A randomized controlled trial comparing efficacy of early video capsule endoscopy with standard of care in the approach to nonhematemesis GI bleeding (with videos).

BACKGROUND AND AIMS: Patients presenting with nonhematemesis GI bleeding (NHGIB) represent a diagnostic challenge for physicians. We performed a randomized controlled trial to assess the benefits of deployment of a video capsule soon after admission in the management of patients presenting with melena, hematochezia, or severe anemia compared with standard of care management. METHODS: Patients admitted with NHGIB were randomized and placed into 1 of 2 study groups. In the experimental group, patients ingested a video capsule soon after admission to the hospital. These patients had further endoscopic workup based on the findings from the capsule. Patients in the control group underwent endoscopic evaluation (ie, upper endoscopy, capsule endoscopy, and/or colonoscopy) to identify the source of bleeding as directed by the attending gastroenterologist's interpretation of their clinical presentation. The primary endpoint for this study was the rate of localization of bleeding during hospitalization. RESULTS: Eighty-seven patients were included in this study: 45 randomized to the standard of care arm and 42 to the early capsule arm. A bleeding source was localized in 64.3% of the patients in the early capsule arm and in 31.1% of the patients in the standard of care arm (P < .01). The likelihood of endoscopic localization of bleeding over time was greater for patients receiving early capsule endoscopy compared with those in the standard of care arm (adjusted hazard ratio, 2.77; 95% confidence interval, 1.36-5.64). CONCLUSIONS: For patients admitted to the hospital for NHGIB, early capsule endoscopy is a safe and effective alternative for the detection of the source of bleeding. (Clinical trial registration number: NCT02442830.).

Lower Endoscopic Diagnostic Yields Observed in Non-hematemesis Gastrointestinal Bleeding Patients.

BACKGROUND: Location of bleeding can present a diagnostic challenge in patients without hematemesis more so than those with hematemesis. AIM: To describe endoscopic diagnostic yields in both hematemesis and non-hematemesis gastrointestinal bleeding patient populations. METHODS: A retrospective analysis on a cohort of 343 consecutively identified gastrointestinal bleeding patients admitted to a tertiary care center emergency department with hematemesis and non-hematemesis over a 12-month period. Data obtained included presenting symptoms, diagnostic lesions, procedure types with diagnostic yields, and hours to diagnosis. RESULTS: The hematemesis group (n = 105) took on average 15.6 h to reach a diagnosis versus 30.0 h in the non-hematemesis group (n = 231), (p = 0.005). In the non-hematemesis group, the first procedure was diagnostic only 53% of the time versus 71% in the hematemesis group (p = 0.02). 25% of patients in the non-hematemesis group required multiple procedures versus 10% in the hematemesis group (p = 0.004). Diagnostic yield for a primary esophagogastroduodenoscopy was 71% for the hematemesis group versus 50% for the non-hematemesis group (p = 0.01). Primary colonoscopies were diagnostic in 54% of patients and 12.5% as a secondary procedure in the non-hematemesis group. A primary video capsule endoscopy yielded a diagnosis in 79% of non-hematemesis patients (n = 14) and had a 70% overall diagnostic rate (n = 33). CONCLUSION: Non-hematemesis gastrointestinal bleeding patients undergo multiple non-diagnostic tests and have longer times to diagnosis and then compared those with hematemesis. The high yield of video capsule endoscopy in the non-hematemesis group suggests a role for this device in this context and warrants further investigation.

Multiplex detection of pancreatic cancer biomarkers using a SERS-based immunoassay.

Early diagnosis of pancreatic cancer (PC) is critical to reduce the mortality rate of this disease. Current biological analysis approaches cannot robustly detect several low abundance PC biomarkers in sera, limiting the clinical application of these biomarkers. Enzyme linked immunosorbent assay and radioimmunoassay are two common platforms for detection of biomarkers; however, they suffer from some limitation. This study demonstrates a novel system for multiplex detection of pancreatic biomarkers CA19-9, MMP7 and MUC4 in sera samples with high sensitivity using surface enhanced Raman spectroscopy. Measuring the levels of these biomarkers in PC patients, pancreatitis patients, and healthy individuals reveals the unique expression pattern of these markers in PC patients, suggesting the great potential of using this approach for early diagnostics of PCs.

The chicken frizzle feather is due to an α-keratin (KRT75) mutation that causes a defective rachis.

Feathers have complex forms and are an excellent model to study the development and evolution of morphologies. Existing chicken feather mutants are especially useful for identifying genetic determinants of feather formation. This study focused on the gene F, underlying the frizzle feather trait that has a characteristic curled feather rachis and barbs in domestic chickens. Our developmental biology studies identified defects in feather medulla formation, and physical studies revealed that the frizzle feather curls in a stepwise manner. The frizzle gene is transmitted in an autosomal incomplete dominant mode. A whole-genome linkage scan of five pedigrees with 2678 SNPs revealed association of the frizzle locus with a keratin gene-enriched region within the linkage group E22C19W28_E50C23. Sequence analyses of the keratin gene cluster identified a 69 bp in-frame deletion in a conserved region of KRT75, an α-keratin gene. Retroviral-mediated expression of the mutated F cDNA in the wild-type rectrix qualitatively changed the bending of the rachis with some features of frizzle feathers including irregular kinks, severe bending near their distal ends, and substantially higher variations among samples in comparison to normal feathers. These results confirmed KRT75 as the F gene. This study demonstrates the potential of our approach for identifying genetic determinants of feather forms.

Computerized 3-dimensional localization of a video capsule in the abdominal cavity: validation by digital radiography.

BACKGROUND: Wireless video capsule endoscopy allows the noninvasive visualization of the small intestine. Currently, capsules do not provide localization information while traversing the GI tract. OBJECTIVE: To report on the radiological validation of 3-dimensional localization software incorporated in a newly developed capsule. By using radiofrequency transmission, the software measures the strength of the capsule's signal to locate the position of the capsule. SETTING: This study was performed at the University of Massachusetts Medical Center, Worcester, Mass. PATIENTS: Thirty healthy volunteers consented to the experimental procedure. DESIGN: After ingestion of the capsule, subjects had 5 sets of anteroposterior and lateral radiographs taken every 30 minutes while the software calculated the position of the capsule. By using the radiographs, we calculated the location of the capsule in the abdominal cavity and compared the results with those generated by the software. RESULTS: Average error (and standard deviation) among the 3-dimensional coordinates was X, 2.00 cm (1.64); Y, 2.64 cm (2.39); and Z, 2.51 cm (1.83). The average total spatial error among all measurements was 13.26 cm(3) (22.72). There was a correlation between increased subject body mass index and the 3-dimensional software measurement error. LIMITATIONS: This study was performed in healthy volunteers and needs further validation in patients with small intestinal disorders. CONCLUSIONS: The new 3-dimensional software provides localization of the capsule consistent with radiological observations. However, further validation of the software's clinical utility is required with a prospective clinical trial.

Timing of video capsule endoscopy relative to overt obscure GI bleeding: implications from a retrospective study.

BACKGROUND: Diagnostic yield of video capsule endoscopy (VCE) may be higher if it is performed closer to the time of overt obscure GI bleeding (OOGIB). OBJECTIVE: To evaluate the diagnostic yield of VCE and rate of therapeutic intervention for OOGIB for inpatients and outpatients with respect to timing of the intervention. DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. PATIENTS: Patients who had VCE for OOGIB between August 2008 and August 2010. INTERVENTIONS: VCE for inpatients versus outpatients. MAIN OUTCOME MEASURES: Diagnostic yield and rate of therapeutic intervention for inpatients versus outpatients. RESULTS: One hundred forty-four inpatients (65 women) and 116 outpatients (49 women) were included. Diagnostic yield was 65.9% for inpatients versus 53.4% for outpatients (P = .054). Inpatients were divided into those who had VCE within 3 days (<3 days; n = 90) of admission versus after 3 days (>3 days; n = 54). Active bleeding and/or an angioectasia was found in 44.4% of the <3-day group compared with 27.8% of the >3-day group (P = .046) versus 25.8% of the outpatients. Therapeutic intervention was performed in 18.9% of the <3-day group versus 7.4% of the >3-day group (P = .046) versus 10.3% of outpatients. Diagnostic yield and therapeutic intervention rate between the >3-day group and outpatients were not significantly different. Length of stay (days) was less in the <3-day cohort, at 6.1 versus 10.3 in the >3-day cohort (P < .0001). LIMITATIONS: Long-term outcomes were not studied. This was a retrospective study. CONCLUSIONS: Early deployment of VCE within 3 days of admission results in a higher diagnostic yield and therapeutic intervention rate and an associated reduction of length of stay.

CE: Febrile Neutropenia in the Chemotherapy Patient.

ABSTRACT: Febrile neutropenia is a serious complication of chemotherapy treatment and may present as the only clinical sign of infection. If not addressed in a timely manner, it may progress to multisystem organ failure and may be fatal. Initial assessment of fever in those receiving chemotherapy requires prompt administration of antibiotics, ideally within one hour of presentation. Depending on the clinical status of the patient, antibiotic treatment may occur in the inpatient or outpatient setting. Nurses play an important role in the identification and treatment of patients at high risk for febrile neutropenia through assessment and adherence to clinical practice guidelines. In addition, nurses play an active role in patient education regarding risk factors, protective measures, and signs and symptoms of infection in the immunocompromised oncology patient.

Association between the Geriatric Giants of urinary incontinence and falls in older people using data from the Leicestershire MRC Incontinence Study.

OBJECTIVE: To determine whether urinary incontinence per se and different types of urinary incontinence individually are associated with an increased risk of falls in those aged 70 years and over. To investigate whether the presence of urinary symptoms, poor quality of life and physical limitations in this population with urinary incontinence is associated with falls. DESIGN: Study using data from the cross-sectional postal questionnaire undertaken in the Leicestershire Medical Research Council Incontinence Study. SETTING: Leicestershire. PARTICIPANTS: A total of 5,474 people aged 70 years or more living in the community randomly selected from general practitioners' lists. RESULTS: Urinary incontinence and both urge and stress incontinence were positively related to falls (P < 0.0001, P < 0.001 and P = 0.007, respectively). The larger the volume of urine lost, the greater the risk of falls (P < 0.0001). Falls were associated with the presence of urinary symptoms (P = 0.01 or less), physical limitations (P = 0.001 or less) and having a poorer quality of life (P = 0.004 or less) in respondents with urinary incontinence. CONCLUSIONS: An association has been shown between falling and urinary leakage including the previously unreported association with stress leakage. Falling and urinary incontinence were found to be associated with physical limitations and had an impact on quality of life.

At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone.

The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment. This necessitates reactivation of developmental signaling molecules, including the hypercalcemia factor parathyroid hormone-related protein. This review covers the variations of epidermal growth factor receptor signaling in cancers that produce bone metastases, regulation of parathyroid hormone-related protein, and evidence that the two molecules drive cancer-mediated diseases of bone.

Assessment of Video Capsule Endoscopy in the Management of Acute Gastrointestinal Bleeding During the COVID-19 Pandemic.

Importance: Evaluation of acute gastrointestinal (GI) bleeding using invasive endoscopic procedures comprising the standard of care (SOC)-upper endoscopy and colonoscopy-can expose the endoscopy staff to SARS-CoV-2. Video capsule endoscopy (VCE) does not generate aerosols and only requires 1 person to manage the procedure. Objective: To examine the safety of VCE for the initial evaluation of GI bleeding at the peak of the COVID-19 pandemic to identify signs of active bleeding while minimizing patient and personnel exposure, saving personal protective equipment, and avoiding invasive or unnecessary procedures. Design, Setting, and Participants: A multicenter (UMass Memorial Medical Center and Louisiana State University Health Sciences Center) retrospective cohort study including 146 patients with COVID-19 who received VCE as the first-line diagnostic modality was conducted from March 15 to June 15, 2020, compared with SOC in January 2020 for evaluation of GI bleeding. The association between treatment and outcomes was estimated using multivariable regression adjusting for potential confounders. Propensity score matching was used to verify the results. Main Outcomes and Measures: The primary end point was detection of active bleeding or stigmata of recent bleeding. Secondary end points included the number of patients requiring any invasive procedures, number of additional procedures, rates of rebleeding and rehospitalization, transfusion requirements, and mortality. Results: Among 146 patients, 92 (63.0%) were men; mean (SD) age was 64.93 (14.13) years in the COVID-19 group and 61.33 (13.39) years in the SOC group. Active bleeding or stigmata of recent bleeding was observed in 44 (59.5%) patients in the COVID-19 group compared with 18 (25.0%) in the SOC group (adjusted odds ratio, 5.23; 95% CI, 2.23 to 12.27). Only 36 patients (48.7%) in the COVID-19 group required any invasive procedure during the hospitalization compared with 70 (97.2%) in the SOC group (adjusted odds ratio, 0.01; 95% CI, 0.001 to 0.08). The mean (SD) number of invasive procedures was 0.59 (0.77) per patient in the COVID-19 group compared with 1.18 (0.48) per patient in the SOC group (adjusted difference, -0.54; 95% CI, -0.77 to -0.31). Both approaches appeared to be safe and there was no significant difference in transfusion requirements, rebleeding, rehospitalization, or in-hospital mortality. No mortality was attributed to GI bleeding in either group. Conclusions and Relevance: In this cohort study, first-line diagnostic evaluation of acute GI bleeding using VCE appeared to be a safe and useful alternative to the traditional approach of upper endoscopy and colonoscopy. Use of VCE was associated with increased detection of active bleeding and a reduced number of invasive procedures and unnecessary exposure of personnel to SARS-CoV-2 and use of personal protective equipment.

Discovery of a novel series of quinoxalines as inhibitors of c-Met kinase.

A series of quinoxaline inhibitors of c-Met kinase is described. The postulated binding mode was confirmed by an X-ray crystal structure and optimisation of the series was performed on the basis of this structure. Future directions for development of the series are discussed together with the identification of a novel quinoline scaffold.

Discovery of 4-azaindoles as novel inhibitors of c-Met kinase.

A series of 4-azaindole inhibitors of c-Met kinase is described. The postulated binding mode was confirmed by an X-ray crystal structure and series optimisation was performed on the basis of this structure. Future directions for series development are discussed.

A multicenter randomized comparison of the Endocapsule and the Pillcam SB.

BACKGROUND: Video capsule endoscopy has been shown to be the single most effective endoscopic procedure for identifying the source of obscure GI bleeding (OGIB). OBJECTIVE: Our purpose was to report on the Food and Drug Administration pivotal trial in which the Endocapsule (EC) (Olympus America, Allentown, Pa) was compared with the Pillcam SB (PSB) (Given Imaging, Yoqneam, Israel) in patients with OGIB. DESIGN: A novel trial design was used in which the EC and the PSB were swallowed by the same patient 40 minutes apart, in randomized order. SETTING: Four academic medical centers. PATIENTS: Patients with OGIB aged 18 to 85 years who had either been transfused or who had a hematocrit of <31% in males or <28% in females. INTERVENTIONS: Both video capsules were swallowed in random order. Videos from the PSB were read locally for patient management. All videos were then read by at least 2 independent readers for normal versus abnormal categorization, a diagnosis, capsule transit time, reading time, and a subjective assessment of image quality. MAIN OUTCOME MEASUREMENT: Categorization of videos as either normal or abnormal. RESULTS: Data from 51 of 63 enrolled patients were analyzed. Nine patients were excluded for technical reasons and 3 for protocol violations. Twenty-four videos were read as normal and 14 as abnormal from both capsules. Disagreement occurred in 13. No adverse events were reported for either capsule. Overall agreement was 38 of 51 (74.5%) with a kappa of 0.48, P = .008. LIMITATIONS: Although ingestion order was randomized, the videos could not be read blind owing to a different shape of the image margin. CONCLUSIONS: (1) Both devices were safe and had a comparable diagnostic yield within the range previously reported. (2) There was a subjective difference in image quality favoring the EC. (3) This study design provided unique information about capsule movement in the small intestine and the lack of electromechanical interference between 2 different capsules.

Video Capsule Endoscopy in the Assessment of Portal Hypertensive Enteropathy.

BACKGROUND: The features of the portal hypertension enteropathy (PHE) vary from mild mucosal changes to varices with or without bleeding. The prevalence and the development are not fully understood. AIM: Our aim is to examine the prevalence and the different manifestations of PHE using video capsule endoscopy (VCE). METHODS: It is a single center retrospective study of patients with cirrhosis, who had VCE. Based on the published literature, we divided the PHE lesions into vascular lesions and mucosal lesions. RESULTS: Of the 100 patients with cirrhosis that had a VCE study, the mean age was 62.82 years. Male gender was predominant (64%), while Caucasians represented 82% of the cohort. The most common etiology of cirrhosis was chronic alcohol abuse followed by chronic hepatitis C virus and nonalcoholic steatohepatitis. VCE detected small bowel lesions in 71% of the patients while the features of PHE were found in 65% from the total cohort. AVMs and inflammatory changes were the most common findings, followed by bleeding. More than 50% of the lesions were vascular in nature. The risk of finding PHE in decompensated cirrhosis is twice that in compensated cirrhosis. Forty-five patients had negative EGD exam for any active bleeding, esophageal varices, portal hypertensive gastropathy, or gastric varices. Of these, 69% had features of PHE in their VCE. CONCLUSIONS: VCE detected small bowel lesions in 71% of our cohort. There is a high prevalence of PHE in decompensated cirrhosis. Vascular lesions are the most common finding in the small bowel of this population.

Acute Charcot foot and diabetes: A primer for the vascular nurse.

The clinical findings of the acute Charcot process includes a swollen, warm, and erythematous foot; although pain may be present, it is often mild and out of proportion to the clinical examination. The diagnosis is confirmed by radiologic imaging, and the diagnosis must be considered in any patient with diabetic neuropathy and unilateral foot swelling. Initial treatment calls for immediate immobilization of the foot. Failure to do so can lead to further foot damage, destruction, and possibly amputation. The patient with acute CN requires referral to a multidisciplinary team experienced in the care of the diabetic patient with this devastating condition. Patient education is a crucial component of the treatment plan when caring for a client with CN.