Microfluidic System Consisting of a Magnetic 3D-Printed Microchannel Filter for Isolation and Enrichment of Circulating Tumor Cells Targeted by Anti-HER2/MOF@Ferrite Core-Shell Nanostructures: A Theranostic CTC Dialysis System.

Low number of circulating tumor cells (CTCs) in the blood samples and time-consuming properties of the current CTC isolation methods for processing a small volume of blood are the biggest obstacles to CTC usage in practice. Therefore, we aimed to design a CTC dialysis system with the ability to process cancer patients' whole blood within a reasonable time. Two strategies were employed for developing this dialysis setup, including (i) synthesizing novel in situ core-shell Cu ferrites consisting of the Cu-CuFe2O4 core and the MIL-88A shell, which are targeted by the anti-HER2 antibody for the efficient targeting and trapping of CTCs; and (ii) fabricating a microfluidic system containing a three-dimensional (3D)-printed microchannel filter composed of a polycaprolactone/Fe3O4 nanoparticle composite with pore diameter less than 200 µm on which a high-voltage magnetic field is focused to enrich and isolate the magnetic nanoparticle-targeted CTCs from a large volume of blood. The system was assessed in different aspects including capturing the efficacy of the magnetic nanoparticles, CTC enrichment and isolation from large volumes of human blood, side effects on blood cells, and the viability of CTCs after isolation for further analysis. Under the optimized conditions, the CTC dialysis system exhibited more than 80% efficacy in the isolation of CTCs from blood samples. The isolated CTCs were viable and were able to proliferate. Moreover, the CTC dialysis system was safe and did not cause side effects on normal blood cells. Taken together, the designed CTC dialysis system can process a high volume of blood for efficient dual diagnostic and therapeutic purposes.

Intratympanic Triamcinolone or Dexamethasone in Sudden Sensory Neural Hearing Loss: A Randomized Clinical Trial.

Sudden sensorineural hearing loss (SSNHL) is a condition in which a person experiences a rapid loss of hearing, often in one ear. The cause of SSNHL is not always clear, but it is thought to be related to issues with the inner ear, auditory nerve, or other parts of the hearing pathway. Intratympanic injection is a treatment method for SSNHL in which a medication (corticosteroids) is injected directly into the middle ear space through the tympanic membrane. This randomized clinical trial was conducted in two hospitals in Tehran, Iran. Patients with SSNHL were randomized (using the 4-block method) and included in this study. 0.5 cc of dexamethasone or triamcinolone was injected via a 25-gauge spinal needle into the cone of light of tympanic membrane. This procedure was repeated six times. In the present study, the rate of response to treatment was compared in the two groups of triamcinolone and dexamethasone, which showed that in the group where intratympanic injection of dexamethasone was performed, 70.9% of patients responded to treatment (48.4% had a complete response and 22.5% had a partial response), and in the group receiving intratympanic triamcinolone, 72.5% responded to the treatment and improved, 50% showed a complete response and 22.5% showed a partial response, and no significant difference was found in the statistical analysis of the two groups. Also, the comparison of audiometric parameters (SDS and SRT) did not show any significant difference before and after the treatment based on the treatment group, and the treatment response was found in the same group. No significant differences were noted in terms of outcome. Intratympanic dexamethasone injection was associated with a 70.9% response and triamcinolone injection with a 72.5% response.

The prevalence and correlation of depression and anxiety with disease activity in rheumatoid arthritis.

Introduction: Depression and anxiety share similar symptoms with rheumatoid arthritis (RA) and these conditions are often not diagnosed or overlooked in RA. This study aimed to determine the prevalence of depression/anxiety in RA and their correlation with RA activity. Material and methods: Rheumatoid arthritis patients who presented at a rheumatology clinic were selected consecutively. The diagnosis of RA was confirmed by the ACR/EULAR criteria, disease activity was assessed by Disease Activity Score based on the 28-joint count (DAS28) and patients with DAS28 > 2.6 were considered to have active RA. The diagnosis of depression and anxiety was made by the Hospital Anxiety and Depression Scale (HADS). The Pearson test was used to determine the correlation between DAS28 and HADS scores. Results: Two-hundred patients (female, 82%) with a mean age of 53.5 ±10.1 years and mean disease duration of 6.6 ±6.8 years were studied. Depression was diagnosed in 27 (13.5%) patients and anxiety in 38 (19%) patients. The DAS28 score correlated positively with depression (r = 0.173, p = 0.014) and anxiety score (r = 0.229, p = 0.001). In multiple logistic regression analysis after adjustment for all covariates, age < 40 years and female sex were independently associated with RA activity in patients with depression, with OR = 4.21 (p = 0.002) and OR = 3.56 (p = 0.028) respectively. Conclusions: These findings indicate that depression and anxiety are prevalent in RA and correlate positively with active disease in particular in depressive female patients aged < 40 years.

Validity evidence for observational ERCP competency assessment tools: a systematic review.

BACKGROUND : Assessment of competence in endoscopic retrograde cholangiopancreatography (ERCP) is critical for supporting learning and documenting attainment of skill. Validity evidence supporting ERCP observational assessment tools has not been systematically evaluated. METHODS : We conducted a systematic search using electronic databases and hand-searching from inception until August 2021 for studies evaluating observational assessment tools of ERCP performance. We used a unified validity framework to characterize validity evidence from five sources: content, response process, internal structure, relations to other variables, and consequences. Each domain was assigned a score of 0-3 (maximum score 15). We assessed educational utility and methodological quality using the Accreditation Council for Graduate Medical Education framework and the Medical Education Research Quality Instrument, respectively. RESULTS : From 2769 records, we included 17 studies evaluating 7 assessment tools. Five tools were studied for clinical ERCP, one for simulated ERCP, and one for simulated and clinical ERCP. Validity evidence scores ranged from 2 to 12. The Bethesda ERCP Skills Assessment Tool (BESAT), ERCP Direct Observation of Procedural Skills Tool (ERCP DOPS), and The Endoscopic Ultrasound (EUS) and ERCP Skills Assessment Tool (TEESAT) had the strongest validity evidence, with scores of 10, 12, and 11, respectively. Regarding educational utility, most tools were easy to use and interpret, and required minimal additional resources. Overall methodological quality (maximum score 13.5) was strong, with scores ranging from 10 to 12.5. CONCLUSIONS : The BESAT, ERCP DOPS, and TEESAT had strong validity evidence compared with other assessments. Integrating tools into training may help drive learners' development and support competency decision making.

The Toronto Upper Gastrointestinal Cleaning Score: a prospective validation study.

BACKGROUND : Assessment of mucosal visualization during esophagogastroduodenoscopy (EGD) can be improved with a standardized scoring system. To address this need, we created the Toronto Upper Gastrointestinal Cleaning Score (TUGCS). METHODS : We developed the TUGCS using Delphi methodology, whereby an international group of endoscopy experts iteratively rated their agreement with proposed TUGCS items and anchors on a 5-point Likert scale. After each Delphi round, we analyzed responses and refined the TUGCS using an 80 % agreement threshold for consensus. We used the intraclass correlation coefficient (ICC) to assess inter-rater and test-retest reliability. We assessed internal consistency with Cronbach's alpha and item-total and inter-item correlations with Pearson's correlation coefficient. We compared TUGCS ratings with an independent endoscopist's global rating of mucosal visualization using Spearman's ρ. RESULTS : We achieved consensus with 14 invited participants after three Delphi rounds. Inter-rater reliability was high at 0.79 (95 %CI 0.64-0.88). Test-retest reliability was excellent at 0.83 (95 %CI 0.77-0.87). Cronbach's α was 0.81, item-total correlation range was 0.52-0.70, and inter-item correlation range was 0.38-0.74. There was a positive correlation between TUGCS ratings and a global rating of visualization (r = 0.41, P = 0.002). TUGCS ratings for EGDs with global ratings of excellent were significantly higher than those for EGDs with global ratings of fair (P = 0.01). CONCLUSION : The TUGCS had strong evidence of validity in the clinical setting. The international group of assessors, broad variety of EGD indications, and minimal assessor training improves the potential for dissemination.

Recommendation Reversals in Gastroenterology Clinical Practice Guidelines.

Background: Recommendations in clinical practice guidelines (CPGs) may be reversed when evidence emerges to show they are futile or unsafe. In this study, we identified and characterized recommendation reversals in gastroenterology CPGs. Methods: We searched CPGs published by 20 gastroenterology societies from January 1990 to December 2019. We included guidelines which had at least two iterations of the same topic. We defined reversals as when (a) the more recent iteration of a CPG recommends against a specific practice that was previously recommend in an earlier iteration of a CPG from the same body, and (b) the recommendation in the previous iteration of the CPG is not replaced by a new diagnostic or therapeutic recommendation in the more recent iteration of the CPG. The primary outcome was the number of recommendation reversals. Secondary outcomes included the strength of recommendations and quality of evidence cited for reversals. Results: Twenty societies published 1022 CPGs from 1990 to 2019. Our sample for analysis included 129 unique CPGs. There were 11 recommendation reversals from 10 guidelines. New evidence was presented for 10 recommendation reversals. Meta-analyses were cited for two reversals, and randomized controlled trials (RCTs) for seven reversals. Recommendations were stronger after the reversal for three cases, weaker in two cases, and of similar strength in three cases. We were unable to compare recommendation strengths for three reversals. Conclusion: Recommendation reversals in gastroenterology CPGs are uncommon but highlight low value or harmful practices.

Factors Associated with Poor Quality of Life in a Canadian Cohort of Patients with Inflammatory Bowel Disease: A Cross-sectional Study.

BACKGROUND: Health-related quality of life (QoL) is often adversely affected in patients with inflammatory bowel disease (IBD). We aimed to identify factors associated with poor QoL among Canadian patients with IBD in clinical remission. METHODS: We enrolled patients at a single academic tertiary care center with inactive IBD. All eligible patients completed a series of questionnaires that included questions on demographics, disease activity, anxiety, depression and the presence of irritable bowel syndrome (IBS) symptoms. Stool sample for fecal calprotectin (FC) was also collected to assess for subclinical inflammation. The primary outcome measure was QoL assessed by the short inflammatory bowel disease questionnaire (SIBDQ), with planned subgroup comparisons for fatigue, anxiety, depression and IBS symptoms. RESULTS: Ninety-three patients were eligible for inclusion in this study. The median SIBDQ scores were lower in patients with anxiety (P < 0.001), depression (P = 0.004), IBS symptoms (P < 0.001) and fatigue (P = 0.018). Elevated FC in patients in clinical remission did not impact QoL. These findings were consistent on multivariate linear regression. CONCLUSIONS: Anxiety, depression, fatigue and IBS symptoms are all independently associated with lower QoL in patients with inactive IBD. Clinicians are encouraged to screen for these important factors as they may detrimentally impact QoL in IBD patients even in clinical remission.

Type 2 diabetes mellitus and non-alcoholic fatty liver disease: a systematic review and meta-analysis.

AIM: The aim of this study was the evaluation of the prevalence of NAFLD in patients with type 2 diabetes mellitus. BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging disease with high prevalence in patients with type 2 diabetes mellitus (T2DM). Many studies have reported the prevalence of NAFLD in type 2 diabetes mellitus patients. However, these results are inconsistent. METHODS: A Literature search was conducted in PubMed, Scopus, web of science and Science Direct from 2005 to August 2017. The necessary information was extracted. Heterogeneity was evaluated using I2 statistic. Meta-regression analyses were performed to the estimation of the relationship between the year of study and sample size with the prevalence of NAFLD. Publication bias was assessed by both Begg rank correlation and Egger tests. Subgroup analysis was performed for identification of sources heterogeneity. RESULTS: Seventeen studies involving 10897 type 2 diabetes mellitus patients with NAFLD were included in this meta-analysis. The overall prevalence of NAFLD in type 2 diabetes mellitus patients by random effects models was 54% (95% CI, 45%- 64%). There is a significant heterogeneity across studies with (I2= 99%, p> 0.01). The funnel plot as graphically and Begg and Egger as statistically showed no publication bias among studies. Subgroup analysis indicated that the prevalence of NAFLD in type 2 diabetes mellitus patients differed in predictive factors such as lipid profile, BMI, HbA1c, AST, and ALT. This finding in spite of heterogeneity of documents is corresponding to the positive correlation between NAFLD and type 2 diabetes mellitus. CONCLUSION: The findings indicated that the overall prevalence of NAFLD among type 2 diabetes mellitus patients is significantly higher. It can be concluded that type 2 diabetes mellitus patients should be managed to prevent NAFLD.

Circulating level of CD4+ CD25+ FOXP3+ T cells in patients with chronic urticaria.

BACKGROUND: CD4+ CD25+ T-regulatory (Treg) cells play critical roles in maintaining peripheral tolerance and preventing autoimmunity. As characteristics of Treg cells have not been precisely investigated in chronic urticaria (CU) yet, this study was performed. OBJECTIVE: To determine the frequencies of circulating CD4+ CD25+ FOXP3+ T cells and serum levels of interleukin (IL)-10, transforming growth factor (TGF)-ß, and IL-17 in patients with chronic autoimmune urticaria and chronic idiopathic urticaria compared to healthy controls. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from patients with CU and healthy controls. The frequency of CD4+ CD25+ T cells in PBMCs and expression levels of FOXP3 were detected by flow cytometry. The serum levels of IL-10, TGF-ß, and IL-17 were measured by enzyme-linked immunosorbent assay. RESULTS: A significant decrease in the percentage of circulating CD4+ CD25+ FOXP3+ T cells was detected in patients with CU, compared to control subjects. However, no significant difference was detected on the serum levels of IL-10, TGF-ß, and IL-17 between patients with CU and control subjects. CONCLUSIONS: This study demonstrated that the frequency of Treg cells in PBMCs was decreased in patients with CU. Further studies are needed to clarify the exact role of Treg cells in the pathogenesis of CU and factors regulating their function.