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Clinical Assessment of Cytokine Profiles and Haematological Parameters in Patients with Systemic Lupus Erythematosus: A Cross-Sectional Study from Saudi Arabia

Front Biosci (Landmark Ed). 2023 Dec 28;28(12):358. doi: 10.31083/j.fbl2812358.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE)-related hematological disorders have different pathogenic mechanisms involving immune dysregulation as well as microangiopathy. The current study aimed to assess the relationship between pro- and anti-inflammatory cytokines and SLE-related hematological abnormalities for Saudi Patients.

METHODS: The current cross-sectional study including 140 participants was performed at the Prince Mohammad bin Abdulaziz Hospital (PMAH), Riyadh, Saudi Arabia. Two blood samples were collected from each of the study participants for evaluation of the haematological indices including complete blood count (CBC), erythrocyte sedimentation rate (ESR), and cytokine profile (i.e., tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)). Statistical analyses were performed using the Statistical Package of Social Sciences (SPSS) software, v25.

RESULTS: Haematological abnormalities were documented in 63% of SLE patients, and anaemia was the highest at 52%. Haemoglobin levels were found to be significantly lower among SLE patients compared to the controls (p < 0.001). In the cytokine profiles, the levels of TNF-α (p < 0.001), IL-6 (p < 0.001), and IL-10 (p = 0.009) were significantly higher among SLE patients compared to the controls. A positive correlation was also identified between TNF-α, platelet count, red cell distribution width (RDW), and ESR.

CONCLUSIONS: Haematological abnormalities were found to be the most common among SLE patients. Further, the correlation between cytokine profile and haematological indices indicates the influence of cytokines in the development of haematological abnormalities. Understanding hematological abnormalities and cytokines’ role in the pathogenesis of these abnormalities may aid in the early diagnosis and development of more specific SLE disease therapies.

PMID:38179775 | DOI:10.31083/j.fbl2812358

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Plant-Derived Extracts Plus Vitamin E and/or Aloe Vera Protect Against Intrinsic/Extrinsic Stressor in Human Skin: In Vitro and Clinical Evidence

Front Biosci (Landmark Ed). 2023 Dec 29;28(12):366. doi: 10.31083/j.fbl2812366.

ABSTRACT

BACKGROUND: Humans are exposed to physical, biological, chemical, and psychological stressor throughout their life span. In recent years many medicinal plants have been shown to induce stress adapting and protective functions. Plant-derived extracts and vitamin E exhibit stress protection or resistance by normalizing cellular homeostasis and enhancing resistance to toxic stimuli to overcome cellular damage. Here we report the evaluation of a topical preparation (product test materials; PTM) containing an ingredient blend of Rhodiola Rosea, Eleutherococcus Senticosus (Siberian Ginseng), Rhaponticum Carthamoides, Inonotus Obliqus, and Slegainella Lepidophylla as the base formula and tested the addition of Lespedeza Capitata (leaf/stem) extract plus vitamin E and/or Aloe Vera to determine the induced protective functions in human skin when challenged with intrinsic and extrinsic stressors.

METHODS: The base topical preparation plus Lespedeza Capitata extract plus vitamin E or the base topical preparation plus vitamin E and Aloe Vera were assayed in vitro on (a) intrinsically stressed excised abdominoplasty skin, (b) full thickness (FT) skin equivalent models post-treated with a combination of ultra-violet (UV) B light (250 mJ/cm2) and diesel particular matter (DPM) (75 µg/mL) skin, for their effect on antioxidant, inflammation, and stress biomarker geners. Additionally, the bioadaptive activity of the PTMs was confirmed in providing resilience and protection against UV-induced erythema. For example, in a clinical study, daily topical application of the PTMs on the buttocks of 20 woman (18-78 years old), average age of 51.1 years, median body mass index (BMI) of 26.5 for 8 weeks followed by 2 minimal erythema dose (MED) of UVB exposure was accessed 24 hours after irradiation. Statistical analysis was performed by t-test and ANOVA, repectively.

RESULTS: Pretreatment with the topical PTMs on intrsinically stressed skin significantly reduced the expression of the stress gene biomarkers, p53, pro-inflammatory cytokines Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNFα) and the pro-apoptotic BCL2 associated X, apoptosis regulator (BAX) values compared to controls. Topical application of the PTMs on Full Thickness (FT) human skin treated with UVB light and DPM significantly enhanced the stress response by activating heat shock transcription factor 4 (HSF4) and heat shock protein family B (small) member 1 (HSPB1) gene levels belonging to the heat shock protein (HSP) family by significantly increasing the expression of heme oxygenase 1 (HMOX1). At the same time, significantly reducing IL-1β levels were observed plus protection of skin cells from toxicity ocurred by significantly increasing the expression of B-cell lymphoma 2 (BCL2) (anti-apoptotic gene). In the clinical study, daily topical applications of the PTMs for 8 weeks followed by 2MED of UVB irradiation with clinical assessment 24 hours later revealed a significantly reduced intensity of erythema when compared to the buttock region treated with UVB alone.

CONCLUSIONS: The PTMs containing adaptogen ingredients may confer stress resistance and induce stress protective responses against intrinsic as well as extrinsic stressors as demonstrated by the obtained in vitro and clinical evidence.

PMID:38179774 | DOI:10.31083/j.fbl2812366

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Elevated serum soluble CD27 levels are associated with both disease activity and humoral immune activity in patients with rheumatoid arthritis

Clin Exp Rheumatol. 2024 Jan 2. doi: 10.55563/clinexprheumatol/fq5d3i. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the serum level of soluble CD27 (sCD27) and its potential clinical significance in rheumatoid arthritis (RA).

METHODS: Serum sCD27 levels in RA patients, idiopathic inflammatory myopathy (IIM) patients, systemic lupus erythematosus (SLE) patients and healthy controls (HCs) were detected by enzyme-linked immunosorbent assay. The medical information and laboratory data of the patients were collected. Serum sCD27 levels in RA patients with different clinical features were analysed, as was the correlation between the clinical data and serum sCD27 levels. Independent samples t test, the Mann-Whitney U-test or Wilcoxon signed-rank test, and Spearman correlation were used for statistical analysis.

RESULTS: Levels of sCD27 were elevated in RA patients (3898 [2525, 5834] pg/mL) compared with IIM patients (2467 [1939, 3324] pg/mL) or HCs (1659 ± 648 pg/mL) (p 0.001). In addition, serum sCD27 levels correlated with age, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A, immunoglobulin G, complement 4 and disease activity score in 28 joints in RA patients. Levels of sCD27 were higher in RF-positive RA patients (6054 ± 5842 pg/mL) than in RF-negative patients (3902 ± 2098 pg/mL), and a similar finding was also observed in anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (5810 ± 5671 pg/mL) and anti-CCP-negative (4183 ± 2187 pg/mL) RA patients. Serum ESR, RF, IgA, IgG levels and DAS28-CRP were elevated in RA patients with higher sCD27 levels than in those with lower sCD27 levels (p<0.01).

CONCLUSIONS: Serum sCD27 might be a promising biomarker that reflects both disease activity and humoral immunity activity in RA.

PMID:38179730 | DOI:10.55563/clinexprheumatol/fq5d3i

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Sex and body mass index impact on digit circumference for Leeds Dactylitis Index calculation

Clin Exp Rheumatol. 2024 Jan 2. doi: 10.55563/clinexprheumatol/v78pc5. Online ahead of print.

ABSTRACT

OBJECTIVES: To estimate digit circumference and the impact of sex and body mass index (BMI) for the calculation of the Leeds Dactylitis Index (LDI) in psoriatic arthritis (PsA) patients with bilateral dactylitis.

METHODS: Digit circumference of the hands and the foot were measured with a dactylometer and were studied according to sex and BMI (divided in 4 weight categories) in healthy Portuguese subjects, using Student’s t-test and One-way ANOVA, respectively. The effect size of sex and BMI were calculated using Cohen’s d test and Eta squared, respectively. Multiple linear regression was used to calculate the effect of sex and BMI, as well as their interaction, to create a formula to predict digit circumference.

RESULTS: Fifty-nine participants (33 women, 26 men) with a mean BMI of 24.8 were included. Men’s mean digit circumferences were statistically higher than those of women (p<0.001), with a large sex effect size in most of the digits. Differences in the mean circumference between the four BMI categories were statistically significant (p<0.05) for all digits, with a large BMI effect size. Sex and BMI were independent variables to predict mean digit circumference (p<0.001). A new tool (based on regression analysis) allowing to estimate the circumference of digits for males and females of different BMIs is presented.

CONCLUSIONS: Our data allows the calculation of digit circumference for males and females of different BMIs in the Portuguese population; and shows that BMI influences digital circumference supporting BMI inclusion in LDI references tables.

PMID:38179711 | DOI:10.55563/clinexprheumatol/v78pc5

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Pharmacogenetics at scale in real-world bioresources: CYP2C19 and clopidogrel outcomes in UK Biobank

Pharmacogenet Genomics. 2023 Dec 29. doi: 10.1097/FPC.0000000000000519. Online ahead of print.

ABSTRACT

OBJECTIVE: The impact of CYP2C19 genotype on clopidogrel outcomes is one of the most well established pharmacogenetic interactions, supported by robust evidence and recommended by the Food and Drug Administration and clinical pharmacogenetics implementation consortium. However, there is a scarcity of large-scale real-world data on the extent of this pharmacogenetic effect, and clinical testing for the CYP2C19 genotype remains infrequent. This study utilizes the UK Biobank dataset, including 10 365 patients treated with clopidogrel, to offer the largest observational analysis of these pharmacogenetic effects to date.

METHODS: Incorporating time-varying drug exposure and repeated clinical outcome, we adopted semiparametric frailty models to detect and quantify exposure-based effects of CYP2C19 (*2,*17) variants and nongenetic factors on the incidence risks of composite outcomes of death or recurrent hospitalizations due to major adverse cardiovascular events (MACE) or hemorrhage in the entire cohort of clopidogrel-treated patients.

RESULTS: Out of the 10 365 clopidogrel-treated patients, 40% (4115) experienced 10 625 MACE events during an average follow-up of 9.23 years. Individuals who received clopidogrel (coverage >25%) with a CYP2C19*2 loss-of-function allele had a 9.4% higher incidence of MACE [incidence rate ratios (IRR), 1.094; 1.044-1.146], but a 15% lower incidence of hemorrhage (IRR, 0.849; 0.712-0.996). These effects were stronger with high clopidogrel exposure. Conversely, the gain-of-function CYP2C19*17 variant was associated with a 5.3% lower incidence of MACE (IRR, 0.947; 0.903-0.983). Notably, there was no evidence of *2 or *17 effects when clopidogrel exposure was low, confirming the presence of a drug-gene interaction.

CONCLUSION: The impact of CYP2C19 on clinical outcomes in clopidogrel-treated patients is substantial, highlighting the importance of incorporating genotype-based prescribing into clinical practice, regardless of the reason for clopidogrel use or the duration of treatment. Moreover, the methodology introduced in this study can be applied to further real-world investigations of known drug-gene and drug-drug interactions and the discovery of novel interactions.

PMID:38179710 | DOI:10.1097/FPC.0000000000000519

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Is cognitive behavioral therapy more effective than pharmacotherapy for binge spectrum disorders? A systematic review and meta-analysis

Aust N Z J Psychiatry. 2024 Jan 5:48674231219593. doi: 10.1177/00048674231219593. Online ahead of print.

ABSTRACT

OBJECTIVES: Binge spectrum disorders are prevalent worldwide. Psychiatric and medical comorbidities are common, and societal costs are significant. Evidence-based treatment remains underutilized. Cognitive behavioral therapy is the recommended first-line treatment, but pharmacotherapy may be easier to access.

INTERVENTIONS: Meta-analytic evidence directly comparing cognitive behavioral therapy with pharmacotherapy is lacking. We aimed to compare the effects of cognitive behavioral therapy interventions with any pharmacological treatment for binge spectrum disorders. We searched PubMed, Embase, CENTRAL, ClinicalTrials.gov and reference lists for randomized controlled trials comparing cognitive behavioral therapy with any pharmacotherapy for bulimia nervosa/binge eating disorder and performed pairwise meta-analytic evaluations.

PRIMARY OUTCOMES: Primary outcomes are remission and frequency of binges. Secondary outcomes are frequency of purges, response, eating disorder psychopathology, weight/body mass index, depression, anxiety, quality of life and dropouts.

RESULTS: Eleven randomized controlled trials comparing cognitive behavioral therapy with fluoxetine/imipramine/desipramine/methylphenidate/sibutramine were identified (N = 531). Cognitive behavioral therapy was superior to antidepressants in terms of remission, frequency of binges and eating disorder psychopathology. There were no statistically significant differences for any of the individual cognitive behavioral therapy vs drug comparisons in terms of response/depression/anxiety/weight/quality of life/dropouts. Cognitive behavioral therapy was not superior to sibutramine/methylphenidate for the primary outcomes.

CONCLUSIONS: Data are scarce, comparisons underpowered and, considering the inherent methodological limitations of psychotherapy trials, questions arise regarding the presumed superiority of cognitive behavioral therapy. Further research is needed.

PMID:38179705 | DOI:10.1177/00048674231219593

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Non-invasive CT imaging biomarker to predict immunotherapy response in gastric cancer: a multicenter study

J Immunother Cancer. 2023 Nov 21;11(11):e007807. doi: 10.1136/jitc-2023-007807.

ABSTRACT

BACKGROUND: Despite remarkable benefits have been provided by immune checkpoint inhibitors in gastric cancer (GC), predictions of treatment response and prognosis remain unsatisfactory, making identifying biomarkers desirable. The aim of this study was to develop and validate a CT imaging biomarker to predict the immunotherapy response in patients with GC and investigate the associated immune infiltration patterns.

METHODS: This retrospective study included 294 GC patients who received anti-PD-1/PD-L1 immunotherapy from three independent medical centers between January 2017 and April 2022. A radiomics score (RS) was developed from the intratumoral and peritumoral features on pretreatment CT images to predict immunotherapy-related progression-free survival (irPFS). The performance of the RS was evaluated by the area under the time-dependent receiver operating characteristic curve (AUC). Multivariable Cox regression analysis was performed to construct predictive nomogram of irPFS. The C-index was used to determine the performance of the nomogram. Bulk RNA sequencing of tumors from 42 patients in The Cancer Genome Atlas was used to investigate the RS-associated immune infiltration patterns.

RESULTS: Overall, 89 of 294 patients (median age, 57 years (IQR 48-66 years); 171 males) had an objective response to immunotherapy. The RS included 13 CT features that yielded AUCs of 12-month irPFS of 0.787, 0.810 and 0.785 in the training, internal validation, and external validation 1 cohorts, respectively, and an AUC of 24-month irPFS of 0.805 in the external validation 2 cohort. Patients with low RS had longer irPFS in each cohort (p<0.05). Multivariable Cox regression analyses showed RS is an independent prognostic factor of irPFS. The nomogram that integrated the RS and clinical characteristics showed improved performance in predicting irPFS, with C-index of 0.687-0.778 in the training and validation cohorts. The CT imaging biomarker was associated with M1 macrophage infiltration.

CONCLUSION: The findings of this prognostic study suggest that the non-invasive CT imaging biomarker can effectively predict immunotherapy outcomes in patients with GC and is associated with innate immune signaling, which can serve as a potential tool for individual treatment decisions.

PMID:38179695 | DOI:10.1136/jitc-2023-007807

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Clinical Efficacy of Mobile App-Based, Self-Directed Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-Analysis

JMIR Mhealth Uhealth. 2024 Jan 4;12:e41753. doi: 10.2196/41753.

ABSTRACT

BACKGROUND: Pulmonary rehabilitation is well known to improve clinical symptoms (including dyspnea), quality of life, and exercise capacity in patients with chronic obstructive pulmonary disease (COPD). However, researchers have reported difficulties in practicing center-based pulmonary rehabilitation. Recently, mobile app-based pulmonary rehabilitation has become available in clinical practice. We investigated the clinical outcomes of mobile app-based pulmonary rehabilitation in patients with COPD.

OBJECTIVE: The objective of our study was to evaluate the clinical efficacy of mobile app-based pulmonary rehabilitation versus conventional center-based pulmonary rehabilitation for patients with COPD, using a systematic review and meta-analysis.

METHODS: A systematic search of the literature published between January 2007 and June 2023 was performed, using the PubMed, Embase, Cochrane, and CINAHL databases to identify relevant randomized controlled trials involving patients with COPD. Pulmonary rehabilitation programs needed to provide an exercise program on a smartphone app. Study outcomes, including exercise capacity, symptom scores, quality of life, and hospitalization, were evaluated. The meta-analysis evaluated mean differences in 6-minute walk test distances (6MWDs), COPD Assessment Test (CAT) scores, modified Medical Research Council (mMRC) dyspnea scale scores, St. George Respiratory Questionnaire (SGRQ) scores, and risk ratios for hospitalization resulting from disease exacerbation.

RESULTS: Of the 1173 screened studies, 10 were included in the systematic review and 9 were included in the meta-analysis. Further, 6 studies were multicenter studies. There were a total of 1050 participants, and most were aged ≥65 years. There were discrepancies in the baseline participant characteristics, smartphone apps, interventions, and study outcomes among the included studies. In the meta-analysis, 5 studies assessed 6MWDs (mean difference 9.52, 95% CI -3.05 to 22.08 m), 6 studies assessed CAT scores (mean difference -1.29, 95% CI -2.39 to -0.20), 3 studies assessed mMRC dyspnea scale scores (mean difference -0.08, 95% CI -0.29 to 0.13), 2 studies assessed SGRQ scores (mean difference -3.62, 95% CI -9.62 to 2.38), and 3 studies assessed hospitalization resulting from disease exacerbation (risk ratio 0.65, 95% CI 0.27-1.53). These clinical parameters generally favored mobile app-based pulmonary rehabilitation; however, a statistically significant difference was noted only for the CAT scores (P=.02).

CONCLUSIONS: Despite some discrepancies in the baseline participant characteristics and interventions among studies, mobile app-based pulmonary rehabilitation resulted in favorable exercise capacity, symptom score, quality of life, and hospitalization outcomes when compared with conventional pulmonary rehabilitation. In the meta-analysis, the CAT scores of the mobile app-based pulmonary rehabilitation group were significantly lower than those of the control group (P=.02). In real-world practice, mobile app-based pulmonary rehabilitation can be a useful treatment option when conventional center-based pulmonary rehabilitation is not feasible.

PMID:38179689 | DOI:10.2196/41753

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Comparison of intraocular lens tilt after capsular sutured scleral fixation with capsular segments versus uneventful cataract surgery

Eur J Ophthalmol. 2024 Jan 5:11206721231223997. doi: 10.1177/11206721231223997. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate and compare intraocular lens (IOL) tilt between uneventful phacoemulsification with in-the-bag IOL implantation and sutured scleral fixation (SSF) of the lens bag with a capsular tension segment (type 6 D / Morcher) using a Sheimpflug camera.

SETTING: Clinical Practice, Hospital. Barcelona and A Coruña, Spain.

DESIGN: Retrospective, comparative multicenter study.

METHODS: IOL tilt was compared between patients who underwent sutured scleral fixation with a capsular tension segment in a single eye (SSF group, n = 15) with patients who underwent uneventful IOL implantation (control group, n = 12) that were matched by biometric measurements. Post-operative refractive accuracy of biometric formulas by means of mean absolute error (MAE) was also reported. All patients underwent a general ophthalmic evaluation, anterior segment photography, and postoperative optical biometry (Zeiss IOLMaster® 500). In addition, IOL tilt was measured with a Scheimpflug camera (Pentacam R, Oculus Optikgerate Gmbh).

RESULTS: Mean vertical tilt was similar in both groups (2.20+/-2.47° SSF vs 1.97 +/- 1.79° control; p = 0.836) but mean horizontal tilt tended to higher values in the SSF series (2.09 +/- 2.74° vs 0.94 +/- 1.17°; p = 0.139). Considering post-operative refractive error in diopters by MAE calculations, there was an underestimation of IOL power in the SSF group which was only statistically significant for Barrett Universal II (1.07 vs 0.32; p = 0.028) and Hill-RBF (0.95 vs 0.26; p = 0.024) formulas, but not for SRK/T (0.99 vs 0.42; p = 0.285) and Kane (0.96 vs 0.33; p = 0.083).

CONCLUSION: Sutured scleral fixation of capsular tension segments in the presence of zonular instability does not seem to induce clinically significant IOL tilt compared to uneventful cataract extraction cases.

PMID:38179681 | DOI:10.1177/11206721231223997

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Student loan debt and mental health: a comprehensive review of scholarly literature from 1900 to 2019

J Evid Based Soc Work (2019). 2024 Jan 5:1-31. doi: 10.1080/26408066.2023.2299019. Online ahead of print.

ABSTRACT

PURPOSE: The review had two purposes. The first was to examine the nature and extent of published literature on student loan and the second was to systematically review the literature on student loans and mental health.

MATERIALS AND METHODS: Data from academic databases (1900-2019) were analyzed using two methods. First, topic modeling (a text-mining tool that utilized Bayesian statistics to extract hidden patterns in large volumes of texts) was used to understand the topical coverage in peer-reviewed abstracts (n = 988) on student debt. Second, using PRISMA guidelines, 46 manuscripts were systematically reviewed to synthesize literature linking student debt and mental health.

RESULTS: A model with 10 topics was selected for parsimony and more accurate clustered representation of the patterns. Certain topics have received less attention, including mental health and wellbeing. In the systematic review, themes derived were categorized into two life trajectories: before and during repayment. Whereas stress, anxiety, and depression dominated the literature, the review demonstrated that the consequences of student loans extend beyond mental health and negatively affect a person’s wellbeing. Self-efficacy emerged as a potential solution.

DISCUSSION AND CONCLUSION: Across countries and samples, the results are uniform and show that student loan burdens certain vulnerable groups more. Findings indicate diversity in mental health measures has resulted into a lack of a unified theoretical framework. Better scales and consensus on commonly used terms will strengthen the literature. Some areas, such as impact of student loans on graduate students or consumers repaying their loans, warrant attention in future research.

PMID:38179674 | DOI:10.1080/26408066.2023.2299019