Nevin Manimala

Dermatology. 2021 Mar 17:1-8. doi: 10.1159/000514503. Online ahead of print.

ABSTRACT

BACKGROUND: A growing body of evidence links various biomarkers to atopic dermatitis (AD). Still, little is known about the association of specific biomarkers to disease characteristics and severity in AD.

OBJECTIVE: To explore the relationship between various immunological markers in the serum and disease severity in a hospital cohort of AD patients.

METHODS: Outpatients with AD referred to the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, were divided into groups based on disease severity (SCORAD). Serum levels of a preselected panel of immunoinflammatory biomarkers were tested for association with disease characteristics. Two machine learning models were developed to predict SCORAD from the measured biomarkers.

RESULTS: A total of 160 patients with AD were included; 53 (33.1%) with mild, 73 (45.6%) with moderate, and 34 (21.3%) with severe disease. Mean age was 29.2 years (range 6-70 years) and 84 (52.5%) were females. Numerous biomarkers showed a statistically significant correlation with SCORAD, with the strongest correlations seen for CCL17/thymus and activation-regulated chemokine (chemokine ligand-17/TARC) and CCL27/cutaneous T cell-attracting-chemokine (CTACK; Spearman R of 0.50 and 0.43, respectively, p < 0.001). Extrinsic AD patients were more likely to have higher mean SCORAD (p < 0.001), CCL17 (p < 0.001), CCL26/eotaxin-3 (p < 0.001), and eosinophil count (p < 0.001) than intrinsic AD patients. Predictive models for SCORAD identified CCL17, CCL27, serum total IgE, IL-33, and IL-5 as the most important predictors for SCORAD, but with weaker associations than single cytokines.

CONCLUSIONS: Specific immunoinflammatory biomarkers in the serum, mainly of the Th2 pathway, are correlated with disease severity in patients with AD. Predictive models identified biomarkers associated with disease severity but this finding warrants further investigation.

PMID:33730733 | DOI:10.1159/000514503

Oncology. 2021 Mar 17:1-8. doi: 10.1159/000514404. Online ahead of print.

ABSTRACT

BACKGROUND: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients.

PATIENTS AND METHODS: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score positivity.

RESULTS: Of the 186 patients, the primary tumor location was intrahepatic cholangiocarcinoma (IHCC) in 72 (38.7%), extrahepatic cholangiocarcinoma (EHCC) in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). Among all the patients, 53 (28.5%) had PD-L1 positivity. The median overall survival (OS) of patients with PD-L1 positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. OS and PFS were not statistically different between groups. In subgroup analysis, EHCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p = 0.002) and PFS (7.8 vs. 5.4 months, p = 0.005) than those who were PD-L1-positive. However, this finding was not reproduced in patients with IHCC or GB cancer.

CONCLUSION: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EHCC but not in patients with IHCC or GB cancer.

PMID:33730723 | DOI:10.1159/000514404

Complement Med Res. 2021 Mar 17:1-8. doi: 10.1159/000514944. Online ahead of print.

ABSTRACT

BACKGROUND: Menopause and estrogen deprivation cause a rise in the number of urogenital tract complaints.

OBJECTIVE: This study was conducted to assess the effectiveness of ginseng on genitourinary syndrome.

METHODS: This randomized trial was conducted on 60 postmenopausal women with genitourinary syndrome. The participants were randomly allocated to ginseng and placebo groups twice daily for 4 weeks. Vaginal maturation index and vaginal pH were evaluated before and 4 weeks after intervention as the primary outcomes. Also, the atrophic vaginitis and incontinence questionnaires were completed before and after intervention as the secondary outcomes. The safety of intervention was assessed by the side effects checklist.

RESULTS: No significant differences were observed between the 2 groups in objective symptoms after the intervention, but the difference was statistically significant (p < 0.001) in terms of subjective symptoms of atrophic vaginitis. One case of insomnia and palpitation and 2 cases of hot flashes were reported in the intervention group, and 1 case of gastric discomfort and change in urine appearance was reported in the placebo group.

CONCLUSION: Ginseng only improved the patient-assessed symptoms and had no significant effect on the clinician-assessed outcomes. Further studies are required to determine the precise pharmacological mechanisms of ginseng on genitourinary syndrome.

PMID:33730722 | DOI:10.1159/000514944

Eur Addict Res. 2021 Mar 17:1-9. doi: 10.1159/000513776. Online ahead of print.

ABSTRACT

INTRODUCTION: Substance use disorders (SUDs) are a leading cause of morbidity and mortality worldwide, having a profound and global impact on health, well-being, safety, and productivity. Although traditionally the prevalence of SUDs in Israel has been estimated to be lower than those in high-income countries, estimates and characteristics of individuals with SUDs in the past decade are lacking. In this work, we explored the prevalence of SUDs among the adult Jewish population in Israel, per different classes of substances across sex, age group, and other sociodemographic factors.

METHODS: Data from an online representative sample of 4,025 respondents were collected, including the alcohol, smoking, and substance involvement screening test (ASSIST) metric and sociodemographic data.

RESULTS: We found that the most common SUDs were alcohol (10.5% [9.5-11.4]), cannabis (9.0% [8.2-9.9]), and sedative (3.6% [3.0-4.2]) use disorders. Alcohol-cannabis (3.2% [2.7-3.7]) and alcohol-sedative (1.04% [0.7-1.35]) were the most prevalent co-occurring SUDs. Among those with cannabis use disorder, the prevalence of alcohol use disorder was found to be 35.3% [30.4-40.2]. The estimated risk for alcohol use disorder was found to be inversely proportional to age, cannabis use disorder increased, peaked, and decreased with age, and that of sedative use disorder increased with age, particularly among women. While older individuals (in the 51-60 years of age group) were at lower risk (OR = 0.5 [0.3, 0.8]) compared to those <20 years of age for alcohol use disorder, they were at increased risk for sedative use disorder (OR = 3.1 [1.2, 9.7]).

CONCLUSIONS: These findings represent substantially higher rates of SUDs in Israel than those previously reported and should affect resources allocated to addiction prevention and treatment. Further research on the role of gender, age, culture, and ethnicity in the propensity to develop SUDs is necessary for the development of more focused preventive and intervention measures. Focusing on non-Jewish populations in Israel and broadening the scope to include behavioral addictions should be addressed in future studies.

PMID:33730716 | DOI:10.1159/000513776

J Phys Condens Matter. 2021 Mar 17. doi: 10.1088/1361-648X/abef9b. Online ahead of print.

ABSTRACT

We explore glassy dynamics of dense assemblies of soft particles that are self-propelled by active forces. These forces have a fixed amplitude and a propulsion direction that varies on a timescale τp, the persistence timescale. Numerical simulations of such active glasses are computationally challenging when the dynamics is governed by large persistence times. We describe in detail a recently proposed scheme that allows one to study directly the dynamics in the large persistence time limit, on timescales around and well above the persistence time. We discuss the idea behind the proposed scheme, which we call “activity-driven dynamics”, as well as its numerical implementation.We establish that our prescription faithfully reproduces all dynamical quantities in the appropriate limit τp→ ∞. We deploy the approach to explore in detail the statistics of Eshelby-like plasticevents in the steady state dynamics of a dense and intermittent active glass.

PMID:33730708 | DOI:10.1088/1361-648X/abef9b

J Med Internet Res. 2021 Mar 16. doi: 10.2196/25504. Online ahead of print.

ABSTRACT

BACKGROUND: Preoperative anxiety is a common occurrence among children and is associated with a host of maladaptive post-operative behaviors. Consequently, increased attention has been placed on interventions to reduce preoperative anxiety and its associated outcomes. Child Life preparation prior to surgery includes evidence-based practices such as age-appropriate distraction and therapeutic play. Virtual reality (VR) is a promising addition to the Child Life toolbox to address anxiety prior to surgery. The current study evaluates the implementation and feasibility of a VR experience, “Doc McStuffins: Doctor for a Day Virtual Reality Experience” (DocVR), developed by Disney Junior in collaboration with Children’s Hospital Los Angeles, to target pediatric preoperative anxiety.

OBJECTIVE: The primary aim of this study was to examine the feasibility and efficacy of DocVR for preoperative anxiety. A secondary aim is to improve patient, caregiver, and healthcare provider satisfaction with the preoperative experience.

METHODS: Fifty-one patients (age 6 to 14 years) scheduled for surgery in the Ambulatory Surgery Center (ASC) and the main Operating Room (OR) at Children’s Hospital Los Angeles were approached for participation in Disney’s DocVR experience. The patients played the DocVR experience for an average of 18 minutes (3 to 55 minutes). Irrespective of surgical procedure, patients and their families were eligible, as long as they had no known marked cognitive or visual impairments, which would interfere with completing the survey and engaging in the DocVR experience.

RESULTS: Patients who tried the DocVR experience (n=51) responded overwhelmingly positively to both the VR technology and to the game itself. Patients experienced a statistically significant decrease in anxiety following DocVR game play (Z = -3.26, P = .001). On the Facial Affective Scale, the percentage of patients who chose the face with the most positive facial expression to represent their affect increased from 24% pre-VR to 49% post-VR. Furthermore, 97% of patients reported feeling more comfortable at the hospital and 74% reported feeling less scared at the hospital after playing the game. 94% of patients enjoyed the game, and 88% of patients reported feeling both ‘Interested’ and ‘Involved’ in the game.

CONCLUSIONS: DocVR is a feasible and beneficial VR experience to relieve pediatric preoperative anxiety and improve satisfaction in the preoperative area. The VR experience resulted in a decrease in overall anxiety and an increase in overall positive affect during the preoperative time. Patients also responded positively to the game, confirming their interest in the content and affirming the quality of the DocVR experience. The positive response to the game indicates that DocVR has the potential to make the overall preoperative experience less anxiety-producing and more comfortable, which leads to improved patient satisfaction. Naturally, improved patient outcomes lead to improved caregiver and healthcare provider satisfaction.

PMID:33730687 | DOI:10.2196/25504

Clin Psychol Rev. 2021 Feb 27;85:102003. doi: 10.1016/j.cpr.2021.102003. Online ahead of print.

ABSTRACT

People with psychosis are reported to be one of the most stigmatised minority groups in society. Mental health stigma can have a detrimental impact on quality of life (QoL), which is a meaningful outcome for service users experiencing psychosis and using mental health services. This paper provides the first systematic literature review, meta-analysis and quality appraisal of studies examining the association between stigma and subjective QoL in non-affective psychosis. An electronic database search identified 45 articles for inclusion. A random-effects meta-analysis of 37 independent samples (n = 5795) found a statistically significant association between higher stigma and lower subjective QoL of medium strength (r = -0.40, 95% CI: -0.45, -0.35). Separate meta-analyses demonstrated medium-to-large negative pooled effects for self-stigma (k = 25, r = -0.44, 95% CI:-0.49, -0.38), perceived stigma (k = 10, r = -0.32, 95% CI:-0.42, -0.21) and experienced stigma (k = 6, r = -0.30, 95% CI:-0.35, -0.24). A narrative summary of 12 studies suggested psychological mechanisms relating to self-concept and social networks may play an important mediating role in the association between stigma and QoL in psychosis. Psychological interventions should target improvements in these psychological processes to reduce the negative impact of stigma on QoL in psychosis. Further longitudinal research is needed to test theoretical models of causal pathways and explanatory mechanisms.

PMID:33730660 | DOI:10.1016/j.cpr.2021.102003

J Colloid Interface Sci. 2021 Mar 2;593:21-31. doi: 10.1016/j.jcis.2021.02.076. Online ahead of print.

ABSTRACT

HYPOTHESIS: The objective is to noninvasively probe the local hydrocarbon dynamics at asphaltene/maltene interfaces to reveal the global characteristics of bitumen at increasing temperatures and under various mechanical constraints.

EXPERIMENTS: We propose multidimensional (1D and 2D) nuclear magnetic relaxation (NMR) experiments to characterize the dynamic properties of hydrocarbons for a set of bitumen from 40 to 180 °C. The convergence towards universal theoretical modelling of NMR relaxation experiments gives a comprehensive understanding of hydrocarbon transport in these very weakly permeable samples. Moreover, a multivariate statistical analysis allows for correlating these NMR relaxation data for all bitumen samples to the main empirical parameters by qualifying the bitumen grading, such as the penetrability, softening and fragility points over a large range of temperatures.

FINDINGS: These new experimental and theoretical multiscale approaches link hydrocarbon interfacial dynamics to the global characteristics of various bitumen types. This is critical for grading these universally encountered materials.

PMID:33730653 | DOI:10.1016/j.jcis.2021.02.076

Lung Cancer. 2021 Feb 19;155:53-60. doi: 10.1016/j.lungcan.2021.02.021. Online ahead of print.

ABSTRACT

OBJECTIVES: This post hoc analysis assessed the safety of pemetrexed and platinum in combination with pembrolizumab, including time-to-onset and time-to-resolution of all-cause any-grade and grade ≥3 adverse events (AEs) and renal AEs.

MATERIALS AND METHODS: Patient-level data from KEYNOTE-189 were analyzed in the all-subjects-as-treated population (pembrolizumab arm, n = 405; placebo arm, n = 202), and among patients who received ≥5 cycles of pemetrexed (pemetrexed/pembrolizumab/platinum arm, n = 310; pemetrexed/placebo/platinum arm, n = 135). All-cause AEs were selected based on ≥2 % incidence from previously reported KEYNOTE-189 data and included neutropenia, febrile neutropenia, anemia, thrombocytopenia, asthenia, fatigue, dyspnea, diarrhea, nausea, vomiting, pneumonitis, and renal events. Descriptive statistics summarized all-cause AEs. Medians and interquartile ranges were used to examine time-to-onset and time-to-resolution. The data cutoff was November 8, 2017.

RESULTS: In both treatment arms, most non-hematologic (nausea, vomiting, diarrhea, and asthenia), and hematologic (febrile neutropenia, thrombocytopenia, and neutropenia) grade ≥3 AEs with ≥2 % incidence had a median time-to-onset within the first 4 cycles, and a median time-to-resolution of within 2 weeks from onset. A small number of AEs had longer median time-to-onset (pneumonitis and fatigue) and median time-to-resolution (pneumonitis, fatigue, acute kidney injury, and anemia). Among patients who received ≥5 cycles of pemetrexed, the incidence of any-grade renal toxicity in the pemetrexed/pembrolizumab/platinum arm was 2.3 % in Cycles 1-4, 4.8 % in Cycles 5-8, 2.6 % in Cycles 9-12, and 2.5 % in Cycles ≥13; and, in the pemetrexed/placebo/platinum arm, 0.7 % in Cycles 1-4, 1.5 % in Cycles 5-8, 1.3 % in Cycles 9-12, and 2.0 % in Cycles ≥13.

CONCLUSION: Pemetrexed/pembrolizumab/platinum has manageable toxicity with longer duration of treatment. While the incidence of renal toxicity was slightly higher in the pembrolizumab combination as compared to pemetrexed, the incidence did not increase in later treatment cycles. These results support the safe use of the KEYNOTE-189 regimen in clinical practice.

CLINICAL TRIAL REGISTRATION NUMBER: NCT02578680 (clinicaltrials.gov).

PMID:33730652 | DOI:10.1016/j.lungcan.2021.02.021

Adv Med Sci. 2021 Mar 14;66(1):215-220. doi: 10.1016/j.advms.2021.03.002. Online ahead of print.

ABSTRACT

PURPOSE: The long-term clinical outcome of adjuvant stereotactic radiotherapy (SRT) in neovascular age-related macular degeneration (nAMD) patients was evaluated.

METHODS: This case-control study included patients with unilateral nAMD, who underwent SRT complementary to standard anti-VEGF treatment. Only patients with monthly follow-up over at least three years were considered. Number of intravitreal injections, visual acuity (VA), central retinal thickness (CRT), and subfoveal choroidal thickness (SFCT) were evaluated and compared to baseline as well as to an age- and gender-matched control group, who received anti-VEGF monotherapy.

RESULTS: Twenty patients were irradiated and had complete follow-up. Cumulatively, SRT patients needed significantly less injections than non-irradiated ones over three years (14 vs. 18, p ​= ​0.014), while median VA did not show statistically significant changes (0.4 logMAR at baseline to 0.65 logMAR at final follow-up, p ​= ​0.061). CRT remained steady, but SFCT showed a continuous thinning of almost 50 ​μm (p ​= ​0.031) in irradiated patients over three years. Multiple linear regression analysis revealed that SFCT and VA at time of irradiation are significant prognostic factors of VA change in SRT patients over the following three years (F(2,17) ​= ​23.946, p<0.001, R² of 0.738).

CONCLUSIONS: SRT significantly reduced the cumulative anti-VEGF treatment burden over three years, however, this was mainly driven by the results of the first year after irradiation. A thinner SFCT at time of irradiation was associated with poorer visual outcome. While further research and investigation are warranted to elucidate the underlying pathogenesis, SFCT could be a potential biomarker when evaluating a patient’s suitability for SRT.

PMID:33730635 | DOI:10.1016/j.advms.2021.03.002