Role of Microenvironment-Associated Chemokines and Cytokines for Binet Stage A CLL Patients Included in a Prospective Trial (CLL1 trial) of the German CLL Study Group (GCLLSG): sIl2Ralpha Is An Independent Predictor of Progression-Free Survival (PFS),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3869-3869
Author(s):  
Till M Seiler ◽  
Roland Aydin ◽  
Tobias Herold ◽  
Raymonde Busch ◽  
Markus Schwarz ◽  
...  
Keyword(s):  
T Cells ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Healthy Controls ◽  
Advisory Committees ◽  
Cytokines And Chemokines ◽  
Small Subgroup ◽  
Median Serum ◽  
Significant Difference

Abstract Abstract 3869 Background: In CLL, proliferation of the leukemic cell clone occurs in the bone marrow and lymphatic tissues rather than peripheral blood. In this microenvironment, CLL cells interact with accessory cells, such as T cells and CD68+ nurselike cells (NLCs) and display signs of B cell receptor (BCR) activation, suggesting that CLL proliferation is T cell- and BCR-driven. In addition, cytokines and chemokines secreted by leukemic cells, stromal cells and T cells are essential in forming the disease-specific microenvironment. However, the exact biological role of cytokines and chemokines needs to be defined, especially in the light of distinct prognostic and biological subgroups of patients (pts). Methods: In order to address this issue, we measured serum levels of chemokines and cytokines in a prospective cohort of 157 previously untreated Binet stage A pts., a small subgroup of the risk-stratified CLL1 trial of the GCLLSG. Median follow-up time of that subgroup was 50.3 months. Median time to progression was 61.3 months. Median time from diagnosis to study entry was 1 year. Serum samples had been centrally collected at study entry and stored at −80°C. Sera were analyzed on a luminex-based multiplex platform, allowing simultaneous screening of multiple serum parameters. In a pilot phase, sera of 21 pts were pre-analytically screened for a total of 62 different chemokines. Median serum levels of 27 different chemokines and cytokines were found to differ from healthy controls in a significant manner. Those 27 chemokines and cytokines were subsequently analyzed in 157 pts. For all parameters univariate and multivariate analyses were performed for progression-free survival. Results: Serum levels of CCL3 and CCL4, chemokines known to be secreted by CLL cells upon BCR engagement, were elevated compared to healthy controls. High CCL3 levels correlated strongly with high CCL4 levels (p<0.001) and tended to be associated with unmutated IgHV status (p=0.06), supporting the role of BCR triggering in biologically selected CLL pts. Concerning CCL3 and CCL4, no significant difference in PFS was detected. Serum levels of CCL2 and CCL17, both binding chemokine receptor CCR4, were concordantly elevated compared to healthy controls (p<0.001), suggesting a possible role of chemoattraction of CCR4+ T cells towards these chemokines in CLL. CXCL12, CCL21, and CXCL10, chemokines associated with chemotaxis of CLL cells, were concordantly elevated compared to healthy controls. Pts with serum levels of CCL21 beyond the median also had higher levels of CXCL10 (p<0.001) and CXCL12 (p=0.02). CLL pts have been found to have abnormal neovascularization in the bone marrow and lymph nodes. Elevated VEGF levels were strongly associated with elevated EGF level (p<0.001). High VEGF levels correlated with high white blood cell counts (p=0.008) and showed a trend towards association with del(11q) (p=0.07) and lymphadenopathy (p=0.165). Concerning VEGF, no significant difference in PFS was detected. In contrast, pts with high levels of sIl2R alpha showed a significant shorter PFS. When confirmed by conventional ELISA, median PFS in pts within the highest quartile of sIl2Ralpha levels were 22 months compared to 72 months in the lower three quartiles (p<0.001). When we analyzed sIl2R alpha together with genetic abnormalities like del(11q), trisomy 12, del(13q), del(17p), the risk stratification model used in CLL1 (high risk versus low risk for disease progression), the hierarchical model as published by Döhner et al., and IgHV status in a multivariate Cox regression, we found that sIl2R alpha (OR 2.5, 95% CI 1.4–4.8, p=0.004) and IgHV mutational status (OR 4.0, 95% CI 2.2–7.3, p<0.001) were both independent prognostic variables. Conclusion: The assessment of sera in a small subgroup of the CLL1 study cohort of the GCLLSG revealed that the levels of several chemokines and cytokines were elevated when compared to healthy controls. Median serum levels of different chemokines correlated with distinct biological characteristics of CLL pts, like genetic abnormalities or clinical parameters. In addition, sIl2R alpha could be identified as an independent prognostic variable for PFS in early CLL. Disclosures: Eichhorst: Hoffmann La Roche: Honoraria, Research Funding, Travel Grants; Mundipharma: Research Funding, Travel Grants; Gilead: Consultancy. Stilgenbauer:Hoffmann La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Travel Grants. Hallek:Hoffmann La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bergmann:Celgene: Honoraria.

scholarly journals The Role of Butyric Acid in Treatment Response in Drug-Naïve First Episode Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Xue Li ◽  
Xiaoduo Fan ◽  
Xiuxia Yuan ◽  
Lijuan Pang ◽  
Shaohua Hu ◽  
...  
Keyword(s):  
Treatment Response ◽  
Butyric Acid ◽  
Serum Levels ◽  
First Episode ◽  
Healthy Controls ◽  
Significant Difference ◽  
Drug Naïve ◽  
First Episode Schizophrenia ◽  
Risperidone Treatment

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's &lt; 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's &lt; 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.

scholarly journals AB0345 Th9 CELLS AND THEIR ASSOCIATED CYTOKINES: THE PROBABLE PLAYERS IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND TYPE 1 DIABETES MELLITUS (T1DM)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1197.2-1198
Author(s):  
N. Mohannad ◽  
M. Moaaz ◽  
R. Mohamed Shehata
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Activity ◽  
Clinical Manifestations ◽  
Moderate Activity ◽  
Healthy Controls ◽  
Group I ◽  
Pancreatic Islets Of Langerhans ◽  
Th9 Cells ◽  
Significant Difference

Background:SLE is an autoimmune disease (AID) of unknown origin. Several factors can contribute to immune dysfunction in SLE.Interleukin 9 (IL9) is a newly emerging T cell-derived factor preferentially expressed by CD4+T cells: T helper 9 (Th9)IL9 targets different cell lineages, and can contribute to the development of allergic & AIDsWhether abnormal expression and secretion of IL9 are present in SLE patients (pts) still unidentified. It is also unclear whether IL9 exerts main proinflammatory or anti-inflammatory activities in SLE. T1DM is characterized by inflammation of the pancreatic islets of Langerhans. Insulitis progresses over time and β cells become destroyed then clinical DM is established. T1DM is regarded as a T cell-driven AIDObjectives:Evaluation of the expression of CD4+ IL9+ T cells & the level of IL9 in SLE pts compared to both healthy subjects & pts with another AID: T1DM.Also, to evaluate the correlation of these expressions with clinical features, laboratory parameters and SLE activityMethods:The study included: Group I 25 SLE pts fulfilling SLICC classification criteria divided into 2 subgroups (gps) according to SLE disease activity index (SLEDAI) IA: 20 pts with mild to moderate activity (<12) IB:5 pts with severe activity (>12) recruited from rheumatology clinic or internal medicine ward (Rheumatology unit), Main University Hospital, Alexandria. Group II 15 healthy individuals as a first control gp. Group III 15 pts with T1DM fulfilling the American Diabetes Association criteria as a second control gp. All pts were subjected to history taking, clinical examination,laboratory investigations: CBC,LFT,KFT,ESR,CRP,ANA,Anti-dsDNA,Th9 cell expression detection by flowcytometry and serum IL9 by ELISAResults:There was no statistical difference between all gps as regards age & sex but a significant increased ESR in SLE compared to controls & T1DM p< 0.001 p=0.001Th9 expression was highly increased in SLE pts, range 0.13-4.54% & mean ±SD=1.50 ± 1.47% than both control gps. In healthy controls Th9 ranged between 0.0-1.29% with mean 0.37 ±0.52%, while in T1DM pts ranged between 0.03 to 2.13% with mean of 0.67 ± 0.59%. A high significant difference was found between SLE pts and controls p=0.001, an insignificant rise was seen in SLE pts compared to T1DM pts p=0.157. A high significant increase in Th9 was found in severe SLE: mean of 3.74 ±1.15% than in pts with mild to moderate SLE: mean 0.94±0.88% p=<0.001IL9 level was highly increased in SLE pts: mean of 42.83± 23.98 pg/ml than both control gps. In healthy controls the mean was 8.54±13.27, while in T1DM with mean of 29.17±16.09 pg/ml. A high significant difference was found between SLE pts and normal controls p<0.001 but an insignificant rise with T1DM p=0.294. A high significant increase in IL9 in pts with severe ds compared to mild to moderate pts p<0.001.A significant direct correlation between Th9 & IL9 and SLEDAI/105 A significant direct correlation between damage index and Th9 p=0.040 but not IL9 p=0.053In SLE no significant relation between Th9 or IL9 & clinical manifestations or disease duration. A direct correlations between Th9 & ESR p=0.046 and CRP p=0.025,a significant correlation between IL9 and CRP p=0.033, no correlations between Th9&IL9 level and anti-dsDNA p=0.593& 0.4 Significant direct correlation between Th9 and IL9 in T1DM pts, still no correlation with glycemic profile. IL9 levels were significantly increased in SLE with elevated CRP p=0.033 & the % of Th9 cells were increased with elevated ESR and CRP p=0.025, 0.046Conclusion:In SLE pts; IL9 level and Th9 cells expression were significantly elevated compared to healthy controls. IL9 levels and the percentages of Th9 directly correlated with the SLE disease activity. IL9 levels also were significantly increased in T1DM pts compared to controls,but they were less expressed than in SLE. This suggests an important role of IL9 in the pathogenesis AIDs as SLEReferences:[1]Tahernia L et al. Cytokines in SLE: their role in pathogenesis of disease and possible therapeutic opportunities. Rheum Res 2017Disclosure of Interests:None declared

scholarly journals T cell–specific STAT3 deficiency abrogates lupus nephritis

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1468-1472 ◽  
Author(s):  
N Yoshida ◽  
F He ◽  
V C Kyttaris
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Cell Responses ◽  
Cytokines And Chemokines ◽  
Novel Approach ◽  
Cell Tissue ◽  
External Stimuli

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.

scholarly journals Role of vitamin D serum levels in prevention of primary and recurrent melanoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Lombardo ◽  
A. Vigezzi ◽  
G. Ietto ◽  
C. Franchi ◽  
V. Iori ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Levels ◽  
Mitotic Rate ◽  
Control Group ◽  
Healthy Population ◽  
Histological Subtype ◽  
Melanoma Diagnosis ◽  
Significant Difference ◽  
Tumour Location

AbstractPatients afflicted with melanoma show lower vitamin D serum levels (VDSL) than the healthy population. This hypothesis agrees with its well-known antiproliferative features. An observational study was carried out to collect VDSL in patients suffering from melanoma. Our aim was to identify a potential connection between low VDSL and the risk to incur melanoma. Furthermore, we studied the association between VDSL at the diagnosis of melanoma and other germane prognostic factors. The population held in regard was composed of 154 patients with a diagnosis of melanoma between 2016 and 2019. These patients were retrospectively collected from our follow-up storage. We compared VDSL to clinical and pathological parameters (age, sex, tumour location, Breslow’s depth, Clark’s level, histological subtype, ulceration, et aliqua). Moreover, we recruited a control group with negative melanoma history. Mean and median of VDSL were significantly lower in the melanoma group. Instead, we found a negative association between melanoma and VDSL > 30 ng/L (OR 0.11; p < 0.0001). No correlation between VDSL and both Breslow’s depth and Clark’s level was discovered, but the VDSL comparison between thin (depth ≤ 1 mm) and thick tumours (depth > 1 mm) revealed a statistically significant difference (21.1 ± 8.2 ng/L vs 17.8 ± 8.1; p = 0.01). Moreover, VDSL were significantly lower in melanomas with mitotic rate ≥ 1/mm2 (22.1 ± 8.3 ng/L; p < 0007). Nevertheless, no connection was found between VDSL and both ulceration and positive sentinel nodes (p = 0.76; p = 0.74). Besides, our study revealed no association between VDSL and histological subtype (p = 0.161). Lower VDSL correlate with thick and high mitotic rate tumours. Future prospective studies would investigate if appropriate upkeep of suitable VDSL can decrease the risk of primary and recurrent melanoma diagnosis.

Exploring The Clinical Significance of Serum Angiopoietin-2 In Breast Cancer Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Abeer I Abd Elmagid ◽  
Hala Abdel Al ◽  
Wessam El Sayed Saad ◽  
Seham Kamal Mohamed
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Tnm Staging ◽  
Control Group ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Female Patients ◽  
Significant Difference ◽  
Angiopoietin 2

Abstract Background Breast cancer is the most common cancer among women and one of the most important causes of death among them.Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Angiopoietins are well-recognized endothelial growth factors that are involved in angiogenesis associated with tumors. Aim To explore the diagnostic significance of serum angiopoietin-2 (Ang-2) in breast cancer and to evaluate its prognostic efficacy through studying the degree of its association with the TNM staging of the disease. Patients and Methods This study was conducted on (35) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Breast Cancer Patients) and (25) female patients with benign breast diseases (Group II, Pathological Control Patients), in addition to (20) age - matched apparently healthy, free mammogram, females serving as healthy controls (Group III, Healthy Controls). For all participants, measurement of serum Ang-2 was done using enzyme linked immunosorbent assay (ELISA) technique. Results A highly significant increased levels of Ang-2 was observed in breast cancer patients when compared to healthy control group (Z = 4.95, p &lt; 0.01). However, no significant difference was observed in Ang-2 levels between breast cancer patients group and pathological control group (Z = 3.37, p &gt; 0.05). No significant difference was detected in Ang-2 levels in relation to TNM stage and histological grade. No significant correlation was found between Ang-2 levels and serum levels of CA15-3, hormone receptors, HER2/new receptor status (p &gt; 0.05, respectively). Conclusion This study revealed that Ang-2 serum levels were significantly increased in patient with breast cancer compared with healthy controls, indicating that high Ang-2 level is a promising non invasive biomarker for breast cancer diagnosis. However, no significant difference of Ang-2 levels was detected in relation of breast TNM staging in the population studied.

scholarly journals Evaluation of serum amyloid A, soluble E-selectin and soluble E-cadherin as lung cancer biomarkers

2017 ◽  
Vol 4 (3) ◽  
pp. 650
Author(s):  
Varinder Saini ◽  
Chikkahonnaiah Prashanth ◽  
Jasbinder Kaur ◽  
Ashok Kumar Janmeja ◽  
Seema Gupta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Sensitivity And Specificity ◽  
Respiratory Diseases ◽  
Serum Levels ◽  
Screening Methods ◽  
Healthy Controls ◽  
Amyloid A ◽  
Significant Difference ◽  
Soluble E Selectin ◽  
E Cadherin

Background: Lung cancer screening is a challenge. Sputum cytology, chest X-ray, low dose computed tomography and other screening methods have not proved to be very effective. Serum biomarkers are a new hope in screening of lung cancer. The present study was planned to evaluate sensitivity and specificity of serum levels of amyloid A (SAA), soluble E- selectin (sE-selectin) and soluble E-cadherin (sE-cadherin) as lung cancer biomarkers.Methods: An observational and cross-sectional study comprised of three groups with 20 subjects each of proven lung cancer cases, patients with non-malignant respiratory diseases and healthy controls. Levels of SAA, sE-selectin and sE-cadherin were measured by solid phase sandwich ELISA. Individual and collective sensitivity and specificity of these biomarkers was analysed and cut off values calculated by receiver operating curves.Results: A statistically significant difference was found in the median levels (ng/ml) of SAA in patients of lung cancer, other non-malignant respiratory diseases, and healthy controls, the levels (Mean±SD) being 24980.50±6564.14,9961.10±2000.24 and 580.95±334.94 respectively in the three groups. A sensitivity of 80% and specificity of 55% was found when SAA levels of 1068 ng/ml were taken as cut off for screening of lung cancer. However, no significant difference was found in the serum levels of sE selectin and sE cadherin between the three groups. Moreover, significant association of biomarkers could also not be established with lung cancer when they were used in combination.Conclusions: In this preliminary report from India, SAA has been found to be a promising biomarker in screening for lung cancer.

scholarly journals Anti-phosphatidylserine/prothrombin Complex Antibodies in Patients With Cutaneous Vasculitis: Possible Involvement in the Pathogenesis

2020 ◽  
Author(s):  
Yuto Tamura ◽  
Tamihiro Kawakami ◽  
Yupeng Dong ◽  
Miku Yoshinari ◽  
Yuka Nishibata ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Systemic Vasculitis ◽  
Serum Levels ◽  
Cutaneous Vasculitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Iga Vasculitis ◽  
Skin Involvement ◽  
Wild Type ◽  
Significant Difference

Abstract Objective. It was previously demonstrated that cutaneous vasculitis, including IgA vasculitis and cutaneous arteritis (CA), is associated with the presence of IgM antibodies (Abs) against the phosphatidylserine/prothrombin complex (PS/PT). Recently, novel enzyme-linked immunosorbent assay kits for the detection of IgG and IgM anti-PS/PT (aPS/PT) Abs have become commercially available.Methods. The prevalence of serum IgG and IgM aPS/PT Abs in both cutaneous and systemic vasculitis was determined using these kits. In addition, to examine whether aPS/PT Abs were involved in the pathogenesis of cutaneous vasculitis, inbred wild-type rats were intravenously administered with a rat IgM class aPS/PT monoclonal Ab established previously or with rat immunoglobulins as controls. To express PS on the surface of vascular endothelium, these rats were given a subcutaneous injection of cell-free histones (250 µg/ml, 300 µl/site) 2 hours in advance. Results. Serum IgM aPS/PT Ab levels were elevated in patients with systemic vasculitis with skin involvement and CA compared to those in patients with systemic vasculitis without skin involvement and healthy controls. There was no significant difference in the serum levels of IgG aPS/PT Abs between the patients and healthy controls. Correspondingly, inbred wild-type rats intravenously administered with the aPS/PT monoclonal IgM Ab after appropriate priming—subcutaneous histone injection—developed cutaneous vasculitis. Some rats given rat IgM instead of the aPS/PT monoclonal Ab also developed cutaneous vasculitis, whereas vasculitis did not occur in rats given IgG or only priming by histones. Conclusion. IgM aPS/PT Abs could be involved in the pathogenesis of cutaneous vasculitis.

scholarly journals VitaminD3 Regulates T Cell Immune Responses in Allergen and Rhinovirus Induced Asthma

2021 ◽  
Author(s):  
Susetta Finotto ◽  
Patricia Haag ◽  
Darja Andreev ◽  
Nina Li ◽  
Alexander Kiefer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Murine Model ◽  
Peripheral Blood ◽  
Serum Levels ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Asthmatic Children ◽  
Rhinovirus Infection

Abstract Background: Serum 25(OH)-Vitamin D3 (VitD3) deficiency during infancy has been associated with asthma. The potential therapeutic role of VitD3 given in the airways and its interference with the allergen and Rhinovirus was the objective of this study. Methods: In two cohorts of children with and without asthma, serum levels of the C-reactive protein (CRP) were correlated to Serum VitD3 and in peripheral blood T cell inhibitor marker Programmed cell death protein 1 (PD1) mRNA was analyzed. In a murine model, VitD3 was given intranasally in vivo and in vitro to lung cells with allergen and Rhinovirus. Results: In the cohorts of pre-school age children without (control) asthma, CRP and VitD3 levels inversely correlated. In preschool asthmatic children that did not receive VitD3 supplementation as infant had more episode of asthma exacerbation associated with high CRP serum level. In peripheral blood cells from control but not asthmatic children with higher serum levels of VitD3 had lower PD1 mRNA levels. In murine model, OVA intranasal challenge induced Innate Lymphoid Cells type 2 (ILC2)-associated markers and Eosinophils in BALF and VitD3 inhibited lung inflammation and ILC2 markers. Furthermore, VitD3 given intranasally, induced CD4+T cells and reduced PD1, T regulatory cells in the lung. Similarly, VitD3 had a suppressive role on CD4+PD1+ T cells involved in T cell exhaustion in the airways in the absence of ST2 after Rhinovirus infection. Conclusion: These data support an inhibitory role of VitD3 on T cell exhaustion after allergen and rhinovirus infection that is relevant for pediatric asthma.

scholarly journals Anti-ceramide antibodies in leprosy: marker for nerve damage?

2010 ◽  
Vol 4 (06) ◽  
pp. 378-381 ◽  
Author(s):  
Kalpana Singh ◽  
Bhawna Singh ◽  
Prakash Ray
Keyword(s):  
Infectious Disease ◽  
Serum Levels ◽  
Serum Marker ◽  
Nerve Damage ◽  
Healthy Controls ◽  
Chi Square ◽  
Leprosy Patients ◽  
Chi Square Test ◽  
Multibacillary Leprosy

Background: Leprosy is a chronic infectious disease primarily affecting the peripheral nervous system and skin. Multibacillary leprosy is associated with nerve damage which could contribute to myelin alteration. As ceramide is a constituent of myelin sheath, the present study aimed to compare anti-ceramide antibody titre in paucibacillary and multibacillary leprosy patients with controls. Methodology: Serum levels of anti-ceramide antibody were measured using enzyme-linked immunosorbent assays (ELISA) in 50 leprosy patients (25 paucibacillary and 25 multibacillary) and 25 healthy controls. Results were reported in OD units as mean ± SD and analyzed by Chi square test (significance at p < 0.05). Results: Patients suffering from multibacillary leprosy had significantly higher anti-ceramide antibody serum levels compared to paucibacillary leprosy patients and healthy controls (p < 0.005). Conclusions: Since nerve damage is the most debilitating effect of leprosy, the search for a serum marker for assessing nerve damage is required in countries where leprosy is still widespread. In multibacillary leprosy patients, the role of anti-ceramide antibody as a marker for nerve damage should be explored.

scholarly journals Repeat Local Treatment of Recurrent Colorectal Liver Metastases, the Role of Neoadjuvant Chemotherapy: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4997
Author(s):  
Madelon Dijkstra ◽  
Sanne Nieuwenhuizen ◽  
Robbert S. Puijk ◽  
Florentine E. F. Timmer ◽  
Bart Geboers ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Hospital Stay ◽  
Colorectal Liver Metastases ◽  
Local Treatment ◽  
Length Of Hospital Stay ◽  
Progression Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Subgroup Analyses

This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan–Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher’s exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts (p = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities (p = 0.010) and primary tumor location (p = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416–1.691; p = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249–1.756; p = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483–1.318; p = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).

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