Peripheral Inflammatory Biomarkers Research Articles

The effects of ketamine and classic hallucinogens on neurotrophic and inflammatory markers in unipolar treatment-resistant depression: a systematic review of clinical trials.

Although results are still preliminary, ketamine and classical hallucinogens have shown promise in recent years as novel, fast-acting antidepressants, especially for the treatment of unipolar treatment-resistant depression (TRD). Depression also seems to be related to abnormal levels of peripheral inflammatory and neurotrophic biomarkers, which may one day help to diagnose of this disorder. In this context, this systematic review of clinical trials evaluated the current evidence that relates the antidepressant effects of ketamine and classical hallucinogens on TRD with changes in inflammatory and neurotrophic biomarkers. Twelve studies were found (n = 587), 2 with oral ayahuasca (1mL/kg) and 10 with ketamine (mostly intravenous 0.5mg/kg) administration. Results for all biomarkers assessed were contradictory and thus inconclusive. Randomized controlled trials with bigger samples and higher statistical power are warranted to clarify if peripheral biomarkers can confidently be used to indicate and measure ketamine's and classical hallucinogens' antidepressant effect. The PROSPERO ID for this study is CRD42021249089.

P593. Inflammatory Chemokine Levels in Plasma and CSF are Positively Correlated in Unmedicated First Episode Psychosis

Early-life exposure to stress has been postulated to induce systemic changes linked to pro-inflammatory cytokines and activated microglia in psychotic illness. We have reported evidence of peripheral inflammation as indexed by both chemokines (Eotaxin-1, IL-8, CCL-2, MDC, MIP-1B, TARC) and cytokines (TNFa) in unmedicated individuals at clinical high risk and in the first episode of psychosis (FEP). In preliminary data we have reported an association between neurometabolites in the dorsal caudate and inflammatory biomarkers. What is not known is to what degree peripheral inflammatory biomarkers are related to those in the CNS.

Biomarkers of neuroprogression and late staging in bipolar disorder: A systematic review.

Bipolar disorder may undertake a progressive course in a subset of patients, and research efforts have been made to understand the biological basis underlying this process. This systematic review examined the literature available on biological markers associated with illness progression in bipolar disorder. Peer-reviewed articles were assessed using Embase, PsycINFO and PubMed, as well as from external sources. After initial screening, a total of 871 citations from databases and other sources were identified. Participants with a diagnosis of bipolar disorder were included in our systematic review; however, studies with participants younger than 15 or older than 65 were excluded. All studies were assessed using the Newcastle-Ottawa Scale assessment tool, and data pertaining to the results were extracted into tabular form using Google Sheets and Google Documents. The systematic review was registered on PROSPERO international prospective register of systematic reviews (ID Number: CRD42020154305). A total of 35 studies were included in the systematic review. Increased ventricular size and reduction of grey matter volume were the most common brain changes associated with illness progression in bipolar disorder. Among the several biomarkers evaluated in this systematic review, findings also indicate a role of peripheral inflammatory markers in this process. The studies evaluating the biological basis of the illness progression in bipolar disorder are still scarce and heterogeneous. However, current evidence supports the notion of neuroprogression, the pathophysiological process related to progressive brain changes associated with clinical progression in patients with bipolar disorder. The increase in peripheral inflammatory biomarkers and the neuroanatomical changes in bipolar disorder suggest progressive systemic and structural brain alterations, respectively.

Inflammation in Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease that impairs people’s wellbeing and quality of life. Inflammation is considered to play an important role in CVT initiation and progression. Several studies have reported the important role of leukocytes, proinflammatory cytokines, and adherence molecules in the CVT-related inflammatory process. Moreover, inflammatory factors exacerbate CVT-induced brain tissue injury leading to poor prognosis. Based on clinical observations, emerging evidence shows that peripheral blood inflammatory biomarkers—especially neutrophil-to-lymphocyte ratio (NLR) and lymphocyte count—are correlated with CVT [mean difference (MD) (95%CI), 0.74 (0.11, 1.38), p = 0.02 and −0.29 (−0.51, −0.06), p = 0.01, respectively]. Moreover, increased NLR and systemic immune-inflammation index (SII) portend poor patient outcomes. Evidence accumulated since the outbreak of coronavirus disease-19 (COVID-19) indicates that COVID-19 infection and COVID-19 vaccine can induce CVT through inflammatory reactions. Given the poor understanding of the association between inflammation and CVT, many conundrums remain unsolved. Further investigations are needed to elucidate the exact relationship between inflammation and CVT in the future.

Characteristic Immune Dynamics in COVID-19 Patients with Cardiac Dysfunction.

Background: We aimed to explore immune parameters in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. Methods: A total of 30 COVID-19 patients >18 years admitted to the ICU were studied on days D1, D3 and D7 after admission. Cardiac function was assessed using speckle-tracking echocardiography (STE). Peripheral blood immunophenotyping, cardiac (pro-BNP; troponin) and inflammatory biomarkers were simultaneously evaluated. Results: Cardiac dysfunction (DYS) was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. High-sensitivity cardiac troponin (hs-cTn) was detectable in 43.3% of the patients with a median value of 13.00 ng/L. There were no significant differences between DYS and nDYS patients regarding mortality, organ dysfunction, cardiac (including hs-cTn) or inflammatory biomarkers. Patients with DYS showed persistently lower lymphocyte counts (median 896 [661–1837] cells/µL vs. 2141 [924–3306] cells/µL, p = 0.058), activated CD3 (median 85 [66–170] cells/µL vs. 186 [142–259] cells/µL, p = 0.047) and CD4 T cells (median 33 [28–40] cells/µL vs. 63 [48–79] cells/µL, p = 0.005), and higher effector memory T cells (TEM) at baseline (CD4%: 10.9 [6.4–19.2] vs. 5.9 [4.2–12.8], p = 0.025; CD8%: 15.7 [7.9–22.8] vs. 8.1 [7.7–13.7], p = 0.035; CD8 counts: 40 cells/µL [17–61] vs. 10 cells/µL [7–17], p = 0.011) than patients without cardiac dysfunction. Conclusion: Our study suggests an association between the immunological trait and cardiac dysfunction in severe COVID-19 patients.

Role of peripheral inflammatory biomarkers, transforming growth factor-beta and interleukin 6 in predicting peritoneal adhesions following repeat cesarean delivery.

Repeat cesarean deliveries (CDs) pose a risk in the development of intra-abdominal adhesions. We aimed to examine the incidence and severity of adhesions in repeat CDs using a specific scoring system and assess the predictive power of the pre-operative value of transforming growth factor (TGF)-β and interleukin (IL)-6 with selected peripheral inflammatory biomarkers (PIBs) in the prediction of adhesion formation. This prospective study enrolled 91 pregnant women at term, who had previously undergone at least one or more scheduled CDs. PIBs, namely C-reactive protein, white blood cell count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index, TGF-β, and IL-6 were studied according to the presence and location of adhesions. There was a significant difference only in the variables of the number of CDs, post-operative adhesion index (PAI) score, IL-6, and TGF-β on the presence of adhesion (p < 0.05). The linear regression model revealed that the effect of the number of CDs, PAI score, and IL-6 values on TGF-β was significant (p < 0.05). The effect of the PAI score on TGF-β was higher than that of IL-6. As a reciprocal relationship, the effect of the TGF-β value on the PAI score was also higher than that of IL-6. In patients with a history of repeat CDs, the preoperative determination of TGF-β seems to be an important independent predictor of POA. The adverse events due to post-operative adhesion caused by repeat CDs can be overcome by detecting high-risk patients with a comprehensive assessment and individualized intervention integrated into overall patient management.

Inflammatory biomarkers in older adults with frailty: a systematic review and meta-analysis of cross-sectional studies.

Systemic chronic inflammation has been proposed as an essential mediating factor in frailty, and several studies tested its relationship with frailty. However, the issue is still controversial. We identified observational studies and pooled their results to assess whether abnormal expression of inflammatory biomarkers is present in the blood of older adults with frailty. We conducted a systematic search on the Medline, Embase, and Web of Science database from inception to 1st September 2021. The quality of included studies was assessed using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies (JBI-MAStARI). Study heterogeneity was assessed with the Cochran Q test and I2 statistic. Pooled estimates were obtained through random-effect models. Sensitivity analyses were conducted by excluding one of the studies. Egger's regression test and observation of funnel plots were used to detect small-study effects and publication bias. PROSPERO registration: CRD42020172853. A total of 53 cross-sectional studies corresponding to 56 independent study populationswere included in this analysis. There were 31 study populations with three frailty categories (3144 frailty, 14,023 pre-frailty, 10,989 robust) and 25 study populations with two frailty categories (2576 frailty, 8368 non-frailty). This meta-analysisperformed pooled analyses for the inflammatory biomarker leukocyte, lymphocytes, CRP, IL-6, IL-10, and TNF-α. Older adults with frailty had lower lymphocytes and higher interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) levels compared with the control group. However, there was no significant difference in leukocyte and IL-10 levels in the two groups. These findings suggest that peripheral inflammatory biomarkers lymphocytes, IL-6, CRP, and TNF-α are related to frailty status. Our findings are not conclusive regarding the causal relationship between chronic inflammation and frailty, so the development of further longitudinal and well-designed studies focused on this is necessary.

Peripheral Inflammatory Biomarkers of Methamphetamine Withdrawal Patients Based on the Neuro-Inflammation Hypothesis: The Possible Improvement Effect of Exercise.

Methamphetamine (MA) induced addiction and neuroinflammation has been implicated. Based on the neuroinflammation hypothesis, this study aims to investigate how exercise influences the craving of patients in MA withdrawal, and explore the mechanism of peripheral inflammation. A total of 90 patients in MA withdrawal were recruited. No difference was noted in the number of years of drug use and the frequency of drug use among patients, and the withdrawal time was within 2 months. The subjects were grouped based on the degree of craving induced by the cues: non-craving control group (NCC group), craving control group (CC group), and craving exercise group (CE group). The CE group was subjected to aerobic combined resistance training. Then, the ELISA method was used to detect plasma IL-6, TNF-α, and IL-1β concentrations; Visual Analog Scale (VAS) measurement of cue-induced cravings under Virtual Reality (VR) exposure (VR-VAS) and the Desires for Drug Questionnaire (DDQ) were used to assess cravings. Consequently, plasma IL-6, TNF-α, IL-1β, levels, and the VR-VAS and DDQ scores of MA withdrawal patients were significantly reduced after exercise. This study confirmed that 8 weeks of incremental load aerobic combined with resistance training reduces peripheral inflammation and significantly reduces the level of craving for MA.

Peripheral inflammation and AD-related hippocampal neurodegeneration in prodromal AD patients.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of beta-amyloid (Aβ42) and phosphorylated tau (P-tau) deposits in the brain, neurodegeneration in specific brain regions, and inflammation. This study aimed at investigating the association of periferal inflammatory signaling with brain structural alterations in MCI patients with or without AD pathology. Study population: 89 consecutive enrolled amnestic MCI patients. AD pathology definition: based on baseline CSF Aβ42/P-tau level as well as APOE genotype (positivity defined as Aβ42/P-tau ratio<7.8 for APOE4 non-carriers, <15.2 for carriers). MRI processing: volumes of the hippocampus and its subfields were extracted with Freesurfer (version 7). Cytokine expression: pro- (IL6, IL8, IL1beta, TNF-alpha, NLRP3) and anti- (IL10) inflammatory molecules were measured by Real Time PCR Assay. Subjects provided written informed consent, validated by the local ethics commitee RESULT: As expected, MCI patients with AD pathology had lower volume in the presubiculum (p=.007), subiculum (p=.030) and CA1 (p=.028) than negative patients. Moreover, positive patients showed lower expression of IL-10 (p=.033) as well as higher expression of NLRP3 (p=.050) and IL-8 (p=.037). Correlation analyses in all MCI patients revealed a negative association between IL10 levels and ADAScog13 (r=-0.27, p=0.01) and P-tau (r=-0.22, p=0.04), and a positive association with CSF Aβ42 (r=0.22, p=0.037), hippocampal volume (r=0.23, p=0.03), temporal lobe (r=0.38, p=0.0004) and precuneus thicknesses (r=0.37 p=0.0006), consistent with a protective effect of IL10 in AD pathology. More analysis are ongoing on the effect of cytokines on different rates of atrophy of brain subfields. Higher expression of anti-inflammatory factors are associated to a lower hippocampal neurodegeneration and better clinical and pathophysiological outcome in prodromal AD patients. These preliminary results suggest that non-invasive peripheral inflammatory biomarkers could represent possible biomarkers to support the early diagnosis of AD.

Impact of data extraction errors in meta-analyses on the association between depression and peripheral inflammatory biomarkers: an umbrella review.

Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies. PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof. Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1β, are associated with depression. These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.

Absolute lymphocyte count is an independent predictor of survival in patients with metastatic renal cell carcinoma treated with nivolumab.

Programmed cell death-1 antibody therapy has demonstrated improved progression-free survival and overall survival in patients with metastatic renal cell carcinoma. However, there are limited studies on biomarkers that can predict the efficacy of immune checkpoint inhibitors. We examined the influence of peripheral inflammatory biomarkers on the clinical outcomes of patients with metastatic renal cell carcinoma treated with nivolumab. Data of 38 patients with metastatic renal cell carcinoma, who were treated with nivolumab monotherapy after receiving at least one molecular targeted therapy from November 2016 to February 2021, were retrospectively reviewed and analyzed. Median progression-free survival and overall survival were significantly shorter in patients with low absolute lymphocyte count (<1300/μl) versus those with high absolute lymphocyte count (progression-free survival: P=0.0102; overall survival: P=0.0026). Median overall survival was shorter in patients with high neutrophil-lymphocyte ratio (≥3.0) versus those with low neutrophil-lymphocyte ratio (P=0.0344). Multivariate analysis showed that absolute lymphocyte count was an independent factor for progression-free survival (hazard ratio=2.332, 95% confidence interval=1.012-5.375, P=0.0468) and overall survival (hazard ratio=4.153, 95% confidence interval=1.108-15.570, P=0.0347). Increased absolute lymphocyte count, 1 month after nivolumab initiation, was a positive predictive factor for progression-free survival (hazard ratio=0.419, 95% confidence interval=0.189-0.926, P=0.0317) and overall survival (hazard ratio=0.285, 95% confidence interval=0.091-0.890, P=0.0308). Our study indicates that peripheral absolute lymphocyte count, before nivolumab initiation, is a predictor of poor response in metastatic renal cell carcinoma. Additionally, increased absolute lymphocyte count, 1 month post-nivolumab initiation, can be a predictor of the effects of nivolumab.

P57.16 Inflammatory Markers as Predictors of Treatment Response and Survival in Patients With Non-Small Cell Lung Cancer Treated with PD-1 Inhibitors

A variety of serum biomarkers have been previously correlated with clinical outcomes in patients with advanced-stage non-small cell lung cancer (NSCLC) treated with PD-1 inhibitors, with widely variable results. The primary aim of our study was to evaluate the prognostic and predictive value of peripheral blood-based inflammatory biomarkers, both at baseline (pre-treatment) and post-treatment, in the above patient population.

Sex Difference in Peripheral Inflammatory Biomarkers in Drug-Naïve Patients with Major Depression in Young Adulthood.

The number of patients with major depressive disorder (MDD) is increasing worldwide. In particular, the early onset of MDD from adolescence to young adulthood is more problematic than the later onset. The specific and expeditious identification of MDD before the occurrence of severe symptoms is significant for future interventions or therapies; however, there is no accurate diagnostic marker that has sufficient sensitivity and specificity for clinical use. In the present study, to identify the possibility of blood markers for depression, we first measured the baseline inflammatory biomarkers in the peripheral blood of 50 treatment-naïve young adults with MDD and 50 matched healthy controls. We then analyzed the correlation between prospective biomarkers and depressive symptoms using scores from various clinical depression indices. We also identified differential responses between males and females in prospective biomarkers. In young adulthood, men with MDD had increased peripheral interleukin (IL)-17 levels, whereas women with MDD had significantly increased IL-1β, IL-6, and C-reactive protein (CRP) levels compared with healthy controls. However, tumor necrosis factor-α (TNF-α), CCL1, CCL2, adiponectin, and cortisol were not significantly different in young adult individuals with MDD. Higher levels of IL-17 in the male group and of IL-1β, IL-6, and CRP in the female group may have been associated with the clinical symptoms of MDD, including depressive moods, hopelessness, suicidal ideation, low self-esteem, and reduced psychological resilience. Our findings will be useful in developing diagnostic tools or treatments for MDD in young adulthood.

Peripheral Blood Mononuclear Cells Oxidative Stress and Plasma Inflammatory Biomarkers in Adults with Normal Weight, Overweight and Obesity.

Background: Obesity is an important pathology in public health worldwide. Obese patients are characterized by higher cardiovascular risk and a pro-inflammatory profile. Objective: To assess the oxidative stress in peripheral blood mononuclear cells (PBMCs) and inflammatory biomarkers in plasma in adults with normal weight, overweight and obesity. Methods: One hundred and fifty adults (55-80-years-old; 60% women) from the Balearic Islands, Spain, were recruited and classified according to body mass index (BMI). Anthropometric measurements were carried out, fasting blood samples were collected and plasma and PBMCs were obtained. Biochemical parameters, hemogram, antioxidant enzyme activities and protein levels, reactive oxygen species production (ROS), malondialdehyde (MDA), and cytokine (tumour necrosis factor, TNFα, and interleukin 6, IL-6) levels were measured. Results: Glycaemia, triglyceridemia, abdominal obesity, and waist-to-height ratio (WHtR) were higher, and HDL-cholesterol was lower in obese patients. MDA and TNFα plasma levels were higher in the obese compared to normal-weight group, while the levels of IL-6 were higher in both obese and overweight subjects with respect to normal-weight peers. The activities of all antioxidant enzymes in PBMCs as well as the production ROS progressively increased with BMI. The protein levels of catalase in PBMCs were higher in obese and glutathione reductase in obese and overweight subjects compared to normal-weight peers. No other differences were observed. Conclusion: The current results show that overweight and obesity are related to an increase in pro-oxidant and proinflammatory status in plasma and PBMCs. The studied biomarkers may be useful for monitoring the progression/reversal of obesity.

Peripheral inflammatory biomarkers predict the deposition and progression of amyloid-β in cognitively unimpaired older adults

IntroductionSystemic inflammation has been increasingly implicated in the pathogenesis of Alzheimer’s disease (AD), yet the mechanistic and temporal specificity of this relationship is poorly understood. We aimed to characterize the cross-sectional and longitudinal associations between peripheral inflammatory biomarkers, cognition, and Aβ deposition in oldest-old cognitively unimpaired (CU) adults. MethodsA large sample of 139 CU older adults (mean age (range) = 85.4 (82–95)) underwent neuropsychological testing, Pittsburgh compound-B (PiB)-PET imaging and structural MRI. Hierarchical regression models examined associations between circulating inflammatory biomarkers (Interleukin-6 (IL-6), soluble Tumor Necrosis Factor receptors 1 and 2 (sTNFr1 and sTNFr2), soluble cluster of differentiation 14 (sCD14), C-reactive protein (CRP)), cognition, and global and regional Aβ deposition at baseline and over follow-up. Indices of preclinical disease, including pathologic Aβ status and hippocampal volume, were incorporated to assess conditional associations. ResultsAt baseline evaluation, higher concentrations of IL-6 and sTNFr2 were associated with greater global Aβ burden in those with lower hippocampal volume. In longitudinal models, IL-6 predicted subsequent conversion to MCI and both IL-6 and CRP predicted greater change in global and regional Aβ deposition specifically among participants PiB-positive at baseline. These relationships withstood adjustment for demographic factors, anti-hypertensive medication use, history of diabetes, heart disease, APOE ε4 carrier status, and white matter lesions. DiscussionIn a large prospective sample of CU adults aged 80 and over, peripheral inflammatory biomarkers were associated with and predictive of the progression of Aβ deposition. This was specific to those with biomarker evidence of preclinical AD at baseline, supporting recent evidence of disease-state-dependent differences in inflammatory expression profiles. Chronic, low-level systemic inflammation may exacerbate the deposition of Aβ pathology among those with emerging disease processes, and place individuals at a higher risk of developing clinically significant cognitive impairment.

Peripheral inflammatory biomarkers and risk factors of dementia in the Chilean GERO cohort

AbstractBackgroundDementia is one of the mean causes of disability in elderly. Peripheral inflammatory biomarkers and ApoE‐ε4 allele have been described as important biological risk factors of dementia in Caucasian population. Currently, there is scarce information about the specific age‐related and predisposition factors to develop dementia in Latino populations. The aim of this study is to investigate these biological risks factors in Chilean elderly with healthy and pathological brain ageing.MethodWe evaluated and quantified plasma samples obtained from the GERO cohort (114 elderly subjects, &gt;70 years, classified in 51 subjects with subjective cognitive complaint (SCC) and 63 with mild cognitive impairment (MCI)), in addition to 36 healthy brain controls (HBC) and 31 subjects with Alzheimer’s disease dementia (ADD). Genotyping of ApoE gene was analyzed by qPCR. We analyzed inflammatory biomarkers using Luminex technique including IL‐2, IL‐6, IL‐10, TNF‐α, CRP and SAP proteins. All subjects receive a clinical and neuropsychological assessment.ResultCRP protein was found significant decrease expression in SCC and ADD groups compared to MCI and HBC (p=0.048). In SAP protein was found a significant decrease in expression in the SSC (p=0.04) and MCI (p=0.0178) groups compared to HBC. It was observed a positive correlation in the SCC, MCI and ADD groups with the IL‐6 and TNFα, and, SAP and CRP. A negative correlation between IL‐2, IL‐6 and IL‐10 cytokines was found with Direct Span Digit test, which assess attentional capacity. Also was identified a negative correlation between SAP protein and the Free and Cued Selective Reminding Test (FCSRT), which assess verbal episodic memory, and IL‐10 cytokine and Montreal Cognitive Assessment (MoCA), which assess global cognition. Finally, a positive correlation was found in CRP protein with Pfeffer Functional Activity Questionnaire. Frequency of the ApoE‐ε4 allele, was significantly higher in ADD (52%) and SCC (27%) patients than controls and MCI (p=1x10‐4).ConclusionThe results shown correlations between the different inflammatory proteins and performance in neuropsychological test suggesting that inflammatory biomarkers are associated with pathological brain ageing. The correlations in SCC and MCI are not being reported previously. Additionally, the frequency of ApoE‐ε4 allele in ADD group is higher than worldwide populations.

Peripheral inflammatory biomarkers as predictors of recurrence in surgically-treated anogenital condylomata acuminata patients.

The aim of this study was to examine the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) in patients with anogenital condylomata acuminata (CA) and their association with recurrence and squamous intraepithelial neoplasia development. We conducted a descriptive study in 95 patients that had undergone surgical treatment for CA. The descriptive data, disease characteristics, and pre-treatment peripheral inflammatory biomarkers (PIBs) were recorded retrospectively. All parameters were compared in those with recurrent and non-recurrent CA. All PIBs were significantly higher in patients with the greatest genital wart size of >2 cm in the squamous intraepithelial lesion (SIL) group. Human papillomavirus (HPV) types 16, 18, 31 and 33, known to carry high risk for anogenital cancer, were significantly related to higher SII. Greater wart size, high-grade squamous intraepithelial lesion (HSIL), and higher PLR and SII values were highly associated with recurrent disease (p = 0.003, 0.006, 0.005 and 0.000, respectively). Of all recurrences, 34.1% were explained by HSIL and increased PLR and SII values. The prediction of CA recurrence is important to determine those patients at high risk. PLR and SII can be used for risk analysis in selected patient groups.

Systemic Inflammatory Biomarkers in Patients with Fuchs' Uveitis Syndrome: Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio.

To evaluate the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with Fuchs' uveitis syndrome (FUS). A case-control study. Department of Ophthalmology, Haydarpasa Numune Training and Research Hospital, Turkey, between July 2016 and June 2019. Twenty-eight patients with unilateral FUS and 30 healthy subjects were enrolled in the study. The NLR and PLR were calculated from complete blood counts tests; and compared between the groups. There were 28 patients (14 females, 14 males; median age: 33.5 (30-47.5) in the FUS group; and 30 patients (16 females, 14 males; median age 37.5 (33-41.8) in the healthy group. The NLR (1.7 v.s 1.2, p = 0.036 was found to be significantly higher and PLR was lower (100.27 ±37.13 v.s. 141.68 ±26.50 p <0.001) in the FUS group compared with the healthy controls. The median WBC (p <0.001), neutrophil (p <0.001), lymphocytes (p <0.001), and monocyte (p=0.041) values were found significantly higher in the FUS group compared with controls. The significant correlations were not seen between the number of anterior chamber cells; which are ocular inflammatory parameter and NLRs (r = 0.312, p = 0.106) and PLRs (r = 0.148, p = 0.453). The current study suggests that a slowly progressive immune-mediated process can affect peripheral blood inflammatory biomarkers and there is evidence of benign subclinical systemic inflammation in patients with FUS. Key Words: Fuchs uveitis syndrome, Neutrophil to lymphocyte ratio, Platelet to lymphocyte ratio.

Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

BackgroundAvailable evidence suggests that adjunctive treatment with immunomodulatory medications may be effective in the treatment of major depressive disorder (MDD). A pilot trial of the tetracycline minocycline as adjunctive treatment in treatment-resistant depression (TRD), produced promising results, however, a larger scale trial is needed to confirm the antidepressant actions of this drug.MethodsThis is a 12-week double blind, placebo-controlled, randomized trial of minocycline as an add-on to standard antidepressants for adults (age > 18) with DSM-5 major depressive episode, who have failed to respond to at least two adequate trials of antidepressant treatment. It is a parallel-arm study with 50 participants in each group. The primary outcome measure is change in 17-item Hamilton Depression Rating Scale (HRSD-17) total scores from baseline to week 12. Secondary measures include the Clinical Global Impression (CGI) scale, World Health Organization Quality of Life Short Version (WHOQOL-BREF) and the Generalized Anxiety Disorder scale (GAD-7). Peripheral inflammatory biomarkers will be collected at baseline, week 6 and 12.DiscussionIf minocycline is well tolerated and effective in reducing depressive symptoms in patients with TRD, it would warrant genuine consideration as a treatment option for TRD. Additionally, if results demonstrate that minocycline has antidepressant properties, and that changes in inflammatory status are associated with its antidepressant action, it will inform the development of individualized treatment for a subset of patients with MDD.Trial registrationClinicaltrials.gov identifier: NCT03947827. Registered 13th May, 2019.

Inflammatory Biomarkers for Mood Disorders - A Brief Narrative Review.

The nervous system and the immune system interact consistently in the brain and peripheries. Inflammation in the brain not only alters the metabolism of neurotransmitters, but also causes network dysfunction, structural changes, and the development of mood symptomology in patients with mood disorders. In addition, the dysregulation of the neuroimmune axis in mood disorders drives multiple-system comorbidities. Furthermore, patients with low-grade inflammation are more likely to exhibit treatment resistance with both pharmacotherapy and non-pharmacotherapy. The aim of this review was to examine the available data regarding not only evidence of inflammation in the pathophysiology of mood disorders and their comorbid conditions, but also potential inflammatory biomarkers of mood disorders. Studies of the use of adjunct anti-inflammatory medications in mood disorders, and inflammatory biomarkers that may guide treatment outcomes in mood disorders, were summarized. Studies have demonstrated that certain adjunct anti-inflammatory medications might help to improve mood symptoms and reduce comorbidities, and the baseline levels of inflammatory biomarkers, such as peripheral C-reactive protein (CRP), could be used to stratify the treatment outcome. All results suggested that the identification of peripheral and brain inflammatory biomarkers for the diagnosis, outcome prediction, staging, and stratification of interventions of mood disorders has emerged as an important area of translational research in psychiatry. Inflammatory biomarkers could guide interventions and enhance treatment response in patients with mood disorders. The main challenge is that substantial complexities might hamper the attainment of this goal.