Use of Fecal Occult Blood Testing as a Diagnostic Tool for Clinical Indications: A Systematic Review and Meta-Analysis.

INTRODUCTION: Fecal occult blood tests (FOBTs) are validated only for colorectal cancer (CRC) screening, but are commonly used as a diagnostic test in other clinical settings. We performed a systematic review to assess performance characteristics of FOBT as a diagnostic test for clinical indications. METHODS: Bibliographic databases were searched to identify studies in adult patients with a specific gastrointestinal symptom or condition who underwent FOBT and a reference test and provided data on diagnoses. Our primary end point was sensitivity. Risk of bias was assessed with the QUADAS-2 tool. RESULTS: Twenty-two studies met the inclusion criteria: 12 in iron deficiency anemia (IDA) (5 fecal immunochemical (FIT) and 7 guaiac based), 8 in ulcerative colitis (FIT), and 2 in acute diarrhea (guaiac based). Only 2 studies had low risk of bias on all domains of the QUADAS-2. On meta-analysis, FOBT had a sensitivity of 0.58 (95% confidence interval [CI] 0.53-0.63) and a specificity of 0.84 (95% CI 0.75-0.89) in predicting presumptive causes of IDA at endoscopy, with comparable results for guaiac-based tests and FIT. Sensitivity was higher for CRC (0.83) than non-CRC lesions (0.54). FIT had a sensitivity of 0.72 (95% CI 0.57-0.84) and a specificity of 0.80 (95% CI 0.67-0.89) in predicting endoscopic activity in UC. Sensitivities of FOBT for positive stool culture in acute diarrhea were 0.38 and 0.87. DISCUSSION: Sensitivity of FOBT is poor for IDA: 42% of patients with identifiable causes of IDA had false-negative FOBT. Our results did not show acceptable performance characteristics for FOBT to guide decisions regarding endoscopic evaluation and do not support its use in IDA.

SPLIT-DOSE BOWEL PREPARATION IS SUPERIOR TO STRAIGHT-DOSE IN HOSPITALIZED PATIENTS UNDERGOING INPATIENT COLONOSCOPY.

BACKGROUND: There is a two-fold higher rate of failed colonoscopy secondary to inadequate bowel preparation among hospitalized versus ambulatory patients. Split-dose bowel preparation is widely used in the outpatient setting but has not been generally adapted for use among the inpatient population. OBJECTIVE: The aim of this study is to evaluate the effectiveness of split versus single dose polyethylene glycol bowel (PEG) preparation for inpatient colonoscopies and determine additional procedural and patient characteristics that drive inpatient colonoscopy quality. METHODS: A retrospective cohort study was performed on 189 patients who underwent inpatient colonoscopy and received 4 liters PEG as either split- or straight-dose during a 6-month period in 2017 at an academic medical center. Bowel preparation quality was assessed using Boston Bowel Preparation Score (BBPS), Aronchick Score, and reported adequacy of preparation. RESULTS: Bowel preparation was reported as adequate in 89% of the split-dose group versus 66% in the straight-dose group (P=0.0003). Inadequate bowel preparations were documented in 34.2% of the single-dose group and 10.7% of the split-dose group (P<0.001). Only 40% of patients received split-dose PEG. Mean BBPS was significantly lower in the straight-dose group (Total: 6.32 vs 7.73, P<0.001). CONCLUSION: Split-dose bowel preparation is superior to straight-dose preparation across reportable quality metrics for non-screening colonoscopies and was readily performed in the inpatient setting. Interventions should be targeted at shifting the culture of gastroenterologist prescribing practices towards use of split-dose bowel preparation for inpatient colonoscopy.

p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus.

The subgranular zone (SGZ) of the dentate gyrus of the hippocampus is a brain region where robust neurogenesis continues throughout adulthood. Cyclin-dependent kinases (CDKs) have a primary role in controlling cell division and cellular proliferation. p21(Cip1) (p21) is a CDK inhibitor that restrains cell cycle progression. Confocal microscopy revealed that p21 is abundantly expressed in the nuclei of cells in the SGZ and is colocalized with NeuN, a marker for neurons. Doublecortin (DCX) is a cytoskeletal protein that is primarily expressed by neuroblasts. By using FACS analysis it was found that, among DCX-positive cells, 42.8% stained for p21, indicating that p21 is expressed in neuroblasts and in newly developing neurons. p21-null (p21(-/-)) mice were examined, and the rate of cellular proliferation, as measured by BrdU incorporation, was increased in the SGZ of p21(-/-) compared with WT mice. In addition, the levels of both DCX and NeuN protein were increased in p21(-/-) mice, further demonstrating increased hippocampal neuron proliferation. Chronic treatment with the tricyclic antidepressant imipramine (10 mg/kg per day i.p. for 21 days) markedly decreased hippocampal p21 mRNA and protein levels, produced antidepressant-like behavioral changes in the forced swim test, and stimulated neurogenesis in the hippocampus. These results suggest that p21 restrains neurogenesis in the SGZ and imipramine-induced stimulation of neurogenesis might be a consequence of decreased p21 expression and the subsequent release of neuronal progenitor cells from the blockade of proliferation. Because many antidepressants stimulate neurogenesis, it is possible that their shared common mechanism of action is suppression of p21.

O preparo intestinal em dose dividida é superior à dose direta em pacientes hospitalizados submetidos à colonoscopia hospitalar / Split-dose bowel preparation is superior to straight-dose in hospitalized patients undergoing inpatient colonoscopy

ABSTRACT Background: There is a two-fold higher rate of failed colonoscopy secondary to inadequate bowel preparation among hospitalized versus ambulatory patients. Split-dose bowel preparation is widely used in the outpatient setting but has not been generally adapted for use among the inpatient population. Objective The aim of this study is to evaluate the effectiveness of split versus single dose polyethylene glycol bowel (PEG) preparation for inpatient colonoscopies and determine additional procedural and patient characteristics that drive inpatient colonoscopy quality. Methods: A retrospective cohort study was performed on 189 patients who underwent inpatient colonoscopy and received 4 liters PEG as either split- or straight-dose during a 6-month period in 2017 at an academic medical center. Bowel preparation quality was assessed using Boston Bowel Preparation Score (BBPS), Aronchick Score, and reported adequacy of preparation. Results: Bowel preparation was reported as adequate in 89% of the split-dose group versus 66% in the straight-dose group (P=0.0003). Inadequate bowel preparations were documented in 34.2% of the single-dose group and 10.7% of the split-dose group (P<0.001). Only 40% of patients received split-dose PEG. Mean BBPS was significantly lower in the straight-dose group (Total: 6.32 vs 7.73, P<0.001). Conclusion: Split-dose bowel preparation is superior to straight-dose preparation across reportable quality metrics for non-screening colonoscopies and was readily performed in the inpatient setting. Interventions should be targeted at shifting the culture of gastroenterologist prescribing practices towards use of split-dose bowel preparation for inpatient colonoscopy.

RESUMO Contexto: Há uma taxa duas vezes maior de colonoscopia com falha secundária ao preparo intestinal inadequado entre pacientes hospitalizados versus ambulatoriais. O preparo intestinal em dose dividida é amplamente utilizado em ambulatório, mas geralmente não foi adaptado para uso entre a população hospitalar. Objetivo: O objetivo deste estudo é avaliar a eficácia da preparação do intestino de polietilenoglicol (PEG) em dose única versus doses separadas para colonoscopias hospitalares e determinar características adicionais do procedimento e do paciente que promovam a qualidade da colonoscopia do paciente internado. Métodos Um estudo de coorte retrospectivo foi realizado em 189 pacientes que foram submetidos a colonoscopia hospitalar e receberam 4 litros de PEG como dose dividida ou direta durante um período de 6 meses em 2017 em um centro médico acadêmico. A qualidade do preparo intestinal foi avaliada usando-se o Boston Bowel Preparation Score (BBPS), o Aronchick Score, e relatório sobre a adequação do preparo. Resultados O preparo intestinal foi relatado como adequado em 89% do grupo de dose dividida versus 66% no grupo de dose direta (P=0,0003). Preparações intestinais inadequadas foram documentadas em 34,2% do grupo de dose única e 10,7% do grupo de dose dividida (P<0,001). Apenas 40% dos pacientes receberam PEG em dose fracionada. O BBPS médio foi significativamente menor no grupo de dose direta (total: 6,32 vs 7,73, P<0,001). Conclusão O preparo intestinal em dose dividida é superior ao preparo de dose única em todas as métricas de qualidade relacionadas para colonoscopias sem triagem e foi adequadamente realizado no ambiente de internação. As intervenções devem ser direcionadas para mudar a cultura das práticas de prescrição de gastroenterologistas para o uso de preparação intestinal em dose dividida para colonoscopia hospitalar.

Postoperative Gastrointestinal Telemetry with an Acoustic Biosensor Predicts Ileus vs. Uneventful GI Recovery.

BACKGROUND: Postoperative ileus (POI) can worsen outcomes, increase cost, and prolong hospitalization. We previously found that a disposable, non-invasive acoustic gastrointestinal surveillance (AGIS) biosensor distinguishes healthy controls from patients recovering from abdominal surgery. Here, we tested whether AGIS can prospectively predict which patients will develop POI in a multicenter study. STUDY DESIGN: AGIS is a disposable device embedded with a microphone that adheres to the abdominal wall and connects to a computer that measures acoustic intestinal rate (IR), defined as motility events/minute. We applied AGIS for 60 min before and continuously after abdominal surgery. Clinicians blinded to AGIS recordings clinically separated patients into those with vs. without POI. We used receiver operating characteristic curve analysis to calculate sensitivity, specificity, and negative predictive value (NPV) of AGIS to predict POI. RESULTS: There were 28 subjects; nine developed POI. Median IR was 3.01/min and 4.46/min between POI and non-POI groups, respectively (P = 0.03). AGIS predicted POI onset with a sensitivity, specificity, and NPV of 63, 72, and 81%, respectively. CONCLUSION: Non-invasive, abdominal, acoustic monitoring prospectively predicts POI. Surgeons may use AGIS to rule out POI with over 80% certainty; this offers added confidence to advance feeding earlier in those for whom it is safe.

Balancing opioid-induced gastrointestinal side effects with pain management: Insights from the online community.

Opioids cause gastrointestinal (GI) symptoms such as nausea, vomiting, pain, and (in 40 percent) constipation that diminish patients' quality of life. Outside traditional surveys, little is known about the opioid-induced constipation (OIC) patient experience and its impact on pain management. The purpose of this study was to use data from social media platforms to qualitatively examine patient beliefs about OIC and other prominent GI side effects, their impact on effective pain management and doctor-patient interaction. The authors collected Tweets from March 25 to July 31, 2014, and e-forum posts from health-related social networking sites regardless of timestamp. The authors identified specific keywords related to opioids and GI side effects to locate relevant content in the dataset, which was then manually coded using ATLAS.ti software. The authors examined 2,519,868 Tweets and more than 1.8 billion e-forum posts, of which, 88,586 Tweets and 9,767 posts satisfied the search criteria. Three thousand three individuals experienced opioidinduced GI side effects, mostly related to phenanthrenes (n = 1,589), and 1,274 (42.4 percent) individuals described constipation. Over-the-counter medications and nonevidence-based natural approaches were most commonly used to alleviate constipation. Many individuals questioned, rotated, reduced, or stopped their opioid treatments as a result of their GI side effects. Investigation of social media reveals a struggle to balance pain management with opioid-induced GI side effects, especially constipation. Individuals are often unprepared to treat OIC, to modify opioid regiments without medical advice, and to resort to using natural remedies and treatments lacking scientific evidence of effectiveness. These results identify opportunities to improve physician-patient communication and explore effective treatment alternatives.

Dkk-3, a secreted wnt antagonist, suppresses tumorigenic potential and pulmonary metastasis in osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3/REIC) has been known to inhibit canonical Wnt/ ß -catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using in vivo and in vitro studies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector. In vitro experiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy.