Tag: pubmed

J Electrocardiol. 2021 Mar 31;66:79-83. doi: 10.1016/j.jelectrocard.2021.03.011. Online ahead of print.

ABSTRACT

INTRODUCTION: The clinical utility of inferolateral early repolarisation (ER) and late potentials (LP) in children with Brugada Syndrome (BrS) has not been previously evaluated. The aim of this study was to determine the prevalence of electrocardiographic (ECG) abnormalities in children with BrS, and to investigate their relationship with clinical outcomes.

METHODS: 43 patients with BrS and 47 controls aged ≤18 undergoing systematic clinical and ECG evaluation, including signal-averaged ECG (SAECG) and pharmacological provocation testing, between 2003 and 2019 were included.

RESULTS: Four patients with BrS (9%) presented with a spontaneous type 1 Brugada pattern; the remaining 39 (91%) were diagnosed following ajmaline provocation testing. Twelve BrS patients (28%) had late potentials (LP) on SAECG compared to 1 (2%) in controls (p = 0.001). LP were more common in 5 patients with a high-risk phenotype (60% vs 24%) but this was not statistically significant. Twelve patients with BrS (28%) had inferolateral early repolarisation (ER) and 2 (5%) had fractionated QRS (f-QRS), but there were no statistically-significant differences with controls in these parameters. A significant arrhythmia (non-sustained ventricular tachycardia or atrial fibrillation) was seen in 4 patients (9%).

CONCLUSIONS: This study shows a high prevalence of SAECG abnormalities in children with BrS compared with controls, but this was not significantly associated with a high-risk phenotype.

PMID:33831794 | DOI:10.1016/j.jelectrocard.2021.03.011

AIDS. 2021 Apr 6. doi: 10.1097/QAD.0000000000002900. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a protease-inhibitor regimen to raltegravir/maraviroc.

DESIGN: Substudy of ROCnRAL-ANRS157 with investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end.

METHODS: We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used Wilcoxon-paired test.

RESULTS: The patients (n = 8) were mainly male (7/8), aged (mean±SEM) 54.9 ± 1.2 years, BMI 26.1 ± 1.2 kg/m2, CD4: 699 ± 56 cells/mm3, all viral load (VL)<50 copies/mL. After a follow-up of 6 ± 0.5 months, all PLWH remained with VL<50 copies/mL. BMI, trunk and limb fat amounts were unchanged yet systemic insulin resistance increased. Adipose tissue histology was unchanged except for borderline increased adipocyte diameter (P = 0.1). Amongst the 16,094 RNA transcripts, 458 genes were up-regulated and 244 down-regulated. Analyses of the KEGG and GO databases, evaluating modifications in the main functional pathways, revealed that genes related to immune recognition/function were less expressed as were genes encoding T-cell receptor and receptor signaling pathways. The gene expression profiles indicated decreased inflammation but genes involved in adipogenesis and insulin resistance were overexpressed.

CONCLUSION: After 6 months of raltegravir/maraviroc, adipogenesis-related gene profile was enhanced in SCAT, in agreement with a tendency for increased adipocyte size. Enhanced SCAT insulin resistance-related profile was concordant with higher systemic insulin resistance. However, immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.

PMID:33831906 | DOI:10.1097/QAD.0000000000002900

Gait Posture. 2021 Mar 26;86:278-286. doi: 10.1016/j.gaitpost.2021.03.029. Online ahead of print.

ABSTRACT

BACKGROUND: Common etiologies for post-traumatic ankle osteoarthritis are ankle fractures and chronic ankle instability. As the nature of trauma is different for these two etiologies, it might be expected that the two subtypes of post-traumatic ankle osteoarthritis would display different foot mechanics during gait.

RESEARCH QUESTION: The objective of this exploratory cross-sectional study was to compare the foot kinematics and kinetics of patients suffering from post-fracture ankle osteoarthritis with those of patients suffering from post-sprain ankle osteoarthritis.

METHODS: Twenty-nine subjects with end-stage post-traumatic ankle osteoarthritis and fifteen asymptomatic control subjects participated in this study. All patients suffered from post-traumatic ankle osteoarthritis secondary to ankle-related fracture (Group 1; n = 15) or to chronic ankle instability (Group 2; n = 14). A four-segment kinematic and kinetic foot model was used to calculate intrinsic foot joint kinematics and kinetics during gait. Vector field statistical analysis MANOVA was used to assess differences between groups for the entire three-component intrinsic foot joint angles and moments.

RESULTS: MANOVA showed significant differences between the groups. Post-hoc analyses suggested that the differences between post-fracture ankle osteoarthritis group and controls were caused by a combination of less adducted Shank-Calcaneus position and less plantarflexion at this joint. Post-hoc analyses also suggested that both pathological groups exhibited a decreased plantarflexion moment for Shank-Calcaneus, Chopart, Lisfranc joints compared to controls. Analyses of both pathological groups versus controls for power suggested lower Shank-Calcaneus and Lisfranc power generation during pre-swing phase.

SIGNIFICANCE: No significant differences were found between the two pathological groups in this exploratory study. Alterations in foot kinematics and kinetics were mainly found about the dorsi-/plantarflexion axis during the pre-swing phase of the stance phase for both pathological groups compared to controls. Observed differences were not limited to the painful ankle joint, but seem also to have affected the kinetics of the neighbouring foot joints.

PMID:33831743 | DOI:10.1016/j.gaitpost.2021.03.029

Cell Immunol. 2021 Mar 23;364:104345. doi: 10.1016/j.cellimm.2021.104345. Online ahead of print.

ABSTRACT

Previously, we generated IL233, a hybrid cytokine composed of interleukin (IL)-2 and IL-33, with better therapeutic potential than either cytokine in multiple inflammatory diseases, in part through promoting T-regulatory cells (Tregs). Here we test the potential of IL233 pretreatment in a murine model of excessive Th1 activation, the parent-into-F1 model of acute GVHD (aGVHD). Five days of IL233 pretreatment of the recipients blocked or delayed the aGVHD-linked loss of B cells as seen in either the peripheral blood (day-11) or lymph nodes (day-14). IL233 pretreatment also prevented the expansion of donor CD8 T-cells in blood and LN at day-14 and significantly reduced day-14 serum IFNγ and TNFα compared to saline treated GVHD mice although, the level of Tregs did not statistically differ between saline and IL233-treated mice. Overall, the current study provides support for the use of IL233 as a therapeutic option in excessive Th1/CD8-driven conditions.

PMID:33831754 | DOI:10.1016/j.cellimm.2021.104345

J Environ Manage. 2021 Apr 5;289:112474. doi: 10.1016/j.jenvman.2021.112474. Online ahead of print.

ABSTRACT

In this study, a sequencing batch reactor (SBR) with aerobic granular sludge (AGS) was operated with synthetic wastewater containing environmental relevant concentrations of 17β-estradiol (E2), 17α-ethinylestradiol (EE2) and sulfamethoxazole (SMX). Despite the presence of the studied PhAC, the granular fraction clearly predominated (TSS_gran/TSS ranging from 0.82 to 0.98) throughout the monitoring period, presenting aggregates with high organic fraction (VSS/TSS above 0.83) and good settling characteristics (SVI₅ ranging from 15 to 39 mL/gTSS). A principal component analysis (PCA) with quantitative image analysis (QIA) based data allowed to distinguish the different operational periods, namely with mature granules (CONT), and the E2, EE2, and SMX feeding periods. It further revealed a positive relationship between the biomass density, sludge settling ability, overall and granular biomass contents, granulation properties, granular biomass fraction and large granules fraction and size. Moreover, a discriminant analysis (DA) allowed to successfully discriminate not only the different operational periods, mainly by using the floccular apparent density, granular stratification and contents data, but also the PhAC presence in samples. The filamentous bacteria contents, sludge settling properties, settling properties stability and granular stratification, structure and contents parameters were found to be crucial for that purpose.

PMID:33831759 | DOI:10.1016/j.jenvman.2021.112474

Clin Transl Sci. 2021 Apr 8. doi: 10.1111/cts.12980. Online ahead of print.

ABSTRACT

The current success rate of a drug candidate, from the beginning of the clinical trial to receiving marketing approval, is about 10%-20%, and it has not changed during the past few decades. Therefore, pharmaceutical companies are under pressure to select one compound, among many others, with a high probability of success. The differences in drug features affect their probabilities of approval success. In this study, we examined the approval success rates of drug candidates, developed in the United States, the European Union, or Japan, by focusing on four parameters (“drug target,” “drug action,” “drug modality,” and “drug application”) and their combinations, and identified factors that conditioned the outcome of the drug development process. We obtained a total success rate of 12.8%, after evaluating 3999 compounds. Moreover, after analyzing the combinations of these parameters, the approval success rates of drugs that corresponded to the following categories-a stimulant in drug action or an enzyme in drug target and biologics (excluding monoclonal antibody) in drug modality-were high (34.1% and 31.3%, respectively). Univariate and multivariate logistic regression analyses revealed that stimulant in drug action, and “B” (blood and blood forming organs), “G” (genito-urinary system and sex), and “J” (anti-infectives for systemic use) in drug application were statistically associated with high approval success rates. We found several parameters and their combinations that affected drug approval success rates. Our results could assist pharmaceutical companies in evaluating the probability of success of their drug candidates and, thus, in efficiently conducting the clinical development process.

PMID:33831276 | DOI:10.1111/cts.12980

Interact Cardiovasc Thorac Surg. 2021 Apr 8;32(3):343-350. doi: 10.1093/icvts/ivaa265.

ABSTRACT

OBJECTIVES: The inflammatory response after surgery is associated with patient prognosis. Patients who undergo thoracic surgery exhibit a profound systemic inflammatory response due to the surgical procedures used and application of one-lung ventilation. The aim of this study was to compare perioperative inflammatory changes in patients after intubated and non-intubated thoracic surgery for primary lung cancer resection.

METHODS: This prospective randomized controlled study included forty patients who underwent surgical resection for stage I non-small-cell lung cancer. Blood samples for cytokine analysis were collected just before induction, at 1 and 24 h after surgery. Levels of the pro-inflammatory cytokine and anti-inflammatory cytokines were measured using quantitative sandwich enzyme immunoassay kits.

RESULTS: The basal values of cytokines were comparable between 2 groups. Within each group, the postoperative levels of interleukin (IL)-1, IL-6 and tumour necrosis factor-α increased, while those of IL-4 and IL-10 did not change significantly. The levels of IL-6 and tumour necrosis factor-α were significantly lower in group NI at 1 and 24 h postoperatively. Other cytokines did not differ in both groups during postoperative period. The IL-6/IL-10 ratio at 1 h after surgery was lower in non-intubated patients than in intubated patients, but there was no difference at 24 h after surgery.

CONCLUSIONS: Non-intubated thoracic surgery may attenuate the early inflammatory cytokine changes following major resection for primary lung cancer compared with intubated conventional surgery.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registry number NCT04007354.

PMID:33831216 | DOI:10.1093/icvts/ivaa265

Interact Cardiovasc Thorac Surg. 2021 Apr 8;32(3):371-379. doi: 10.1093/icvts/ivaa277.

ABSTRACT

OBJECTIVES: Depression is common in patients with cardiac disease. The importance of preoperative depression for development of postoperative delirium (POD) following cardiac surgery is not well known. The aim is to provide a summary estimate of depression as a predictor of POD following cardiac surgery.

METHODS: Systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection and Psycinfo (Ovid) was performed from inception to October 2019, including cohort studies reporting odds ratios (ORs) and 95% confidence intervals (CIs) for POD following cardiac surgery in patients with preoperative depression compared to patients without depression. ORs and 95% CIs for POD were calculated using random-effects meta-analyses. Subgroup and sensitivity analyses were performed.

RESULTS: Seven studies were included with a combined study population of 2066 patients. The pooled prevalence of POD in the combined study population was 26% and preoperative depression was present in ∼9% of the total study population. All studies showed a positive association between preoperative depression and POD; and in 5 studies, the association was statistically significant. Patients with depression had a pooled OR of 2.31 (95% CI 1.37-3.90) for POD.

CONCLUSIONS: This systematic review and meta-analysis confirm the findings that the previous association between preoperative depression and increased risk for developing POD reported for other patient groups is found also in cardiac surgery. Depression screening prior to cardiac surgery may be effective in identifying patients at higher risk for POD.

PMID:33831217 | DOI:10.1093/icvts/ivaa277

J Clin Psychol. 2021 Apr 8. doi: 10.1002/jclp.23137. Online ahead of print.

ABSTRACT

OBJECTIVES: Difficulties with sexual desire and arousal are common in women, but most lack access to effective treatment such as cognitive-behavioral therapy (CBT). eSense is a recently created online CBT intervention for sexual difficulties with promising evidence of usability. The current study assessed the feasibility of women completing the full eSense CBT program without guidance.

METHODS: Eleven women with Sexual Interest/Arousal Disorder completed eSense and provided feedback via semi-structured interviews.

RESULTS: Participants reported high satisfaction with eSense’s functionality, improved knowledge about sexuality, greater awareness of their thought patterns, and better perspective around their sexual difficulties. Despite some difficulty completing homework, participants exhibited statistically significant pre-post improvements in sexual desire (d = 1.04), sexual arousal (d = 1.83), sexual satisfaction (d = 1.35), and sexual distress (d = 1.79).

CONCLUSION: The findings add to the growing evidence that self-guided online interventions are feasible and potentially efficacious in treating female sexual dysfunction.

PMID:33831258 | DOI:10.1002/jclp.23137

Am J Epidemiol. 2021 Apr 8:kwab098. doi: 10.1093/aje/kwab098. Online ahead of print.

ABSTRACT

Serological surveys can provide evidence of cases that were not previously detected, depict the spectrum of disease severity, and estimate the proportion of asymptomatic infections. To capture these parameters, survey sample sizes may need to be very large, especially when the overall infection rate is still low. Therefore, we propose the use of “snowball sampling” to enrich serological surveys by testing contacts of infected individuals identified in the early stages of an outbreak. For future emerging pandemics, this observational study sampling design can answer many key questions, such as estimating the asymptomatic proportion of all infected cases, the probability of a given clinical presentation for a seropositive individual, or the association between characteristics of either the host or the infection and seropositivity among contacts of index individuals. We provide examples, in the context of the coronavirus disease 2019 (COVID-19) pandemic, of studies and analysis methods using a snowball sample and perform a simulation study that demonstrates scenarios where snowball sampling can answer these questions more efficiently than other sampling schemes. We hope such study designs can be applied to provide valuable information to slow the present pandemic as it enters its next stage and in early stages of future pandemics.

PMID:33831177 | DOI:10.1093/aje/kwab098