The Impact of Patient Education Level on Split-Dose Colonoscopy Bowel Preparation for CRC Prevention.

INTRODUCTION: AGA guidelines emphasize split-dose bowel preparation (BP) to ensure high-quality colonoscopy for the prevention of colorectal cancer (CRC). Split dose results in higher-quality preparation, but understanding instructions might be more difficult. Lower education levels may negatively influence BP quality. The confounding role of education level on BP quality was investigated. METHODS: This was a cross-sectional study of 60 patients given split-dose BP. Patients consented and were asked three Likert scale questions based on BP instructions before the procedure. Compliance was self-reported. BP adequacy and the number of adenomas were recorded. BP was characterized as adequate (excellent, good) or inadequate (fair, poor). Data was analyzed with chi-square, odds ratio, Mann-Whitney, and regression analysis. RESULTS: Thirty-one (52%) patients were high school graduates, 21 (38%) completed some college, and 6 (10%) were college graduates. College-educated patients had adequate BP (72%) more often than high school graduates (51%) (p = 0.02). Adenoma findings were not significantly different. The Likert scale mean ranks for patient understanding and reviewing of instructions were comparable between the two groups. Patient rating of scheduler explanations of the importance of following instructions was significantly better in the college group (mean ranks 2.59 and 1.83, respectively; p = 0.018). DISCUSSION: Patient education level significantly affected the success of BP. Split BP can be more complex to comprehend, and instructions should consider patient education level. Specific intervention programs should be implemented to advise patients with less education that poor preparation may result in missed advanced neoplasias and subsequent procedures.

LRRK2(I2020T) functional genetic interactors that modify eye degeneration and dopaminergic cell loss in Drosophila.

Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta is the primary cause for motor symptoms observed in Parkinson's disease (PD). Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most commonly linked contributor to familial PD. LRRK2 is suggested to be involved in a wide variety of cellular processes, but deciphering its role in the pathogenesis of PD has been difficult. Modelling PD in rodents has been a persistent challenge for the field. However, the fruit fly has been exploited to recapitulate PD gene related dopaminergic cell loss. Using the GAL4-UAS system and established models of hLRRK2 induced eye degeneration in Drosophila, we conducted an unbiased suppressor/enhancer screen to uncover genetic modifiers of LRRK2. We have identified 36 candidate interactors that modify LRRK2 induced toxicity in the Drosophila eye. Importantly, we determined that a subset of these interactors also modified hLRRK2(I2020T) induced dopaminergic neuronal loss in the fly brain and uncovered 16 candidates that modify dopaminergic cell loss. Our results suggest LRRK2 may be involved in a wide variety of cellular processes and the results from this screen provide an important genetic resource for further evaluation of LRRK2 function.

Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease.

Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's disease (PD). However, its physiological and pathological functions are unknown. Therefore, we generated several independent Drosophila lines carrying WT or mutant human LRRK2 (mutations in kinase, COR or LRR domains, resp.). Ectopic expression of WT or mutant LRRK2 in dopaminergic neurons caused their significant loss accompanied by complex age-dependent changes in locomotor activity. Overall, the ubiquitous expression of LRRK2 increased lifespan and fertility of the flies. However, these flies were more sensitive to rotenone. LRRK2 expression in the eye exacerbated retinal degeneration. Importantly, in double transgenic flies, various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin. This evidence suggests a genetic interaction between these PD-relevant genes.

Parkinson's disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures.

Sequence variants at or near the leucine-rich repeat kinase 2 (LRRK2) locus have been associated with susceptibility to three human conditions: Parkinson's disease (PD), Crohn's disease and leprosy. As all three disorders represent complex diseases with evidence of inflammation, we hypothesized a role for LRRK2 in immune cell functions. Here, we report that full-length Lrrk2 is a relatively common constituent of human peripheral blood mononuclear cells (PBMC) including affinity isolated, CD14(+) monocytes, CD19(+) B cells, and CD4(+) as well as CD8(+) T cells. Up to 26% of PBMC from healthy donors and up to 43% of CD14(+) monocytes were stained by anti-Lrrk2 antibodies using cell sorting. PBMC lysates contained full-length (>260 kDa) and higher molecular weight Lrrk2 species. The expression of LRRK2 in circulating leukocytes was confirmed by microscopy of human blood smears and in sections from normal midbrain and distal ileum. Lrrk2 reactivity was also detected in mesenteric lymph nodes and spleen (including in dendritic cells), but was absent in splenic mononuclear cells from lrrk2-null mice, as expected. In cultured bone marrow-derived macrophages from mice we made three observations: (i) a predominance of higher molecular weight lrrk2; (ii) the reduction of autophagy marker LC3-II in (R1441C)lrrk2-mutant cells (<31%); and (iii) a significant up-regulation of lrrk2 mRNA (>fourfold) and protein after exposure to several microbial structures including bacterial lipopolysaccharide and lentiviral particles. We conclude that Lrrk2 is a constituent of many cell types in the immune system. Following the recognition of microbial structures, stimulated macrophages respond with altered lrrk2 gene expression. In the same cells, lrrk2 appears to co-regulate autophagy. A pattern recognition receptor-type function for LRRK2 could explain its locus' association with Crohn's disease and leprosy risk. We speculate that the role of Lrrk2 in immune cells may also be relevant to the susceptibility of developing PD or its progression.

Open-access colonoscopy quality indicators and patient perception using split-dose bowel preparation.

BACKGROUND AND AIM: Open-access (OA) colonoscopies are defined as those scheduled without a gastrointestinal (GI) office visit. Past research has not focused on split preparation use and patient perception within OA. We aim to identify differences in bowel preparation (BP) adequacy, adenoma detection rate (ADR), self-reported compliance, and patient perception between OA and GI providers using split prep. METHODS: This was a cross-sectional study using split BP for colonoscopies. Patients completed a survey, and demographics, BP adequacy, and ADR were recorded. BP compliance was self-reported. Patients were asked three questions qualifying the BP instructions. Data were analyzed using chi square and Mann-Whitney tests by SPSS. RESULTS: BP adequacy was reported for 56 of 60 patients. Twenty-one participants (38%) were scheduled on OA, and 35 participants (62%) were scheduled after a GI office visit. Adequate BP was more frequent in 86% (18/21) of OA patients compared to 60% (21/35) in the GI group (P = 0.043). OA patients reported better review and explanation of the BP instructions compared to GI patients. There was no statistical difference between the demographics of the OA and GI groups or self-reported compliance and patient understanding of instructions. CONCLUSION: OA scheduled colonoscopies were associated with more adequate BP. This could be explained by patients' self-motivation or an explanation of the importance of completing BP. This study supports the use of OA procedures as a standard of care.

Metastatic Esophageal Cancer Presenting as an Orbital Mass.

We report a case of adenocarcinoma of the esophagus presenting as an orbital metastasis prior to the primary diagnosis. A 66-year-old white male presented to his ophthalmologist with right orbital swelling for several months. Magnetic resonance imaging revealed a supraorbital infiltrative mass. Pathology from the mass revealed findings consistent with adenocarcinoma of gastrointestinal origin. Upper endoscopy revealed distal esophageal stricture and irregularities. Pathology from the esophagus showed the same malignancy found in the orbit. An orbital swelling can manifest as the initial presentation of metastatic disease and should be taken seriously to avoid delay in diagnosis and treatment.

Hepatobiliary Tumors: Update on Diagnosis and Management.

Tumors of the liver and biliary tree, mainly hepatocellular carcinoma and cholangiocarcinoma, are the second leading cause of cancer related death worldwide and the sixth leading cause of cancer related death among men in developed countries. Recent developments in biomarkers and imaging modalities have enhanced early detection and accurate diagnosis of these highly fatal malignancies. These advances include serological testing, micro-ribonucleic acids, fluorescence in situ hybridization, contrast-enhanced ultrasound, and hepatobiliary-phase magnetic resonance imaging. In addition, there have been major developments in the surgical and nonsurgical management of these tumors, including expansion of the liver transplantation criteria, new locoregional treatments, and molecularly targeted therapies. In this article, we review various types of hepatobiliary tumors and discuss new developments in their diagnosis and management.

Bone-anchored hearing aid: why do some patients refuse it?

OBJECTIVE: Bone-anchored hearing aid (BAHA™) is a proven tool to improve hearing. Nevertheless, there are patients who are candidates for BAHA™ implants that end up refusing the surgery. The objective of this study is to review our BAHA™ experience with particular emphasis on reasons behind the refusal of some candidates. METHODS: A prospective cohort of 100 consecutive new candidates referred to The BAHA™ program in a tertiary health care center. Candidates' demographics, hearing status, Co-morbidities and audiometeric tests were all recorded. Patients' acceptance or refusal was noted alongside the reasons to refuse BAHA™. RESULTS: 100 new candidates were seen for BAHA™ assessment, 10 patients were excluded due to incomplete data. There were 68 children and 22 adults. Unilateral Conductive Hearing Loss was the most common reason for consultation (40%), followed by unilateral SNHL (23.3%). Aural Atresia was the commonest clinical finding (36.6%). The commonest reason for refusal was social acceptance by the parents due to concern with cosmesis. CONCLUSION: The main reason of BAHA™ surgery refusal, in otherwise eligible candidates, is related to cosmesis. Patients with congenital anomalies were the most likely candidates to accept BAHA™ implants.