Outcomes of use of electromagnetic guidance with responsive insertion technology (RIT) during colonoscopy: a prospective randomized controlled trial.

Background and study aims Colonoscopy can be technically challenging and cause discomfort in patients. The integrated Scope Guide assist is built in to show that with its use outcomes are improved during colonoscopy. We aimed to test the usefulness of the Magnetic Scope Guide Assist (ScopeGuide ) with respect to cecal intubation time, and other procedural quality outcomes. Patients and methods We conducted a prospective study of outpatients undergoing elective colonoscopy at the endoscopic units of the University of Alabama at Birmingham (UAB) from March 2016 to July 2016. Patients were randomly assigned in a 1:1 block design to groups that either had standard colonoscopy or Scope-guided colonoscopy. The primary outcome measure was cecal intubation time (CIT). Secondary outcome measures included use of manual pressure, position changes for cecal intubation and sedation requirements. Results Three hundred patients were randomized to either group; standard (n = 150) vs. Scope-guided (n = 150). The mean CIT was not statistically different for the standard and the Scope-guided groups (4.6 vs. 4.3 minutes; P  = 0.46). There were also no statistical differences in frequency of manual pressure applied (16.7 % for Scope-guided vs. 19.1 % for standard; P  = 0.65) or position changes (11.4 % for scope guided vs. 8.8 % standard; P  = 0.56). Sedation requirements showed lesser use of midazolam (3.9 mg vs. 4.7 mg, P  = 0.003) in the Scope-guide group, while there was no significant difference in use of fentanyl (fentanyl - 62.1 mg vs. 68.9 mg, P  = 0.09 similar between groups, for Scope-guided vs. standard groups, respectively). Adverse events were similar in both groups. Conclusions In patients undergoing routine elective colonoscopy, use of ScopeGuide by experienced colonoscopists did not improve CIT or affect the frequency of ancillary maneuvers. The benefit of this device during training of endoscopists could be considered for further studies.

Case series on multimodal endoscopic therapy for gastric antral vascular ectasia, a tertiary center experience.

AIM: To study and describe patients who underwent treatment for gastric antral vascular ectasia (GAVE) with different endoscopic treatment modalities. METHODS: We reviewed patients with GAVE who underwent treatment at University of Alabama at Birmingham between March 1, 2012 and December 31, 2016. Included patients had an endoscopic diagnosis of GAVE with associated upper gastrointestinal bleeding or iron deficiency anemia. RESULTS: Seven out of 15 patients had classic watermelon description for GAVE, 1/15 with diffuse/honeycomb pattern and 6/15 with nodular GAVE per EGD description. Seven out of 15 patients required multimodal treatment. Four out of six of patients with endoscopically nodular GAVE required multimodal therapy. Overall, mean pre- and post-treatment hemoglobin (Hb) values were 8.2 ± 0.8 g/dL and 9.7 ± 1.6 g/dL, respectively (P ≤ 0.05). Mean number of packed red blood cells transfusions before and after treatment was 3.8 ± 4.3 and 1.2 ± 1.7 (P ≤ 0.05), respectively. CONCLUSION: Patients with nodular variant GAVE required multimodal approach more frequently than non-nodular variants. Patients responded well to multimodal therapy and saw decrease in transfusion rates and increase in Hb concentrations. Our findings suggest a multimodal approach may be beneficial in nodular variant GAVE.

PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum.

Background and Aims:Patatin-like phospholipase domain protein 3 (PNPLA3) polymorphisms (rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals. Results: Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16-1.85) and 2.76 (2.30-3.13), and were 1.75 (1.24-2.46) and 4.44 (2.92-6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90-6.13) and 5.05 (1.47-17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2-3 to grade 0-1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43-3.80), 1.80 (1.36-2.37), 1.66 (1.42-1.94), 1.58 (1.19-2.10), and 2.63 (1.87-3.69) respectively. Subgroup analysis based on ethnicity showed similar results. Conclusions:PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs. PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD.

Acute multifocal hemorrhagic retinal vasculitis in a child: a case report.

BACKGROUND: Acute Multifocal Hemorrhagic Retinal Vasculitis (AMHRV) is a rare disease with unknown incidence that presents with abrupt onset of visual loss associated with retinal vasculitis, retinal hemorrhage, non-confluent posterior retinal infiltrates, vitreous cellular inflammation and papillitis in, otherwise, healthy adult individuals. The reported treatment options for Acute Multifocal Hemorrhagic Retinal Vasculitis are oral corticosteroids, intravitreal ganciclovir and laser photocoagulation or vitrectomy. We report a child with Acute Multifocal Hemorrhagic Retinal Vasculitis who was treated with aggressive immunosuppressive therapy resulting in a favorable visual outcome. CASE PRESENTATION: A retrospective case report of a 10-year-old African American girl who developed unilateral Acute Multifocal Hemorrhagic Retinal Vasculitis, which later on progressed bilaterally. We conducted a review of the clinical, laboratory and photographic records to evaluate her functional and anatomic outcome after aggressive immunosuppressive treatment. During the first 4 months of treatment of OD with intravitreal ganciclovir, intravitreal dexamethasone and systemic prednisone, the change in vision in OD improved from light perception (LP) to counting fingers (CF). During the next 18 months of aggressive systemic treatment of OD and the newly affected left eye (OS), the change in vision improved from CF in OD and CF in OS to 20/200 in OD and 20/80 in OS. Management during the 18-month interval included rituximab infusions, cyclophosphamide/methylprednisolone infusions, prednisone and mycophenolate. CONCLUSIONS: This is the first reported case of Acute Multifocal Hemorrhagic Retinal Vasculitis occurring in a child. Ophthalmologists should be aware of the need to treat severe Acute Multifocal Hemorrhagic Retinal Vasculitis with aggressive immunosuppressive agents in collaboration with rheumatologists to obtain the best possible visual outcome.

Cell mediated immune responses through TLR4 prevents DMBA-induced mammary carcinogenesis in mice.

Toll-like receptors (TLRs) activate signals that are critically involved in the initiation of adaptive immune responses and many tumorigenic chemicals have been associated with activation of those pathways. To determine the role of TLR-4 (TLR4) in mammary carcinogenesis, we subjected TLR4 deficient and wild type (WT) mice to oral gavage with carcinogenic polyaromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA). TLR4 deficient mice developed more tumors relative to the WT mice. T cells of TLR4 deficient mice produced elevated levels of IL-17 and lower levels of IFN-γ relative to WT mice. IL-12 secreted by CD11c(+) cells was higher in WT mice, whereas greater amounts of IL-23 were produced by CD11c(+) cells from TLR4 deficient mice. Moreover, there was higher incidence of regulatory T cells in TLR4 deficient mice than WT mice. Similarly, various markers of angiogenesis [matrix metalloproteinases (MMP)-2 and MMP-9, CD31 and vascular endothelial growth factor] were highly expressed in tumors from TLR4 deficient mice than WT mice. The results of this study indicate that TLR4 plays an important role in the prevention of DMBA induced mouse mammary tumorigenesis and efforts to divert the cell-mediated immune response may, therefore, prove to be beneficial in the prevention of mammary tumors.

Protective role of Toll-like receptor 4 during the initiation stage of cutaneous chemical carcinogenesis.

Toll-like receptors (TLR) activate multiple steps in inflammatory reactions in innate immune responses. They also activate signals that are critically involved in the initiation of adaptive immune responses. Many tumorigenic chemicals have been associated with endotoxin hypersensitivity mediated through TLR4. To determine the role of TLR4 in cutaneous skin carcinogenesis, we treated TLR4-deficient C3H/HeJ mice and the TLR4-normal C3H/HeN mice with the carcinogenic polyaromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA). TLR4-deficient C3H/HeJ mice developed more tumors relative to the TLR4-normal C3H/HeN mice. Both C3H/HeN and C3H/HeJ mice developed a T-cell-mediated immune response to topically applied DMBA. Interestingly, the cell-mediated immune response was mediated by IFN-gamma in C3H/HeN mice and by interleukin (IL)-17 in C3H/HeJ mice. Moreover, C3H/HeN mice had elevated circulating levels of IFN-gamma following topical application of DMBA, whereas IL-17 was elevated in C3H/HeJ mice. The results of this study indicate that TLR4 plays an important role in the prevention of DMBA skin tumorigenesis and that this is associated with differences in the T-cell subtype activated. Efforts to divert the cell-mediated immune response from one that is IL-17 mediated to one that is IFN-gamma mediated may prove to be beneficial in the prevention of DMBA-induced cutaneous tumors.