Circulating Tumor Cells as Potential Biomarkers in Bladder Cancer.

PURPOSE: We explored the diagnostic use of circulating tumor cells in patients with neoadjuvant bladder cancer using enumeration and next generation sequencing. MATERIALS AND METHODS: A total of 20 patients with bladder cancer who were eligible for cisplatin based neoadjuvant chemotherapy were enrolled in an institutional review board approved study. Subjects underwent blood draws at baseline and after 1 cycle of chemotherapy. A total of 11 patients with metastatic bladder cancer and 13 healthy donors were analyzed for comparison. Samples were enriched for circulating tumor cells using the novel IsoFlux™ System microfluidic collection device. Circulating tumor cell counts were analyzed for repeatability and compared with Food and Drug Administration cleared circulating tumor cells. Circulating tumor cells were also analyzed for mutational status using next generation sequencing. RESULTS: Median circulating tumor cell counts were 13 at baseline and 5 at followup in the neoadjuvant group, 29 in the metastatic group and 2 in the healthy group. The concordance of circulating tumor cell levels, defined as low-fewer than 10, medium-11 to 30 and high-greater than 30, across replicate tubes was 100% in 15 preparations. In matched samples the IsoFlux test showed 10 or more circulating tumor cells in 4 of 9 samples (44%) while CellSearch® showed 0 of 9 (0%). At cystectomy 4 months after baseline all 3 patients (100%) with medium/high circulating tumor cell levels at baseline and followup had unfavorable pathological stage disease (T1-T4 or N+). Next generation sequencing analysis showed somatic variant detection in 4 of 8 patients using a targeted cancer panel. All 8 cases (100%) had a medium/high circulating tumor cell level with a circulating tumor cell fraction of greater than 5% purity. CONCLUSIONS: This study demonstrates a potential role for circulating tumor cell assays in the management of bladder cancer. The IsoFlux method of circulating tumor cell detection shows increased sensitivity compared with CellSearch. A next generation sequencing assay is presented with sufficient sensitivity to detect genomic alterations in circulating tumor cells.

Does this patient have a severe upper gastrointestinal bleed?

CONTEXT: Emergency physicians must determine both the location and the severity of acute gastrointestinal bleeding (GIB) to optimize the diagnostic and therapeutic approaches. OBJECTIVES: To identify the historical features, symptoms, signs, bedside maneuvers, and basic laboratory test results that distinguish acute upper GIB (UGIB) from acute lower GIB (LGIB) and to risk stratify those patients with a UGIB least likely to have severe bleeding that necessitates an urgent intervention. DATA SOURCES: A structured search of MEDLINE (1966-September 2011) and reference lists from retrieved articles, review articles, and physical examination textbooks. STUDY SELECTION: High-quality studies were included of adult patients who were either admitted with GIB or evaluated in emergency departments with bedside evaluations and/or routine laboratory tests, and studies that did not include endoscopic findings in prediction models. The initial search yielded 2628 citations, of which 8 were retained that tested methods of identifying a UGIB and 18 that identified methods of determining the severity of UGIB. DATA EXTRACTION: One author abstracted the data (prevalence, sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality, with confirmation by another author. Data were combined using random effects measures. DATA SYNTHESIS: The majority of patients (N = 1776) had an acute UGIB (prevalence, 63%; 95% CI, 51%-73%). Several clinical factors increase the likelihood that a patient has a UGIB, including a patient-reported history of melena (LR range, 5.1-5.9), melenic stool on examination (LR, 25; 95% CI, 4-174), a nasogastric lavage with blood or coffee grounds (LR, 9.6; 95% CI, 4.0-23.0), and a serum urea nitrogen:creatinine ratio of more than 30 (summary LR, 7.5; 95% CI, 2.8-12.0). Conversely, the presence of blood clots in stool (LR, 0.05; 95% CI, 0.01-0.38) decreases the likelihood of a UGIB. Of the patients clinically diagnosed with acute UGIB, 36% (95% CI, 29%-44%) had severe bleeding. A nasogastric lavage with red blood (summary LR, 3.1; 95% CI, 1.2-14.0), tachycardia (LR, 4.9; 95% CI, 3.2-7.6), or a hemoglobin level of less than 8 g/dL (LR range, 4.5-6.2) increase the likelihood of a severe UGIB requiring urgent intervention. A Blatchford score of 0 (summary LR, 0.02; 95% CI, 0-0.05) decreases the likelihood that a UGIB requires urgent intervention. CONCLUSIONS: Melena, nasogastric lavage with blood or coffee grounds, or serum urea nitrogen:creatinine ratio of more than 30 increase the likelihood of a UGIB. Blood clots in the stool make a UGIB much less likely. The Blatchford clinical prediction score, which does not require nasogastric lavage, is very efficient for identifying patients who do not require urgent intervention.

Role and significance of c-KIT receptor tyrosine kinase in cancer: A review.

c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.

Physician-initiated rapid HIV testing in an urban emergency department: comparison of testing using a point-of-care versus a laboratory model.

STUDY OBJECTIVE: We compare the outcomes of 2 models of physician-initiated rapid HIV testing in an emergency department (ED). METHODS: One-year retrospective cohort comparing 2 6-month models of physician-initiated rapid HIV testing, point-of-care versus laboratory. Patients aged 12 years or older and able to give verbal consent were eligible for physician-initiated rapid HIV testing if their treating physician believed testing was clinically indicated. During the point-of-care phase, nursing staff performed oral fluid testing. During the laboratory phase, the laboratory performed whole-blood testing. The proportion of potentially eligible patients who had physician-initiated rapid HIV testing ordered (order rate), proportion of ordered tests completed (test completion rate), and proportion of potentially eligible patients who completed testing (overall testing rate) during each phase were assessed. ED length of stay and testing times were also compared. RESULTS: For the point-of-care versus laboratory phase, respectively, there were 24,345 potentially eligible patients versus 26,363; order rate was 3.3% versus 2.4% (P<.001); test completion rate was 75.3% versus 86.8% (P<.001); overall testing rate was 2.5% versus 2.1% (P=.009). Eighteen (3.0%) of the point-of-care-tested patients and 15 (2.7%) of the laboratory-tested patients had reactive tests (P=0.02). The total testing time was greater in the laboratory phase (88 versus 66 minutes; P<.001); however, there was no significant difference in the length of stay between phases (6.2 versus 6.9 hours; P=.15). CONCLUSION: Relatively few ED patients undergo physician-initiated rapid HIV testing regardless of whether a point-of-care or laboratory approach is used. Differences exist in most outcome measures when point-of-care and laboratory models are compared, which should be considered when testing is implemented.

Chemical stability of 4'-azidocytidine and its prodrug balapiravir.

BACKGROUND: R1479, a 4'-azidocytidine nucleoside analog, was developed for the treatment of Hepatitis C virus infection. Balapiravir (R1626) is the tri-isobutyrate ester prodrug of R1479 under clinical development to improve exposure of R1479 upon oral administration. OBJECTIVE: The chemical stability and the rate of azide release of R1479 and balapiravir were studied. METHODS: R1479 and balapiravir solutions were prepared at different pH values and stored at various temperatures. An ion pair high-performance liquid chromatography (HPLC) method with gradient elution was employed to analyze the prodrug, parent, and degradation products. Azide was measured using a reversed phase HPLC method with UV detection after formation of the 3,5-dinitrobenzoyl azide derivative with 3,5-dinitrobenzoyl chloride. The data were analyzed using initial rate and conventional first-order kinetic methods. RESULTS: R1479 degrades to cytosine and azide in aqueous solutions, whereas balapiravir mainly degrades to R1479 and mono- and diesters of R1479. The rates of azide release from R1479 and balapiravir were generally comparable with the corresponding amount formed of cytosine. CONCLUSION: Azide release is pH dependent and is faster in acidic solutions than in neutral solutions. The amount of azide released is significantly less from balapiravir than that from R1479, suggesting a potential advantage of the prodrug over the parent drug.

Physicochemical properties of the nucleoside prodrug R1626 leading to high oral bioavailability.

The nucleoside analog R1479 is a potent and highly selective inhibitor of NS5b-directed hepatitis C virus (HCV) RNA polymerase in vitro. Because of its limited permeability, lipophilic prodrugs of R1479 were screened. Selection of the prodrug involved optimization of solubility, permeability, and stability parameters. R1626 has dissociation constant, intrinsic solubility, log partition coefficient (n-octanol water), and Caco-2 permeability of 3.62, 0.19 mg/mL, 2.45, and 14.95 x 10(-6) cm/s, respectively. The hydrolysis of the prodrug is significantly faster in the Caco-2 experiments than in hydrolytic experiments, suggesting that the hydrolysis is catalyzed by enzymes in the cellular membrane. Using GastroPlus, the physical properties of R1626 successfully predict the dose dependence of the pharmacokinetics in humans previously studied. The program predicts that if the particle size of R1626 is less than 25 microm, it will be well absorbed. Prodrugs with a solubility of greater than 100 microg/mL and permeability in the Caco-2 assay greater than 3 x 10(-6) cm/s are expected to achieve a high fraction absorbed.

Sex-dependent difference in the relationship between adipose-tissue cholesterol efflux and estradiol concentrations in young healthy humans.

BACKGROUND: Impaired adipose tissue function and lower levels of high density lipoprotein cholesterol (HDL-C) have been implicated in the development of vascular dementia, and metabolic diseases such as hypertension, atherosclerosis, type 2 diabetes (T2D) and metabolic syndrome. Interestingly, both the substrate fluxes in adipose tissue and HDL-C concentration differ between men and women. Moreover, adipose tissue cholesterol efflux has been implicated in modulation of HDL-C levels. Thus, we aimed to determine if the association between serum estradiol levels and adipose tissue cholesterol efflux is sex-dependent. METHOD: We evaluated the serum estradiol levels and adipose tissue cholesterol efflux in young healthy men (n=5) and women (n=3). Adipose tissue cholesterol efflux was determined using subcutaneous microdialysis probes. Linear regression analyses were used to determine the relationship between the parameters, p<0.05 was considered as statistically significant. RESULTS: Our data demonstrated that serum estradiol levels directly associated with adipose tissue cholesterol efflux; however, the relationships may be sex-dependent. We discussed our results in the context of currently available data regarding sex-dependent variability in adipose tissue function and HDL-C metabolism as a potential contributor to higher rates of vascular dementia in men. Further research is required to understand the sex-dependent and -independent variabilities in adipose tissue metabolism to determine novel targets for interventions to prevent the development of vascular dementia.

EphB3: an endogenous mediator of adult axonal plasticity and regrowth after CNS injury.

Endogenous mechanisms underlying the remodeling of neuronal circuitry after mammalian CNS injury or disease remain primarily unknown. Here, we investigated axonal plasticity after optic nerve injury and found that macrophages recruited into the injury site and adult retinal ganglion cell (RGC) axons, which undergo injury-induced sprouting and terminal remodeling, were linked by their respective expression of a ligand and receptor pair active in axon guidance. Recruited macrophages specifically upregulated mRNA encoding the guidance molecule EphB3 and expressed EphB proteins capable of binding Ephrin B molecules in vivo and in vitro. Injured adult RGC axons in turn expressed EphrinB3, a known receptor for EphB3, and RGC axons bound recombinant EphB3 protein injected into the optic nerve. In vitro, EphB3 supported adult RGC axon outgrowth, and axons turned toward a source of this guidance molecule. In vivo, both reduction of EphB3 function in adult heterozygous animals and loss of function in homozygous animals greatly decreased RGC axon re-extension or sprouting after optic nerve injury. Comparisons of axon re-extension in EphB3 null and wild-type littermates showed that this loss of axonal plasticity was not attributable to a difference in intrinsic axon growth potential. Rather, the results indicated an essential role for local optic nerve-derived EphB3 in regulating adult RGC axon plasticity after optic nerve injury. Of note, the loss of EphB3 did not affect the ability of injured RGC axons to elaborate complex terminal branching, suggesting that additional EphB3-independent mechanisms governed adult axon branching triggered by CNS damage.

Upregulation of EphB2 and ephrin-B2 at the optic nerve head of DBA/2J glaucomatous mice coincides with axon loss.

PURPOSE: To identify genes with upregulated expression at the optic nerve head (ONH) that coincides with retinal ganglion cell (RGC) axon loss in glaucomatous DBA/2J mice. To further demonstrate that the proteins encoded by these genes bind to RGC axons and influence fundamental axon physiology. METHODS: In situ hybridization and cell-type-specific immunolabeling were performed on ONH sections from DBA/2J mice (3 to 11 months old) and C57Bl/6NCrl mice (10 months old). EphB2-Fc and ephrin-B2-Fc chimeric proteins were applied to adult RGC axons in vitro and in vivo at the ONH to demonstrate protein binding on axons. EphB2-Fc or control Fc protein was applied in a bath or locally to axons preloaded with the calcium indicator Fluo-4-AM, and changes in intra-axonal calcium were determined. RESULTS: EphB2 and ephrin-B2 were specifically upregulated at the ONH of DBA/2J mice starting at 9 months of age, but not in age-matched C57Bl/6NCrl mice or in DBA/2J animals that did not have axon loss. EphA4 was also present at the ONH, but no difference in expression was detected between unaffected and affected animals. EphB2 was expressed by F4/80(+), MOMA2(+), ED1(-) macrophage-like cells, ephrin-B2 was expressed by Iba-1(+) microglia and GFAP(+) astrocytes, whereas EphA4 was expressed by GFAP(+) astrocytes. EphB2-Fc and ephrin-B2-Fc protein bound to RGC axons in culture and to ONH RGC axons in vivo. Adult RGC axons in vitro elevated intra-axonal calcium in response to EphB2-Fc but not to control Fc protein. CONCLUSIONS: The expression of EphB2 and ephrin-B2 is upregulated at the ONH of glaucomatous DBA/2J mice coinciding with RGC axon loss. The direct binding of EphB2 and ephrin-B2 on adult RGC axons at the ONH and the ability of EphB2 to elevate intra-axonal calcium indicate that these proteins may affect RGC axon physiology in the setting of glaucoma and thus affect the development or progression of the disease.

A Study of Global Health Elective Outcomes: A Pediatric Residency Experience.

Background and Objectives: To identify the effects of global health electives over a decade in a pediatric residency program. Methods: This was an anonymous email survey of the Boston Combined Residency alumni funded for global health electives from 2002 to 2011. A test for trend in binomial proportions and logistic regression were used to document associations between elective and participant characteristics and the effects of the electives. Qualitative data were also analyzed. Results: Of the 104 alumni with available email addresses, 69 (66%) responded, describing 94 electives. Elective products included 27 curricula developed, 11 conference presentations, and 7 academic publications. Thirty-two (46%) alumni continued global health work. Previous experience, previous travel to the site, number of global electives, and cumulative global elective time were associated with postresidency work in global health or with the underserved. Conclusions: Resident global electives resulted in significant scholarship and teaching and contributed to long-term career trajectories.

Improved DNA probe detection of Listeria monocytogenes in enrichment culture after physical-chemical fractionation.

Bacterial detection in foods by nucleic acid probes is limited by microflora competition during selective enrichment. Probe target concentration by extraction and fractionation of enrichments may diminish this limitation. The 1-h AccuProbe chemiluminescent culture identification test for Listeria monocytogenes was used as a model. Its high detection threshold provides a stringent challenge for evaluating enrichment work-up protocols. Detection of L. monocytogenes, at 1-4 colony-forming units/g food, was not consistently possible in 48 h enrichment cultures using AccuProbe. Concentration by cell sedimentation was occasionally helpful but the volume of co-sedimented food limited concentration to about 10-fold. To improve concentration, enrichment sediments were sonicated or enzymatically lysed to release the probe's target, r-RNA. The RNA was separated from non-RNA material by extraction with phenol and precipitation with ethanol. Enrichments (250 mL) were concentrated 2500-fold, and the limitation was food RNA volume. A strongly competitive Enterococcus faecium food isolate was used to demonstrate the effect of artificial competition on the kit's ability to detect L. monocytogenes in enrichments. High competitor concentrations repressed the level of the target below the detection threshold, but concentration of r-RNA enabled detection of L. monocytogenes. The effectiveness of this enrichment sample work-up was demonstrated with naturally contaminated hummus.

Examining clinical outcomes utilizing low-pressure pneumoperitoneum during robotic-assisted radical prostatectomy.

The objective of the study was to assess the safety and clinical outcomes of performing RARP utilizing LPP 12 mmHg with locally confined adenocarcinoma of the prostate. Utilizing the Metro Health RALP database registry and the Michigan Urological Clinic records, we retrospectively reviewed the records of consecutive RALPs performed between December 2012 and March 2015 by a single robotic surgeon. 100 patients underwent RARP utilizing 15 mmHg of standard pressure pneumoperitoneum (SPP) and 100 patients underwent RALP utilizing 12 mmHg lower pressure pneumoperitoneum (LPP). Intraoperative parameters reviewed included operative time (OT) and blood loss (BL). Postoperative parameters reviewed included length of hospital stay (LOS), postoperative ileus, fistulas, urinary retention and hematoma formation. Surgical outcomes reviewed included pathological stage and combined Gleason score. Patient age, BMI, mean combined Gleason score and pathological stage were similar in both groups. Mean OT for the LPP group was 105.49 (66-166) and for the standard pressure pneumoperitoneum (SPP) group 111.31 (61-231) min. The length of stay in both groups was similar, averaging 1.53 (1-6) days for the LPP group and 1.57 (1-6) days for the SPP group. The LPP group had a lower postop ileus rate of 4 vs 8 % in the SPP group, but they were not statistically different. Likewise, the positive margin rate, readmission rate, hematoma rate, retention rate and urinary fistula rate were similar and not statistically different for both groups. Pneumoperitoneum of 12 mmHg is noninferior to 15 mmHg during RARP and does not alter the clinical outcomes.

Inflammatory mediators and the failing heart: a translational approach.

Recent studies have identified the importance of proinflammatory mediators in regulating cardiac structure in health and disease. Recent studies suggest that cytokines that are expressed within the myocardium in response to a environmental injury, namely tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and the interleukin-6 (IL-6) family of cytokines play an important role in initiating and integrating homeostatic responses within the heart. However, these "stress-activated" cytokines all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations. Indeed, there is now a growing appreciation that these molecules may play an important role in mediating disease progression in the failing heart. The growing appreciation of the pathophysiological consequences of sustained expression of proinflammatory mediators in pre-clinical and clinical heart failure models culminated in a series of multicenter clinical trials that utilized "targeted" approaches to neutralize tumor necrosis factor (TNF) in patients with moderate to advanced heart failure. However, these targeted approaches have resulted in worsening heart failure, thereby raising a number of important questions about what role, if any, proinflammatory cytokines play in the pathogenesis of heart failure. This review will summarize the tremendous growth of knowledge that has taken place in this field, with a focus on what we have learned from the negative clinical trials, as well as the potential direction of future research in this area.

Review of complications associated with endoscopic pancreatic cyst-gastrostomy: a single-institution experience.

BACKGROUND: Pancreatic fluid collections can form after episodes of pancreatitis, either acute or chronic. The majority will resolve spontaneously but when decompression is mandated, endoscopic drainage is the method of choice. However, it is not void of complications. METHODS: We retrospectively reviewed the charts of 65 patients who underwent endoscopic drainage of pancreatic fluid collections in our institution. The primary outcomes examined included the incidence and type of complications associated with the endoscopic approach. RESULTS: Endoscopic ultrasound was utilized in 86.2% and transgastric approach was used in 81.5% of the cases. The complication rate was 17%. Specifically, complications recorded were infection (6%), perforation and acute abdomen necessitating surgical intervention (4.6%), pneumoperitoneum that was managed nonoperatively (3%), upper gastrointestinal bleed in the knife puncture site that resolved spontaneously (1.5%), and stent migration (1.5%). One patient died remotely to the endoscopic drainage after paracentesis of ascites that resulted in hemorrhagic shock. CONCLUSIONS: This study is one of the largest studies reporting the associated morbidity and mortality after endoscopic cyst-gastrostomy. Major and minor complications occurred at a rate of 17% in our study. Endoscopic approach is a safe draining method and should remain the approach of choice for pancreatic fluid collection decompression.

Guillain-Barre Syndrome After Robotically Assisted Laparoscopic Prostatectomy: First Case Report.

Guillain-Barre Syndrome is a well described acute demyelinating polyradiculoneuropathy with a likely autoimmune basis characterized by progressive ascending muscle paralysis. Classically, GBS is attributed to antecedent upper respiratory and gastrointestinal infections. We present the first case of GBS after Robotically Assisted Laparoscopic Prostatectomy using the daVinci(®) Surgical System.

Microbial evaluation of selected fresh produce obtained at retail markets.

The microbial quality of five types of fresh produce obtained at the retail level was determined by standard quantitative techniques. These techniques included aerobic plate count (APC), total coliform counts, Escherichia coli counts, and yeast and mold counts. Three different methods were used to determine total coliform counts, which consisted of MacConkey agar plate counts, Colicomplete most probable number counts, and Petrifilm E. coli (EC) plate counts. The mean APCs for sprouts, lettuce, celery, cauliflower, and broccoli were 8.7, 8.6, 7.5, 7.4. and 6.3 log10 CFU/g, respectively. MacConkey agar counts indicated that 89 to 96% of the APCs consisted of gram-negative bacteria. Yeast and mold counts were in a range expected of fresh produce. Fresh produce was also analyzed for human pathogens. Samples were analyzed for Staphylococcus spp., Bacillus spp., Salmonella spp., Listeria spp., and Campylobacter spp. One isolate of Staphylococcus was found to be enterotoxigenic, and one species of Bacillus was also toxigenic. Neither Salmonella spp. nor Campylobacter spp. were detected in any of the produce samples. A variety of Listeria spp., including Listeria monocytogenes, were found in fresh produce.

An evaluation framework and a pilot study of a mobile platform for diabetes self-management: insights from pediatric users.

According to WHO, pediatric diabetes is a rising global public health problem, with increasing impact on developing nations. This study summarizes a multidimensional, scalable pilot evaluation of a diabetes self-management platform combining mobile technology with social networking to capture four key metrics of Type 1 diabetes self-management, associated social interactions, and gaming features providing targeted feedback to 8 pediatric users. Based on their 2-month interaction with the application, we analyze click-stream data from social interactions, key health metrics, text comments, and usability and satisfaction surveys to evaluate engagement with the platform and effectiveness in controlling blood glucose using a product-process-program framework. Our preliminary results indicate that this framework was successful in demonstrating the potential of the mobile health platform to effectively leverage the growing use of mobile applications and social media to present a unique benefit that engaged pediatric users and provided useful insights for self-health management.

Mutational Analysis of Circulating Tumor Cells Using a Novel Microfluidic Collection Device and qPCR Assay.

Circulating tumor cells (CTCs) provide a readily accessible source of tumor material from patients with cancer. Molecular profiling of these rare cells can lead to insight on disease progression and therapeutic strategies. A critical need exists to isolate CTCs with sufficient quantity and sample integrity to adapt to conventional analytical techniques. We present a microfluidic platform (IsoFlux) that uses flow control and immunomagnetic capture to enhance CTC isolation. A novel cell retrieval mechanism ensures complete transfer of CTCs into the molecular assay. Improved sensitivity to the capture antigen was demonstrated by spike-in experiments for three cell lines of varying levels of antigen expression. We obtained spike-in recovery rates of 74%, 75%, and 85% for MDA-MB-231 (low), PC3 (middle), and SKBR3 (high) cell lines. Recovery using matched enumeration protocols and matched samples (PC3) yielded 90% and 40% recovery for the IsoFlux and CellSearch systems, respectively. In matched prostate cancer samples (N = 22), patients presenting more than four CTCs per blood draw were 95% and 36% using IsoFlux and CellSearch, respectively. An assay for detecting KRAS mutations was described along with data from patients with colorectal cancer, of which 87% presented CTCs above the assay's limit of detection (four CTCs). The CTC KRAS mutant rate was 50%, with 46% of patients displaying a CTC KRAS mutational status that differed from the previously acquired tissue biopsy data. The microfluidic system and mutation assay presented here provide a complete workflow to track oncogene mutational changes longitudinally with high success rates.

Effect of audit and feedback on improving handovers: a nonrandomized comparative study.

BACKGROUND: High-quality, shift-to-shift handovers by residents are critical to ensuring to patient safety. The 2011 Accreditation Council for Graduate Medical Education duty hour requirements have increased the number of handovers occurring daily, necessitating new approaches to this challenge. Research suggests standardized approaches, electronic systems, and education programs can improve the handover process. METHODS: We conducted a 2-phase, observational study comparing an electronic handover system (experimental) in one clinical setting to a standard card-based system (control) at a second site. Outcome data included an objective assessment of the completeness and accuracy of handovers, and resident assessment of the handover systems. In phase 1, data were recorded at both sites and not shared with residents. In phase 2, data from the experimental system were used to provide standardized feedback to residents on the quality of their handovers. RESULTS: A total of 3184 individual patient sign-outs were evaluated during the 11-month period. Following introduction of a feedback intervention in the experimental arm, errors were present in only 5.2% of handovers, compared with 16.1% of controls (P < .001), and 67% of the 38 residents responding reported they perceived the experimental system as facilitating better patient care. CONCLUSION: Regular, real-time feedback through an electronic handover system can improve the accuracy and completeness of handovers in patient care.