Severe Post Thrombotic Syndrome Is Associated to Lower Echogenicity of the Residual Venous Thrombosis

Abstract Introduction: The post-thrombotic syndrome (PTS) is a common chronic complication of deep venous thrombosis (DVT) of the lower limbs and may occur even after an appropriate anticoagulant treatment. PTS may develop in the first two years after DVT in about 20-50% of patients; 5–10% of those may present severe manifestations of the disease. PTS is associated to an increased risk for DVT recurrence, morbidity, poor quality of life and significant cost to public health. The diagnosis of PTS is performed by clinical evaluation; particularly, the Villalta scale is recommended by the ISTH for PTS diagnosis and severity evaluation. The PTS-associated medical conditions are poorly understood, and it seems that hypercoagulability and inflammation, after the first episode of DVT, may play an important role in the disease development. Therefore, we performed a comprehensive analysis of clinical parameters, inflammation and ultrasound (US) examination of the affected limb in patients with history of previous DVT and PTS. Objective: The aim of this study was to evaluate possible medical conditions associated to PTS and its severity. Material and Methods: Between February 2013 and October 2013, consecutive patients with history of previous unprovoked DVT of lower limbs (> 6 months from the diagnosis), attended at the Hematology Center of the University of Campinas, Brasil, were included. Patients were submitted to physical evaluation for body mass index (BMI) determination and PTS diagnosis, by Villalta scale. Levels of the IL-8, IL-6 and TNF-α were performed by ELISA, D-dimer by turbidimetry and CRP by nephelometry. US examination was performed by duplex. In patients with residual venous thrombosis (RVT), the thrombus echogenicity was determined by grayscale median (GSM) evaluation, as described for atherosclerotic plaques. The GSM analysis was performed by a computer based US using specific software. Only the region containing the thrombus was analyzed, the image was depicted manually point by point to trace the line surrounding the thrombus, the final GSM values were automatic calculated and translated the thrombus echogenicity. A low GSM value (<25) suggests acute thrombosis and a high GSM vlaue (> 25) suggest subacute thrombosis.. Continuous variables were analyzed by Kruskal-Wallis test and categorical variables were compared using the Fisher´ s exact test. Results: From the 56 patients included, 15 did not present PTS, 23 were classified as mild, 11 as moderate and 7 as severe PTS. Serum levels of CRP was significantly higher in patients with severe PTS when compared to patients with mild+moderate PTS and to those without PTS (respectivelly 0.64mg/dL, 0.31mg/dL and 0.13mg/dL; P=0.02).Serum levels of IL-6 and TNF-α were higher in patients with severe PTS compared to patients with mild/moderate PTS and without PTS (IL-6= 2.81pg/mL vs. 1.48pg/mL vs. 0.80pg/mL respectively, and TNF 1.68pg/mL vs. 1.33pg/mL vs 1.17pg/mL respectively), however the differences did not reach statistical significance. Levels of IL-8 and DD were similar between severe PTS and the other two groups. The presence of RVT was similar between groups, however US-generated GSM was significantly lower in patients with severe PTS compared to patients with mild+moderate PTS and patients without PTS (GSM= 22, 31 and 28.5, respectively; P=0.04). As predicted, the BMI was also higher in patients with severe PTS when compared to mild+moderate PTS and no PTS group (BMI= 34,8 vs. 29,3 vs. 25,9, respectively P=0.007). Conclusion: Our results suggest that severe PTS may be associated with a chronic inflammatory response, characterized by obesity and higher levels of CRP. Besides, we could also observe that severe PTS may be associated with the persistence of a hypoechoic residual thrombus, determined by lower US-generated GSM values. The finding about the persistence of a hypoechoic thrombus in patients with severe PTS, even long time after the acute thrombosis event, is new and may possibly suggest that an adequate thrombus organization process is required to avoid the development of PTS. Disclosures No relevant conflicts of interest to declare.

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Insulin Resistance and Inflammation in Black Women with and without Breast Cancer: Cause for Concern

Ethnicity & Disease ◽

10.18865/ed.26.4.513 ◽

2016 ◽

Vol 26 (4) ◽

pp. 513 ◽

Cited By ~ 2

Author(s):

Kathleen A. Griffith ◽

Seon Yoon Chung ◽

Shijun Zhu ◽

Alice S. Ryan

Keyword(s):

Breast Cancer ◽

Insulin Resistance ◽

Black Women ◽

White Women ◽

Cancer Recurrence ◽

Control Group ◽

Study Objective ◽

Increased Risk ◽

Tnf Α ◽

History Of

Objective: After chemotherapy for breast cancer, Black women gain more weight and have an increased mortality rate compared with White women. Our study objective was to compare biomarkers associated with obesity in Black women with and without a history of breast cancer.Design: Case-controlSetting: Academic/federal institutionParticipants: Black women with a history of breast cancer (cases) and age-matched controls.Methods: We compared insulin resistance, inflammation, and lipids in overweight and obese Black women with a history of breast cancer (n=19), age similar controls (n=25), and older controls (n=32). Groups did not differ on mean body mass index (BMI), which was 35.4 kg/m2, 36.0 kg/m2, and 33.0 kg/m2, respectively.Main Outcome Measures: Insulin resistance (HOMA-IR); inflammation (TNF-α, IL-1b, IL-6, IL-8, CRP); lipids (cholesterol, triglycerides).Results: Cases had 1.6 and 1.38 times higher HOMA-IR values compared with age similar and older controls, respectively (P≤.001 for both). TNF-α and IL-1b were significantly higher in cases compared with both control groups (P<.001 for both). IL-6 was also higher in cases compared with age-similar controls (P=.007), and IL-8 was lower in cases compared with older controls (P<.05). Lipids did not differ between cases and either control group.Conclusions: Black women with breast cancer were significantly more insulin resistant with increased inflammation compared not only with age similar controls but with women who were, on average, a decade older. These biomarkers of insulin resistance and inflammation may be associated with increased risk of breast cancer recurrence and require ongoing evaluation, especially given the relatively abnormal findings compared with the controls in this underserved group. Ethn Dis. 2016;26(4):513-520; doi:10.18865/ed.26.4.513

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Decreased anticoagulant response to tissue factor pathway inhibitor in patients with venous thromboembolism and otherwise no evidence of hereditary or acquired thrombophilia

Thrombosis and Haemostasis ◽

10.1160/th03-05-0329 ◽

2004 ◽

Vol 91 (01) ◽

pp. 80-86 ◽

Cited By ~ 8

Author(s):

Brigitte Piccapietra ◽

Johanna Boersma ◽

Joerg Fehr ◽

Thomas Bombeli

Keyword(s):

Venous Thromboembolism ◽

Venous Thrombosis ◽

Mean Value ◽

Healthy Controls ◽

Crude Odds Ratio ◽

Sensitivity Ratio ◽

Increased Risk ◽

History Of ◽

Anticoagulant Response ◽

Acquired Thrombophilia

SummaryNo relevant deficiency of TFPI or genetic polymorphisms could thus far consistently be associated with venous thromboembolism. We hypothesized that the substrates of the TFPI protein, including FVII or FX (rather than the protein itself) could induce a hypercoagulable state. We created a novel TF-based clotting assay that evaluated the anticoagulant response to exogenously added recombinant TFPI. The response to TFPI was expressed as the ratio of the clotting time with and without TFPI. By using 118 healthy controls, we established a reference range between 1.31 and 1.93 (mean value ± 2 standard deviations (SD), 1.62 ± 0.31). We then evaluated samples from 120 patients with a history of venous thromboembolism but no evidence of hereditary and acquired thrombophilia. The range of the patients’ ratios was significantly (P < 0.001) lower, falling between 1.2 and 1.78 (mean value ± 2 SD, 1.49 ± 0.29). Of the 120 patients, 39 (32.5%) had a TFPI sensitivity ratio below the 10th percentile of the controls, compared with 11 (9.3%) of the healthy controls. The crude odds ratio for venous thrombosis for subjects with a TFPI sensitivity ratio below the 10th percentile was 13 (95% CI; range, 3.1 to 54.9) compared with those with a ratio above 1.8 (90th percentile). Patients with idiopathic thromboembolism did not have a decreased TFPI sensitivity ratio more often than patients with thrombosis with a circumstantial risk factor. Based on these results, a reduced response to TFPI may lead to an increased risk of venous thrombosis.

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Mannan-Binding Lectin Levels and Activity Are Not Altered in Atopic Dermatitis Patients with a History of Eczema Herpeticum

Dermatology Research and Practice ◽

10.1155/2011/769890 ◽

2011 ◽

Vol 2011 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Kemp W. Bundy ◽

Laura Y. McGirt ◽

Lora G. Bankova ◽

Andreas Wollenberg ◽

Lisa A. Beck ◽

...

Keyword(s):

Atopic Dermatitis ◽

Functional Activity ◽

Viral Infections ◽

Serum Levels ◽

Small Samples ◽

Eczema Herpeticum ◽

Increased Risk ◽

History Of ◽

Mannan Binding Lectin ◽

Binding Lectin

Background. Eczema herpeticum (EH) is a potentially serious, systemic complication in subjects with atopic dermatitis (AD) caused by herpes simplex virus (HSV). The innate immune dysregulation that predisposes these subjects to cutaneous viral infections is not well understood. We tested the hypothesis that defects in mannan-binding lectin (MBL) may be associated with an increased risk of EH.Methods. We evaluated serum MBL levels and functional activity in 13 AD subjects with a history of EH (EH+) and 21 AD subjects with no history of EH (EH−). MBL levels were detected by enzyme immunoassay. MBL pathway functional activity was evaluated by determining MBL C4b deposition capacity.Results. We found no statistical difference in MBL serum levels or function between EH+ and EH− groups.Conclusion. Considering the limitations of this study (e.g., small samples size) our findings suggest that MBL defects do not play a role in EH.

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General medical disorders with psychiatric implications

10.1093/med/9780199360574.003.0038 ◽

2015 ◽

Author(s):

Erik J. Garcia ◽

Warren J. Ferguson

Keyword(s):

Mental Illness ◽

Psychiatric Symptoms ◽

The United States ◽

Prior History ◽

Medical Illness ◽

Medical Conditions ◽

Presenting Symptoms ◽

Medical Disorders ◽

Increased Risk ◽

History Of

Traditionally the domain of consultation/ liaison psychiatry, the challenge of recognizing and then appropriately treating the psychiatric complications of general medical disorders requires thoughtful planning and attention in corrections. Medical conditions that have psychiatric symptoms represent a significant diagnostic dilemma, particularly in the correctional health setting. Over half of the inmates in the United States have symptoms of a major mental illness, but the pervasiveness of substance use disorders, the increasing prevalence of elderly inmates, and limited access to a patient’s past medical and psychiatric records all contribute to the challenge of discerning when a psychiatric presentation results from an underlying medical condition. One early study underscored this challenge, noting that 46% of the patients admitted to community psychiatric wards had an unrecognized medical illness that either caused or exacerbated their psychiatric illness. A more recent study observed that 2.8% of admissions to inpatient psychiatry were due to unrecognized medical conditions. Emergency room medical clearance of patients presenting for psychiatric admission has revealed an increased risk for such underlying medical conditions among patients with any of five characteristics: elderly, a history of substance abuse, no prior history of mental illness, lower socioeconomic status, or significant preexisting medical illnesses. This chapter examines several of these risk groups and focuses on the presenting symptoms of delirium, mood disorders, and psychosis and the underlying medical conditions that can mimic or exacerbate them.

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Metabolic and Inflamatory Proteins Differently Expressed in Platelets From Deep Venous Thrombosis Patients

Blood ◽

10.1182/blood.v118.21.5256.5256 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5256-5256

Author(s):

Mariane Cristina Flores Nascimento ◽

Karina Kleinfelder-Fontanesi ◽

Fernanda Loureiro de Andrade Orsi ◽

Steven H Seeholzer ◽

Harry Ischiropoulos ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Conflicts Of Interest ◽

Lower Limbs ◽

Apolipoprotein A1 ◽

Blood Samples ◽

Orbitrap Mass Spectrometer ◽

Inflammatory Processes ◽

History Of

Abstract Abstract 5256 BACKGROUND: Deep venous thrombosis (DVT) is multi-causal disease associated to a high morbi-mortality due to complications as pulmonary embolism and post-flebitic syndrome. The incidence is about 20 to 30%, and 25% of the patients will present recurrence in 5 years. The identification of new risk factors is important in clinical practice to prevent new thrombotic events. The role of the platelets on DVT is still not well defined. AIM: The objective of this study was to analyze the hole proteins profile of platelets obtained from DVT patients and compare to the same matherial derived from healthy controls. PATIENTS: peripheral blood samples were collected from 3 spontaneous DVT patients and from 1 sibling and 1 neighbor for each patient in order to minimize the genetic and environmental interferences. These patients presented spontaneous and recurrent episodes of lower limbs proximal DVT and all of them mentioned a familiar history of coagulation disorders. METHODS: the platelets were washed, lysed, and the proteins were alkylated, reduced, precipitated with acetone and hydrolyzed by trypsin. 100mg of peptides were then separated by hydrophobicity using HPLC, and 8 fractions were obtained and directed to the LTQ-Orbitrap mass spectrometer. The proteins search was performed by Sorcerer-SEQUEST. RESULTS: We identified 5 proteins that were present on patients and absent in all the controls: Apolipoprotein A1 Binding-Protein, Coatomer (z1 sub-unit), Estradiol 11–17-b Dehydrogenase, Leucotriene A-4 Hydrolase and Sorbitol Dehydrogenase. Western-Blotting was performed with specific antibodies and validated the results. CONCLUSIONS: with this study it was possible to identify proteins up to date non-related to the physiopathology of DVT, that could be involved with metabolic and inflammatory processes. Disclosures: No relevant conflicts of interest to declare.

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Polymorphism of the IL13 gene may be associated with Uterine leiomyomas in Slovenian women

Balkan Journal of Medical Genetics ◽

10.1515/bjmg-2016-0036 ◽

2016 ◽

Vol 19 (2) ◽

pp. 51-60 ◽

Cited By ~ 1

Author(s):

J Krsteski ◽

S Jurgec ◽

M Pakiž ◽

I But ◽

U Potočnik

Keyword(s):

Tumor Biology ◽

Serum Levels ◽

Uterine Leiomyomas ◽

Nucleotide Polymorphisms ◽

First Sexual Intercourse ◽

Pelvic Tumors ◽

Increased Risk ◽

Pcr Rflp ◽

History Of ◽

First Time

AbstractUterine leiomyomas (ULM) are a common cause of solid pelvic tumors in women. Their etiopathogenesis remains unclear. Interleukins (ILs) and their receptors can influence tumor biology of ULM. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) exhibited in the genes IL4 (rs2070874), IL4R (rs1801275), IL12RB1 (rs11575934), IL12B (rs6887695), IL13 (rs20541) and IL23R (rs7517847) as risk factors for ULM in Slovenian women and to identify associations between corresponding clinical parameters and the analyzed SNPs. In addition, solitary and multiple ULM were compared to identify clinical and/or genetic parameters influencing their occurrence. We conducted a case-control study that included 181 women with leiomyomas and 133 control subjects. Genotyping of selected SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and high resolution melting (HRM) techniques. The TT genotype of rs20541 (IL13) was significantly associated with decreased risk of ULM compared to both the CC and CT genotypes [p = 0.018; odds ratio (OR) = 0.184; 95% confidence interval (95% CI) = 0.048-0.7121. Using genetic and clinical data to develop a predictive model with logistic regression, we found that adenomyosis, higher age at diagnosis, family history of ULM occurrence, earlier menarche, lower number of pregnancies and lower age at first sexual intercourse, the G allele and genotypes AG and GG of rs1801275 (IL4R) were associated with an increased risk of multiple ULM occurrence. We also found an association between rs20541 (IL13) and 17ß-estradiol serum levels in patients with multiple ULM (p 0.003). Our study showed, for the first time, that rs20541 (IL13) may contribute to susceptibility of ULM development and that rs1801275 (IL4R) can predispose patients to develop multiple ULM.

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General medical disorders with psychiatric implications

10.1093/med/9780199360574.003.0038_update_001 ◽

2017 ◽

Author(s):

Erik J. Garcia ◽

Warren J. Ferguson

Keyword(s):

Mental Illness ◽

Psychiatric Symptoms ◽

The United States ◽

Prior History ◽

Medical Illness ◽

Medical Conditions ◽

Presenting Symptoms ◽

Medical Disorders ◽

Increased Risk ◽

History Of

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Increased risk of venous thrombosis in persons with clinically diagnosed superficial vein thrombosis: results from the MEGA study

Blood ◽

10.1182/blood-2011-05-356071 ◽

2011 ◽

Vol 118 (15) ◽

pp. 4239-4241 ◽

Cited By ~ 28

Author(s):

Kirsten van Langevelde ◽

Willem M. Lijfering ◽

Frits R. Rosendaal ◽

Suzanne C. Cannegieter

Keyword(s):

Venous Thrombosis ◽

Factor V Leiden ◽

Population Based ◽

Factor V ◽

Superficial Vein ◽

Vein Thrombosis ◽

Increased Risk ◽

Superficial Vein Thrombosis ◽

History Of ◽

Deep Vein

Abstract Superficial vein thrombosis (SVT) is regarded a self-limiting disorder, although the authors of recent studies showed that ultrasonographically diagnosed SVT is a precursor for venous thrombosis. We aimed to determine whether the same holds true for clinically diagnosed SVT and to what extent it is associated with thrombophilia in a population-based case-control study (ie, Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). We found that a history of clinical SVT was associated with a 6.3-fold (95% confidence interval [CI] 5.0-8.0) increased risk of deep-vein thrombosis and a 3.9-fold (95% CI 3.0-5.1) increased risk of pulmonary embolism. Blood group non-O and factor V Leiden showed a small increase in SVT risk in controls, with odds ratios of 1.3 (95% CI 0.9-2.0) and 1.5 (95% CI 0.7-3.3), respectively. In conclusion, clinically diagnosed SVT was a risk factor for venous thrombosis. Given that thrombophilia was only weakly associated with SVT, it is likely that other factors (varicosis, obesity, stasis) also play a role in its etiology.

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Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0228 ◽

2017 ◽

Vol 95 (4) ◽

pp. 474-481 ◽

Cited By ~ 7

Author(s):

Rehab A. Karam ◽

Haidy E. Zidan ◽

Mohamed H. Khater

Keyword(s):

Elevated Serum ◽

Serum Levels ◽

Intercellular Adhesion Molecule ◽

Control Group ◽

Intercellular Adhesion Molecule 1 ◽

Inflammatory Parameters ◽

Increased Risk ◽

Tnf Α ◽

Ifn Γ

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

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Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China

BMC Infectious Diseases ◽

10.1186/s12879-021-05937-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sainan Chen ◽

Wenjing Gu ◽

Min Wu ◽

Chuangli Hao ◽

Canhong Zhu ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Independent Risk Factor ◽

Severe Disease ◽

Recurrent Wheezing ◽

Increased Risk ◽

Tnf Α ◽

History Of ◽

Outpatient Appointments

Abstract Background Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial. Our study was to investigate risk factors of post-bronchiolitis recurrent wheezing. Methods Infants with bronchiolitis were enrolled from November 2016 through March 2017. 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 up 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 history of 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); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P > 0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR] = 5.622; 95% confidence interval [CI], 1.3–24.9; P = 0.023). Conclusion The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of 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.

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