Chronic obstructive pulmonary disease (COPD) exacerbations are prone to nonrecovery, but there are no data about the effectiveness of retreatment for these prolonged events. We examined whether ...further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event.
To assess whether incompletely recovered COPD exacerbations benefit from additional treatment with ciprofloxacin, at Day 14.
In a multicenter, randomized double-blind placebo-controlled trial, we studied retreatment with oral ciprofloxacin 500 mg or matched placebo twice daily for 7 days in patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV COPD and persistent symptoms and/or serum C-reactive protein ≥8 mg/L initiated 14 (±3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period.
Among 826 patients screened at four centers, 144 eligible participants with incomplete recovery were randomized to receive ciprofloxacin (
= 72) or placebo (
= 72). Within 90 days of randomization, 57% of the patients in the ciprofloxacin group and 53% in the placebo group experienced one or more exacerbations. The median time to the next exacerbation was 32.5 days (interquartile range 13-50) in the placebo arm and 34 days (interquartile range 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio, 1.07; 95% confidence interval, 0.68-1.68;
= 0.76). No significant differences were seen in quality-of-life scores or lung function between the treatment groups.
In patients with persistent symptoms and/or raised C-reactive protein 14 days after a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared with placebo. This suggests that nonrecovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with antiinflammatory therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02300220).
•Hydroxychloroquine is used in pregnancy for inflammatory conditions.•Understanding of the effects of hydroxychloroquine on the human placenta is limited.•Hydroxychloroquine does not have detrimental ...effects on human placental explants.•Hydroxychloroquine may attenuate placental inflammation in vitro.•Further research is needed to determine the placental actions of hydroxychloroquine.
Hydroxychloroquine (HCQ), a toll like receptor (TLR) 7 and 9 antagonist, is used during pregnancy for inflammatory conditions with limited understanding of its placental toxicology. We hypothesized that HCQ does not have toxic effects on the placenta and can modulate cytokine release in response to TLR7/9 activation. A systematic review was conducted and no studies of HCQ on multicellular human placental tissue were identified. Accordingly, placental villous explants were cultured for 7 days with HCQ +/- TLR7/9 agonists. HCQ did not affect cell turnover, nutrient transport or cytokine release but increased IL-10 (anti-inflammatory) secretion and promoted syncytiotrophoblast regeneration. Cytokine release stimulated by TLR7/9 agonists was unaffected by HCQ. In conclusion, HCQ did not adversely affect placental tissue and may have a protective anti-inflammatory function. Further research is needed to determine the mechanisms of HCQ actions on human placenta and whether they could be utilized to improve pregnancy outcomes.
Fiber-rich fractions (FRF) derived from roller milling of waxy (W) and high amylose (HA) starch hull-less barley genotypes were evaluated for suitability as functional ingredients in fresh and dried ...white salted (WSN) and fresh yellow alkaline (YAN) noodles. FRF-W and FRF-HA both contained over 300 g kg(-1) dietary fiber, and over 200 g kg(-1) of beta-glucans. Replacement of 250 g kg(-1) Canada Prairie Spring White (cv AC Vista) wheat patent flour with the FRF posed no problems in noodle processing, although water absorption had to be substantially increased. All three noodle types enriched with the FRF were significantly darker and contained more brown specks than the wheat flour control noodles. The presence of the FRF reduced cooking time of fresh YAN and WSN by approximately 50%. The addition of FRF improved cooked YAN texture, as evidenced by increased firmness and resistance to compression. FRF-enriched fresh WSN were comparable to the wheat flour control noodles for those parameters, whereas enrichment of dry WSN by FRF imparted less firmness and less chewiness. FRF-enriched fresh YAN and WSN offer consumer convenience due to shorter cooking time, improved nutritional quality and acceptable cooking quality. These features might make FRF-enriched noodles sufficiently attractive to health-conscious consumers to overcome the negative effects of color and appearance
Objective Our objective was to characterize the predictive impact of computed tomography (CT) scan volumetric analysis on the natural history of acute uncomplicated type B aortic dissections (ADs). ...Methods We conducted a retrospective review of patients with acute type B ADs from 2009 to 2014. On an iNtuition workstation (TeraRecon, Foster City, Calif), volume measurements were obtained using the true lumen volume (TLV), false lumen volume (FLV), and total aortic volume from the left subclavian artery to the celiac artery. Growth rate was calculated as the change in maximal diameter between first and last available CT scans during the time interval. The primary outcome of the study was delayed aortic intervention. P < .05 was considered statistically significant. Results During a 5-year period, 164 patients had CT scan evidence of acute type B ADs; 11 patients were excluded for lack of subsequent follow-up imaging; 36 patients who underwent urgent repair (<14 days from presentation) were also excluded. We evaluated a total of 117 patients: 85 patients who did not require intervention and 32 who underwent delayed (>14 days) thoracic endovascular aneurysm repair (29) or open repair (3). Mean age was 66 ± 12 years. Mean TLV/FLV ratio on initial CT scan was significantly higher in patients who did not eventually require an operation (1.55 vs 0.82; P = .02). The mean growth rate was higher in those eventually requiring operation (2.47 vs 0.42 mm/mo; P = .003). Patients were divided into three subgroups on the basis of their initial imaging TLV/FLV ratios (<0.8, 0.8-1.6, and >1.6). There was a significant difference in the growth rates between these three groups (4.6 vs 2.4 vs 0.8 mm/mo; P < .025). Area under the receiver operating characteristic curve analysis revealed that a TLV/FLV ratio <0.8 was highly predictive for requiring an intervention (area = 0.8; sensitivity, 69%; specificity, 84%: positive predictive value, 71%; negative predictive value, 81%), with an odds ratio of 12.2 (confidence interval, 5-26; P < .001). Conversely, a TLV/FLV ratio of >1.6 was highly predictive for freedom from delayed operation (sensitivity, 91%; specificity, 42%; positive predictive value, 61%; negative predictive value, 86%). After Kaplan-Meier analysis, 1-year and 2-year survival free of aortic interventions was 60% and 42% with a TLV/FLV ratio <0.8 and 92% and 82% with a ratio >1.6 ( P = .001). Conclusions Initial CT scan volumetric analysis in patients presenting with uncomplicated acute type B ADs is a useful tool to predict growth and need for future intervention.
Context.
GCIRS 7, the brightest star in the Galactic central parsec, formed 6 ± 2 Myr ago together with dozens of massive stars in a disk orbiting the central black-hole. It has been argued that ...GCIRS 7 is a pulsating body, on the basis of photometric variability.
Aims.
Our goal is to confirm photospheric pulsations based on interferometric size measurements to better understand how the mass loss from these massive stars enriches the local interstellar medium.
Methods.
We present the first medium-resolution (
R
= 500),
K
-band spectro-interferometric observations of GCIRS 7, using the GRAVITY instrument with the four auxiliary telescopes of the ESO VLTI. We looked for variations using two epochs, namely 2017 and 2019.
Results.
We find GCIRS 7 to be moderately resolved with a uniform-disk photospheric diameter of
θ
UD
*
= 1.55 ± 0.03 mas (
R
UD
*
= 1368 ± 26
R
⊙
) in the
K
-band continuum. The narrow-band uniform-disk diameter increases above 2.3 μm, with a clear correlation with the CO band heads in the spectrum. This correlation is aptly modeled by a hot (
T
L
= 2368 ± 37 K), geometrically thin molecular shell with a diameter of
θ
L
= 1.74 ± 0.03 mas, as measured in 2017. The shell diameter increased (
θ
L
= 1.89 ± 0.03 mas), while its temperature decreased (
T
L
= 2140 ± 42 K) in 2019. In contrast, the photospheric diameter
θ
UD
*
and the extinction up to the photosphere of GCIRS 7 (
A
K
S
= 3.18 ± 0.16) have the same value within uncertainties at the two epochs.
Conclusions.
In the context of previous interferometric and photo-spectrometric measurements, the GRAVITY data allow for an interpretation in terms of photospheric pulsations. The photospheric diameter measured in 2017 and 2019 is significantly larger than previously reported using the PIONIER instrument (
θ
*
= 1.076 ± 0.093 mas in 2013 in the
H
band). The parameters of the photosphere and molecular shell of GCIRS 7 are comparable to those of other red supergiants that have previously been studied using interferometry. The extinction we measured here is lower than previous estimates in the direction of GCIRS 7 but typical for the central parsec region.
Abstract
Background
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young infants. However, it is also a significant pathogen in older adults. Validated biomarkers of ...RSV disease severity would benefit diagnostics, treatment decisions, and prophylactic interventions. This review summarizes knowledge of biomarkers for RSV disease in adults.
Methods
A literature review was performed using Ovid Medline, Embase, Global health, Scopus, and Web of Science for articles published 1946–October 2016. Nine articles were identified plus 9 from other sources.
Results
From observational studies of natural infection and challenge studies in volunteers, biomarkers of RSV susceptibility or disease severity in adults were: (1) lower anti-RSV neutralizing antibodies, where neutralizing antibody (and local IgA) may be a correlate of susceptibility/severity; (2) RSV-specific CD8+ T cells in bronchoalveolar lavage fluid preinfection (subjects with higher levels had less severe illness); and (3) elevated interleukin-6 (IL-6), IL-8, and myeloperoxidase levels in the airway are indicative of severe infection.
Conclusions
Factors determining susceptibility to and severity of RSV disease in adults have not been well defined. Respiratory mucosal antibodies and CD8+ T cells appear to contribute to preventing infection and modulation of disease severity. Studies of RSV pathogenesis in at-risk populations are needed.
This systematic literature review compares the clinical outcomes of heparin-bonded expanded polytetrafluoroethylene with autologous saphenous vein in the management of patients undergoing ...below-the-knee bypass to treat peripheral arterial disease.
An electronic literature search was conducted in MEDLINE and Embase to identify comparative studies in patients who underwent below-the-knee surgical bypass. Studies were screened at abstract and full text review using predefined inclusion criteria by two independent reviewers and critically appraised for risk of bias. Meta-analyses were conducted using Review Manager 5 software (Nordic Cochrane Centre).
Eight retrospective cohort studies were identified. Meta-analysis of primary patency demonstrated no significant difference between heparin-bonded expanded polytetrafluoroethylene and autologous saphenous vein grafts after 1 (odds ratio: 0.91, 95% confidence interval: 0.52-1.59; P = .74), 2 (1.12 0.60-2.10; P = .77), 3 (0.62 0.26-1.48; P = .28), and 4 years (0.70 0.36-1.39; P = .31). Similarly, for secondary patency, no significant difference was detected at 1 (0.62 0.33-1.15; P = .13), 2 (0.83 0.32-2.13; P = .69), 3 (0.60 0.27-1.32; P = .20), and 4 years (0.66 0.32-1.36; P = .26). There was no significant difference between autologous veins and heparin-bonded expanded polytetrafluoroethylene for limb salvage and mortality at all time points. A sensitivity analysis to compare outflow vessels was conducted in only tibial bypass and identified no differences. All analyses were considered at high-risk bias because of heterogeneity in study populations and attrition in follow-up.
This meta-analysis demonstrates similar outcomes between autologous saphenous vein and heparin-bonded expanded polytetrafluoroethylene for patency, limb salvage, and mortality through 4 years. The use of heparin-bonded expanded polytetrafluoroethylene synthetic grafts is a satisfactory option to prevent amputation, particularly when autologous saphenous vein grafts are not available. Controlled clinical studies are needed to further inform future decision-making and economic modeling related to the choice of conduit for below-the-knee graft construction.
Reduced fetal movement, defined as a decrease in the frequency or strength of fetal movements as perceived by the mother, is a common reason for presentation to maternity care. Observational studies ...have demonstrated an association between reduced fetal movement and stillbirth and fetal growth restriction related to placental insufficiency. However, individual intervention studies have described varying results. This systematic review and meta-analysis aimed to determine whether interventions aimed at encouraging awareness of reduced fetal movement and/or improving its subsequent clinical management reduce the frequency of stillbirth or other important secondary outcomes.
Searches were conducted in MEDLINE, Embase, CINAHL, The Cochrane Library, Web of Science, and Google Scholar. Guidelines, trial registries, and gray literature were also searched. Databases were searched from inception to January 20, 2022.
Randomized controlled trials and controlled nonrandomized studies were eligible if they assessed interventions aimed at encouraging awareness of fetal movement or fetal movement counting and/or improving the subsequent clinical management of reduced fetal movement. Eligible populations were singleton pregnancies after 24 completed weeks of gestation. The primary review outcome was stillbirth; a number of secondary maternal and neonatal outcomes were specified in the review.
Risk of bias was assessed using the Cochrane Risk of Bias 2 and Risk of Bias in Non-Randomized Studies I tools for randomized controlled trials and nonrandomized studies, respectively. Variation caused by heterogeneity was assessed using I2. Data from studies employing similar interventions were combined using random effects meta-analysis.
A total of 1609 citations were identified; 190 full-text articles were evaluated against the inclusion criteria, 18 studies (16 randomized controlled trials and 2 nonrandomized studies) were included.
The evidence is uncertain about the effect of encouraging awareness of fetal movement on stillbirth when compared with standard care (2 studies, n=330,084) with a pooled adjusted odds ratio of 1.19 (95% confidence interval, 0.96–1.47). Interventions for encouraging awareness of fetal movement may be associated with a reduction in neonatal intensive care unit admissions and Apgar scores of <7 at 5 minutes of age and may not be associated with increases in cesarean deliveries or induction of labor.
The evidence is uncertain about the effect of encouraging fetal movement counting on stillbirth when compared with standard care with a pooled odds ratio of 0.69 (95% confidence interval, 0.18–2.65) based on data from 3 randomized controlled trials (n=70,584). Counting fetal movements may increase maternal-fetal attachment and decrease anxiety when compared with standard care.
When comparing combined interventions of fetal movement awareness and subsequent clinical management with standard care (1 study, n=393,857), the evidence is uncertain about the effect on stillbirth (adjusted odds ratio, 0.86; 95% confidence interval, 0.70–1.05).
The effect of interventions for encouraging awareness of reduced fetal movement alone or in combination with subsequent clinical management on stillbirth is uncertain. Encouraging awareness of fetal movement may be associated with reduced adverse neonatal outcomes without an increase in interventions in labor. The meta-analysis was hampered by variations in interventions, outcome reporting, and definitions. Individual studies are frequently underpowered to detect a reduction in severe, rare outcomes and no studies were included from high-burden settings. Studies from such settings are needed to determine whether interventions can reduce stillbirth.
•A luciferase immunoprecipitation system (LIPS) assay was developed for the detection of antibodies against human norovirus (HuNoV).•The LIPS assay detected higher end-point titers in serum than an ...ELISA.•The LIPS assay allowed comparative analyses of the immune response to individual capsid protein domains.•A competitive LIPS assay proved useful in further assessment of the antibody specificity in complex polyclonal sera.
A luciferase immunoprecipitation systems (LIPS) assay was developed to define the antigenic specificity and titer of antibodies directed against human norovirus (HuNoV). Recombinant proteins, expressed by plasmid constructs encoding Renilla luciferase (Ruc) fused to the full-length HuNoV major capsid protein (VP1) (Ruc-antigen), were generated for ten HuNoV strains. In addition, subdomain constructs Ruc-Shell (S) and Ruc-Protruding (P) were engineered for a representative GII.4 norovirus (strain GII.4/2006b). The LIPS assay measured antibody levels in a well-defined panel of HuNoV-specific sera, and the results were compared to an ELISA standard. In hyperimmune sera, the LIPS produced titers similar to or higher than those measured by the ELISA of HuNoV-specific antibodies. The specificity of antibodies in various sera was profiled by LIPS with a panel of diverse Ruc-antigens containing full-length HuNoV VP1 proteins or VP1 subdomains, and the assay detected both specific and cross-reactive antibodies. Competition assays, in which antibodies were pre-incubated with one or more intact VLPs representing different genotypes, proved useful in further assessment of the antibody specificity detected by LIPS in complex polyclonal sera. The profiling of HuNoV-specific antibodies in the high-throughput LIPS format may prove useful in defining the strength or specificity of the adaptive immune response following natural infection or vaccination.
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