Presence Of Inflammatory Markers Research Articles

Cardiovascular risk in patients with chronic obstructive pulmonary disease and metabolic syndrome

Chronic obstructive pulmonary disease is a cause of morbidity and mortality worldwide. The presence of infl ammatory markers in circulation, sputum, and broncho-alveolar fl uid suggest systemic infl ammation is one of the potential mechanisms responsible for both chronic obstructive pulmonary disease and metabolic syndrome. Circulating markers of infl ammation, on the other hand, are those that have been found to predict future cardiovascular events as well. One of the main causes of increased cardiovascular risk in patients with chronic obstructive pulmonary disease and metabolic syndrome is hyperglycemia. It induces oxidative stress and subsequently micro- and macrovascular complications. This review describes in details the various components of metabolic syndrome and its impact on long outcomes in chronic obstructive pulmonary disease and cardiovascular pathology.

The impact of inflammatory and metabolic markers on depression, anxiety, and cognition after COVID-19: A narrative review.

There has been growing concern about the long-term effects of COVID-19 on mental health. The biological factors common to psychiatric conditions and COVID-19 are not yet fully understood. We narratively reviewed prospective longitudinal studies that measured metabolic or inflammatory markers and assessed psychiatric sequalae and cognitive impairment in individuals with COVID-19 at least 3 months after the infection. A literature search identified three relevant cohort studies. Overall, depressive symptomatology and cognitive deficits persisted for up to one year after COVID-19; depression and cognitive changes were predicted by acute inflammatory markers, and changes in these markers correlated with changes in depressive symptomatology; female sex, obesity, and the presence of inflammatory markers were associated with more severe clusters of physical and mental health status in patients' self-perceived recovery; and plasma metabolic profiles of patients continued to differ from those of healthy controls three months after hospital discharge, which were associated with widespread alterations in neuroimaging, reflecting issues with white matter integrity. This is a non-systematic review and cautions should be made while interpreting the conclusions. In individuals affected by the COVID-19, prolonged exposure to stress and alterations in metabolic and inflammatory markers plays a central role in psychiatric sequalae and cognitive deficits in the long term.

Macrophage migration inhibitory factor (MIF) and IgA anti CD74 antibodies in Indian patients with enthesitis-related arthritis category of Juvenile idiopathic arthritis.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in pathogenesis of ankylosing spondylitis (AS). CD 74 is the receptor for MIF and IgA antiCD74 autoantibodies have been described from different parts of the world in patients with AS. As enthesitis-related arthritis (ERA) is a form of juvenile spondyloarthropathy, we studied the serum and synovial fluid levels of MIF in ERA and looked for the IgA antiCD74 antibodies in patients with ERA in our population. Patients with JIA (ILAR classification) were studied. Serum MIF levels were measured by ELISA in 101 patients of ERA (synovial fluid also where available) and compared to 28 patients of other categories of JIA, 25 patients each of ankylosing spondylitis and rheumatoid arthritis, and 38 healthy controls. In addition, associationof MIF with disease activity was assessed. Ig A antiCD74 antibodies were measured in sera of ERA, AS and healthy controls. Median serum MIF levels were higher in ERA [2.50 (1.20-4.85) ng/ml] than in healthy controls [0.28 (0.16-0.48); p < 0.0001] and patients with RA [1.13 (0.44-2.45); p < 0.01] MIF levels in ERA were comparable to other categories of JIA [2.63 (1.70-4.05)] and patients with AS [3.62 (0.52-6.51)]. Synovial fluid MIF levels were higher than serum levels (p < 0.01). Serum MIF level had an association with the JSpADA score (r = 0.29, p < 0.01). Serum MIF levels had no association with presence of inflammatory markers, enthesitis, inflammatory back pain or sacroiliitis. IgA AntiCD74 antibody was positive only in 3/88 (3.41%) of ERA patients and was not detected in any patients of AS or healthy controls. Patients with ERA have high MIF levels that show modest correlation with disease activity. Higher synovial fluid MIF levelssuggest that it may play a role in synovitis seen in ERA. IgA antiCD74 antibodies are rarely seen in ERA.

Presence of Magnetic Resonance Imaging-Defined Inflammation Particularly in Overweight and Obese Women Increases Risk of Radiographic Knee Osteoarthritis: The POMA Study.

The present study was undertaken to assess whether the odds for incident radiographic osteoarthritis (OA) differ between men and women in regard to body mass index (BMI) and inflammatory magnetic resonance imaging (MRI) markers 1 and 2 years prior, and whether the presence of inflammation on MRI differs between normal-weight and overweight/obese individuals who develop radiographic OA up to 4 years prior. We studied 355 knees from the Osteoarthritis Initiative study that developed incident radiographic OA and 355 matched controls. MRIs were read for effusion-synovitis and Hoffa-synovitis for up to 4 consecutive annual time points. Subjects were classified as normal-weight (BMI <25), overweight (BMI ≥25 and <30), or obese (BMI ≥30). Conditional logistic regression was used to assess odds of incident radiographic OA for effusion-synovitis and Hoffa-synovitis at 1 and 2 years prior to radiographic OA incidence (i.e., "P-1" and "P-2") considering BMI category. Bivariate logistic regression was used to assess odds of inflammation for cases only. One hundred seventy-eight (25.1%) participants were normal weight, 283 (39.9%) overweight, and 249 (35.1%) obese. At P-2, being overweight with Hoffa-synovitis, which had an odds ratio [OR] of 3.26 (95% confidence interval [95% CI] 1.39-7.65), or effusion-synovitis (OR 3.56 [95% CI 1.45-8.75]) was associated with greater odds of incident radiographic OA in women. For those with incident radiographic OA, there were no increased odds of synovitis in the overweight/obese subgroup for most time points, but increased odds for effusion-synovitis were observed at P-2 (OR 2.21 [95% CI 1.11-4.43]). Presence of inflammatory markers seems to play a role especially in overweight women, while obese women have increased odds for radiographic OA also in the absence of these markers.

Antioxidant and inflammatory biomarkers in herpes zoster.

The risk of herpes zoster (HZ) increases as cell-mediated immunity declines with age. Even though oxidative stress plays a crucial role in the development of HZ, there are few serum biomarkers of the disease's antioxidant activity. The purpose of this study is to investigate the blood levels of major antioxidants in HZ patients. To the best of our knowledge, this is the first study on this issue in the literature. The serum levels of antioxidants including uric acid (UA), total bilirubin (TBİL), albumin (ALB), vitamin D levels, and inflammatory markers such as homocysteine (Hcy) and C-reactive protein (CRP) was retrospectively analyzed in 53 patients with HZ and 53 age-and sex-matched healthy controls (HCs). The relationships between these markers and postherpetic neuralgia (PHN) and the clinical severity of HZ were also evaluated. Serum levels of UA, TBIL, and ALB in patients with HZ were significantly lower than those in the HCs (p < 0.001), while no statistical differences were found in vitamin D levels between the groups. Hcy and CRP levels were significantly increased in HZ patients compared to HCs. Significant differences were observed in the serum levels of UA, Hcy, CRP, and vitamin D in the PHN group versus the non-PHN group (p < 0.001). The presence of inflammatory markers was found to be positively related to disease activity. Furthermore, when compared to the mild or moderate clinical types of HZ, these biomarkers were statistically significant in the severe clinical type. These results suggest that uncontrolled varicella-zoster virus reactivation, acute nerve damage, and PHN may all be associated with low antioxidant levels. These biomarkers may be a protective factor for HZ, but more research is needed to clarify the underlying mechanism.

Increase of circulating inflammatory molecules in preeclampsia, an update.

Special hormonal and immunological changes are required for normal pregnancy continuation. To escape from rejection by the maternal immune system, pregnancy needs an optimum environment with the integration and the balance of immune factors. As an immunologically unique site that permits allogenic fetus to be tolerated by mother, the maternal-fetal interface has a vital role. Microorganisms may trigger innate immune responses at the maternal-fetal interface and this may have a significant impact on the success of pregnancy. While the presence of inflammatory markers are slightly increased in healthy pregnancies, their significant increase in preeclampsia suggests that the balance between the inflammatory and antiinflammatory mechanisms may be disrupted by a shift towards inflammation. Based on these immunological observations, we aimed to review the literature for the link between the inflammatory response and preeclampsia since its etiology has not yet been clarified.

P098 Worsening Colitis and Congestive Heart Failure Related to Mesalamine Use

BACKGROUND: Five-amino salicylic acid derivatives are generally well-tolerated agents commonly used to treat ulcerative colitis. Serious reactions are rare. We present a case of paradoxical worsening of ulcerative colitis and acute heart failure in a young woman on mesalamine therapy. CASE: A 37-year old white female with a history of sleeve gastrectomy and recently diagnosed mild to moderate extensive ulcerative colitis (UC) had been on oral mesalamine for 1 month. She endorsed worsening symptoms, with 10-12 watery bowel movements daily along with 3-4 episodes of hematochezia and generalized abdominal cramps. Lack of response to prednisone prompted admission. She was found to be severely dehydrated, hyponatremic with a sodium of 132 mEq/L, and anemic with a hemoglobin of 10.2 g/dL (from normal three months earlier). Albumin was decreased at 3.1 g/dL and C-reactive protein (CRP) was elevated at 4.2 mg/dL. Stool tests for Clostridioides difficile, other bacteria, and viruses, were negative. Flexible sigmoidoscopy showed Mayo 3 colitis despite 3 days of IV methylprednisolone. Her hospital course was complicated by acute heart failure presenting as leg edema and shortness of breath. Brain natruretic peptide level was elevated at 550 pg/mL. Echocardiogram revealed global hypokinesis of the left ventricle and an estimated ejection fraction of 30-35%. Given this contraindication to anti-tumor necrosis factor agents, she was started on tofacitinib 10 mg thrice daily. Surgical consultation was also obtained. After three doses her abdominal pain improved, diarrhea decreased to 5 bowel movements daily, and CRP decreased to 1.9 mg/dL. After three days, the dose was decreased to 10 mg twice daily. On clinic follow-up 3 weeks later, she was pain-free and bowel movements were back to baseline with no blood and no diarrhea. CRP and albumin normalized. Her shortness of breath and leg edema had also resolved. Multigated acquisition scan 3 months after discharge showed resolution of left ventricle wall motion abnormalities, and a normal ejection fraction of 61%. DISCUSSION: Five-amino salicylic acids (5-ASA) are relatively safe medications. Serious reactions including pancreatitis, interstitial nephritis, blood dyscrasias, pneumonitis, and Stevens Johnson syndrome, are rare. Infrequently, paradoxical worsening of colitis is seen. This phenomenon is not well understood and there is no consistency in the presence of inflammatory markers. Confirmation requires a mesalamine challenge, which is not often feasible. Acute cardiac side effects from mesalamine are extremely uncommon, potentially serious, and appear dose-independent. The exact mechanism by which it might induce myocardial inflammation and heart failure is unclear. Existing hypotheses include: a hypersensitivity reaction due to inhibition of COX enzyme and subsequent acceleration in metabolism of arachidonic acid to lipoxygenases, humoral-mediated hypersensitivity wherein antibodies against mesalamine cross-react with the myocardium, cell-mediated hypersensitivity, and immunoglobulin E-mediated allergic reaction. Symptoms usually manifest within 2-4 weeks of starting the drug. CONCLUSION: The temporal relationship between our patient’s symptom onset and initiation of mesalamine indicates a causal relationship. Mesalamine should remain on the differential of worsening UC, and acute heart failure, after evaluating for more common causes.

Acute portal vein thrombosis in noncirrhotic patients – different prognoses based on presence of inflammatory markers: a long-term multicenter retrospective analysis

Background: Portal vein thrombosis (PVT) is a partial or complete thrombotic occlusion of the portal vein and is rare in noncirrhotic patients.Patients and methods: 78 adult patients with noncirrhotic acute PVT without known malignity were evaluated. Patients with initial CRP level 61–149 mg/l were excluded.Results: Patients were divided into two groups – the first one (33 patients) was characterized with signs of inflammation and CRP over 149 mg/l. The second group (45 patients) was without signs of inflammation and CRP level less than 61 mg/l. The frequency of prothrombotic hematologic factors was statistically significantly different in levels of factor VIII and MTHFR 677 C mutation. All patients from both groups underwent the same oncologic and hemato-oncologic screening which was positive in 23 patients (51.1%) in the group without signs of inflammation. In the group of patients with clinical and laboratory signs of inflammation oncologic and hemato-oncologic screening was positive only in 1 patient (3.0%). Complete portal vein recanalization was achieved in 19.2%, partial recanalization in 26.9%.Conclusions: Patients with clinical signs of inflammation and acute PVT have a low risk of malignancy in contrast to patients without signs of inflammation and acute PVT, which have a high risk of oncologic or hemato-oncologic disease. Patients with negative hemato-oncologic screening should be carefully observed over time because we expect they are at higher risk for the development of hemato-oncologic disease, independent from the presence and number of procoagulation risk factors.

Clinical Features and Inflammatory Markers in Autoimmune Encephalitis Associated With Antibodies Against Neuronal Surface in Brazilian Patients.

Acute encephalitis is a debilitating neurological disorder associated with brain inflammation and rapidly progressive encephalopathy. Autoimmune encephalitis (AE) is increasingly recognized as one of the most frequent causes of encephalitis, however signs of inflammation are not always present at the onset which may delay the diagnosis. We retrospectively assessed patients with AE associated with antibodies against neuronal surface diagnosed in reference centers in Northeast of Brazil between 2014 to 2017. CNS inflammatory markers were defined as altered CSF (pleocytosis >5 cells/mm3) and/or any brain parenchymal MRI signal abnormality. Thirteen patients were evaluated, anti-NMDAR was the most common antibody found (10/13, 77%), followed by anti-LGI1 (2/13, 15%), and anti-AMPAR (1/13, 7%). Median time to diagnosis was 4 months (range 2–9 months). Among these 13 patients, 6 (46.1%) had inflammatory markers and when compared to those who did not present signs of inflammation, there were no significant differences regarding the age of onset, time to diagnosis and modified Rankin scale score at the last visit. Most of the patients presented partial or complete response to immunotherapy during follow-up. Our findings suggest that the presence of inflammatory markers may not correlate with clinical presentation or prognosis in patients with AE associated with antibodies against neuronal surface. Neurologists should be aware to recognize clinical features of AE and promptly request antibody testing even without evidence of inflammation in CSF or MRI studies.

Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy.

We have investigated the contributing role of monosodium urate (MSU) to the pathological processes associated with the induction of diabetic retinopathy (DR). In human postmortem retinas and vitreous from donors with DR, we have found a significant increase in MSU levels that correlated with the presence of inflammatory markers and enhanced expression of xanthine oxidase. The same elevation in MSU levels was also detected in serum and vitreous of streptozotocin-induced diabetic rats (STZ-rats) analyzed at 8 weeks of hyperglycemia. Furthermore, treatments of STZ-rats with the hypouricemic drugs allopurinol (50 mg/kg) and benzbromarone (10 mg/kg) given every other day resulted in a significant decrease of retinal and plasma levels of inflammatory cytokines and adhesion factors, a marked reduction of hyperglycemia-induced retinal leukostasis, and restoration of retinal blood-barrier function. These results were associated with effects of the hypouricemic drugs on downregulating diabetes-induced levels of oxidative stress markers as well as expression of components of the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome such as NLRP3, Toll-like receptor 4, and interleukin-1β. The outcomes of these studies support a contributing role of MSU in diabetes-induced retinal inflammation and suggest that asymptomatic hyperuricemia should be considered as a risk factor for DR induction and progression.

A risk score system to timely manage treatment in Crohn\u2019s disease: a cohort study

BackgroundClinical severity and intestinal lesions of Crohn’s disease (CD) usually progress over time and require a step up adjustment of the therapy either to prevent or to treat complications. The aim of the study was to develop a simple risk scoring system to assess in individual CD patients the risk of disease progression and the need for more intensive treatment and monitoring.MethodsProspective cohort study (January 2002–September 2014) including 160 CD patients (93 female, median age 31 years; disease behavior (B)1 25%, B2 55.6%, B3 19.4%; location (L)1 61%, L3 31.9%, L2 6%; L4 0.6%; perianal disease 28.8%) seen at 6–12-month interval. Median follow-up 7.9 years (IQR: 4.3–10.5 years). Poisson models were used to evaluate predictors, at each clinical assessment, of having the following outcomes at the subsequent clinical assessment a) use of steroids; b) start of azathioprine; c) start of anti-TNF-α drugs; d) need of surgery. For each outcome 32 variables, including demographic and clinical characteristics of patients and assessment of CD intestinal lesions and complications, were evaluated as potential predictors. The predictors included in the model were chosen by a backward selection. Risk scores were calculated taking for each predictor the integer part of the Poisson model parameter.ResultsConsidering 1464 clinical assessments 12 independent risk factors were identified, CD lesions, age at diagnosis < 40 years, stricturing behavior (B2), specific intestinal symptoms, female gender, BMI < 21, CDAI> 50, presence of inflammatory markers, no previous surgery or presence of termino-terminal anastomosis, current use of corticosteroid, no corticosteroid at first flare-up. Six of these predicted steroids use (score 0–9), three to start azathioprine (score 0–4); three to start anti-TNF-α drugs (score 0–4); six need of surgery (score 0–11). The predicted percentage risk to be treated with surgery within one year since the referral assessment varied from 1 to 28%; with azathioprine from 3 to 13%; with anti-TNF-α drugs from 2 to 15%.ConclusionsThese scores may provide a useful clinical tool for clinicians in the prognostic assessment and treatment adjustment of Crohn’s disease in any individual patient.

GDF11 Rejuvenates Cerebrovascular Structure and Function in an Animal Model of Alzheimer's Disease.

Cerebral amyloid angiopathy (CAA) is present in up to 90% of patients with Alzheimer's disease (AD), and may interact with classical neuropathology to exacerbate cognitive decline. Since growth differentiation factor 11 (GDF11) can activate vascular remodeling, we tested its effects on cognitive function and neuroinflammatory changes of AD model mice. We intravenously administered GDF11 or vehicle daily to 12-month-old transgenic mice overexpressing the amyloid-β protein precursor (AβPP)/PS1). Cognitive function was monitored using the Morris water maze, and after conclusion of the treatment, we assessed the morphology and presence of inflammatory markers in the cerebral vasculature. Subchronic treatment of adult AβPP/PS1 mice with GDF11 rescued cognitive function and ameliorated cerebrovascular function. In particular, the de novo genesis of small blood vessels and the expression of vascular-related proteins were significantly higher than in the vehicle-treated AβPP/PS1 mice, whereas the expressions of the inflammatory markers Iba-1 and GFAP significantly decreased in proportion to the lower ratio of two forms of amyloid-β (Aβ40/42). Daily intravenous treatment with GDF11-injection can rejuvenate respects of cognition and cerebrovascular changes in AD mice.

Analysis of Prognostic Factors in Malignant External Otitis.

Objectives Malignant external otitis (MEO) is a potentially fatal infection of the external auditory canal, temporal bone, and skull base. Despite treatment with modern antibiotics, MEO can lead to skull base osteomyelitis. Until now, there have been few studies on the prognostic factors of MEO.Methods We performed a retrospective study to identify prognostic factors of MEO, and a meta-analysis of other articles investigating MEO. On the basis of disease progression the 28 patients in our study were divided into ‘controlled’ and ‘uncontrolled’ groups, consisting of 12 and 16 patients, respectively. We identified three categories of prognostic factors: those related to patient, disease, and treatment. We compared these prognostic factors between the controlled and uncontrolled groups.ResultsIn our study, the duration of diabetes mellitus (DM), presence of inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), and computed tomography or magnetic resonance imaging findings influenced the prognosis of MEO. In contrast, prognosis was unrelated to age, gender, mean glucose level, hemoglobin A1c level, pathogen, comorbidity, or cranial nerve involvement. No factor related to treatment modality was correlated with prognosis, such as surgery, steroid therapy, or interval to the first appropriate treatment. Cranial nerve involvement has been proven to be associated with disease progression, but the relationship between cranial nerve involvement and the prognosis of MEO remains controversial. As a part of this study, we conducted a meta-analysis of cranial nerve involvement as a prognostic factor of MEO. We found that cranial nerve involvement has a statistically significant influence on the prognosis of MEO.Conclusion We found that glycemic control in diabetes mellitus, cranial nerve involvement, and the extent of disease determined from various imaging modalities influence the prognosis of MEO. We suggest that significant prognostic factors should be monitored to determine the prognosis of patients with MEO.

In vivo monitoring of lung inflammation in CFTR-deficient mice

BackgroundExperimentally, lung inflammation in laboratory animals is usually detected by the presence of inflammatory markers, such as immune cells and cytokines, in the bronchoalveolar lavage fluid (BALF) of sacrificed animals. This method, although extensively used, is time, money and animal life consuming, especially when applied to genetically modified animals. Thus a new and more convenient approach, based on in vivo imaging analysis, has been set up to evaluate the inflammatory response in the lung of CFTR-deficient (CF) mice, a murine model of cystic fibrosis.MethodsWild type (WT) and CF mice were stimulated with P. aeruginosa LPS, TNF-alpha and culture supernatant derived from P. aeruginosa (strain VR1). Lung inflammation was detected by measuring bioluminescence in vivo in mice transiently transgenized with a luciferase reporter gene under the control of a bovine IL-8 gene promoter.ResultsDifferences in bioluminescence (BLI) signal were revealed by comparing the two types of mice after intratracheal challenge with pro-inflammatory stimuli. BLI increased at 4 h after stimulation with TNF-alpha and at 24 h after administration of LPS and VR1 supernatant in CF mice with respect to untreated animals. The BLI signal was significantly more intense and lasted for longer times in CF animals when compared to WT mice. Analysis of BALF markers: leukocytes, cytokines and histology revealed no significant differences between CF and WT mice.ConclusionsIn vivo gene delivery technology and non-invasive bioluminescent imaging has been successfully adapted to CFTR-deficient mice. Activation of bIL-8 transgene promoter can be monitored by non-invasive BLI imaging in the lung of the same animal and compared longitudinally in both CF or WT mice, after challenge with pro-inflammatory stimuli. The combination of these technologies and the use of CF mice offer the unique opportunity of evaluating the impact of therapies aimed to control inflammation in a CF background.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0976-8) contains supplementary material, which is available to authorized users.

Left ventricular diastolic dysfunction in patients with chronic obstructive pulmonary disease (COPD), prevalence and association with disease severity: Using tissue Doppler study

BackgroundChronic obstructive pulmonary disease (COPD) is a common preventable and treatable disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. It has some significant extra pulmonary effects that may contribute to its severity in individual patient. Among COPD patients, cardiovascular diseases (CVD) are responsible for approximately 50% of all hospitalizations and 20% of all deaths. Left ventricular diastolic dysfunction (LVDD) is a frequent condition in COPD patients. Inflammation is considered to be one of the systemic manifestations of COPD and provides an alternative hypothesis to explain the relationship between airflow limitation and cardiovascular risk. The present study aimed to assess the prevalence of LV diastolic dysfunction in COPD patients and its relation to the disease severity and presence of inflammatory markers. Patient and methodsForty nine (49) COPD patients were included in this study. All patients were subjected to full medical history, physical examination, chest roentgenogram, spirometry, laboratory blood testing for inflammatory mediators (C-reactive protein, matrix metalloproteinase-9 and tissue inhibitor metalloproteinase-1) and Echo Doppler study (conventional and tissue Doppler analysis). ResultsThe results showed that 36 COPD patients had LVDD (73.3%). There was a good correlation between LVDD parameters and COPD severity across GOLD stages and inflammatory markers. MMP-9 was statistically high in COPD patient with increasing severity with a p-value<0.0001. Also LVDD parameters were correlated with MMP-9 (p-value<0.00001). Other inflammatory markers were also correlated to the degree of airway obstruction (FEV1) and presence of LVDD. ConclusionThere is a high prevalence of LVDD in COPD patients which is associated with increased disease severity and associated with high levels of inflammatory markers (serum MMP-9 and TIMP-1). It is important to exclude decompensated heart failure during COPD exacerbation.

Abstract W MP46: Novel In Vivo Assessment of Unruptured Intracranial Aneurysm Inflammatory Factors: Prospective Analysis of Intra-Aneurysmal Serum Inflammatory Markers in a University Hospital

Background: There are known correlations between intracranial aneurysm size as well as underlying demographic risk factors that lead to aneurysm rupture. The treatment of unruptured aneurysms is predicated on this, however selecting which unruptured aneurysms should be treated can be difficult. It is thought that formation, growth and eventual rupture of aneurysms is due to an underlying inflammatory process, which has been shown in pathological studies to exist within aneurysmal walls. The inflammatory milieu within a live aneurysmal sac and its implications for aneurysmal rupture is not currently known. Objective: To determine the presence of inflammatory markers within unruptured aneurysm sacs. Methods: We analyzed prospectively collected data from a database of patients who presented for unruptured aneurysm coil embolization over the span of 25 months to a University Hospital. These patients had blood samples withdrawn from the aneurysm sac immediately prior to coil embolization. This blood was sent for testing, with controls provided by blood sampled from the aneurysm parent vessel. Complement C3 and C4 levels from the aneurysm and parent vessel were then compared using column tables with paired t-test analysis. Results: A total of 8 patients were enrolled. The mean age (± SD) of treated patients was 68 (±15.3) years and 7 (87.5%) were women. 5 aneurysms (62.5%) were in the anterior circulation. Aneurysm size ranged from 5mm to 14mm, mean size 8.9mm (± 3.1mm). 5 patients (62.5%) were white while 7 patients (87.5%) had history of hypertension. C3 and C4 analysis showed a consistent decrease of complement values within the aneurysm as compared to the parent vessel. (For C3, mean of differences [MD] was 9.375, 95% confidence interval [CI] 5.56-13.19. For C4, MD was 1.500, 95% CI 0.50-2.50.) Conclusion: There is an observed decrease in complement values within unruptured aneurysms, suggestive of ongoing classic complement pathway activation. This supports the aneurysm inflammation model, which shows complement deposition in aneurysm walls. Our data suggests that this process is ongoing in live unruptured aneurysms and could be possibly targeted in future aneurysm trials. Further investigation is needed.

Predictors of recurrence following an initial episode of transverse myelitis.

Objective:This study sought to identify factors that increased the risk of recurrence after an initial transverse myelitis (TM) presentation.Methods:Retrospective cohort study of 192 patients initially presenting with TM of unknown etiology. Patients diagnosed with multiple sclerosis during the first myelitis episode were excluded. Demographic and laboratory data were analyzed for associations with recurrence.Results:One hundred ten of 192 patients (57%) eventually developed recurrent symptoms: 69 (63%) neuromyelitis optica (NMO) or NMO spectrum disorder, 34 (31%) non-NMO recurrent TM, and 7 (6%) systemic autoimmune disease. Multiple independent risk factors for recurrence were identified: African American race (risk ratio 1.60, p < 0.001, 95% confidence interval 1.26–2.03; similarly noted hereafter), female sex (1.88, p = 0.007, 1.19–2.98), longitudinally extensive myelitis at onset (1.34, p = 0.036, 1.01–1.78), Sjogren syndrome antigen A (1.89, p = 0.003, 1.44–2.48), vitamin D insufficiency (4.00, p < 0.001, 1.60–10.0), antinuclear antibody titer ≥1:160 (1.69, p = 0.006, 1.23–2.32), and the presence of inflammatory markers (e.g., immunoglobulin G index) in the CSF (2.14, p < 0.001, 1.44–3.17).Conclusions:Sex, race, and serologic biomarkers warrant consideration when assessing risk of TM recurrence. Male sex and Caucasian American race were independently associated with risk of monophasic idiopathic TM. Recurrence risk in female and African American patients appears driven by a greater likelihood of developing NMO or NMO spectrum disorder.

Chronic obstructive pulmonary disease and the metabolic syndrome: Consequences of a dual threat.

The metabolic syndrome is found to be more frequent in chronic obstructive pulmonary disease (COPD). The presence of inflammatory markers in circulation, sputum, and broncho-alveolar fluid suggest systemic inflammation is one of the potential mechanisms responsible for both COPD and metabolic syndrome. Physical inactivity, skeletal muscle dysfunction, hypogonadism, and steroid use are also important causes of the metabolic syndrome in COPD. Obesity and insulin resistance is found to be more common in mild to moderate stages (I and II) of COPD. Patients with COPD and the metabolic syndrome have increase risk of morbidity and mortality due to cardiovascular disease. This review describes in details the various components of metabolic syndrome and its impact on long outcomes in COPD patients.

Gremlin-1 Identifies Fibrosis and Predicts Adverse Outcome in Patients With Heart Failure Undergoing Endomyocardial Biopsy

BackgroundGremlin-1 (Grem1), an antagonist of bone morphogenetic proteins, is involved in fibrotic tissue formation in kidney and lung. The impact of myocardial Grem1 expression is unknown. We investigated the prognostic value of Grem1 expression in 214 consecutive patients with nonischemic heart failure (HF) undergoing endomyocardial biopsy. MethodsIn all patients, the following risk factors were assessed: Grem1 expression (semiquantitative score scheme ranging from 1 to 4), presence of inflammatory markers, detection of viral genome, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association functional class (NYHA), troponin I, and B-type natriuretic peptide. Degree of myocardial fibrosis was defined as an index. Study end point was a combination of all-cause death and HF-related rehospitalization within 3 years of follow-up. ResultsGrem1 expression significantly correlated with the degree of myocardial fibrosis (correlation coefficient r = 0.619; P < .0001). Patients with the highest Grem1 expression (score 4) showed the most severely impaired LVEF and highest LVEDD (P < .0001 and P = .030, respectively, for comparison of semiquantitative scores). During follow-up, 33 patients (15.4%) reached the study end point. Grem1 expression and NYHA ≥II were independent predictors of the end point (Grem1: hazard ratio [HR] 7.5, 95% confidence interval [CI] 1.8–32.2; P = .006; NYHA ≥II: HR 2.0, 95% CI 1.0–4.1; P = .048). ConclusionsGrem1 correlates with the degree of myocardial fibrosis and left ventricular dysfunction and is an independent predictor of adverse outcome in patients with nonischemic HF.

Use and Misuse of Small Bowel Video Capsule Endoscopy in Clinical Practice

Video capsule endoscopy (VCE) was introduced into the United States in 2000 and has significantly advanced the ability to visualize the small intestinal mucosa by using noninvasive technology. Compared with traditional imaging with small bowel barium imaging, the use of VCE has demonstrated the ability to enhance diagnostic yield in patients with suspected small bowel pathology by approximately 25%‐50% in patients with suspected small bowel disorders. 1‐3 Although the use of VCE has been recommended as the next step in patients with obscure gastrointestinal hemorrhage after a negative upper and/or lower endoscopic examination, 4 its use in other clinical scenarios such as small bowel inflammatory disorders may not be associated with similar diagnostic yields. The major complication associated with the use of VCE remains small bowel retention. Although the risk of this event is virtually nil in patients with obscure bleeding, it can approach 10% in patients with known inflammatory bowel disease (IBD). 5 A critical appraisement of appropriate use of this technology may help physicians and third-party payers to determine which subset of patients with suspected or known small bowel disorders would benefit the most from undergoing a VCE procedure. To critically examine the use of VCE in clinical practice, an evidence-based approach was performed by using the GRADE system, 6,7 and a critical review of the literature on capsule endoscopy was performed by using PubMed, SCOPUS, and the Cochrane Database from 2000‐2012. The quality of evidence could range from high (implying that further research was unlikely to change the authors’ confidence in the estimate of the effect) to moderate (further research would be likely to have an impact on the confidence in the estimate of effect) or low (further research would be expected to have an important impact on the confidence in the estimate of the effect and would be likely to change the estimate). The strength of a recommendation was graded as strong when the desirable effects of an intervention clearly outweigh the undesirable effects and as conditional when there was uncertainty about the tradeoffs. The evidence-based statements generated from this review are shown in Table 1. Studies including more than 20 patients were included for each topic to increase data quality when metaanalyses or randomized controlled trials were not available.