Ariella Bar-Gil Shitrit

An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome

D-dimer, a degradation product of fibrin, is being increasingly used as a marker and prognostic factor in various thrombotic diseases. Previous reports have shown that obstructive sleep apnea is associated with platelet activation and hypercoagulability. The aim of the study was to assess the potential role of the plasma D-dimer test in patients with obstructive sleep apnea. We designed a prospective group comparison study in a tertiary-care, university-affiliated medical center. One hundred and three patients of mean age 57 years (range 50-76 years) with symptoms suggestive of obstructive sleep apnea were included. Polysomnography was performed in all cases, and blood was collected for plasma D-dimer measurement by MiniQuant turbidmetric assay. The demographic and polysomnograph data were compared between patients with normal and high (> 250 ng/ml) D-dimer levels. The group with higher D-dimer values had lower mean minimal oxygen saturation (72.1 +/- 16.4 vs. 81.7 +/- 11.6%, p = 0.008) and a longer mean period of oxygen saturation below 90% (84.1 +/- 86.2 vs. 38.5 +/- 70.8 minutes, p = 0.032). There was no correlation of respiratory disturbance index and sleep architecture with D-dimer values. We concluded that sleep apnea syndrome is associated with fibrinolytic activity. Oxygen desaturation seems to be one of the mediatory factors in the putative connection between obstructive sleep apnea and hypercoagulability state.

Comparison of a new PillCam™ SB2 video capsule versus the standard PillCam™ SB for detection of small bowel disease

Yoav C Metzger1 Samuel N Adler2 Ariella Bar-Gil Shitrit3 Binyamin Koslowsky4 Ingvar Bjarnason5 1School of Medicine, Hebrew University of Jerusalem, Israel; 2Department of Gastroenterology, Bikur Holim Hospital, Jerusalem, Israel; 3Department of Gastroenterology, Shaare Zedek Medical Center, Jerusalem, Israel; 4Department of Medicine, Hadassah Medical Organization, Jerusalem, Israel; 5Department of Gastroenterology, King’s College Hospital, London, UK

From airway inflammation to inflammatory bowel disease: eotaxin-1, a key regulator of intestinal inflammation.

Eotaxin-1 (CCL-11) is a potent eosinophil chemoattractant that is considered a major contributor to tissue eosinophilia. Elevated eotaxin-1 levels have been described in various pathologic conditions, ranging from airway inflammation, to Hodgkin lymphoma, obesity and coronary artery disease. The main receptor for eotaxin-1 is CCR3; however, recent evidence indicates that eotaxin-1 may also bind to other receptors expressed by various cell types, suggesting a more widespread regulatory role for eotaxin-1 beyond the recruitment of eosinophils. Eotaxin-1 is also strongly associated with various gastrointestinal (GI) disorders. Although the etiology of inflammatory bowel disease (IBD) is still unknown, eotaxin-1 may play a key role in the development of mucosal inflammation. In this review, we summarize the biological context and effects of eotaxin-1, as well as its potential role as a therapeutic target, with a special focus on gastrointestinal inflammation.

Maternal inflammatory bowel disease has short and long-term effects on the health of their offspring: A multicenter study in Israel

BACKGROUND There are concerns about the effect of inflammatory bowel diseases (IBD) on fertility, pregnancy and pregnancy outcomes, but no long-term data on the health of offspring born to IBD mothers. The aims were to assess the short- and long-term effects of maternal IBD on the morbidity and development of their offspring. METHODS Female IBD patients and controls completed questionnaires on their pregnancy outcome, and their offsprings short- and long-term health and development. RESULTS IBD and control mothers (159 and 175, respectively) were recruited. Medical data of 412 IBD and 417 control offspring were recorded. IBD mothers had significantly more singleton pregnancies, their offsprings birth weight was significantly lower, and they breastfed significantly less compared to controls (P=0.028, 0.007, and <0.0001, respectively). There were significantly more congenital anomalies (mainly limb deformities) among the IBD offspring (P<0.035). Offspring born post-maternal IBD diagnosis, compared to pre-diagnosis, tended to have more neurodevelopmental problems (e.g., gross motor delay, P=0.03). IBD was significantly more prevalent in the offspring of IBD mothers, while allergies and atopic dermatitis were more frequent in offspring of control mothers. More offspring of IBD mothers taking medications during pregnancy were born preterm and had lower birth weights compared to offspring of IBD mothers not taking medications during pregnancy. Children of mothers taking steroids had the lowest birth weights, compared to those of IBD mothers taking 5ASAs or immunomodulators. CONCLUSIONS Maternal IBD affects pregnancy and the offsprings immediate and long-term morbidity, specifically, congenital anomalies and neurodevelopmental problems.

Prognostic value of a new quantitative D-dimer test in critically ill patients 24 and 48 h following admission to the intensive care unit.

A D-dimer assay may predict mortality in medical critically ill patients, although no consensus on the clinical utility of this diagnostic test has been reached. A prospective single-center study was designed to evaluate whether D-dimer levels, as measured by a new, rapid assay, correlate with poor outcome in critically ill patients. A total of 95 blood samples were collected from medical and surgical adult patients 24 and 48 h following admission to the intensive care unit (ICU). D-dimer was assayed by the Miniquant quantitative test and correlated to the ICU length of stay, the hospital length of stay, the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Simplified Acute Physiology Score (SAPS) 24 and 48 h following admission to the ICU, organ system failure index and hospital mortality. The 24-h D-dimer level correlated with the 48 h APACHE II and SAPS scores (r = 0.41, P = 0.01; and r = 0.39, P = 0.01, respectively). The 48-h D-dimer level correlated with the APACHE II and SAPS scores at 48 h and with the organ system failure index (number of organ failure) (r = 0.54, P = 0.0008; r = 0.60, P = 0.0001; and r = 0.37, P = 0.02, respectively). Neither the 24-h nor the 48-h D-dimer levels were predictive of in-hospital mortality in a multivariate model. We conclude that this simple and new laboratory test may serve as an additional tool to predict the clinical severity of patients admitted to the ICU.

Role of Soluble Interleukin-2 Receptor Levels in Patients with Latent Tuberculosis

Serum soluble interleukin-2 receptor (sIL-2R) serves as a marker of disease activity in patients with tuberculosis (TB). However, little is known about its role in latent TB. The aim of this study was to assess the levels of sIL-2R in patients with latent TB and correlate them with the purified protein derivate (PPD) test results. Patients with a diagnosis of latent TB were divided into three subgroups by induration size: <10 mm, 10–20 mm, >20 mm. Blood was collected for sIL-2R assay. Findings were compared to a healthy control group. The study group consisted of 44 patients (68% male) of mean ( ± SD) age 20 ± 10 years, and the control group consisted of 41 subjects (42% male) aged 31 ± 11 years. Comparison of the two groups yielded a significantly higher serum sIL-2R level in the patients (450 ± 224 U/ml vs. 374 ± 30 U/ml, p = 0.03). Mean sIL-2R levels were significantly correlated with the presence of latent TB (p = 0.03), and with purified protein derivative (PPD) subgroups: 387 ± 177 U/ml for induration size <10 mm, NS; 450 ± 238 U/ml for 10–20 mm, p = 0.04, and 605 ± 235 U/ml for >20 mm, p < 0.0001. sIL-2R assay may serve as an additional tool to estimate the extent of the immune response in patients with latent TB.

Pregnancy and the Immune System: General Overview and the Gastroenterological Perspective.

Pregnancy represents a unique immune tolerant condition that cannot be attributed merely to generalized immunosuppression. A variety of mechanisms have been described, ranging from the non-self recognition, immunomodulation of specific inflammatory cell populations and a Th2-directed shift of the immune response, which are mediated by both localized and systemic mediators. Furthermore, an inflammatory response directed toward the conceptus is no longer considered an obligatory deleterious response; instead, it is considered an important factor that is necessary for normal growth and development. These immunomodulatory changes during pregnancy may also affect concurrent conditions and alter the course of inflammatory diseases. Herein, we review the main immunomodulatory changes that occur during pregnancy and their effect on coexisting inflammatory conditions, with a specific focus on gastrointestinal disorders.

Gastrointestinal Involvement of Posttransplant Lymphoproliferative Disorder in Lung Transplant Recipients: Report of a Case

PURPOSELymphoproliferative disorder is a well-recognized complication of lung transplantation. Risk factors include Epstein-Barr virus infection and immuno-suppression. The gastrointestinal manifestations of posttransplant lymphoproliferative disorder in lung transplant recipients have not been fully characterized.METHODSCase presentation and 16 previously reported cases of posttransplant lymphoproliferative disorder with gastrointestinal involvement are reviewed.RESULTSPatient ages ranged from 25 to 65 (median, 52) years. Median time from lung transplantation to onset of posttransplant lymphoproliferative disorder was 36 (range, 1–109) months; 35 percent of cases (6/17) occurred within 18 months; Eighty-eight percent of patients (15/17) had positive Epstein-Barr virus serology before transplantation. In five patients (29 percent), the posttransplant lymphoproliferative disorder also involved sites other than the gastrointestinal tract. The most common gastrointestinal site of posttransplant lymphoproliferative disorder was the colon, followed by the small intestine and stomach. Clinical features included abdominal pain, nausea, and bloody diarrhea. Diagnosis was based on typical pathologic changes on gastrointestinal tract biopsy obtained mainly by colonoscopy. Treatment included a reduction in the immunosuppressive regimen in 15 of 17 cases (88 percent) and surgical resection in 10 (59 percent). One patient was untreated. Seven of 16 patients (44 percent) responded to treatment and 9 patients died. Median time from onset of posttransplant lymphoproliferative disorder to death was 70 (range, 10–85) days.CONCLUSIONSPosttransplant lymphoproliferative disorder with gastrointestinal involvement is a unique entity that should be considered in all Epstein-Barr-Virus-positive lung transplant recipients who present with abdominal symptoms. Although immunosuppressive modulation and resection can lead to remission, the risk of death is 50 percent.

Cogan’s Syndrome in Patients With Inflammatory Bowel Disease – A Case Series

BACKGROUND Cogans syndrome (CSy) is a very rare autoimmune disorder, mainly affecting the inner ear and the eye, and is associated with inflammatory bowel disease (IBD). METHODS This was a European Crohns and Colitis Organisation (ECCO) retrospective observational study, performed as part of the CONFER project. A call to all ECCO members was made to report concomitant CSy and inflammatory bowel disease (IBD) cases. Clinical data were recorded in a standardized questionnaire. RESULTS This international case series reports on 22 concomitant CSy-IBD cases from 14 large medical centres. Mean duration of IBD until diagnosis of CSy was 8.7 years (range 0.0-38.0) and mean age at CSy diagnosis was 44.6 years (range 9.0-67.0). Six patients had underlying ulcerative colitis (UC) and 16 had Crohns disease. Eleven patients (50%) had active disease at CSy diagnosis. Sixteen patients were under IBD treatment at the time of CSy diagnosis, of whom 6 (37.5%) were on anti-tumour necrosis factor (TNF). Seven out of 10 patients, who were treated for CSy with immunomodulators (mostly with corticosteroids), demonstrated at least partial response. CONCLUSION This is the largest CSy-IBD case series so far. Although CSy is considered to be an autoimmune disease and is associated with IBD, immunomodulatory IBD maintenance treatment and even anti-TNF therapy do not seem to prevent disease onset. Moreover, IBD disease activity does not seem to trigger CSy. However, vigilance may prompt early diagnosis and directed intervention with corticosteroids at inception may potentially hinder audiovestibular deterioration. Finally, vigilance and awareness may also offer a better setting to study the pathophysiological mechanisms of this rare but debilitating phenomenon.

The role of enzyme-linked immunosorbent assay D-dimer in patients with acute coronary syndrome presenting with normal cardiac enzymes.

Plasma D-dimer levels, the primary degradation product of cross-linked fibrin, are elevated in acute coronary syndrome (ACS). However, the role of D-dimer in patients presenting to the Emergency Department with ACS and normal cardiac enzymes is unknown. We conducted a prospective, observational study in the Emergency Department of a major tertiary university-affiliated center. The study included 124 patients presented to the Emergency Department with ACS and normal cardiac enzymes. Blood samples were collected and assayed for D-dimer levels with the enzyme-linked immunosorbent assay (ELISA) test. The D-dimer values were correlated with the clinical, laboratory and electrocardiographic findings on admission, as well as with the catheterization findings and with hospital length of stay. ELISA D-dimer levels positively correlated with sex, hypertension and smoking (r = −0.27, P = 0.002; r = 0.33, P = 0.0002; and r = −0.24, P = 0.007, respectively). Significant correlation was also observed between ELISA D-dimer and cardiac medications including β-blocker (r = 0.22, P = 0.01), aspirin (r = 0.18, P = 0.04), nitrate (r = 0.20, P = 0.002), acute phase reactants fibrinogen (r = 0.45, P = 0.0001) and C-reactive protein (r = 0.29, P = 0.004), ischemic electrocardiographic changes (r = 0.21, P = 0.02) and length of stay (r = 0.29, P = 0.001). The catheterization findings were also correlated with the ELISA D-dimer levels (r = 0.31, P = 0.02). The ELISA D-dimer test may add important clinical data concerning patients with ACS and normal cardiac enzymes.