. Subretinal drusenoid deposits were detected in 109 eyes. The median (interquartile range) RMDA for the Beckman classification (Beckman 0–3, with 3 being intermediate age-related macular degeneration iAMD) groups was 6.0 (4.5–8.7), 6.6 (4.7–10.5), 5.7 (4.4–7.4), and 13.2 (6–21.1) minutes, respectively. OCT classifications OCT0–OCT2 yielded different median (interquartile range) values: 5.8 (4.5–8.5), 8.4 (5.2–13.3), and 11.1 (5.3–20.1) minutes, respectively. After correcting for age, eyes in Beckman 3 (iAMD) had statistically significantly worse RMDA than eyes in the other Beckman groups (P ≤ 0.005 for all), with no statistically significant differences between the other Beckman groups. Similarly, after age correction, eyes in OCT2 had worse RMDA than eyes in OCT0 (P ≤ 0.001) and OCT1 (P < 0.01); however, there was no statistically significant difference between eyes in OCT0 and eyes in OCT1 (P = 0.195). The presence of SDDs was associated with worse RMDA in OCT2 (P < 0.01) but not in OCT1 (P = 0.285).
Eyes with a structural definition of iAMD have delayed RMDA, regardless of whether a CFP- or OCT-based criterion is used. In this study, after correcting for age, the RMDA did not differ between groups of eyes defined to have early AMD or normal aging, regardless of the classification. The presence of SDDs has some effect on RMDA at different grades of AMD severity.
Genetic modifiers of lung disease in cystic fibrosis Drumm, Mitchell L; Konstan, Michael W; Schluchter, Mark D ...
New England journal of medicine/The New England journal of medicine,
10/2005, Letnik:
353, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Polymorphisms in genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene may modify the severity of pulmonary disease in patients with cystic fibrosis.
We performed two ...studies with different patient samples. We first tested 808 patients who were homozygous for the DeltaF508 mutation and were classified as having either severe or mild lung disease, as defined by the lowest or highest quartile of forced expiratory volume in one second (FEV1), respectively, for age. We genotyped 16 polymorphisms in 10 genes reported by others as modifiers of disease severity in cystic fibrosis and tested for an association in patients with severe disease (263 patients) or mild disease (545). In the replication (second) study, we tested 498 patients, with various CFTR genotypes and a range of FEV1 values, for an association of the TGFbeta1 codon 10 CC genotype with low FEV1.
In the initial study, significant allelic and genotypic associations with phenotype were seen only for TGFbeta1 (the gene encoding transforming growth factor beta1), particularly the -509 and codon 10 polymorphisms (with P values obtained with the use of Fisher's exact test and logistic regression ranging from 0.006 to 0.0002). The odds ratio was about 2.2 for the highest-risk TGFbeta1 genotype (codon 10 CC) in association with the phenotype for severe lung disease. The replication study confirmed the association of the TGFbeta1 codon 10 CC genotype with more severe lung disease in comparisons with the use of dichotomized FEV1 for severity status (P=0.0002) and FEV1 values directly (P=0.02).
Genetic variation in the 5' end of TGFbeta1 or a nearby upstream region modifies disease severity in cystic fibrosis.
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