scholarly journals Novel inflammatory biomarkers in primary hyperparathyroidism

2015 ◽  
Vol 173 (1) ◽  
pp. 9-17 ◽  
Author(s):  
M H E Christensen ◽  
I S Fenne ◽  
Y Nordbø ◽  
J E Varhaug ◽  
K O Nygård ◽  
...  

ObjectivePrimary hyperparathyroidism (PHPT) has been associated with low-grade inflammation and increased risk of cardiovascular disease (CVD). The aim of the study was to investigate systemic levels of pro-inflammatory proteins that previously have not been examined in patients with PHPT. The selection of the pro-inflammatory biomarkers included in this study, MMP9, S100A4, S100A8/A9 and the receptors sCD14 and RAGE, was based on a previous microarray screen of mRNAs in adipose tissue from PHPT patients.DesignA prospective study was conducted on a total of 57 patients with PHPT and a control group of 20 healthy blood donors.MethodsPHPT patients with normalisation of serum calcium levels after parathyroidectomy were followed for 6 months. Forty-two patients participated in the longitudinal study, in which blood samples were taken at inclusion, and 1, 3 and 6 months after surgery.ResultsWe observed increased serum levels of MMP9 (P=0.029), S100A4 (P<0.001) and sCD14 (P=0.002) in the 57 patients with PHPT compared to the control-group. During 6 months of follow up, S100A4 (P=0.022) and sCD14 (0.002) decreased significantly, while serum levels of MMP9 increased (P=0.025).ConclusionsThe results demonstrate an increased inflammatory response in PHPT patients shown by elevated MMP9, S100A4 and sCD14 at inclusion. During the 6 months of follow-up, MMP9 increased further, possibly due to the tissue repair process after parathyroidectomy. S100A4 and sCD14 decreased after surgery demonstrating a partial reversal of the systemic inflammation.

2013 ◽  
Vol 23 (9) ◽  
pp. 1663-1669 ◽  
Author(s):  
Stefania Cortecchia ◽  
Giuseppe Galanti ◽  
Cecilia Sgadari ◽  
Silvano Costa ◽  
Margherita De Lillo ◽  
...  

ObjectiveThe p16Ink4a (p16) tumor-suppressor protein is a biomarker for activated expression of human papillomavirus oncogenes. However, data are insufficient to determine whether p16 overexpression predicts the risk for progression of low-grade cervical intraepithelial neoplasia (CIN). This study was aimed at evaluating the risk for progression to CIN2 or worse during a 3-year follow-up of an unselected series of 739 patients with CIN1 biopsy specimens tested for p16 expression.MethodsPositivity of p16 was defined as a diffuse overexpression in the basal/parabasal cell layers. Selection biases were ruled out using a control group of 523 patients with CIN1 biopsies not tested for p16 expression. Analysis was based on the ratio of progression rates.ResultsIn the first year of follow-up, the 216 patients (29%) with p16-positive CIN1 had a higher progression rate (12.3%) than did the 523 patients with p16-negative CIN1 (2.2%) (rate ratio, 5.5; 95% confidence interval [CI], 2.59–11.71). In the second and third years, differences were smaller (rate ratio, 1.32 and 1.14, respectively) and not significant. The patients with p16-positive CIN1 also had a lower risk for regression to normal in the first year of follow-up (rate ratio, 0.55; 95% confidence interval, 0.42–0.71) and nonsignificant changes in the second and third years (rate ratio, 0.81 and 0.84, respectively).ConclusionsThe patients with p16-positive CIN1 had an increased risk for progression that was concentrated in the first year of follow-up. Immunostaining of p16 could have a role in short-term surveillance of patients with CIN1. Further research should focus on midterm/long-term outcomes of p16-positive CIN1.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2945-2945
Author(s):  
Maja Ludvigsen ◽  
Maja Ølholm Vase ◽  
Rikke Hjortebjerg ◽  
Irma Petruskevicius ◽  
Court Pedersen ◽  
...  

Abstract Introduction. HIV infected individuals have an increased risk of developing lymphoma compared to sex- and age matched non-immunocompromised control population and approximately 2% of HIV infected individuals developed lymphoma (Gopal et al, J Natl cancer Inst 2013). Our group has been among the first who identified novel serum protein markers present at time of HIV diagnosis, which were predictive of subsequent lymphoma development (Vase et al, AIDS 2016). Galectins are important regulators of cell adhesion, apoptosis, cell cycle, and mRNA processing. Galectin-1 (Gal-1) is a known lectin-binding protein able to mediate Th2 skewed microenvironment in lymphomas (Juszczynski et al, Proc Natl Acad Sci U S A 2007; Cedeno-Laurent et al, Blood 2012), and facilitates HIV-infection (Sato et al, Ann N Y Acad Sci 2012). Increased serum Gal-1 levels were correlated to increased tumor burden and adverse clinical features in Hodgkin lymphoma (HL) (Kamper et al, Blood 2011; Ouyang et al, Blood 2013) and low Gal-1 levels were associated with an increased risk of chronic graft-versus-host disease in patients with hematologic malignancies treated with non-myeloablative hematopoietic stem cell transplantation (Petruskevicius et al, BMT 2016). In this study, we investigated whether the serum level of Gal-1 at the time of HIV diagnosis was predictive for subsequent lymphoma development. Methods. We determined the serum levels of Gal-1 in serum samples from19 HIV infected patients collected at the time of HIV diagnosis. Measurements were performed using a time-resolved immunofluorometric assay, as previously described (Petruskevicius et al, BMT 2016). Patients were grouped based on clinical outcomes in (i) future HIV-associated lymphoma (HIV/lymphoma), (ii) future HIV-associated benign lymphadenopathy (HIV/adenopathy), and (iii) no future neoplasia (HIV/no neoplasia), Table 1. Furthermore, serum Gal-1 levels were compared to those of a healthy control group (n=30), as previously reported (Petruskevicius et al, BMT 2016). Gal-1 sample concentrations were calculated by regression anaysis on basis of a standard curve of recombinant Gal-1 at concentrations of 100 to 0.78 ng/mL with 1:4 sample dilutions. Gal-1 levels > 400ng/mL was included in the analyses with a value of 400ng/mL. Estimates of differences between groups were evaluated using Student's t-test or ANOVA on log transformed data. A ROC analysis was computed to establish cut-off values for serum galectin-1, with respect to development of lymphoma. Results. Overall, the serum Gal-1 level in the HIV cohort was lower than in the healthy control group (p<0.001), Figure 1A. At HIV diagnosis, those HIV patients who would subsequently develop lymphoma had significantly lower levels of serum Gal-1 compared to the remaining cohort, Figure 1B (p=0.017). There was no gender-related difference (p=0.436) and Gal-1 serum levels did not correlate with either CD4 count (p=0.553) or viral load (p=0.600) at time of HIV diagnosis. In this size-limited study population, it was not possible to show any significant difference between HIV/lymphoma, HIV/adenopathy, and HIV/no neoplasia. ROC calculated cut-off of 2.6 ng/mL was able to separate HIV patients with future lymphoma from the remaining HIV patients and controls with a specificity of 78% and sensitivity of 100%. At this cut-off 13 (31%) patients were allocated to the low Gal-1 group, including all future lymphoma patients. Conclusion. HIV infected patients had significant lower serum Gal-1 levels than compared to a healthy control cohort. All HIV infected patients that later developed lymphoma belonged to the subset with lowest serum Gal-1 levels. If confirmed in independent cohorts of HIV patients from the cART era, this observation will support the use of low serum levels of Gal-1 as an early predictive biomarker for subsequent lymphoma development in HIV infected individuals. This may in turn have potential implications on the clinical monitoring strategy of these patients. Table 1 Characteristics of HIV patients in the serum galectin-1 study *Time before lymphoma or day of follow up (death or study end) Table 1. Characteristics of HIV patients in the serum galectin-1 study. / *Time before lymphoma or day of follow up (death or study end) Figure 1 Serum levels of Gal-1. A: Serum Gal-1 levels in the HIV cohort (n=19) were significant lower than in the healthy control group (n=30). B: At HIV diagnosis, significant lower serum Gal-1 levels was observed in HIV-patients with future lymphoma diagnosis (n=5) compared to the remaining cohort (n=44). Figure 1. Serum levels of Gal-1. A: Serum Gal-1 levels in the HIV cohort (n=19) were significant lower than in the healthy control group (n=30). B: At HIV diagnosis, significant lower serum Gal-1 levels was observed in HIV-patients with future lymphoma diagnosis (n=5) compared to the remaining cohort (n=44). Disclosures d'Amore: Servier: Honoraria, Other: Advisory Boards; CTI LIfe Sciences: Honoraria, Other: Advisory Boards.


2015 ◽  
Vol 114 (09) ◽  
pp. 519-529 ◽  
Author(s):  
Sanne Bøjet Larsen ◽  
Erik Lerkevang Grove ◽  
Morten Würtz ◽  
Søs Neergaard-Petersen ◽  
Anne-Mette Hvas ◽  
...  

SummaryInflammation is likely to be involved in all stages of atherosclerosis. Numerous inflammatory biomarkers are currently being studied, and even subtle increases in inflammatory biomarkers have been associated with increased risk of cardiovascular events in patients with coronary artery disease (CAD). Low-grade inflammation may influence both platelet production and platelet activation potentially leading to enhanced platelet aggregation. Thrombopoietin is considered the primary regulator of platelet production, but it likely acts in conjunction with numerous cytokines, of which many have altered levels in CAD. Previous studies have shown that high-sensitive C-reactive protein (CRP) independently predicts increased platelet aggregation in stable CAD patients. Increased levels of CRP, fibrinogen, interleukin-6, stromal cell-derived factor-1, CXC motif ligand 16, macrophage migration inhibitory factor, RANTES, calprotectin, and copeptin have been associated with increased risk of cardiovascular events in CAD patients. Additionally, some of these inflammatory markers have been associated with enhanced platelet activation and aggregation. However, CRP and other inflammatory markers provide only limited additional predictive value to classical risk factors such as smoking, blood pressure, and cholesterol levels. Existing data do not clarify whether inflammation simply accompanies CAD and increased production and aggregation of platelets, or whether a causal relationship exists. In this review, we provide a comprehensive overview of inflammatory markers in stable CAD with particular emphasis on platelet production, activation, and aggregation in CAD patients.


2020 ◽  
Author(s):  
Sainan Chen ◽  
Wenjing Gu ◽  
Min Wu ◽  
Chuangli Hao ◽  
Canhong Zhu ◽  
...  

Abstract Background: Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the association between bronchiolitis and recurrent wheezing remains controversial.Objective: To investigate the incidence of post-bronchiolitis recurrent wheezing and associated risk factors.Methods: Infants with bronchiolitis were enrolled from November 2016 through March 2017. We also enrolled 24 healthy children with no history of wheezing from the department of children's health prevention as a control group. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed every 3 months for a duration of 2 years by telephone or at outpatient appointments.Results: We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P<0.05); The serum level of TNF‑ α was lower in the recurrent wheezing group (P<0.05), and the serum levels of IL-4, IL-5, IL-25, IL-33 were significantly higher among patients without recurrent wheezing (P<0.05). Logistic regression analysis showed that eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR]=7.488; 95% confidence interval [CI], 1.447–38.759; P=0.016). Conclusion: The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. Eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesco Santoro ◽  
Tecla Zimotti ◽  
Adriana Mallardi ◽  
Alessandra Leopizzi ◽  
Enrica Vitale ◽  
...  

AbstractTakotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9–14.8, HR = 7.8 95% CI 2.4–25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6–52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.


2015 ◽  
Vol 52 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Sílvia Maria Perrone CAMILO ◽  
Élia Cláudia de Souza ALMEIDA ◽  
Benito André Silveira MIRANZI ◽  
Juliano Carvalho SILVA ◽  
Rosemary Simões NOMELINI ◽  
...  

Background Proton-pump inhibitors have been used for at least two decades. They are among the most commonly sold drugs in the world. However, some controversy remains about the indications for their use and the consequences of their prolonged use. Objectives To evaluate and compare the endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors to changes in non-users. Methods A prospective study performed at a tertiary Public Hospital involving 105 patients undergoing upper-gastrointestinal endoscopy. Subjects included 81 proton-pump inhibitor users and 24 non-users (control group). Biopsies of the antral-type mucosa, the antral-fundic transition, and the fundus were evaluated by the Sydney System. The presence of erosion or ulceration, lymphatic follicles, reactive gastropathy, and polypoid or epithelial hyperplasia was also determined. Serum levels of gastrin were measured. Results We found two polyps, one in each group, both of which were negative for Helicobacter pylori. There were two cases of parietal cell hyperplasia in users of proton-pump inhibitors. Gastrin was elevated in 28 users of proton-pump inhibitors and in four members of the control group. We did not find statistically significant differences in the endoscopic or histopathologic findings between the two groups. Conclusions Chronic use of proton-pump inhibitors for the duration examined was not associated with significant gastric changes. An interesting finding was that the 4 chronic users of proton-pump inhibitors who had serum gastrin levels above 500 pg/mL also had positive serology for Chagas disease.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jin-Ning Ma ◽  
Xiao-Lin Li ◽  
Pan Liang ◽  
Sheng-Li Yu

Abstract Background The optimal timing to perform a total knee arthroplasty (TKA) after knee arthroscopy (KA) was controversial in the literature. We aimed to 1) explore the effect of prior KA on the subsequent TKA; 2) identify who were not suitable for TKA in patients with prior KA, and 3) determine the timing of TKA following prior KA. Methods We retrospectively reviewed 87 TKAs with prior KA and 174 controls using propensity score matching in our institution. The minimum follow-up was 2 years. Postoperative clinical outcomes were compared between groups. Kaplan-Meier curves were created with reoperation as an endpoint. Multivariate Cox proportional hazards regressions were performed to identify risk factors of severe complications in the KA group. The two-piecewise linear regression analysis was performed to examine the optimal timing of TKA following prior KA. Results The all-cause reoperation, revision, and complication rates of the KA group were significantly higher than those of the control group (p < 0.05). The survivorship of the KA group and control group was 92.0 and 99.4% at the 2-year follow-up (p = 0.002), respectively. Male (Hazards ratio [HR] = 3.2) and prior KA for anterior cruciate ligament (ACL) injury (HR = 4.4) were associated with postoperative complications in the KA group. There was a non-linear relationship between time from prior KA to TKA and postoperative complications with the turning point at 9.4 months. Conclusion Prior KA is associated with worse outcomes following subsequent TKA, especially male patients and those with prior KA for ACL injury. There is an increased risk of postoperative complications when TKA is performed within nine months of KA. Surgeons should keep these findings in mind when treating patients who are scheduled to undergo TKA with prior KA.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomonori Akasaka ◽  
Seiji Hokimoto ◽  
Noriaki Tabata ◽  
Kenji Sakamoto ◽  
Kenichi Tsujita ◽  
...  

Background: Several cytochrome P450 (CYP) enzyme families have been identified in extra hepatic tissues such as heart, vasculature, kidney, and lung. CYP2C19 localized in vascular smooth muscle and endothelium contributes to the regulation of vascular tone and homeostasis. However, it is unknown whether CYP2C19 genotype is associated with the vascular tonus in patients with VSA. The aim of this study was to examine the impact of CYP2C19 genotype on coronary artery spasm in patients with VSA. Methods: We examined the distribution of CYP2C19 genotype in patients with VSA (n=129) who were diagnosed by intra-coronary acetylcholine infusion test and healthy subjects (n=455) as control group. CYP2C19 genotypes were divided into 3 groups; (1) CYP2C19*1/*1: EM, (2) one loss-of-function allele (*1/*2, *1/*3: IM), and (3) two loss-of-function alleles (*2/*2, *2/*3, *3/*3: PM). Moreover, we measured the level of high-sensitive CRP (hs-CRP) as a degree of low glade inflammation in each group. Results: The ratios of CYP2C19 genotype (EM, IM, and PM) were 30, 42, and 28% in VSA group, and 32, 49, and 19% in control group. In short, PM frequency was significantly higher in VSA than in control (28% vs 19%, P=0.026). In VSA group, the ratios of CYP2C19 genotype were 36, 44, and 20% in male, and 20, 39, and 41% in female, respectively. Briefly, the PM frequency was significantly higher in female than in male (41% vs 20%, P<0.001). Moreover, the level of hs-CRP was significantly higher in VSA group than in control group (0.17±0.367 vs 0.10.±0.240, P=0.02). When patients were stratified by gender, the level of hs-CRP was significantly higher in VSA group in female (0.11±0.198 vs 0.06±0.105, P=0.031) and male (0.20±0.438 vs 0.12±0.277, P=0.044). Multivariate analysis for coronary spasm indicated high age, hypertension, and high level of hs-CRP as predictive factors among all subjects. PM is a predictive factor for coronary spasm in female group only (OR3.1, 95%RI 1.525-6.317, P=0.002), but not in male (OR0.829, 95%RI 0.453-1.518, P=0.543). Conclusion: The CYP2C19 two loss-of-function alleles (PM) and low grade inflammation may be associated with pathophysiology of coronary artery spasm and the regulation of coronary tonus, especially in female.


2011 ◽  
Vol 30 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Kai-Sheng Hsieh ◽  
Tsung-Jen Lai ◽  
Yu-Tung Hwang ◽  
Ming-Wei Lin ◽  
Ken-Pen Weng ◽  
...  

Kawasaki disease (KD) is the most common cause of pediatric acquired heart disease. KD patients have spontaneously high plasma/serum levels of IL-10 during the acute phase. Therefore, two independent studies were carried out to investigate the association between genetic variants in IL-10 promoter (−1082, −819, and −592) and risk of KD. A total of 134 trios were included for the family-based association study. A significantly preferential transmission of the C allele at loci −819 T > C and −592 A > C for KD cases was observed (Ppermutation= 0.029 and Ppermutation= 0.034, respectively). There was a significant increase in the transmission of haplotype CC (p= 0.016) at the above two loci (OR, 1.632; 95% CI, 1.090–2.443; Ppermutation= 0.019). We also carried out a follow-up case-control study that included 146 KD cases and 315 unrelated healthy children. {The haplotype CC (−819, −592) showed an increased risk of KD (but statistically non-significant; OR, 1.332; 95% CI, 0.987–1.797;p= 0.061). In diplotype analysis, a trend was found between number of CC haplotype and risk of KD (but non-significant,p= 0.061). In conclusion, CC genotype and CC/CC diplotype at IL-10-819T > C and −592A > C were significantly associated with risk of KD in case-parent trio study, which were replicated partially in our follow-up case-control study.


Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2202
Author(s):  
Micaelle Oliveira de Luna Freire ◽  
Luciana Caroline Paulino do Nascimento ◽  
Kataryne Árabe Rimá de Oliveira ◽  
Alisson Macário de Oliveira ◽  
Thiago Henrique Napoleão ◽  
...  

High-fat diet (HFD) consumption has been linked to dyslipidemia, low-grade inflammation and oxidative stress. This study investigated the effects of a mixed formulation with Limosilactobacillusfermentum 139, L. fermentum 263 and L. fermentum 296 on cardiometabolic parameters, fecal short-chain fatty acid (SCFA) contents and biomarkers of inflammation and oxidative stress in colon and heart tissues of male rats fed an HFD. Male Wistar rats were grouped into control diet (CTL, n = 6), HFD (n = 6) and HFD with L. fermentum formulation (HFD-Lf, n = 6) groups. The L.fermentum formulation (1 × 109 CFU/mL of each strain) was administered twice a day for 4 weeks. After a 4-week follow-up, biochemical parameters, fecal SCFA, cytokines and oxidative stress variables were evaluated. HFD consumption caused hyperlipidemia, hyperglycemia, low-grade inflammation, reduced fecal acetate and propionate contents and increased biomarkers of oxidative stress in colon and heart tissues when compared to the CTL group. Rats receiving the L. fermentum formulation had reduced hyperlipidemia and hyperglycemia, but similar SCFA contents in comparison with the HFD group (p < 0.05). Rats receiving the L. fermentum formulation had increased antioxidant capacity throughout the colon and heart tissues when compared with the control group. Administration of a mixed L. fermentum formulation prevented hyperlipidemia, inflammation and oxidative stress in colon and heart tissues induced by HFD consumption.


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