Impact of time to esophagogastroduodenoscopy in patients with nonvariceal upper gastrointestinal bleeding: A systematic review and meta-analysis.

INTRODUCTION: There is conflicting evidence regarding the benefit of urgent esophagogastroduodenoscopy (EGD) for reducing mortality and rebleeding, in the context of nonvariceal upper gastrointestinal bleeding. AIM: To describe the decrease in the risk for mortality, rebleeding, and red blood cell transfusion, with the performance of urgent EGD, in patients with nonvariceal upper gastrointestinal bleeding. MATERIALS AND METHODS: We carried out a search for cohort studies or controlled clinical trials, published from December 1966 to May 2020, that compared urgent EGD versus elective EGD in the management of adults with nonvariceal upper gastrointestinal bleeding, utilizing the MEDLINE, Embase, LILACS, and Cochrane Central Register of Controlled Trials databases. Our primary outcome was the hospital mortality comparison. The incidence of rebleeding and the mean number of red blood cell units transfused were also compared. A random effects model was utilized for the meta-analysis. RESULTS: Twenty-one studies that met the eligibility criteria were included, involving 489,622 patients. We found no differences in the mortality of subjects exposed to urgent EGD versus elective EGD (RR 1.12 [0.72-1.72]). There was a significant increase in the risk for rebleeding (RR 1.30 [1.05-1.60]) in the subjects exposed to urgent EGD, and fewer red blood cell units were transfused in those patients (RR 0.52 [0.05-0.99]). CONCLUSIONS: Urgent EGD in subjects with nonvariceal upper gastrointestinal bleeding does not appear to have a significant impact on short-term mortality.

Effect of successive endoscopic procedures in polyp and adenoma detection rates: Too early is not always too good.

BACKGROUND AND AIMS: There is conflicting evidence regarding the impact of hypothetical cumulative fatigue after performing too many endoscopic procedures on both polyp and adenoma detection rates (PDR, and ADR, respectively). The aim of this study is to evaluate the effect of successive endoscopic procedures on PDR and ADR. METHODS: A retrospective cross-sectional study was undertaken among consecutive patients on whom colonoscopy and/or esophagogastroduodenoscopy were performed between January 2012 and August 2014. Data regarding polyp and adenoma detection, cecal intubation, and bowel cleansing quality as well as demographical data of subjects were extracted. Endoscopic procedures were classified according to the time slots of the procedures throughout the endoscopy session in three groups: from the 1st to 4th endoscopy study (round 1), from the 5th to the 8th study (round 2), above the 9th study (round 3). We compared PDR and ADR among rounds. RESULTS: Overall, 3388 patients were enrolled. Median age was 50 years (range 18-95) and 52.39% were female. There was a significant difference in terms of PDR among rounds (36.83%, 41.24%, and 43.38%, respectively, p = 0.007) and a non-significant numerical difference when ADR was compared (23.2%, 25.71%, and 26.78%, p = 0.07). On multivariate analysis, ADR was significantly associated with age (odds ratio [OR] 1.02 [1.01-1.03]), and male sex (OR 1.64 [1.38-1.94]). CONCLUSION: Theoretical endoscopist's fatigue due to cumulative performance of endoscopies does not diminish colonoscopy quality. Both PDR and ADR seem to improve after endoscopist's cumulative rounds of performed endoscopies. This could be due to a "warm-up" effect.

Large-scale secretome analyses unveil the superior immunosuppressive phenotype of umbilical cord stromal cells as compared to other adult mesenchymal stromal cells.

Mesenchymal stromal cells (MSCs), given their regenerative potential, are being investigated as a potential therapeutic tool for cartilage lesions. MSCs express several bioactive molecules which act in a paracrine fashion to modulate the tissue microenvironment. Yet, little is known about the divergence of these signalling molecules in different MSC populations. The present study investigated secretomes of stromal cells harvested from Hoffa's fat pad (HFPSCs), synovial membrane (SMSCs), umbilical cord (UCSCs) and cartilage (ACs) by quantitative liquid chromatography-mass spectrometry (LC-MS/MS) proteomics. Also, multiplex protein arrays and functional assays were performed to compare the constitutive immunomodulatory capabilities of different MSCs. Proteins involved in extracellular matrix degradation and inflammation, such as matrix metalloproteinases (MMPs), interleukin (IL)-17 and complement factors, were downregulated in UCSCs as compared to adult cell sources. Additionally, secretion of transforming growth factor (TGF)-ß1 and prostaglandin E2 (PGE2) was enhanced in UCSC supernatants. UCSCs were superior in inhibiting peripheral blood mononuclear cell (PBMC) proliferation, migration and cytokine secretion as compared to adult stromal cells. SMSCs significantly suppressed the proliferation of PBMCs only if they were primed with pro-inflammatory cytokines. Although all cell types repressed human leukocyte antigen-DR isotype (HLA-DR) surface expression and cytokine release by activated macrophages, only UCSCs significantly blocked IL-6 and IL-12 production. Furthermore, UCSCs supernatants increased aggrecan gene expression in two-dimensional chondrocyte cultures. The data demonstrated that UCSCs displayed superior anti-inflammatory and immunosuppressive properties than stromal cells from adult tissues. This allogeneic cell source could potentially be considered as an adjuvant therapy for articular cartilage repair.

Risk of colorectal adenomas in patients with celiac disease: a systematic review and meta-analysis. / Riesgo de adenomas colorrectales en pacientes con enfermedad celiaca: una revisión sistemática y metaanálisis.

INTRODUCTION AND AIMS: Whether celiac disease increases the risk of presenting with colorectal adenoma or not, has not been extensively evaluated. This question becomes relevant when considering early screening methods in patients with the disease. The aim of our article was to determine the risk of colorectal adenomas in celiac disease patients. MATERIALS AND METHODS: A computer-assisted search of the MEDLINE-Pubmed, EMBASE, LILACS, Cochrane Library, and Google Scholar databases was carried out, encompassing the time frame of 1966 to December 2016. The search strategy consisted of the following MESH terms: 'celiac disease' OR 'celiac sprue' AND 'colorectal' OR 'colorectal neoplasia' OR 'colorectal adenoma'. A fixed-effect model was used for the analyses. The first analysis dealt with the prevalence of all presentations of colorectal adenoma in patients with celiac disease and the second was on the prevalence of advanced adenomas. The outcomes were described as odds ratios (OR) with their 95% confidence intervals. RESULTS: The search identified 480 bibliographic citations, 17 of which were chosen for evaluation. Fourteen of those studies were rejected, leaving a final total of three for the analysis. Those studies included 367 cases of celiac disease and 682 controls. No significant heterogeneity was observed (I2=26%). There was no increased prevalence of colorectal adenomas in the celiac disease patients, when compared with the controls (OR: 0.94 [0.65-1.38]), and no significant difference was observed when assessing the prevalence of advanced adenomas (OR: 0.97 [0.48-1.97]). CONCLUSION: Celiac disease was not associated with an increased risk of colorectal adenomas. However, due to the limited evidence available, more studies are necessary to determine whether there is an actual association.

Non-linear optical microscopy as a novel quantitative and label-free imaging modality to improve the assessment of tissue-engineered cartilage.

OBJECTIVE: Current systems to evaluate outcomes from tissue-engineered cartilage (TEC) are sub-optimal. The main purpose of our study was to demonstrate the use of second harmonic generation (SHG) microscopy as a novel quantitative approach to assess collagen deposition in laboratory made cartilage constructs. METHODS: Scaffold-free cartilage constructs were obtained by condensation of in vitro expanded Hoffa's fat pad derived stromal cells (HFPSCs), incubated in the presence or absence of chondrogenic growth factors (GF) during a period of 21 d. Cartilage-like features in constructs were assessed by Alcian blue staining, transmission electron microscopy (TEM), SHG and two-photon excited fluorescence microscopy. A new scoring system, using second harmonic generation microscopy (SHGM) index for collagen density and distribution, was adapted to the existing "Bern score" in order to evaluate in vitro TEC. RESULTS: Spheroids with GF gave a relative high Bern score value due to appropriate cell morphology, cell density, tissue-like features and proteoglycan content, whereas spheroids without GF did not. However, both TEM and SHGM revealed striking differences between the collagen framework in the spheroids and native cartilage. Spheroids required a four-fold increase in laser power to visualize the collagen matrix by SHGM compared to native cartilage. Additionally, collagen distribution, determined as the area of tissue generating SHG signal, was higher in spheroids with GF than without GF, but lower than in native cartilage. CONCLUSION: SHG represents a reliable quantitative approach to assess collagen deposition in laboratory engineered cartilage, and may be applied to improve currently established scoring systems.

Mesenchymal stromal cells from human umbilical cords display poor chondrogenic potential in scaffold-free three dimensional cultures.

Many researchers world over are currently investigating the suitability of stromal cells harvested from foetal tissues for allogeneic cell transplantation therapies or for tissue engineering purposes. In this study, we have investigated the chondrogenic potential of mesenchymal stromal cells (MSCs) isolated from whole sections of human umbilical cord or mixed cord (UCSCs-MC), and compared them with cells isolated from synovial membrane (SMSCs), Hoffa's fat pad (HFPSCs) and cartilage. All MSCs were positive for surface markers including CD73, CD90, CD105, CD44, CD146 and CD166, but negative for CD11b, CD19, CD34, CD45 and HLA-DR in addition to CD106 and CD271. Chondrogenic potential of all cell sources was studied using 3D pellet cultures incubated in the presence of different combinations of anabolic substances such as dexamethasone, IGF-1, TGF-ß1, TGF-ß3, BMP-2 and BMP-7. BMP-2 and dexamethasone in combination with TGF-ß1 or TGF-ß3 excelled at inducing chondrogenesis on SMSCs, HFPSCs and chondrocytes, as measured by glycosaminoglycans and collagen type II staining of pellets, quantitative glycosaminoglycan expression, quantitative PCR of cartilage signature genes and electron microscopy. In contrast, none of the tested growth factor combinations was sufficient to induce chondrogenesis on UCSCs-MC. Moreover, incubation of UCSCs-MC spheroids in the presence of cartilage pieces or synovial cells in co-cultures did not aid chondrogenic induction. In summary, we show that in comparison with MSCs harvested from adult joint tissues, UCSCs-MC display poor chondrogenic abilities. This observation should alert researchers at the time of considering UCSCs-MC as cartilage forming cells in tissue engineering or repair strategies.

Small intestinal bacterial overgrowth prevalence in celiac disease patients is similar in healthy subjects and lower in irritable bowel syndrome patients.

BACKGROUND: Untreated celiac disease has traditionally been linked to a greater risk for small intestinal bacterial overgrowth, but the existing evidence is inconclusive. AIMS: To compare the prevalence of small intestinal bacterial overgrowth in subjects with celiac disease compared with control subjects and patients with irritable bowel syndrome. MATERIAL AND METHODS: The study included 15 untreated celiac disease patients, 15 subjects with irritable bowel syndrome, and 15 healthy controls. All enrolled patients underwent a lactulose breath test measuring hydrogen and methane. Small intestinal bacterial overgrowth was defined according to previously published criteria. RESULTS: No differences were found in relation to age or sex. The prevalence of small intestinal bacterial overgrowth was similar between the celiac disease patients and the controls (20 vs. 13.33%, P=NS), whereas it was higher in patients with irritable bowel syndrome (66.66%, P<05). CONCLUSION: There was no difference in the prevalence of small intestinal bacterial overgrowth between the untreated celiac disease patients and healthy controls.

Impact of the endoscopic teaching process on colonic adenoma detection.

BACKGROUND: There has been little reported experience in the Latin American hospital setting in relation to the impact of the endoscopic training process on colonoscopy quality. AIMS: To determine the effect that training in the technique of colonoscopy has on adenoma detection in an Argentinian teaching hospital. MATERIAL AND METHOD: Within the time frame of July 2012 and July 2013, 3 physicians received training in colonoscopy from 4 experienced endoscopists. The colonoscopies performed by the supervised trainees were compared with those carried out by the experienced endoscopists. RESULTS: A total of 318 colonoscopies performed by any one of the 3 supervised trainees and 367 carried out by any one of the experienced endoscopists were included. The univariate analysis showed a non-significant difference in the detection rate of adenomas (30.4 vs. 24.7%, P=.09). In the multivariate analysis, the detection rate of adenomas was significantly higher in the colonoscopies performed by one of the 3 trainees (odds ratio = 1.72 [1.19-2.48]). CONCLUSIONS: The supervised involvement of endoscopic trainees has a positive effect on adenoma detection.

Dynamics of circulating tumor cells in early breast cancer under neoadjuvant therapy.

At present, the majority of patients with breast cancer are diagnosed at early stages of disease development. However, a considerable number of such cases develop secondary malignancies after a relatively short period of time. The presence of circulating tumor cells (CTCs) has been proposed as a strong biomarker to predict disease recurrence in metastatic breast cancer. However, the prognostic significance is not clear in early breast cancer. We present results on CTC determination in peripheral blood in non-metastatic breast cancer patients in the context of neoadjuvant treatment. Twenty-six breast cancer patients, scheduled for neoadjuvant therapy, were enrolled in a prospective study, of which 24 were able to complete therapy. CTC assessment was performed by sorting out cytokeratin-positive cells from 10 ml of peripheral blood using immunomagnetic separation, followed by immunocytochemical characterization of cells. Seventeen blood samples out of 24 patients were CTC-positive when collected prior to neoadjuvant chemotherapy. No significant correlations were found between the presence of CTCs and lymph node status (p=0.1), histological type (p=0.802), stage (p=0.43) or overall survival (OS) (p=0.599). Thirteen CTC-positive samples were observed in blood samples collected after treatment. Univariate analyses revealed that the presence of CTCs was related to OS when the detection was positive both before and after treatment (p=0.023). CTCs can be a strong prognostic marker in early breast cancer. The persistence of CTCs before and after treatment can identify a subpopulation of patients with an increased risk of recurrence.

Clinical relevance associated to the analysis of circulating tumour cells in patients with solid tumours

The distant growth of tumour cells escaping from primary tumours, a process termed metastasis, represents the leading cause of death among patients affected by malignant neoplasias from breast and colon. During the metastasis process, cancer cells liberated from primary tumour tissue, also termed circulating tumour cells (CTCs), travel through the circulatory and/or lymphatic systems to reach distant organs. The early detection and the genotypic and phenotypic characterisation of such CTCs could represent a powerful diagnostic tool of the disease, and could also be considered an important predictive and prognostic marker of disease progression and treatment response. In this article we discuss the potential relevance in the clinic of monitoring CTCs from patients suffering from solid epithelial tumours, with emphasis on the impact of such analyses as a predictive marker for treatment response (AU)

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