Publications by authors named "Orit Picard"

Aims And Background: Matrix metalloproteinase-7 (MMP-7) and Syndecan-1 (SDC1) are involved in multiple functions during tumorigenesis. We aimed to evaluate the diagnostic and prognostic performance of these serum proteins, as potential biomarkers, in patients with pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic cysts.

Methods: In this case-control study, patients with newly diagnosed PDAC (N = 121) were compared with the benign cyst (N = 66) and healthy control (N = 48) groups.

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  • - The increase in Crohn disease (CD) cases, especially with urbanization and globalization, is more related to environmental factors rather than genetics, suggesting changes in lifestyle impact gut health.
  • - The SOURCE study examined diet, microbiome, and genetic expression among newly diagnosed CD patients and controls from rural and urban settings in China and Israel to uncover links between lifestyle changes and CD.
  • - Findings reveal that time spent in urban environments alters gut bacteria and metabolites in rural residents, with specific dietary factors like coffee and vitamin D showing potential protective roles against CD-related changes.
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  • A study investigated the effectiveness of adalimumab, an anti-TNFα monoclonal antibody, in ulcerative colitis (UC) patients, revealing that fewer UC patients continued treatment compared to those with Crohn's disease (CD).
  • In a cohort of 50 UC patients, only 22% maintained treatment through the follow-up period, while 51% of 98 CD patients did.
  • The loss of response to treatment was notably higher in UC patients, with 34% developing antibodies against adalimumab, although immunogenicity rates were similar between both patient groups.
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  • - Ustekinumab is a monoclonal antibody used to treat Crohn's disease, with about 50% of patients achieving clinical remission after one year; the study aimed to find predictors of response to this treatment by analyzing blood samples before initiation.
  • - RNA from blood samples of 36 adults with Crohn's was sequenced, identifying 22 responders and 14 nonresponders, but no significant gene expression signature was found between the two groups after correcting for false discovery rates.
  • - Despite the lack of major differences in gene expression, nonresponders showed an increased inflammatory response with certain cytokine and chemokine receptor pathways, suggesting that further research with a larger sample is needed for validation.
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Background And Aims: The expression of tissue and serum matrix metalloproteinase-7 (MMP-7) was shown to be elevated both in colon cancer and dysplastic lesions. We aimed to evaluate, for the first time, its role as a diagnostic marker in Lynch syndrome (LS) carriers, a hereditary syndrome with predisposition to colon cancer.

Methods: This was a case control study.

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: Vedolizumab trough serum levels have been associated with clinical and endoscopic response in patients with inflammatory bowel disease (IBD). A recent study demonstrated that higher trough levels before dose escalation are associated with favorable outcomes. : We aimed to identify whether vedolizumab trough levels predict outcome of subsequent therapy.

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Background & Aims: Noninvasive modalities for assessing active endoscopic and histologic inflammation in Crohn's disease and ulcerative colitis patients are critically needed. Fecal wash host shed-cell transcriptomics has been shown to be a robust classifier of endoscopic and histologic inflammation in inflammatory bowel disease patients with distal colitis. Whether such fecal washes can inform on inflammatory processes occurring in more proximal intestinal segments is currently unknown.

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  • The study examined the levels of hTERT-mRNA in exosomes from the serum of colon cancer patients, Lynch syndrome carriers, and healthy controls to assess its potential as a diagnostic marker.
  • Results showed that colon cancer patients had significantly higher hTERT-mRNA levels compared to healthy individuals, and those with metastatic disease had even higher levels that correlated with CEA levels.
  • The findings also indicated that Lynch syndrome carriers had a higher occurrence of positive hTERT-mRNA in exosomes than controls, suggesting the need for further research to understand its role in cancer development.
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  • The study aimed to evaluate the immune response in infants exposed to anti-TNFα or azathioprine due to their mothers' inflammatory bowel disease, focusing on T and B cell distribution and function.
  • Conducted from 2014 to 2017, the research involved measuring anti-TNFα levels in cord blood and analyzing T-cell function and immunoglobulin levels in infants at 3 and 12 months.
  • Findings indicated that infants exposed to anti-TNFα had normal immune responses, with adequate B-cell counts and no severe infections, but further research with untreated controls is necessary for confirmation.
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Background: Higher infliximab trough levels (TLs) correlate with better clinical, inflammatory, and endoscopic outcomes among inflammatory bowel disease (IBD) patients. Although standard scheduled infliximab therapy regimen consists of infusions at pre-defined time-points (weeks 0, 2, 6, and every 8 weeks), short-period deviations from therapeutic schedule are common in 'real life', but the pharmacokinetic impact of these deviations has not been explored. In this study, we aim to determine whether short-period deviations from infusion schedule affect infliximab-TL.

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A comprehensive characterization of chronic HBV (CHB) patients is required to guide therapeutic decisions. The cumulative impact of classical and novel biomarkers on the clinical categorization of these patients has not been rigorously assessed. We determined plasma HBV-RNA and HBsAg levels, HBV in peripheral lymphocytes (PBMCs) and HBV mutation profiles in CHB patients.

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Introduction: Syndecan-1 (SDC1) has multiple functions in tumorigenesis in general and specifically in pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic and prognostic biomarker in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: In this case-control study, patients newly diagnosed with a biopsy-proven PDAC were enrolled alongside healthy individuals in a derivation-validation cohort design.

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Background: Colonoscopy is the gold standard for evaluation of inflammation in inflammatory bowel diseases (IBDs), yet entails cumbersome preparations and risks of injury. Existing non-invasive prognostic tools are limited in their diagnostic power. Moreover, transcriptomics of colonic biopsies have been inconclusive in their association with clinical features.

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Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic is still ongoing along with the global vaccination efforts against it. Here, we aimed to understand the longevity and strength of anti-SARS-CoV-2 IgG responses in a small community (n = 283) six months following local SARS-COV-2 outbreak in March 2020. Three serological assays were compared and neutralisation capability was also determined.

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Background: Real life data regarding pharmacokinetics of vedolizumab in patients needing dose optimisation are scarce. We set to examine whether pre-optimisation vedolizumab levels associate with therapy outcomes and which mechanisms explain the associations.

Methods: A multicentre observational study assessed the outcome of dose increase in association with pre-escalation levels in vedolizumab-treated patients.

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  • Universal vaccination has significantly reduced hepatitis A (HAV) cases in Israel, but sporadic outbreaks still happen, highlighting the need for improved surveillance.
  • A comprehensive HAV surveillance program was implemented in 2017-2018, analyzing 146 human cases and 240 sewage samples, revealing that most cases involved unvaccinated individuals, particularly among men, including a notable number of men who have sex with men (MSM) in 2017.
  • Genetic analysis showed that different HAV genotypes were predominant each year, with findings suggesting a connection between genetic sequences of cases and sewage samples, indicating ongoing viral circulation and the potential for better tracking through combined clinical and environmental data.
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Background: Immunomodulators and anti tumor-necrosis-α antibodies (anti-TNFs) have been implicated in increased risk of Epstein-Barr virus (EBV)-driven B-cell lymphoproliferative disorders in inflammatory bowel disease (IBD) patients. However, the underlying mechanisms are poorly understood.

Methods: An in-vitro model of lymphoblastoid cell line (LCL) was established by co-incubation of EBV-infected human peripheral blood mononuclear cells (PBMC) with Cyclosporin-A (CSA).

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Background: Extra-intestinal manifestations (EIM) are common in inflammatory bowel diseases (IBD) and may affect up to 40% of the patients during the course of the disease. Peripheral arthralgia (PA) is by far the most common EIM. To date, TNFα inhibitors are the most established treatment for EIMs in IBD.

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Drugs formulated from monoclonal antibodies (mAbs) are clinically effective in various diseases. Repeated administration of mAbs, however, elicits an immune response in the form of anti-drug-antibodies (ADA), thereby reducing the drug's efficacy. Notwithstanding their importance, the molecular landscape of ADA and the mechanisms involved in their formation are not fully understood.

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Background: Matrix metalloproteinase-9 (MMP-9) is a novel marker of intestinal inflammation. The aim of this study was to assess if serum MMP-9 levels predict clinical flare in patients with quiescent Crohn's disease (CD).

Methods: This study was a analysis of a prospective observational study in which quiescent CD patients were included and followed until clinical relapse or the end of a 2-year follow-up period.

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Introduction: Loss of response (LOR) to infliximab occurs in ∼30% of IBD patients. At time of LOR, lower infliximab-trough-levels (TL), in the absence of anti-drug-antibodies (ATI), have been associated with the need for therapy escalation. Nevertheless, few studies have examined the outcome of infliximab-therapy intensification, based on different TL.

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Objectives: Crohn's disease (CD) is a chronic relapsing-remitting gut inflammatory disorder with a heterogeneous unpredictable course. Dysbiosis occurs in CD; however, whether microbial dynamics in quiescent CD are instrumental in increasing the risk of a subsequent flare remains undefined.

Methods: We analyzed the long-term dynamics of microbial composition in a prospective observational cohort of patients with quiescent CD (45 cases, 217 samples) over 2 years or until clinical flare occurred, aiming to identify whether changes in the microbiome precede and predict clinical relapse.

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Background And Aims: Discontinuation of thiopurine analogues is common prior to live vaccines, during infection or when de-escalating therapy. Data regarding clearance of active metabolites and immune re-constitution is scant. We aimed to determine drug elimination and immune re-constitution following thiopurine cessation.

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Objectives: While infliximab pharmacokinetics are associated with therapy outcome in adult inflammatory bowel disease (IBD) population, limited data are available in pediatric patients. We aimed to define the relationship between infliximab trough and antibodies' levels (IFX-TL, ATI) and clinical, biomarker remission.

Methods: IFX-TL and ATI were routinely obtained between 2011 and 2017.

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