Tova Rainis

Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

Diagnostic yield and safety of colonoscopy in Israeli patients in an open access referral system.

Background Open access endoscopy allows reference of patients for endoscopic procedures without prior gastrointestinal consultation, allowing the procedure to be more accessible. This practice is becoming increasingly widespread in the United States and other countries and has become commonplace in clinical practice in Israel. The objective of our study is to bring forward our experience with an open access referral system for colonoscopy and to measure the yield and safety of colonoscopy in this system. Methods Between January 2001 and September 2003, 10,866 colonoscopies were performed. Patients charts were reviewed for the following data: demographics, indication for endoscopy, endoscopic and histopathologic findings, and complications. The practice guidelines of the American Society for Gastrointestinal Endoscopy were used to assess appropriateness of colonoscopy. Results 3533 pathologic findings were found, in 2978 colonoscopies. 2336 polyps were removed, including 18% hyperplastic, 26% tubular adenomata, 13% villous adenomata, 11% tubulovillous adenomata. Advanced disease was found in 41% of pathologic findings, 11% were invasive cancer. Rate of colonoscopies “generally indicated” according to American Society for Gastrointestinal Endoscopy guidelines was 78% with a rate of colonoscopies “generally not indicated” of 22%. Colonoscopy was completed successfully to the cecum in 93% of patients. 0.08% had serious complications during or immediately after colonoscopy. Conclusions Our results suggest that open access colonoscopy is a reliable and safe method for screening average risk population. As colonoscopy is becoming the recommended screening model for colorectal cancer this attitude of performing screening in an open access system could both cut costs in the future and improve availability, in an aim to become common practice.

Adenosine deaminase activity in patients with Crohn's disease: distinction between active and nonactive disease

Background Crohns disease (CD) is a common chronic inflammatory bowel disease. During the disease a cascade of immunologic events occur including mucosal influx of inflammatory cells like neutrophils. Adenosine deaminase (ADA) is important in inflammatory responses and serves as a marker of activated leukocytes. Materials and methods In this study, we investigated the activity of total ADA (tADA) and its isoenzymes, ADA1 and ADA2, in serum and neutrophils derived from 20 active patients with CD, 20 patients in remission, as well as in 15 healthy controls. Results Patients with active disease had significantly (P<0.001) higher levels of tADA in serum (22.9±4.9 U/l) than patients in remission or healthy controls (14.0±3.4 U/l and 13.2±2.4 U/l respectively). ADA2, the main isoenzyme in the serum was higher in active patients by 60% as compared with patients in remission and healthy controls (19.7±1.9 U/l, 12.3±1.2 U/l, and 12.2±0.9 U/l respectively). We did not find a significant difference in these parameters between healthy controls and stable patients. There was a positive correlation (R2=0.516) between tADA activity and C-reactive protein levels in patients with CD. Enhanced activity in tADA was also detected in neutrophils that were obtained from all patients with CD as compared with healthy controls (15.3±2.9 U/g, 14.1±2.3 U/g, and 9.4±2.9 U/g protein, respectively). This is mainly due to a significant increment (up to 51%) in ADA1 activity, the main isoenzyme in the neutrophils (84% out of the tADA). The cause of this increment remains to be elucidated. Conclusion The results obtained in this study demonstrated elevated levels of tADA and ADA2 in patients with active disease. As the patient improves and becomes clinically stable these levels decrease, approaching normal values. tADA and ADA2 can be used as markers of inflammation, and provide a supportive indicator of CD activity.

A nine-year audit of open-access upper gastrointestinal endoscopic procedures: results and experience of a single centre.

BACKGROUND The appropriateness and safety of open-access endoscopy are very important issues as its use continues to increase. OBJECTIVE To present a review of a nine-year experience with open-access upper gastrointestinal endoscopy with respect to indications, diagnostic efficacy, safety and diseases diagnosed. METHODS A retrospective, observational case series of all patients who underwent open-access endoscopy between January 2000 and December 2008 was conducted. Indications were classified as appropriate or not appropriate according to American Society of Gastrointestinal Endoscopy (ASGE) guidelines. Endoscopic diagnoses were based on widely accepted criteria. Major complication rates were assessed. RESULTS A total of 20,620 patients with a mean age of 58 years were assessed, of whom 11,589 (56.2%) were women and 9031 (43.8%) were men. Adherence to ASGE indications led to statistically significant, clinically relevant findings. The most common indications in patients older than age 45 years of age were dyspepsia (28.5%) and anemia (19.7%) in the ASGE-appropriate group, and dyspepsia in patients younger than 45 years of age without therapy trial (6.6%) in the nonappropriate group. Of the examinations, 38.57% were normal. Hiatal hernia and nonerosive gastritis were the most common findings. Important diagnoses such as malignancies and duodenal ulcers would have been missed if endoscopies were performed only according to appropriateness. There were only two major complications and no mortalities. CONCLUSIONS Open-access upper gastrointestinal endoscopy is a safe and effective system. More relevant findings were found when adhering to the ASGE guidelines. However, using these guidelines as the sole determining factor in whether to perform an endoscopy is not advisable because many clinically relevant diagnoses may be overlooked.

Acute Pancreatitis and Upper Gastrointestinal Bleeding as Presenting Symptoms of a Duodenal Brunner’s Gland Hamartoma

Brunners gland hamartomas are rare, benign small bowel tumours. There were fewer than 150 cases reported in the English literature until the end of the last century. These hamartomas may be discovered incidentally during an upper gastrointestinal tract endoscopy. Otherwise, they may be diagnosed in patients presenting with acute upper gastrointestinal bleeding, anemia or symptoms of intestinal obstruction. The case of a young woman admitted for acute upper gastrointestinal bleeding along with acute pancreatitis is presented. The investigation revealed a giant Brunners gland hamartoma in the second part of the duodenum. After total endoscopic resection of the tumour, the patient has remained completely asymptomatic for a follow-up period of seven months.

Incidental Colorectal Computed Tomography Abnormalities: Would You Send every Patient for a Colonoscopy?

BACKGROUND The clinical significance of colorectal wall thickening (CRWT) in patients undergoing abdominal computed tomography (CT) has not yet been definitively established. OBJECTIVES To compare alleged findings on abdominal CT with those of a follow-up colonoscopy. METHODS Ninety-four consecutive patients found to have large-bowel abnormalities on abdominal CT were referred for colonoscopy. Of these patients, 48 were referred for a suspected colorectal tumour and 46 for CRWT. Colonoscopy was performed and findings were compared. RESULTS Of the 48 suspected colorectal tumours, 34 were determined to be neoplastic lesions on colonoscopy. Of these, 26 were malignant and eight were benign. Colonoscopy revealed no abnormality in 30 of 46 patients with CRWT as a solitary finding, and revealed some abnormality in 16 patients (12 had diverticular disease, four had benign neoplastic lesions). CONCLUSIONS CRWT as an incidental and solitary finding on CT should not be regarded as a pathology prompting a colonoscopy. Approximately two-thirds of the patients had a normal colonoscopy and the remaining patients had benign lesions (12 had diverticular disease and four had benign neoplastic lesions). However, many of these patients seem to warrant colonoscopy regardless of CT findings, particularly patients who have a family history of colorectal cancer, have positive fecal occult blood test results or who are older than 50 years of age.

The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel Diseases (IBDs).

Background and Aims Immune semaphorins are a large family of proteins involved in the pathogenesis of inflammatory diseases through the regulation of immune homeostasis and tissue inflammation. We aim to assess the possible involvement of semaphorin3A (sema3A) and 4A (sema4A) in peripheral immune responses and bowel tissue inflammation of patients suffering from Crohn’s disease (CD) and ulcerative colitis (UC). Patients and Methods Twenty-seven CD patients and 10 UC patients were studied and compared to 10 patients followed for acute diverticulitis (disease control) and 12 healthy individuals. All were evaluated for sema3A expression on T regulatory cells (Tregs), serum levels of sema3A and sema4A, and tissue expression of sema3A and sema4A in bowel biopsies. Results The percentage (%) of T regulatory cells (Tregs) expressing sema3A in patients with active CD (64.5% ±14.49%) and active UC (49.8% ±16.45%) was significantly lower when compared to that of healthy controls (88.7% ±3.6%, p< 0.001 and p< 0.0001, respectively). This expression was seen to be in negative correlation with CD activity. Serum levels of Sema4A were significantly lower in patients with CD and UC when compared to that of controls (5.69±1.48ng\ml for CD, 5.26±1.23 ng/ml for UC patients vs 9.74±2.73ng/ml for normal controls, P<0.001). Sema4A was highly expressed in lymphocytes of the lamina propria of CD and UC patients but absent in patients with diverticulitis or in normal individuals. Conclusions Altered % of Tregs expressing sema3A in patients with inflammatory bowel diseases (IBD) is partially responsible for their failure in preventing CD4+ effector T cell induced inflammation in IBD in peripheral blood. The increased expression of sema4A in bowel biopsies from CD and UC patients is suggestive of its central role in regulating local tissue inflammation in the bowel.

Programmed Nanoparticles for Tailoring the Detection of Inflammatory Bowel Diseases and Irritable Bowel Syndrome Disease via Breathprint

Chemical sensors based on programmable molecularly modified gold nanoparticles are tailored for the detection and discrimination between the breathprint of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). The sensors are examined in both lab- and real-world clinical conditions. The results reveal a discriminative power accuracy of 81% between IBD and IBS and 75% between Crohns and Colitis states.

Primary duodenal mucosa-associated lymphoid tissue (MALT) lymphoma - A rare presentation of gastric outlet obstruction

Malignant lymphoma of mucosa-associated lymphoid tissue (MALT) can arise in a variety of anatomical sites. The majority of these tumors arise in the stomach, with fewer than 30% arising in the small intestine. Primary duodenal MALT lymphoma is a very rare neoplasm. There are very few cases of duodenal MALT lymphoma reported in the literature. This is the third published case presenting clinically as a gastric outlet obstruction. The patient was successfully treated with a combination of chemotherapy and rituximab.

Correlation between incidental FDG PET/CT colorectal observations and endoscopic and histopathological results

Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is used in the imaging workup of various malignancies. Incidental gastrointestinal observations on FDG PET/CT may be of clinical significance. The aim of the present study was to evaluate endoscopic and histopathological observations in patients referred for colonoscopy due to incidental FDG colonic uptake on a PET/CT study. Fifty-six patients with incidental colonic findings on FDG PET/CT underwent colonoscopy. Normal colonoscopies were observed in 63% of the patients. In 37% of the colonoscopies, we identified an endoscopic observation, including 67% with benign adenomatous polyps, 3% with hyperplastic polyps, 20% with advanced histological lesions and 10% with a malignancy.