Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The POETIC Study.

OBJECTIVES: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. METHODS: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. RESULTS: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively). CONCLUSIONS: When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

Helicobacter pylori prevalence and clinical significance in patients with quiescent Crohn's disease.

BACKGROUND: Helicobacter pylori (HP) infection is present in about 50% of the global population, and is associated with chronic gastritis, peptic disease and gastric malignancies. HP prevalence in Crohn's disease (CD) patients was shown to be low compared to the general population, and its influence on disease activity is yet to be determined. Our aims were to determine the prevalence of HP in a selected group of CD patients with quiescent disease, and to assess the influence of its eradication on disease activity and endoscopic and laboratory activity measures. METHODS: Consecutive CD patients with quiescent disease underwent meticulous disease evaluation with MR enterography (MRE), video capsule endoscopy (VCE), CRP, fecal calprotectin and CDAI. All patients were tested for the presence of HP using stool antigen detection kit. Patients infected with HP were offered eradication treatment with sequential therapy. HP eradication was confirmed using urease breath test and stool antigen test. The influence of HP eradication on disease activity was assessed. RESULTS: Out of 56 patients enrolled, six patients (10.7%) had HP infection. Of them, five patients had gastro- duodenitis per VCE. All HP positive patients were offered eradication treatment and underwent successful eradication. Notably, 23 (50%) of patients had proximal disease per VCE, most of them (78%) were HP negative. CDAI, CRP, fecal calprotectin and VCE Lewis inflammatory score did not change significantly following HP eradication, Gastric findings on VCE were not impacted by HP eradication. CONCLUSIONS: The prevalence of HP infection in patients with quiescent CD is relatively low. Eradication of the bacteria did not significantly change neither disease activity measures nor the presence of gastro- duodenitis per VCE, suggesting it might be part of proximal CD. The influence of HP on CD activity merits further investigation.

Rarity of adenomatous polyps in ulcerative colitis and its implications for colonic carcinogenesis.

BACKGROUND AND STUDY AIMS: Despite ample research on the dysplasia to carcinoma risk in ulcerative colitis, there are scant data on the prevalence of adenomatous polyps in this population. METHODS: The number and histology of all polyps detected at colonoscopies of ulcerative colitis patients aged > 50 during 2006 - 2012 were compared with similarly aged controls undergoing screening colonoscopy. RESULTS: There were 206 patients with ulcerative colitis and 624 controls included in the study (mean age 61.7 ±â€Š8.7 vs. 60.8 ±â€Š6.1, respectively; P = 0.15). Adenomatous polyps were detected in only 13/206 colonoscopies for ulcerative colitis compared with 162 /624 controls (6.3 % vs. 25.9 %, respectively; odds ratio [OR] 0.19, 95 % confidence interval [CI] 0.1 - 0.34; P < 0.0001). When also considering all prior colonoscopies performed over 7.7 ±â€Š4.6 years of follow-up (mean 4.1 ±â€Š2.9 colonoscopies/patient, range 1 - 15, total 832 colonoscopies), the risk of ever finding an adenoma in ulcerative colitis patients was still significantly lower compared with controls (14.1 % vs. 25.9 %, respectively; OR 0.47, 95 %CI 0.3 - 0.72; P = 0.0005). On multivariable analysis, adenomas were positively associated with advanced age (OR 1.07/year, 95 %CI 1.03 - 1.1; P < 0.0001) and with increasing body mass index (BMI; OR 1.06/kg/m(2), 95 %CI 1.01 - 1.1; P = 0.01) and negatively associated with having ulcerative colitis (OR 0.15, 95 %CI 0.09 - 0.44; P = 0.0005). Among 115 Crohn's disease patients aged > 50 years, the rate of ever-adenomas in small-bowel Crohn's disease was similar to the controls (P = 0.8) and not influenced by 5-aminosalicylic acid use, whereas patients with colonic Crohn's disease had a significantly lower rate of adenomas compared with the controls (3.9 % vs. 25.9 %; P = 0.002). CONCLUSION: Unlike patients with small-bowel Crohn's disease, patients with ulcerative colitis or with colonic Crohn's disease seldom develop sporadic adenomatous polyps. These data may provide novel clues to a possible role for colonic immune activation in restricting the adenoma to carcinoma sequence while propagating the dysplasia to carcinoma pathway.

Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial.

BACKGROUND & AIMS: The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC. METHODS: We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy. Patients were randomly assigned to groups who were given curcumin capsules (3 g/day, n = 26) or an identical placebo (n = 24) for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (SCCAI ≤2) at week 4. Clinical and endoscopic responses were also recorded. RESULTS: In the intention-to-treat analysis, 14 patients (53.8%) receiving curcumin achieved clinical remission at week 4, compared with none of the patients receiving placebo (P = .01; odds ratio [OR], 42; 95% confidence interval [CI], 2.3-760). Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. 3 patients (12.5%) in the placebo group (P < .001; OR, 13.2; 95% CI, 3.1-56.6). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with none of 16 patients evaluated in the placebo group (P = .043; OR, 20.7; 95% CI, 1.1-393). Adverse events were rare and comparable between the 2 groups. CONCLUSIONS: Addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects. Curcumin may be a safe and promising agent for treatment of UC. Clinicaltrials.gov number: NCT01320436.

Acute diverticulitis: a decade of prospective follow-up.

BACKGROUND: Acute diverticulitis (AD) is the most common complication of diverticular disease and affects 10% to 25% of patients. Data regarding the natural history of AD are lacking. GOALS: Our aim was to prospectively assess the occurrence of recurrent attacks, surgeries, and accompanying symptoms in patients who were hospitalized with AD. STUDY: All patients hospitalized with first episode of AD between January 2000 and November 2006 were enrolled. Patients were followed up both during hospitalization and after discharge. Data regarding operations and complications were collected. Special attention was paid to patients younger than 45 years of age and compared with older patients. RESULTS: A total of 261 patients were identified-of them 103 were men. Thirty patients (11.5%) were 45 years old or younger. The mean follow-up period was 88±22 months (range, 52 to 184 mo). Younger patients experienced significantly more complications during hospitalization (37% vs. 12.5%, P=0.001) and underwent more often a sigmoidectomy in the follow-up period (42.3% vs. 18.3%, P=0.01). Older patients tended to be more often asymptomatic after discharge (P=0.053). The average time from index hospitalization to the sigmoidectomy was 18.17±23.35 months (range, 1 to 120 mo). The odds ratio for sigmoidectomy after complicated AD is 16.2 (95% confidence interval, 13.4 to 19.6). Age did not affect the risk for surgery. CONCLUSIONS: Younger patients with AD experience more complications during hospitalization and undergo surgery after discharge more frequently. Complicated AD at index hospitalization is a risk factor for sigmoidectomy. Our data can help predict the outcome of patients suffering from AD and enable tailoring an individual treatment.

Severe and morbid obesity in Crohn's disease patients: prevalence and disease associations.

BACKGROUND: Crohn's disease (CD) is frequently associated with weight loss and malnutrition. However, as the prevalence of obesity increases worldwide, it may become a clinical problem even in CD. AIM: To assess the prevalence of severe/morbid obesity in CD patients and to compare their disease characteristics to nonobese CD patients. METHODS: A retrospective analysis of a computerized CD patient database was performed to identify severely/morbidly obese patients (BMI >35). Prevalence was compared to data of the general population. Severely/morbidly obese CD patients were then compared to randomly selected nonobese CD patients (BMI <30) in a 1:3 ratio. RESULTS: Thirteen severely/morbidly obese patients out of 560 CD patients were found (2.3%), which is significantly lower than the prevalence in the general population (5.6%, p = 0.001). When compared to 39 nonobese CD patients, colonic disease was significantly more common among severely/morbidly obese CD patients (odds ratio: 6, 95% CI: 1.35-26.3, p = 0.02), while there was no difference in other disease parameters. Interestingly, 4 morbidly obese CD patients had undergone laparoscopic sleeve gastrectomy for treatment of morbid obesity with a favorable surgical course. CONCLUSION: CD in severely/morbidly obese patients is more often colonic, but otherwise no different than CD in nonobese patients. Sleeve gastrectomy is a viable therapeutic option for morbidly obese CD patients.

Prevalence and predictive factors for gastrointestinal pathology in young men evaluated for iron deficiency anemia.

BACKGROUND: The prevalence of gastrointestinal lesions in young men with iron deficiency anemia (IDA) is unknown, and there are no evidence-based recommendations for the evaluation of the gastrointestinal tract in this population. AIMS: The purpose of this study was to assess the prevalence of significant GI lesions among young males with IDA, and to shed light on potential predictors of their presence. METHODS: Clinical, endoscopic, and histological data was retrospectively collected from medical records of 347 young males with IDA. RESULTS: Clinically significant GI lesions were diagnosed in 62 %. Upper GI lesions were found in 35 %. Peptic disease was the most common finding, diagnosed in 30 %. Celiac disease was diagnosed in 4 %. Lower GI tract lesions were diagnosed in 34 %. The most common findings were hemorrhoids (17 %) and inflammatory bowel disease (16 %). Malignant lesions were not detected. GI lesions were encountered more frequently when respective symptoms were obtained. Multivariate analysis showed that the presence of GI symptoms and the use of proton pump inhibitors were associated with an increased likelihood of significant GI lesions. CONCLUSIONS: GI lesions are common among young men with IDA. GI evaluation is mandatory in symptomatic men and in asymptomatic men when the anemia is resistant to iron therapy. Symptoms may dictate the order of evaluation.

Utility of early colonoscopy for acute lower gastrointestinal bleeding: a retrospective cohort study.

Background: Early colonoscopy (within 8-24 h) is recommended in different guidelines for acute lower gastrointestinal bleeding (LGIB). Despite this recommendation, evidence for its effectiveness are conflicting, and early colonoscopy is often not performed. Objectives: We aimed to evaluate the utility of early colonoscopy by examining the findings during the procedure, and by comparing in-hospital and long-term outcomes between patients who did and did not undergo early colonoscopy. Design: This is a retrospective cohort study based on the electronic medical records of a large tertiary hospital in Israel. Methods: All patients hospitalized with acute LGIB to acute wards between 2012 and 2022 were included. First, structured and free-text procedure notes from patients who did undergo early colonoscopy were examined. Second, we compared in-hospital and long-term outcomes between patients who did and did not undergo early colonoscopy while adjusting for possible confounders using multivariable regression of the type appropriate for each outcome. Results: Overall, 953 patients were included, of which 90 underwent early colonoscopy. The majority (54%) were found insufficiently prepared. Common findings were diverticulosis (38%) and colon polyps (20%). The procedure was effective for hemostasis in only 13% of the cases. Early colonoscopy was not significantly associated with increased survival (exponentiated coefficient = 1.19, 95% CI: 0.76, 1.87), decreased length of hospitalization (exponentiated coefficient = 1.08, 95% CI: 0.97, 1.21), or increased blood hemoglobin at discharge (coefficient =-0.27, 95% CI: -0.58, 0.03). Conclusions: Early colonoscopy was often not effective and was not associated with significantly improved outcomes.

Evaluating the Utility of a Large Language Model in Answering Common Patients' Gastrointestinal Health-Related Questions: Are We There Yet?

BACKGROUND AND AIMS: Patients frequently have concerns about their disease and find it challenging to obtain accurate Information. OpenAI's ChatGPT chatbot (ChatGPT) is a new large language model developed to provide answers to a wide range of questions in various fields. Our aim is to evaluate the performance of ChatGPT in answering patients' questions regarding gastrointestinal health. METHODS: To evaluate the performance of ChatGPT in answering patients' questions, we used a representative sample of 110 real-life questions. The answers provided by ChatGPT were rated in consensus by three experienced gastroenterologists. The accuracy, clarity, and efficacy of the answers provided by ChatGPT were assessed. RESULTS: ChatGPT was able to provide accurate and clear answers to patients' questions in some cases, but not in others. For questions about treatments, the average accuracy, clarity, and efficacy scores (1 to 5) were 3.9 ± 0.8, 3.9 ± 0.9, and 3.3 ± 0.9, respectively. For symptoms questions, the average accuracy, clarity, and efficacy scores were 3.4 ± 0.8, 3.7 ± 0.7, and 3.2 ± 0.7, respectively. For diagnostic test questions, the average accuracy, clarity, and efficacy scores were 3.7 ± 1.7, 3.7 ± 1.8, and 3.5 ± 1.7, respectively. CONCLUSIONS: While ChatGPT has potential as a source of information, further development is needed. The quality of information is contingent upon the quality of the online information provided. These findings may be useful for healthcare providers and patients alike in understanding the capabilities and limitations of ChatGPT.

Evaluating the use of large language model in identifying top research questions in gastroenterology.

The field of gastroenterology (GI) is constantly evolving. It is essential to pinpoint the most pressing and important research questions. To evaluate the potential of chatGPT for identifying research priorities in GI and provide a starting point for further investigation. We queried chatGPT on four key topics in GI: inflammatory bowel disease, microbiome, Artificial Intelligence in GI, and advanced endoscopy in GI. A panel of experienced gastroenterologists separately reviewed and rated the generated research questions on a scale of 1-5, with 5 being the most important and relevant to current research in GI. chatGPT generated relevant and clear research questions. Yet, the questions were not considered original by the panel of gastroenterologists. On average, the questions were rated 3.6 ± 1.4, with inter-rater reliability ranging from 0.80 to 0.98 (p < 0.001). The mean grades for relevance, clarity, specificity, and originality were 4.9 ± 0.1, 4.6 ± 0.4, 3.1 ± 0.2, 1.5 ± 0.4, respectively. Our study suggests that Large Language Models (LLMs) may be a useful tool for identifying research priorities in the field of GI, but more work is needed to improve the novelty of the generated research questions.

Travel-associated health risks for patients with inflammatory bowel disease.

BACKGROUND & AIMS: There are few data on risk of travel for patients with inflammatory bowel disease (IBD). We assessed rates of illness while traveling among patients with IBD. METHODS: We performed a retrospective, case-controlled study of illnesses among 222 patients with IBD and 224 healthy individuals (controls) during 1099 total trips. Data were retrieved by structured questionnaires, personal interviews, and chart review. RESULTS: Participants had 142 episodes of illness during the trips; 92% were enteric disease. An episode of illness occurred during 79/523 (15.1%) trips made by patients with IBD compared with 63/576 (10.9%) trips made by controls (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.01-2.0; P = .04). However, this difference was mostly attributable to the increased incidence of illness among IBD patients traveling in industrialized countries. In contrast, the rate of illness among travelers to developing countries was similar among patients with IBD and controls (34/200, 17% vs 52/243, 21% of trips, respectively; P = .24). Moreover, numerically more controls that traveled to the tropics developed illness than travelers with IBD (43/135 vs 23/97, respectively; P = .18). In multivariate analysis, factors that increased risk for travel illness included frequent flares of IBD (OR, 1.9; 95% CI, 1.1-3.4; P = .02) and prior IBD-related hospitalizations (OR, 3.5; 95% CI, 1.3-9.3; P = .01); remission within 3 months before traveling reduced the risk for illness (OR, 0.3; 95% CI, 0.16-0.5; P < .001). Use of immunomodulatory drugs was not independently associated with risk of illness during travel. CONCLUSIONS: Patients with IBD have a higher rate of illness compared with controls during trips to industrialized countries, but not to developing or tropical regions. These findings indicate that most travel-associated illnesses stem from sporadic IBD flares rather than increased susceptibility to enteric infections.

The risk of advanced histology in small-sized colonic polyps: are non-invasive colonic imaging modalities good enough?

PURPOSE: The study aims to evaluate the risk of advanced histology within small colonic polyps and assess whether this risk warrants different recommendation for surveillance and treatment of such polyps. METHODS: A retrospective study of all patients undergoing their first ever colonoscopy and polypectomy in a tertiary hospital for one of three indications: screening, positive family history,and positive occult blood in stool. The histological reports of all resected polyps were retrieved and stratified according to the various polyps' sizes. Advanced neoplasia was defined as tubular adenoma ≥10 mm or any size polyp with advanced histology, i.e., villous or tubulovillous adenoma, high-grade dysplasia, intramucosal carcinoma, or invasive cancer. RESULTS: Seven hundred forty-one patients who had a total of1,192 resected polyps were included. Of polyps ≤5 mm in size, 1.6% harbored invasive cancer or high-grade dysplasia,and additional 4.1% contained villous component. The rate of advanced histology for polyps sized 6-9 mm was over 15%. The rate of advanced histology in polyps ≤5 mm was not significantly different when employing sensitivity analysis accounting for possible under or overestimation of polyp sizes by 1 and 2 mm. However, 4.6% of polyps sized 6-9 mm were found to harbor an invasive or high-grade dysplasia component when taken into account a 2-mm overestimation. CONCLUSIONS: A non-negligible fraction of small polyps harbor advanced histology. This finding suggests that expectant follow-up by non-invasive colonic imaging modalities for small polyps or not reporting them may put more than 5% of patients at risk of dysplasia progression.

Obesity, metabolic syndrome and the risk of development of colonic diverticulosis.

INTRODUCTION: Colonic diverticulosis is a common condition with obscure pathogenesis. Obesity, hyperlipidemia and hypertension have been demonstrated to increase the risk of complicated diverticular disease, but the impact of metabolic risk factors on the prevalence of uncomplicated diverticulosis has not been clearly determined. AIMS: The aim of the study was to examine the impact of obesity and metabolic syndrome on the prevalence of colonic diverticulosis. METHODS: This retrospective case-control study included patients aged 40-85 years who were followed up by the Institute of Medical Screening in Israel and underwent colonoscopy in 2006-2011 for indication of colorectal cancer screening. Patients with diverticulosis as detected by colonoscopy were compared to patients without diverticulosis. The comparison parameters included medical history, biometric parameters, biochemical and lipid profile. RESULTS: The study included 3,175 patients. Diverticulosis was diagnosed in 17.4% of the cohort. On univariate analysis, age, male gender, BMI (continuous variable), obesity, systolic blood pressure, low-density lipoprotein cholesterol level, history of hypertension, ischemic heart disease, hypothyroidism, and absence of diabetes mellitus were associated with an increased risk of colonic diverticulosis. On multivariate analysis, advanced age, male gender, obesity (BMI >30), history of hypothyroidism and absence of diabetes mellitus were associated with an increased risk of diverticulosis. Prevalence of colonic polyps was similar in patients with and without diverticulosis. CONCLUSION: Colonic diverticulosis was associated with age, male gender, obesity and hypothyroidism. Diabetes mellitus was associated with a decreased risk of colonic diverticulosis.

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. OBJECTIVE: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. METHODS: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. RESULTS: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. CONCLUSION: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Long-term clinical outcome of patients with gastric gastrointestinal stromal tumors.

BACKGROUND: About 10-30% of gastrointestinal stromal tumors prove to be malignant. Nevertheless, the natural history of gastric gastrointestinal stromal tumors has not been fully elucidated. AIMS: To determine the long-term clinical outcome of nonresected gastric gastrointestinal stromal tumors. METHODS: Clinical follow-up of patients with endosonographic characteristics compatible with gastric gastrointestinal stromal tumors was conducted based on Israeli population registry. Lesions with features suggesting malignancy were usually referred to surgery. Follow-up endoscopic ultrasound examinations of nonoperated patients were reviewed. RESULTS: Seventy-one patients with presumable gastric gastrointestinal stromal tumors were followed. Seventeen patients underwent operation; median tumor size was 43 mm (range 29-70 mm). Within a median of 43 months (range 2-131 months) ten patients died of causes unrelated to gastrointestinal stromal tumor. Forty-four patients with endosonographic diagnosis of gastric gastrointestinal stromal tumors were followed expectantly for a median of 12 years (range 5-15 years). All these patients are alive and without complications associated with gastrointestinal stromal tumor. Follow-up endoscopic ultrasound examinations demonstrated no change in tumor size in six, decrease (by 1-5 mm) in six, and increase (by 2-21 mm) in eight. CONCLUSIONS: Therapeutic decisions guiding surgical interventions may be based on clinical presentation, comorbidity, and endosonographic characteristics. Nonoperated patients may be safely followed conservatively.

A High Temperature Environment Regulates the Olive Oil Biosynthesis Network.

Climate change has been shown to have a substantial impact on agriculture and high temperatures and heat stress are known to have many negative effects on the vegetative and reproductive phases of plants. In a previous study, we addressed the effects of high temperature environments on olive oil yield and quality, by comparing the fruit development and oil accumulation and quality of five olive cultivars placed in high temperature and moderate temperature environments. The aim of the current study was to explore the molecular mechanism resulting in the negative effect of a high temperature environment on oil quantity and quality. We analyzed the transcriptome of two extreme cultivars, 'Barnea', which is tolerant to high temperatures in regard to quantity of oil production, but sensitive regarding its quality, and 'Souri', which is heat sensitive regarding quantity of oil produced, but relatively tolerant regarding its quality. Transcriptome analyses have been carried out at three different time points during fruit development, focusing on the genes involved in the oil biosynthesis pathway. We found that heat-shock protein expression was induced by the high temperature environment, but the degree of induction was cultivar dependent. The 'Barnea' cultivar, whose oil production showed greater tolerance to high temperatures, exhibited a larger degree of induction than the heat sensitive 'Souri'. On the other hand, many genes involved in olive oil biosynthesis were found to be repressed as a response to high temperatures. OePDCT as well as OeFAD2 genes showed cultivar dependent expression patterns according to their heat tolerance characteristics. The transcription factors OeDof4.3, OeWRI1.1, OeDof4.4 and OeWRI1.2 were identified as key factors in regulating the oil biosynthesis pathway in response to heat stress, based on their co-expression characteristics with other genes involved in this pathway. Our results may contribute to identifying or developing a more heat tolerant cultivar, which will be able to produce high yield and quality oil in a future characterized by global warming.

High temperature environment reduces olive oil yield and quality.

Global warming is predicted to have a negative effect on plant growth due to the damaging effect of high temperatures. In order to address the effect of high temperature environments on olive oil yield and quality, we compared its effect on the fruit development of five olive cultivars placed in a region noted for its high summer temperatures, with trees of the same cultivars placed in a region of relatively mild summers. We found that the effects of a high temperature environment are genotype dependent and in general, high temperatures during fruit development affected three important traits: fruit weight, oil concentration and oil quality. None of the tested cultivars exhibited complete heat stress tolerance. Final dry fruit weight at harvest of the 'Barnea' cultivar was not affected by the high temperature environment, whereas the 'Koroneiki', 'Coratina', 'Souri' and 'Picholine' cultivars exhibited decreased dry fruit weight at harvest in response to higher temperatures by 0.2, 1, 0.4 and 0.2 g respectively. The pattern of final oil concentration was also cultivar dependent, 'Barnea', 'Coratina' and 'Picholine' not being affected by the high temperature environment, whereas the 'Koroneiki' and 'Souri' cultivars showed a decreased dry fruit oil concentration at harvest under the same conditions by 15 and 8% respectively. Regarding the quality of oil produced, the 'Souri' cultivar proved more tolerant to a high temperature environment than any other of the cultivars analyzed in this study. These results suggest that different olive cultivars have developed a variety of mechanisms in dealing with high temperatures. Elucidation of the mechanism of each of these responses may open the way to development of a variety of olives broadly adapted to conditions of high temperatures.

The outcome of a second preparation for colonoscopy after preparation failure in the first procedure.

BACKGROUND: There are scant data regarding the outcome of consecutive repeated procedures in patients who failed to adequately clean their colon for colonoscopy. OBJECTIVE: To investigate the outcome of a second colonoscopy after preparation-associated failure of the first colonoscopy. DESIGN AND SETTING: A retrospective study in a tertiary-referral center. PATIENTS: All patients with failure of colonoscopy because of poor preparation within a 1-year period. RESULTS: Of a total of 6990 colonoscopies performed during the study period, 307 procedures (4.4%) failed because of inadequate preparation. Data on subsequent repeated colonoscopies were available for 235 patients. The repeated procedure again failed because of unsatisfactory preparation in 54 of these patients (23%). The failure rate in subsequent third and fourth colonoscopies was also high (more than 25%). Of the various patient and procedure-related parameters examined, only the use of calcium channel blockers (CCB) was found to be predictive of a failed repeated preparation (odds ratio [OR] 3.2 [95% CI, 1.6-6.3], P < .001). In contrast, a next-day colonoscopy after failure of the index procedure was associated with a reduced risk of unsatisfactory second preparation (OR 0.31 [95% CI, 0.1-0.92], P = .03). LIMITATIONS: Validated data on the specific bowel purgatives used were not available. CONCLUSIONS: Almost a fourth of patients with an unacceptable colonic preparation will also fail the repeated colonoscopy, and patients who use CCB are at particular risk for failure. Strategies to manage this difficult-to-treat patient group should be investigated and may possibly include a preference for next-day colonoscopy.

Chromoendoscopy or white light endoscopy for neoplasia detection in Lynch syndrome, a meta-analysis.

BACKGROUND: Lynch syndrome carries an increased risk of colorectal neoplasia, hence annual surveillance colonoscopy is recommended. This study aimed to compare the diagnostic yields of image enhancement modalities for colorectal neoplasia in patients with Lynch syndrome. METHODS: Meta-analysis of pooled ratios of lesion detection rates (RRs) and odds ratios (ORs) with 95% confidence intervals (CIS), comparing white light endoscopy (WLE) and chromoendoscopy (ChE). RESULTS: Four studies comparing WLE to ChE were analyzed. ChE fared better than WLE in overall lesion detection (RR 1.97, 95% CI 1.63-2.38) and detection of adenomas (RR 1.53, 95% CI 1.07-2.17), flat lesions (RR 3.4, 95% CI 2.47-4.67) and proximally-located lesions (RR 2.93, 95% CI 1.91-4.5). The odds of a patient having any lesion found were higher in ChE compared to WLE (OR 2.42, 95% CI 1.56-3.75). The odds of a patient having adenoma(s) found on endoscopy were not significantly higher in chromoendoscopy compared to white light endoscopy (OR 1.81, 95% CI 0.65-5.01). CONCLUSION: Using standard definition technology, ChE allows detection of more lesions, especially adenomas, flat lesions and proximal lesions in Lynch syndrome patients, compared to WLE. The results show that surveillance colonoscopy of Lynch syndrome patients should be performed using ChE.

Green Olive Browning Differ Between Cultivars.

Currently, table olives, unlike oil olives, are harvested manually. Shortage of manpower and increasing labor costs are the main incentives to mechanizing the harvesting of table olives. One of the major limiting factors in adopting mechanical harvest of table olives is the injury to fruit during mechanical harvest, which lowers the quality of the final product. In this study, we used the Israeli germplasm collection of olive cultivars at the Volcani Institute to screen the sensitivity of many olive cultivars to browning in response to injury. The browning process after induced mechanical injury was characterized in 106 olive cultivars. The proportional area of brown coloring after injury, compared to the total fruit surface area, ranged from 0 to 83.61%. Fourteen cultivars were found to be resistant to browning and did not show any brown spot 3 h after application of pressure. Among them, there are some cultivars that can serve as table olives. The different response to mechanical damage shown by the cultivars could be mainly due to genetic differences. Mesocarp cells in the fruits of the sensitive cultivars were damaged and missing the cell wall as a result of the applied pressure. The cuticles of resistant cultivars were thicker compared to those of susceptible cultivars. Finally, we showed that the browning process is enzymatic. We suggest cuticle thickness as an indicator of table olive cultivars suitable for mechanical harvest. A shift to browning-resistant cultivars in place of the popular cultivars currently in use will enable the mechanical harvest of table olive without affecting fruit quality.