bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed Neuroendocrine-Nonneuroendocrine Carcinoma Arising in the Gallbladder: A Rare Case of a Three-Component Composite Neoplasm
Authors: Alawad Mouyed , Schoninger Scott , Gupta Raavi
Published: September 2019

Introduction

Neuroendocrine gallbladder neoplasms are rare, comprising 0.5% of all neuroendocrine cancers and about 2% of gallbladder cancers. Interestingly, those neoplasms can also be observed along with other malignant components of epithelial origin, mostly adenocarcinomas. Herein we report an unusual case of a patient with a gallbladder neoplasm composed of a neuroendocrine carcinoma, a squamous cell carcinoma, and an adenocarcinoma.

Methods

The patient was a 62-year-old woman who presented with right upper quadrant abdominal pain with a positive Murphy’s sign on physical examination. She was clinically diagnosed with acute cholecystitis and underwent cholecystectomy. Gross examination showed a 5-cm exophytic mass at the gallbladder fundus. Histopathologic examination of the mass showed an infiltrating squamous cell carcinoma and an adjacent high-grade neuroendocrine carcinoma; each of these two components composed more than 30% of the neoplasm and infiltrated into the perimuscular connective tissue with no serosal involvement. Additionally, a superficial adenocarcinoma component was also seen composing 10% of the neoplasm. The squamous cell carcinoma showed moderate differentiation with areas of keratinization; it was positive for Ck7, p40, and p63. The neuroendocrine carcinoma showed areas of geographic necrosis, and the cells had inconspicuous nucleoli and granular chromatin, with numerous mitotic figures; it was positive for synaptophysin and chromogranin. The adenocarcinoma showed gland formation with mucicarmine stain, highlighting the mucin within the neoplastic cells; it was positive for Ck7 but negative for p40. Subsequently, the patient underwent resection of the liver bed, which was negative for metastasis, and was then referred for chemotherapy.

Conclusion

Our review of the literature revealed seven documented cases of three-component gallbladder neuroendocrine neoplasms. Generally, patients with these tumors have a poor prognosis, and due to their rarity, no specific treatment guidelines have yet been established. It has been suggested that a multipotent common stem cell is the origin of these tumors.
Improving Augmented Human Intelligence to Distinguish Burkitt Lymphoma From Diffuse Large B-Cell Lymphoma Cases
Authors: Mohlman Jeffrey , Leventhal Samuel , Pascucci Valerio , Salama Mohamed
Published: September 2019

Introduction

Our objective is to improve the assistive role of a deep, densely connected convolutional neural network (CNN) to hematopathologists in differentiating histologic images of Burkitt lymphoma (BL) from diffuse large B-cell lymphoma (DLBCL). We hypothesized that for the majority of cases, a CNN would accurately differentiate BL from DLBCL and attempted to identify design and input variables to improve performance.

Methods and Materials

In total, 3608 images of BL were collected from 18 cases and 2,071 images of DLBCL were collected from 20 cases using Aperio Image Scope (Leica Biosystems, Buffalo Grove, IL). Cases were randomized into training and unknowns, and three separate CNNs were trained and applied to unknown images. Networks differed by either the size in pixels of the images (network 1 used 32 × 32 while networks 2 and 3 used 224 × 224) or absence of color (in network 2). Decreased numbers of training images were used to evaluate network 3.

Results

Network 3 performed the best with 17 of 19 (89%) cases classified correctly, 10 with 100% of images correct. Overall, network 3 had 88% accuracy, 80% precision, 81% recall, and an F1 score of 0.81. Receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.89 for DLBCL and 0.88 for BL. Networks 1 and 2 performed more poorly with F1 scores of 0.63 and 0.39, respectively. Decreasing training images by one-half and one-fourth resulted in decreased F1 scores of 0.63 and 0.60, respectively.

Conclusions

CNNs are promising augmented human intelligence tools for differentiating DLBCL from BL cases and potentially could contribute to improved workflow in the laboratory. More training images, larger image size, and color significantly improved performance of the CNN because of the added information available to the network. More research is under way to optimize the performance of CNNs’ lymphoma application.
Status of Histopathology Services in Ethiopia
Authors: Yeabyo Giorgis
Published: September 2019

Objectives

The main purpose of this study is to evaluate the accessibility of pathology services in Ethiopia.

Methods

Checklist was prepared for the assessment of the availability of histopathology services in Ethiopia, types of equipment, turnaround time (TAT), and intended number of population to use it.

Results

There are 13 histopathology laboratories in the Ethiopia and a survey was conducted at all facilities in the nation. Out of 13 institutions, 7 (53.8%) of them are located in the capital, Addis Ababa. Six (46.2%) of them are out of the capital located in four different regions. No service is given in regions of afar, Somali, Benishangul-gumuz, Gambella, Harari, and Diredawa city administration where 40,239,100 population resides.

Conclusion

There are very limited histopathology laboratories in the country; as a result, diagnosis and prevention of cancer diseases are inadequate throughout the country.
A Loop-Mediated Isothermal Amplification (LAMP) Assay for the Detection of Treponema pallidum subsp. pertenue
Authors: Anthony Basing Laud
Published: September 2019

Objectives

The eradication of yaws, a childhood disease caused by Treponema pallidum subsp. pertenue, is constrained by the lack of rapid, accurate diagnosis. We sought to develop a molecular point-of-care test for the diagnosis of yaws.

Methods

A loop-mediated isothermal amplification (LAMP) assay with primers targeting the conserved gene, tp0967, with visual detection by lateral flow test strip was developed. The assay was optimized by varying the concentrations of reagents as well as the temperature and time of the reaction. The limit of detection and selectivity of the assay were evaluated. Subsequently, 63 clinical samples from yaws-infected lesions were used to determine the sensitivity of the assay from both unextracted and DNA extracted swab samples as compared to the current molecular testing protocol (CDC PCR assay) as the gold standard. A further five clinical samples from lesions containing PCR-confirmed syphilis pathogen (Treponema pallidum subsp. pallidum) were tested to ensure specificity of the assay for yaws alone.

Results

The developed LAMP assay was found to be optimal when run at 65oC for 30 minutes. The limit of detection was 2.7*104 copies DNA per mL. Out of the 63 yaws samples tested, the CDC assay, extracted DNA LAMP assay, and unextracted DNA using the LAMP assay resulted in 12, 14, and 8 positive results, respectively. None of the syphilis samples tested positive in any of the assays.

Conclusion

We show the development of a fast and sensitive LAMP assay for Treponema pallidum subsp. pertenue detected by lateral flow test strip. Using extracted DNA, the assay sensitivity is on par with gold standard detection. Further, the assay can be adapted to minimal sample processing required for in-field detection without DNA extraction.
Evaluation of Forward Laser Light Scatter Technology as a Preculture Screen of Unpreserved Urine Specimens
Authors: Coberly Jared , Prabhakaran Nitya
Published: September 2019

Introduction

Urine cultures are standard of care for the diagnosis of urinary tract infections. Reflexively culturing specimens only after an effective screening test could minimize the number of samples cultured, improving laboratory efficiency. We evaluated a commercial forward laser light scatter system as a screening tool for urine cultures.

Methods

One hundred ninety (190) consecutive unpreserved urine specimens were screened by the BacterioScan 216Dx system (BacterioScan) prior to urine culture. Performance characteristics were compared against traditional culture methods.

Results

Urine specimens from 40 men and 150 women were evaluated. In total, 182 specimens were obtained by clean-catch, 7 by catheter, and 1 via nephrostomy; 134 specimens were negative by urine culture (70%). Fifty-six were positive, with the most commonly identified organism being E coli (35 specimens, 62.5%). Compared to urine culture, forward laser light scatter identified 132 positives and 58 negatives (31%) for a sensitivity of 98%, specificity of 42%, positive predictive value of 42%, negative predictive value of 98%, and an overall accuracy of 59%. Average time from collection to result for light scatter analysis was 25 hours and 28 minutes (95% CI, ±74 minutes) versus 52:37 (±280 minutes) for urine culture (P < .01). Time to negative results was 25:51 (±77 minutes) for light scatter versus 53:17 (±320 minutes) for culture (P < .01). Time to positive results was 26:36 (±66 minutes) versus 51:02 (±146 minutes) for culture (P < .01).

Conclusions

Time to negative result and assay sensitivity showed an improvement over direct urine culture and could reduce number of cultures by ~30%; however, low positive predictive value and accuracy would lead to reflexive culture in the majority of specimens tested, limiting overall utility. Cost analyses may prove the modest efficiency gains do not outweigh the additional expense.
Epithelial-to-Mesenchymal Transition (EMT) and Signal Transducers and Activators of Transcription (STAT3) Are a Novel Therapeutic Strategy for Hepatocellular Carcinoma (HCC) Prognosis
Authors: Fyala Amira , Sultan Ahmed
Published: September 2019

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and is the second most common cancer in Egypt. Poor diagnosis of HCC is correlated with vascular invasion and metastasis. Epithelial-to-mesenchymal transition (EMT) is the main step in the tumor invasion process whereby epithelial cells lose cell polarity with each other and then undergo a dramatic remodeling of the cytoskeleton. Also, EMT plays a pivotal role in metastasis when epithelial cell layers lose cell-cell contacts in tumor progression due to the loss of E-cadherin and increasing the ability of the spread into surrounding tissues. Signal transducers and activators of transcription (STAT) play a different cellular function as signal transducers in the cytoplasm and transcription activators in the nucleus. STAT3 gene plays a crucial role to affect EMT in cancer progression by promoting cell proliferation and survival through its function as a transcription factor of the tumor. The aim of our study is to investigate the gene expression of STAT3 in HCC (HepG-2) cell lines and the expression of cell differentiation and proliferation markers. Western blotting was used to examine the protein expression of STAT3, E-cadherin, and β-catenin signaling. Our results showed that STAT3 expression levels were detected, as well as a significant increase in the expression of proliferation marker as β-catenin and a significant decrease of differentiation marker as E-cadherin protein expression levels in HepG-2 cell lines.

Conclusion

Our finding provides novel evidence for using a molecular gene therapy as STAT3, which showed an effect on EMT that plays a pivotal role in the prognosis of HCC. The loss of E-cadherin expression is a hallmark of EMT, because β-catenin is associated with the cytoplasmic domain of E-cadherin. We have emphasized the significant role of EMT and STAT3 in HCC progression, which could be a potential application as a novel therapeutic strategy for HCC treatment.
Analysis of the Expression of Genes Related to Lipidic and Glycogenic Metabolism in Pleomorphic Adenomas and Carcinomas Ex Pleomorphic Adenomas
Authors: Egal Erika , Scarini Joao , Fernandes Larissa , Sabino Welligton , Souza Reydson , Tincani Alfio , Del Negro Andre , Paulo Kowaski Luiz , Campanela Debora , Altemani Albina , Mariano Fernanda
Published: September 2019

Introduction

The carcinoma ex pleomorphic adenoma (CXPA) arises from a pleomorphic adenoma (PA) and is supposed to gain lipogenesis and glycogenesis during its malignant transformation. Increased lipogenesis is a characteristic of cancer cells, consisting of increased fatty acid synthesis by the enzyme fatty acid synthase (FASN) and by the accumulation of cytoplasmic lipid droplets, which express adipophilin. The increase in glycolytic metabolism has been associated with the activity of glycolytic enzymes and glucose transporters (GLUTs), whose expression is induced by HIF-1 (inducing factor of hypoxia 1).

Objectives

To analyze the gene expression of FASN, adipophilin, HIF-1α, and GLUT-1 in PA and CXPA samples.

Methodology

Gene expression analysis of the FASN, adipophilin, HIF1-α, and GLUT-1 genes was performed by the real-time PCR (qPCR) method. Fourteen cases of PA and 14 cases of CXAP were evaluated.

Results

FASN, adipophilin, HIF-1α, and GLUT-1 were more expressed in CXAP than in AP, although there was no significant difference between levels of adipophilin expression in CXPA and PA.

Conclusion

Increased expression of FASN, HIF1-α, and GLUT-1 in CXAP may be associated with malignant transformation of PA, while additional studies are needed to understand the role of adipophilin in PA carcinogenesis. Moreover, this is the first study to investigate the role of these genes in the malignant transformation of PA.
Performance Improvement Utilizing Multidisciplinary Collaborations and Analytics Are the Key Drivers in Paradigm Shift From Volume to Value in Improving Test Utilization, Patient Safety, and Quality of Care
Authors: Gupta Sachin , Bean Jo , Pieretti Maura , Bischof Larry , Hruszczyk Victor , Chandler Suzanne , King Rita
Published: September 2019

Objectives

The objective of this session is to understand the value of performance improvement, teamwork, and laboratory analytics to improve test utilization, quality, and patient safety. This presentation will highlight BayCare Health System’s journey to achieve clinical excellence.

Methods

Laboratory performance improvement team collaborated with the Enterprise Data Warehouse team to build in-house Laboratory Analytics dashboards. The dashboard reports were used to identify opportunities and to implement best practices in collaboration with multidisciplinary teams. The improvements were achieved by using performance improvement tools and were measured by various process and outcome metrics.

Results: (

1) Lab collaborated with the infection prevention team and standardized the admission screening policies for rapid PCR testing. This has resulted in 50% and 85% reduction in MRSA and VRE testing, respectively, which led to annual savings of over $1 million/year. (2) Collaborating with the antibiotic stewardship team and introducing new urinalysis reflex criteria resulted in an about 18,000 fewer urines reflexed to culture per year. This change led to about $190,000 per year reduction in expense of reagents and labor. (3) Collaborating with the team of nursing, as well as monitoring and implementing best practices to reduce the blood contamination rates, has resulted in <1.4% blood contamination rates. (4) Multidisciplinary teams were able to reduce transfusion rates for various blood products in our hospitals to less than 7%, which brings us to top-decile performers in Premier database. (5) Collaboration with nursing and lab, by using lab analytics, was able to reduce emergency department lab orders result time by 21% and improve patient throughput. (6) The analytics reports also improved staff planning and efficiencies in specimen collection.

Conclusion

Performance improvement utilizing multidisciplinary collaborations and Lab Analytics are the key players in shifting the paradigm from volume to value, which eventually helps in appropriate test utilization and better patient care.
Rapid Identification of Bloodstream Pathogens and Timely Reporting Resulting in Effective Antibiotic Interventions Optimizing Patient Care
Authors: Lin Bo , Christian Manan , Kogan Margarita , Zuretti Alejandro
Published: September 2019

Objectives

Bloodstream infection is a major cause of morbidity and mortality in the United States. Rapid identification of bloodstream pathogens is a critical laboratory practice that allows rapid transition to direct targeted therapy, providing timely and effective patient care. Here, we examined the utilization impact of Biofire blood culture identification panel in identifying bloodstream pathogens and subsequent implementation of treatment on patient care at our medical center.

Methods

Results of patients’ blood culture results and the subsequent medical interventions were reviewed. A policy of reviewing and reporting positive blood culture results every 2 hours was implemented and the results before and after the policy implementation were compared.

Results

We reviewed blood culture results from 288 patients during 1/20/2018 to 4/30/2018. In total, 96.5% of patients had antibiotic interventions. Based on the blood culture results, the interventions were adjusted: 32% changed in dosing, 32% escalated, 25% deescalated, and 11% added sensitivity. After the every 2-hour blood culture result reporting policy was implemented, the median time for physicians to order escalation dropped from 3 hours to 1 hour and median time to deescalate also dropped from 2 hours to 1 hour.

Conclusion

We were able to improve the timeliness of identifying bloodstream pathogens and support effective patient care by using the Biofire blood culture identification panel with timely result reports. Rapid identification of bloodstream pathogens had impacted patient outcomes in multiple ways, including reductions in mortality, morbidity, hospital length of stay, antibiotic use, and patient care cost.
Laboratory Medicine Impact on Population Health in Arizona: Sonora Quest Implementation of the Kidney Profile
Authors: Montgomery Elizabeth , Ivie James , Zeigler Kim , Cohen Robert , Clark Jennifer
Published: September 2019

Introduction

Thirty million American adults are estimated to be living with chronic kidney disease (CKD), with over 80% unaware of the condition that puts them at increased risk for cardiovascular events and progression to kidney failure and death. In primary care populations, almost 90% of adults with type 2 diabetes and CKD are not currently diagnosed, and as many as 50% of patients with advanced CKD remain undiagnosed. There is underutilization of urinary albumin-creatinine ratio (uACR) testing in people at risk for CKD. Less than 10% of those with hypertension and less than 40% of those with diabetes are assessed for albuminuria.

Sonora Quest Laboratories (SQL) extracted data regarding CKD testing in Arizona. Of 604,328 people with laboratory evidence of diabetes, 79% were overdue for albuminuria testing. Significant gaps in diagnosis of individuals with laboratory evidence of CKD were identified as well.

Methods

The National Kidney Foundation (NKF) and the American Society for Clinical Pathology (ASCP) have implemented a national strategy to promote utilization of the Kidney Profile and improve CKD outcomes. NKF and ASCP are working in concert with SQL and NKF of Arizona to engage Arizona’s primary care providers in this effort. The goal is to enhance CKD-related data accuracy in the laboratory information system and to improve CKD recognition, diagnosis, and risk stratification in primary care population health throughout Arizona.

Conclusion

Widespread implementation of the Kidney Profile will improve recognition and risk stratification for CKD. This campaign will positively impact primary care utilization of the NKF/ASCP Choosing Wisely recommendation for CKD assessment: do not request just a serum creatinine to test adult patients with diabetes and/or hypertension for CKD; use the Kidney Profile (serum Creatinine with eGFR and urinary albumin-creatinine ratio).
Review of Inpatient Thrombophilia Testing at a Tertiary Care Center
Authors: Hall Andrew , Lopez Ortega , Powers Amy
Published: September 2019

Introduction

Testing for thrombophilic risk factors is common in patients with thrombosis. However, inpatient hereditary thrombophilia work-ups are prone to false-positive and false-negative results due to concurrent acute phase changes, protein consumption, anticoagulation therapy, and liver disease. A recent ASCP Choosing Wisely guideline recommends against measuring protein C (PC), protein S (PS), or antithrombin III (AT3) to diagnose a hereditary deficiency during an active clotting event.

We aimed to review inpatient PC, PS, and AT3 activity assay ordering practices at a tertiary care center. The goal of this study was to determine appropriateness and identify areas for improvement in inpatient thrombophilia ordering practices.

Methods

A retrospective review of inpatients who underwent thrombophilia testing was performed. Inclusion criteria consisted of adult inpatients with PC, PS, and/or AT3 activity results. Patients for whom AT3 was ordered alone were excluded. The timeframe of testing relative to an acute thrombotic event, anticoagulation therapy, and liver disease was determined via electronic medical record review. Other conditions that can affect PC, PS, or AT3 levels were recorded if noted.

Results

Over 5 months, 50 inpatients underwent testing for PC, PS, and/or AT3. Testing was performed within 2 weeks of an acute thrombotic event in 92% of patients; 32% received anticoagulation therapy prior to testing and 16% had liver disease. Test results below the reference range were found in the following percentage of patients: 16% PC, 34% PS, and 16% AT3. In total, 23 of 50 (46%) patients had one or more abnormal results; all 23 had potential confounding conditions/drug.

Conclusions

Inpatient PC, PS, and AT3 testing was frequently performed in clinical settings, which may cause false-positive or false-negative results. This demonstrates the need for increased education and dialogue between the laboratory and clinicians to improve test utilization practices. Potential interventions are currently being analyzed.
Routine Use of Flow Cytometry in the Initial Diagnosis of Myelodysplastic and Myeloproliferative Neoplasms Is Not Justified
Authors: Lynch David , Williams Grant , Eden Rina
Published: September 2019

Objectives

To retrospectively assess the utility of flow cytometry on bone marrow aspirates with respect to the initial diagnosis of myelodysplastic and myeloproliferative neoplasms.

Methods

Flow cytometry results at Brooke Army Medical Center from January 1, 2016, to January 1, 2019, were reviewed on all bone marrow biopsies performed for the initial diagnosis of myelodysplastic (MDS) or myeloproliferative neoplasms (MPN). Results were categorized as normal, abnormal myeloid population, or abnormal lymphoid population.

Results

A total of 197 cases were identified (134 for MDS and 76 for MPN). Of the biopsies for MDS, 27% showed an abnormal myeloid population, and 1% showed an abnormal lymphoid population. Three cases were diagnosed as acute myeloid leukemia. Of the biopsies for MPN, 8% showed an abnormal myeloid population, and 1% showed an abnormal lymphoid population. Cases with incidental abnormal lymphoid populations were small (<5% of events).

Conclusion

In all cases except those diagnosed as acute myeloid leukemia (1.4% of cases), flow cytometry findings did not affect the diagnosis. Based on these findings and the diagnostic criteria in the updated WHO 2016 revision, flow cytometry does not need to be routinely performed on the bone marrow specimens for the diagnosis of MDS or MPN. However, identification of possible cases of acute myeloid leukemia is critical since flow cytometry is required in those cases. Screening of a bone marrow aspirate slide by a pathologist would allow for canceling of unnecessary flow cytometry in these cases and allow for better test utilization.
Evidence-Based Duplicate Order Alerts Promote Effective Test Utilization and Reduce Unnecessary Laboratory Testing
Authors: Coberly Jared , Coberly Emily , Dettenwanger Katie , Ross Brandi , Pierce Robert
Published: September 2019

Introduction

Unnecessary and inappropriate laboratory testing contributes to increased health care costs, increases length of stay, and increases odds for blood product transfusion. The Choosing Wisely campaign recommends a judicious use of laboratory blood testing to combat iatrogenic anemia. Reducing the number of duplicate test orders may help address these issues. We evaluated duplicate order alert thresholds in our electronic health record for 10 common laboratory tests at an academic medical center.

Methods

In January 2019, alert intervals for 10 common inpatient laboratory tests (thyroid stimulating hormone, complete blood count, hemoglobin A1c, troponin, lactic acid, hemoglobin and hematocrit, urinalysis, vitamin D, urine beta HCG, and triglycerides) were adjusted to evidence-based, disease-specific thresholds. If a test was ordered within a timeframe shorter than this threshold, an alert interrupted the provider’s workflow. The provider was allowed to override the alert based on clinical judgment. This is a change from the previous settings, which alerted any test if ordered more frequently than 8 hours. Postintervention duplicate order alerts were compared to baseline rates and adjusted for number of inpatient discharges.

Results

In total, 914 orders were cancelled in 1 month as a result of tailored duplicate order alerts versus the baseline mean of 710 (95% CI, 633-786) and a predicted 552 (95% CI, 475-628) when adjusted for number of inpatient discharges, with the majority of cancelled orders being for CBC (530 accepted alerts). Overall, this reduction in unnecessary duplicate tests is equivalent to 3,092 mL of blood not collected from patients per month.

Conclusion

Tailoring duplicate order alert interval thresholds to evidence-based criteria helps reduce unnecessary testing, reduces costs, and may play an important role in reducing hospital-acquired anemia.
A Rare Case of Congenital Factor X Mild Deficiency Presenting as Life-Threatening Hemorrhagic Shock in a Neonate
Authors: Mendoza Rachelle , Haidary Tahmineh , Kang Steven
Published: September 2019

Introduction

Congenital factor X deficiency is one of rarest bleeding disorders, occurring in 1 out of 1 million births. Its rarity limits its consideration in newborns presenting with hemodynamic instability. It is autosomal recessive and seen frequently in the consanguineous population. Patients with factor X deficiency are classified into three groups, based on factor X activity level: severe (<1%), moderate (1%-4%), and mild (6%-10%). Severe deficiency presents with bleeding diathesis early in life.

Methods

A 3-day-old male newborn, delivered at term via spontaneous vaginal delivery, presented in a well-baby clinic for a routine bilirubin check. Family history was negative for bleeding disorder or consanguinity. Nurse noted persistent blood oozing at heel stick site and oral, nasal, and umbilical stump bleeding. The patient immediately developed respiratory distress and shock. Sepsis, vitamin K deficiency, and congenital metabolic syndrome were considered. Liver function, WBC count, and other chemistry were normal, and cultures were negative. Hemoglobin was low and platelet count was elevated. PT (30.3 seconds) and aPTT (53.3 seconds) were both prolonged. Mixing patient’s sample with normal plasma corrected PT (13.1 seconds) and aPTT (25.7 seconds), indicating a factor deficiency.

Results

Coagulation factor assays revealed normal levels of factors VII, VIII, IX, and II. Factor X activity (12.9%) was low. The patient’s condition improved after multiple pRBC and plasma transfusions. He was placed on a daily 25-mL/kg dose of fresh-frozen plasma, which maintained his PT at 17.6 to 19.1 seconds and aPTT at 34.1 to 48.0 seconds. Factor X level increased to 20% after plasma transfusion.

Conclusion

Congenital bleeding disorder should be considered for neonates presenting with bleeding and shock. Factor X deficiency is suspected when both PT and aPTT are prolonged and corrected with mixing studies. Although factor levels of 10% to 40% are considered adequate for hemostasis, our patient with 12% factor X activity presented with a life-threatening bleeding event.
Eucalyptol Masks the Olfactory But Not the Trigeminal Sensation of Ammonia
Authors: Müschenich Franziska S , Sijben Rik , Gallenmüller Felix , Singer Marco , Rodriguez-Raecke Rea , Di Francesco Maria Elisa , Wiesmann Martin , Freiherr Jessica
Published: September 2019

Eucalyptol is a substance with rather pleasant olfactory and trigeminal characteristics and is thus suggested as an efficient tool for malodor coverage. In this study ammonia would be the malodor substance such as is found in cat litter or hair coloration. We investigated the potential of eucalyptol to inhibit both the olfactory as well as the trigeminal sensation of ammonia. For this purpose, we mixed eucalyptol and ammonia and compared odor component intensities. After being presented with either the pure odors or a binary mixture thereof, 21 young and healthy participants had to lateralize the odors and rate component (eucalyptol and ammonia) and total intensity. Analysis of intensity ratings revealed hypoadditivity (total mixture intensity was less than the sum of the total intensity of the single components). Significant interaction effects verified that mixing eucalyptol and ammonia only affected the perceived intensity of ammonia. Comparing the odor components within the pure and mixed stimuli, the ammonia component was rated as significantly less intense in the mixture compared to pure ammonia whereas the eucalyptol component was rated equal in the pure and mixed condition. On the basis of lateralization scores, we observed trigeminal mixture enhancement. We conclude that eucalyptol is a suitable masking agent to cover the unpleasant smell of ammonia; however, it fails to serve as an ammonia counterirritant because it lacks the ability to mask the trigeminal sensation of ammonia.
Baloxavir Marboxil in Japanese Pediatric Patients With Influenza: Safety and Clinical and Virologic Outcomes
Authors: Hirotsu Nobuo , Sakaguchi Hiroki , Sato Chisako , Ishibashi Toru , Baba Keiko , Omoto Shinya , Shishido Takao , Tsuchiya Kenji , Hayden Frederick G , Uehara Takeki , Watanabe Akira
Published: September 2019

Background

We assessed the safety and effectiveness of baloxavir marboxil administration in Japanese children with influenza.

Methods

This open-label study administered 1 weight-adjusted dose of baloxavir to 107 children aged 1–11 years with laboratory-confirmed, febrile influenza virus infection of ≤48 hours duration.

Results

Adverse events (AEs) were reported in 34.6% of patients, most commonly vomiting (7.5%); no serious AEs or AEs causing discontinuation occurred. The median time to alleviation of influenza illness was 44.6 hours (95% confidence interval, 38.9–62.5 hours), to resolution of fever was 21.4 hours, and to sustained cessation of infectious viral shedding was 24.0 hours. However, viruses with amino acid substitutions in the viral polymerase acidic protein at position I38 (PA/I38T/M) emerged in 18 of 77 (23.4%) patients. Emergence was associated with longer infectious virus detectability (median time, 180.0 hours) and time to illness alleviation (median, 79.6 vs 42.8 hours in patients without PA/I38T/M-substituted viruses). Among patients with PA/I38T/M-substituted virus emergence, those with baseline hemagglutinin inhibition (HAI) antibody titer <40 experienced delay in time to illness alleviation (median, 85.4 vs 56.0 hours in patients with higher baseline HAI antibody titer).

Conclusions

A single, oral dose of baloxavir marboxil was well tolerated and rapidly reduced viral titers, but the common emergence of PA/I38T/M-substituted viruses warrants consideration of alternative dosing regimens in young children.

Clinical Trials Registration

Japan Pharmaceutical Information Center Clinical Trials Information (Japic CTI-163417).
Usefulness of Procalcitonin in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
Authors: Cheung Donna Ann , Tamariz Leonardo , Nemeth Zsuzsanna , Langshaw Amber Hamid
Published: September 2019

Background

Mixed results are reported for procalcitonin (PCT) as biomarkers of infection and disease activity in inflammatory bowel disease (IBD).

Method

We systematically evaluated and performed a meta-analysis on the usefulness of PCT in assessing infection and disease activity in IBD.

Results

The pooled standardized mean difference of PCT for those with infection compared with those without was 1.59 (95% CI, 0.72–2.46, P < 0.01) and those with active disease compared with those without was 1.22 (95% CI, 0.66–1.78, P < 0.01), respectively.

Conclusion

PCT may potentially be useful in differentiating an infectious process from IBD and active from inactive IBD.
A novel secreted-cAMP pathway inhibits pulmonary hypertension via a feed-forward mechanism
Authors: Jones Carly , Bisserier Malik , Bueno-Beti Carlos , Bonnet Guillaume , Neves-Zaph Susana , Lee Sang-Yong , Milara Javier , Dorfmüller Peter , Humbert Marc , Leopold Jane A , Hadri Lahouaria , Hajjar Roger J , Sassi Yassine
Published: September 2019

Aims

Cyclic adenosine monophosphate (cAMP) is the predominant intracellular second messenger that transduces signals from Gs-coupled receptors. Intriguingly, there is evidence from various cell types that an extracellular cAMP pathway is active in the extracellular space. Herein, we investigated the role of extracellular cAMP in the lung and examined whether it may act on pulmonary vascular cell proliferation and pulmonary vasculature remodelling in the pathogenesis of pulmonary hypertension (PH).

Methods and results

The expression of cyclic AMP-metabolizing enzymes was increased in lungs from patients with PH as well as in rats treated with monocrotaline and mice exposed to Sugen/hypoxia. We report that inhibition of the endogenous extracellular cAMP pathway exacerbated Sugen/hypoxia-induced lung remodelling. We found that application of extracellular cAMP induced an increase in intracellular cAMP levels and inhibited proliferation and migration of pulmonary vascular cells in vitro. Extracellular cAMP infusion in two in vivo PH models prevented and reversed pulmonary and cardiac remodelling associated with PH. Using protein expression analysis along with luciferase assays, we found that extracellular cAMP acts via the A2R/PKA/CREB/p53/Cyclin D1 pathway.

Conclusions

Taken together, our data reveal the presence of an extracellular cAMP pathway in pulmonary arteries that attempts to protect the lung during PH, and suggest targeting of the extracellular cAMP signalling pathway to limit pulmonary vascular remodelling and PH.
Small Bowel Adenocarcinoma: Is There a Difference in Survival for Crohn's Versus Sporadic Cases?
Authors: Fields Adam C , Hu Frances Y , Lu Pamela , Irani Jennifer , Bleday Ronald , Goldberg Joel E , Melnitchouk Nelya
Published: September 2019

Background and Aims

It is well known that Crohn's disease is a risk factor for the development of small bowel adenocarcinoma. However, the association between Crohn's disease-associated small bowel adenocarcinoma and survival is less understood. The goal of this study was to determine the impact of Crohn's disease on survival in small bowel adenocarcinoma.

Methods

Patients with small bowel adenocarcinoma, either associated with Crohn's disease or diagnosed sporadic, were identified in the National Cancer Database from 2004–2016. The primary outcome was overall survival.

Results

Of 2668 patients, 493 had Crohn's disease-associated small bowel adenocarcinoma and 2175 had sporadic small bowel adenocarcinoma. Crohn's disease patients were more likely to present at a younger age [62 vs 65, p < 0.001], have tumours located in the ileum [62.7% vs 25.0%, p < 0.001], and have poorly differentiated tumours [47.0% vs 31.7%, p < 0.001] compared with sporadic small bowel adenocarcinoma. Factors associated with significantly decreased survival included older age (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.02–1.03, p < 0.00)], higher Charlson score [HR: 1.39, 95% CI: 1.13–1.72, p = 0.002], higher tumour grade [HR: 1.09, 95% CI: 1.04–1.14, p < 0.001], positive surgical margins [HR: 1.60, 95% CI: 1.39–1.84, p < 0.001], and higher stage of disease [HR: 1.90, 3.75, 8.13, 95% CI: 1.37–2.64, 2.68–5.24, 5.77–11.47, for II, III, IV, respectively, compared with I, all p < 0.001]. Receipt of chemotherapy was associated with significantly improved survival [HR: 0.61, 95% CI: 0.53–0.70, p < 0.001]. Crohn's disease [HR: 1.01, 95% CI: 0.99–1.02, p = 0.39], was not significantly associated with survival.

Conclusion

Compared with sporadic patients, Crohn's disease patients have similar overall survival, and Crohn's disease is not an independent risk factor for mortality.
Right ventricular systolic dysfunction but not dilatation correlates with prognostically significant reductions in exercise capacity in repaired Tetralogy of Fallot
Authors: Rashid Imran , Mahmood Adil , Ismail Tevfik F , O’Meagher Shamus , Kutty Shelby , Celermajer David , Puranik Rajesh
Published: September 2019

Aims

The optimal timing for pulmonary valve replacement in asymptomatic patients with repaired Tetralogy of Fallot (rTOF) and pulmonary regurgitation remains uncertain but is often guided by increases in right ventricular (RV) end-diastolic volume. As cardiopulmonary exercise testing (CPET) performance is a strong prognostic indicator, we assessed which cardiovascular magnetic resonance (CMR) parameters correlate with reductions in exercise capacity to potentially improve identification of high-risk patients.

Methods and results

In all, 163 patients with rTOF (mean age 24.5 ± 10.2 years) who had previously undergone CMR and standardized CPET protocols were included. The indexed right and left ventricular end-diastolic volumes (RVEDVi, LVEDVi), right and left ventricular ejection fractions (RVEF, LVEF), indexed RV stroke volume (RVSVi), and pulmonary regurgitant fraction (PRF) were quantified by CMR and correlated with CPET-determined peak oxygen consumption (VO2) or peak work. On univariable analysis, there was no significant correlation between RVEDVi and PRF with peak VO2 or peak work (% Jones-predicted). In contrast, RVEF and RVSVi had significant correlations with both peak VO2 and peak work that remained significant on multivariable analysis. For a previously established prognostic peak VO2 threshold of <27 mL/kg/min, receiver-operating characteristic curve analysis demonstrated a Harrell’s c of 0.70 for RVEF (95% confidence interval 0.61–0.79) with a sensitivity of 88% for RVEF <40%.

Conclusion

In rTOF, CMR indices of RV systolic function are better predictors of CPET performance than RV size. An RVEF <40% may be useful to identify prognostically significant reductions in exercise capacity in patients with varying degrees of RV dilatation.
Are Policymakers Ambiguity Averse?*
Authors: Berger Loïc , Bosetti Valentina
Published: September 2019

We investigate the ambiguity preferences of a unique sample of real-life policymakers at the Paris UN climate conference (COP21). We find that policymakers are generally ambiguity averse. Using a simple design, we are moreover able to show that these preferences are not necessarily due to an irrational behavior, but rather to intrinsic preferences over unknown probabilities. Exploring the heterogeneity within our sample, we also show that the country of origin and the degree of quantitative sophistication affect policymakers’ attitudes towards compound risk, but not towards ambiguity. Robustness results are obtained in a lab experiment with a sample of university students.
Deep septal deployment of a thin, lumenless pacing lead: a translational cadaver simulation study
Authors: Jastrzębski Marek , Moskal Paweł , Hołda Mateusz K , Strona Marcin , Bednarek Agnieszka , Kiełbasa Grzegorz , Czarnecka Danuta
Published: September 2019

Aims

The recently introduced technique of direct transseptal pacing of the left bundle branch is poorly characterized with many questions with regard to the optimal implantation strategy and safety concerns largely left unanswered. We developed a cadaver model for deep septal lead deployment in order to investigate the depth of penetration in relation to lead behaviour, lead tip position, and the number of rotations.

Methods and results

Five fresh human hearts and five lumenless, 4.1-Fr pacing leads were used for deep septal deployment simulations. The leads were positioned with the use of a dedicated delivery sheath and screwed into the interventricular septum at several sites progressively more distal from the atrioventricular ring with a predetermined number of lead rotations. During each lead deployment, the depth of tip penetration was measured and the lead behaviour was noted. Four distinct lead behaviours were observed: (i) helix only penetration, no matter how many rotations were performed, due to the ‘endocardial entanglement effect’ (43.1% cases) or (ii) ‘endocardial barrier effect’ (19.6% cases), (iii) shallow/moderate penetration, with ensuing ‘drill effect’ when more rotations were added (9.8% cases), and (iv) deep progressive penetration with each additional rotation, occurring when the ‘screwdriver effect’ was present (27.4% cases, including three septal perforations). These different lead behaviours seemed to be determined by the lead position—mainly the strength of the initial endocardial layer—and the number of fully transmitted rotations.

Conclusion

New insights into deep septal lead deployment technique were gained with regard to safe and successful implantation.
Comparison of the plant growth-promotion performance of a consortium of Bacilli inoculated as endospores or as vegetative cells
Authors: Hashmi Isha , Paul Christophe , Al-Dourobi Andrej , Sandoz Frederic , Deschamps Priscilla , Junier Thomas , Junier Pilar , Bindschedler Saskia
Published: September 2019

The effect of three plant growth-promoting Bacillus strains inoculated either alone or as a consortium was tested on oat (Avena sativa) growth. The bioinoculants were applied as vegetative cells or endospores at low cell densities on the seeds and their effect was tested in sterile in vitro conditions, pot experiments, and a field trial. The in vitro seed germination assay showed that both individual bacterial inocula and bacterial consortia had positive effects on seed germination. Greenhouse pot experiments with sterile and non-sterile soil showed that consortia increased the total dry biomass of oat plants as compared to single strain inoculation and uninoculated controls. However, the positive impact on plant growth was less prominent when the bioinoculated strains had to compete with native soil microbes. Finally, the field experiment demonstrated that the consortium of vegetative cells was more efficient in promoting oat growth than the endospore consortium and the uninoculated control. Moreover, both consortia successfully colonized the roots and the rhizosphere of oat plants, without modifying the overall structure of the autochthonous soil microbial communities.
The Draft Genome of Kochia scoparia and the Mechanism of Glyphosate Resistance via Transposon-Mediated EPSPS Tandem Gene Duplication
Authors: Patterson Eric L , Saski Christopher A , Sloan Daniel B , Tranel Patrick J , Westra Philip , Gaines Todd A
Published: September 2019

Increased copy number of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene confers resistance to glyphosate, the world’s most-used herbicide. There are typically three to eight EPSPS copies arranged in tandem in glyphosate-resistant populations of the weed kochia (Kochia scoparia). Here, we report a draft genome assembly from a glyphosate-susceptible kochia individual. Additionally, we assembled the EPSPS locus from a glyphosate-resistant kochia plant by sequencing select bacterial artificial chromosomes from a kochia bacterial artificial chromosome library. Comparing the resistant and susceptible EPSPS locus allowed us to reconstruct the history of duplication in the structurally complex EPSPS locus and uncover the genes that are coduplicated with EPSPS, several of which have a corresponding change in transcription. The comparison between the susceptible and resistant assemblies revealed two dominant repeat types. Additionally, we discovered a mobile genetic element with a FHY3/FAR1-like gene predicted in its sequence that is associated with the duplicated EPSPS gene copies in the resistant line. We present a hypothetical model based on unequal crossing over that implicates this mobile element as responsible for the origin of the EPSPS gene duplication event and the evolution of herbicide resistance in this system. These findings add to our understanding of stress resistance evolution and provide an example of rapid resistance evolution to high levels of environmental stress.
The Race to Forget? Bi-racial Descendants of the First Rhineland Occupation in 1950s West German Debates about the Children of African American GIs*
Authors: Roos Julia
Published: September 2019

After the First World War, the German children of colonial French soldiers stationed in the Rhineland became a focal point of nationalist anxieties over ‘racial pollution’. In 1937, the Nazis subjected hundreds of biracial Rhenish children to compulsory sterilization. After 1945, colonial French soldiers and African American GIs participating in the occupation of West Germany left behind thousands of out-of-wedlock children. In striking contrast to the open vilification of the first (1920s) generation of biracial occupation children, post-1945 commentators emphasized the need for the racial integration of the children of black GIs. Government agencies implemented new programmes protecting the post-1945 cohort against racial discrimination, yet refused restitution to biracial Rhenish Germans sterilized by the Nazis. The contrasts between the experiences of the two generations of German descendants of occupation soldiers of colour underline the complicated ways in which postwar ruptures in racial discourse coexisted with certain long-term continuities in antiblack racism, complicating historians’ claims of ‘Americanization’ of post-1945 German racial attitudes.
Portrait of a Caregiver: Ethnodrama Development and Its Influence on Caregiver Well-Being
Authors: Eaton Jacqueline
Published: September 2019

Background and Objectives

The majority of long-term care needs are placed upon family members who often receive minimal support. In this study, we collaborate with family caregivers to create an ethnodrama about their experience and assess outcomes of participation, including caregiver well-being.

Methods

Participants met over 4 months to discuss their roles as informal caregivers. Discussions were analyzed in a two-phase process and themes were developed into a script. Member checks included script review and revisions, culminating in viewing a professional performance of the play followed by a post-performance discussion and reflection. Data were gathered at six timepoints to assess caregiver well-being and longitudinal analysis was used to assess change during the course of the intervention.

Results

Twenty-two caregivers completed intervention activities. Participant reactions to the process evolved overtime, from an initial hesitance about what individuals had to offer leading to an acknowledgement of feeling heard and a desire to help others. Caregivers had high levels of burden and positive perceptions towards caregiving. Those with high levels of self-rated health had the lowest levels of burden and the most positive perceptions of caregiving.

Discussion and Implications

Developing an ethnodrama in partnership with caregivers is a unique and feasible method of caregiver support, mentoring, reflexivity, and meaning making. Promoting caregiver health early in the caregiving trajectory has the potential of reducing burden and elevating positivity towards caregiving.