bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Acid-Fast Stain and Auramine Rhodamine Fluorescent Smear on Bronchoalveolar Lavage Specimens Submitted for Cytologic Examination
Authors: Samra Hasan , Ledeboer Nathan , Buchan Blake
Published: September 2019

Objectives

Testing of bronchoalveolar lavage specimens with acid-fast bacilli (AFB) stain is not routinely performed in many institutions. In 2017, we began performing AFB stain on all BAL specimens submitted for cytologic examination. Herein, we evaluate the diagnostic value of this test in comparison to the auramine rhodamine fluorescent stain performed in parallel by the microbiology laboratory for specimens also submitted for AFB culture.

Methods

We retrospectively reviewed all BAL specimens that were reported as culture positive for Mycobacteria spp. (n = 109) by our microbiology laboratory between 7/20/2017 and 12/30/2018. Of these, 84 (77.0%) specimens were concurrently submitted for cytologic examination and reviewed by a board-certified cytopathologist.

Results

Of the 84 culture-positive BAL specimens submitted for cytologic exam, only 2 cases were positive for acid-fast bacilli on cytologic examination with AFB stain, yielding a sensitivity of 2.38%. In comparison, 11 of those specimens were identified on auramine rhodamine fluorescent stain, yielding a sensitivity of 13.1%. Both cases identified by the AFB stain on cytology were also identified by auramine rhodamine stain in microbiology. These data indicate that AFB stain conducted in cytology is 81.2% less sensitive for detection of AFB when compared to auramine rhodamine stain. All cases identified on smear and AFB stain (n = 11) belonged to the Mycobacterium avium-intracellulare complex.

Conclusion

Our study results suggest that in a low-prevalence population, the use of AFB stain on BAL specimens sent for cytologic examination lacks sensitivity and is unnecessary if the same specimen is also sent for microbiologic culture and auramine rhodamine stain. The use of AFB stain on BAL specimens that were not sent for AFB culture is suboptimal but may identify AFB in specimens obtained from patients for whom mycobacterial infection is not in the differential and may be clinically insignificant.
Erysipelothrix rhusiopathiae Native Value Endocarditis: A Unique Case Presentation
Authors: Patel Krutika , Liu S Shawn , Dasaraju Sandhya , Carter J Elliot
Published: September 2019

ER is a facultative, non-spore-forming, non-acid-fast, gram-positive bacillus. It is a ubiquitous commensal in wild and domestic animals, birds, and fish and has an enormous economic impact on animal husbandry and marine industry, causing animal erysipelas. Human infections are extremely rare, occupationally acquired zoonosis. Human infections are acquired through wounds, contact with sick animals, and carriers and commonly includes localized or generalized self-limited cutaneous erysipelas. Seldom, systemic infection and septicemia occur. We present here, a case of a 50-year-old immunocompetent retired shipyard welder who enjoyed fishing in his spare time and presented to the emergency room with fever, chest pain, significant weight loss, and dry cough lasting 2 to 3 months. He did not report any bites or injuries, intravenous drug abuse, or travel history. An echocardiogram showed mobile vegetation on aortic valve with severe regurgitation. Blood and tissue cultures grew E rhusiopathiae, identified by MALDI-TOF method. He was treated with empiric vancomycin followed by penicillin and aortic valve replacement with a mechanical valve. Cases of E rhusiopathiae–induced native valve endocarditis and septicemia are extremely infrequent in immunocompetent individuals, especially when occupation-related exposure is not noted. Even after surgery, it may entail fatality rates as high as 40%, higher than endocarditis caused by other bacteria. While some current reports suggest incidences of human infections are declining due to technological advances in animal industry, infection still occurs in specific environments. Additionally, it may be underdiagnosed due to its resemblance to other infections and problems encountered in isolation and identification. The natural resistance of E rhusiopathiae to glycopeptides underlines the importance of a prompt microbiological diagnosis of such an uncommon human infection, especially when presented in an unusual clinical presentation. Clinicians and microbiologists working with exposed population should be aware of this microbe and its manifestations.
Mycobacterium chimaera Infection: A Case Report and Review of Literature
Authors: Salas Dongpo , Zhao Xing , Cavalieri Stephen
Published: September 2019

Mycobacterium chimaera (MCH) is a non-tuberculous mycobacterium commonly found in the environment. It is a member of the M. avium complex (MAC), and rarely causes infections in humans. However, invasive MCH infections have been reported associated with heater-cooler devices during cardiac surgery. Detection of MCH infections in this setting has been impeded by inadequate clinical awareness and laboratory tests. A 77-year-old man had aorta valve replacement 3 years ago. He recently presented with constitutional symptoms, including fatigue, night sweats, and 50 pounds of weight loss. PET CT showed ground-glass and nodular opacities in the lungs. Bone marrow biopsy demonstrated noncaseating granulomas. Transesophageal echocardiogram revealed severe stenosis and regurgitation of aortic valves. Despite antibiotics and heart surgery to relieve stenosis, the patient succumbed. Autopsy showed multiple small granulomas in the lung and multifocal chronic inflammation in the heart. Premortem mycobacterial cultures of aortic valves were performed, which grew MAC by DNA probe in 1 week. Subsequently, it was identified as MCH by sequencing of the ITS1/ITS2 region. The cause of death was heart failure due to MCH endocarditis. MCH infection is rare but potentially fatal if not promptly treated. Therefore, it is critical to identify patients at risk for infection. Since 2013, over 100 cases of MCH endocarditis have been reported worldwide, specifically associated with contaminated heater-cooler units during heart surgery. Characteristically, MCH infection has a long incubation period after exposure (median 17 months, range 3-72 months). Signs and symptoms are generally nonspecific and often include fatigue, fever, and weight loss. The risk of MCH infection in patients undergoing open heart surgery is low, but clinicians should be aware of the risks especially when heater-cooler units are utilized. A close follow-up over a long period may be necessary due to the long incubation period of this infection.
Paracoccus yeei, a Rare Cause of Ocular Infection
Authors: Masood Hassan Muhammad , Naab Tammey , Afsari Ali
Published: September 2019

Objectives

Paracocci are nonfermenting obligate aerobes. The genus Paracoccus is classified in the family Rhodobacteraceae and contains 31 species. Gram stains reveal gram-negative cocci, diplococci, or coccobacilli/short rods, sometimes described as having an O shape due to peripheral stain. It may be confused with Neisseria sp. or Moraxella sp. due to oxidase positivity. Paracoccus yeei, a rare cause of infection in patients ranging from 6 weeks to 77 years, has been isolated from abdominal dialysate, wounds (ankle, toe), incision drainage, cerebrospinal fluid, bile, skin, blood, ear, and eye (uveitis, conjunctivitis, corneal transplant graft infection). It is a rare emerging pathogen with low pathogenic potential.

Methods

A 65-year-old heroin-dependent male with a nonfunctional left eye due to gasoline injury presented with a traumatic injury to the right eye. The ophthalmological exam revealed a central corneal ulcer, hazy pupil, right upper and lower lid swelling, periorbital edema with central vision loss, and conjunctival chemosis. B-scan showed no vitreous debris. Cultures of the ulcer were taken, and fortified tobramycin and fortified vancomycin drops were started.

Results

Nonhemolytic, whitish-gray, convex colonies, measuring 0.5 to 1 mm in diameter, grew on Columbia sheep blood and chocolate agar plates at 48 hours. Tiny pinpoint colonies were identified on MacConkey agar plate at 3 days. Gram stain revealed a small short gram-negative rod, which was oxidase and catalase positive. Microscan identified the isolate as P yeei. Antibiotic susceptibilities revealed low MICs for beta-lactam antibiotics and higher MICs for cephalosporins. The ulcer healed very well. The patient’s vision improved. The patient was subsequently discharged with instructions to follow up with clinic.

Conclusion

Our case reinforces the need to consider uncommon pathogens, including P yeei in eye infections and the role of microbiology in correctly identifying the organism where delay or incorrect treatment can lead to permanent damage.
Assessment of Anaerobic Culture Incubation Time: A Tertiary Care Center Experience
Authors: Gupta Akanksha , Easwar Arti , Maldonado Yanice , Hamilton Pam , Baumgartner Lori , Aslanzadeh Jaber
Published: September 2019

Background

Currently, there is no consensus on the ideal incubation time for anaerobic cultures. A recent survey of CliniMicroNet reported anaerobic culture incubation times from 2 to 7 days. The goal of this study is to determine the ideal anaerobic culture incubation time and to retrospectively determine if longer incubation time affected management.

Methods

In this prospective study at Hartford Hospital, an 869-bed level I trauma center, 838 consecutive anaerobic cultures were Gram stained and planted on anaerobic blood, colistin and nalidixic acid (CNA), and kanamycin and vancomycin (KV) agar plates (BD Diagnostic Sparks). Plates were incubated in jars at 35°C and Anoxomat system (Advanced Instruments) was used to create anaerobic conditions. Plates were checked for growth on days 2, 3, 5, and 7. Although not all patient records (EPIC) were available, the type and duration of antibiotics were recorded for more than 100 records.

Results

Out of 74 cultures from bronchoalveolar lavage (1), bone (2), fluid (21), tissue (14), and wound (36), 53 grew 1 isolate, 15 grew 2 isolates, 5 grew 3 isolates, and 1 grew 4 isolates, for a total of 102 isolates. Sixty percent of isolates were Gram negative and 40% were Gram positive. Of these, 43% were detected on day 2, 21% on day 3, 20% on day 5, and 17% on day 7. In a majority of cases, broad-spectrum antibiotics (vancomycin/cefepime) were administered until culture results were obtained.

Conclusion

Overall, 73% Gram-negative isolates and 50% Gram-positive isolates were detected on day 2 or 3. Days 5 and 7 yielded 20% and 17% of all isolates, respectively. We conclude and corroborate with CLSI recommendations that anaerobic cultures should be incubated for at least 5 to 7 days.
Clinical Utilization of Next-Generation Sequencing-Based Clonality Assays for Immunoglobulin Heavy Chain in Evaluating Suspected B-Cell Proliferation
Authors: Katerji Hani , Katerji Roula , Campbell Andrew , Rothberg Paul , Ding Yi
Published: September 2019

Objectives

B-cell clonality assays of the immunoglobulin heavy chain (IGH) and light chain (IGK) genes have been used widely in the workup of B-cell neoplasms. PCR is the current gold standard test for clonality. Recently, NGS has been suggested to both improve sensitivity and identify the specific V-(D-)J sequence required to track clones. Here we report our experience with using NGS for complementing our current procedures.

Methods

Our validated NGS test is performed by amplifying patients’ DNA using IGH-FR1 assay panel. Pooled amplicons get sequenced. The sequence data then get analyzed using in-house bioinformatics software, which sorts sequences and generates frequency distributions. Each sequence is ranked by its frequency. A clonal population is designated if the top sequence read is at least 1% of the total reads. For the standard PCR gene rearrangement test, we use a BIOMED-2 PCR-based B-cell assay.

Results

We retrospectively searched our database for all cases in which IGH and IGK clonality was tested by either standard PCR or NGS from 8/2016 to 7/2017. A total of 253 cases were tested by PCR while 21 cases were tested by NGS, which showed higher success rates. Of the 253 cases tested by conventional PCR, 39% (n = 98) were clonal (either IGH, IGK, or both), 34% (n = 86) were polyclonal, and the rest 28% (n = 69) showed a weak inconclusive signal or failed. Of the 21 cases analyzed by NGS, 71% (n = 15) were clonal, 24% (n = 5) were polyclonal, and just 5% (n = 1) failed.

Conclusion

Our experience indicates that NGS for IGH clonality, even more expensive, is an effective and more sensitive tool that produces higher informational content and yields higher success rates when compared to conventional PCR assay. NGS captures multidimensional data and provides a more precise determination of the clonal relationship between different lymphoid proliferations, which also is essential for the detection and measurement of minimal residual disease.
Quantification of BCR-ABL1 Fusion Transcripts in Patients With Acute B Lymphoblastic Leukemia by Multiplex Droplet Digital PCR
Authors: Martinez Ryan , Nennig Davis , Mroz Pawel
Published: September 2019

Droplet digital PCR (ddPCR) is a novel PCR platform that provides quantification of amplification targets by massive sample partitioning and analysis in a single sample. These results are independent of a calibration curve and may increase detection when compared to quantitative RT-PCR (qRT-PCR). The t(9;22)(BCR-ABL1) translocation is associated with chronic myelogenous leukemia (CML) and a subset of acute B lymphoblastic leukemias (B-ALLs). Several studies have demonstrated the clinical utility of quantifying BCR-ABL1 fusion transcript levels for detecting minimal residual disease (MRD). qRT-PCR is a well-established method for MRD monitoring but has inherent limitations with regard to lower limit of detection and quantification (LOD and LOQ). Here we report the results of a pilot project to compare and evaluate ddPCR and qRT-PCR in detecting BCR-ABL1 e1a2 transcripts for MRD monitoring in B-ALL. We developed and optimized a single-step, multiplexed ddPCR assay for detecting BCR-ABL1 e1a2 and ABL1 e10 from RNA. Droplets were prepared using a QX100 or QX200 droplet generator (Bio-Rad, Hercules, California), and PCR products were run on a QX100 droplet reader and analyzed with QuantaSoft software. Method comparison of droplet generation was assessed between manual and automated methods, finding automated methods gave an 8.2% increase in total droplets generated (15,082 vs 13,940). Next, assay performance was evaluated using the Invivoscribe BCR-ABL1 e1a2 RNA dilution set and t(9;22)-positive SUPB15 cell line. ddPCR demonstrates a limit of detection to 10–6 dilution in the Invoscribe kit and a minimum input of 10–3 to 10–4 ng of RNA from the SUPB15 cell line. Future studies will include multiplexed ddPCR in BCR-ABL1-positive B-ALL patients at time points day 0 (diagnostic sample) and days 33 and 78 postinduction for MRD determination. The performance of ddPCR will be compared with standard qPCR along with clinicopathologic correlation to determine if ddPCR can improve MRD and clinical outcomes of patients with t(9;22)+ B-ALL.
Relationship Between Gene Polymorphism and Type 2 Diabetes in a Palestinian Population: A Study of Five Gene Polymorphisms
Authors: Najjar Mahmoud
Published: September 2019

Objectives

To investigate the association between KCNQ1 rs2237892, KLF14 rs972283, ZBED3 rs4457053, COL8A1 rs792837, and FTO rs8050136; gene polymorphisms; and T2DM in the male Palestinian population.

Methods

In this case-control study, 100 T2DM male patients and 100 control men were examined. The two groups were genotyped for the five gene polymorphisms using restriction fragment length polymorphism–PCR (RFLP-PCR) and allele-specific (AS-PCR) techniques. Body mass index (BMI), glycated hemoglobin (HbA1c), insulin (C-peptide), total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were measured for all the study participants. The relation between the five gene polymorphisms, T2DM, and the measured clinical parameters were statistically analyzed using appropriate tests.

Results

Among the tested polymorphisms, significant associations were evident between KLF14 “GG” genotype (P = .014), FTO “CC” genotype (P = .043), and COL8A1 TC genotype (P = .015) and increased risk of T2DM. The KLF14 G-containing genotypes exerted a significant effect on lowering HDL-c (P = .026) and on elevating LDL-c (P = .045) and cholesterol level (P = .042) in the control group. The FTO “CC” genotype showed a significant effect on raising HbA1c level in the patients (P = .007). KCNQ1 (rs2237892 T>C), ZBED3 (rs4457053 A>G), and COL8A1 (rs792837 T>C) genotypes did not reveal significant effects on the tested parameters.

Conclusion

KLF14 “GG,” FTO “CC,” and COL8A1 C allele and “TC” genotypes are significantly associated with T2DM in the investigated population. KLF14 “GG” and “AG” have an association with the levels of HDL-c, LDL-c, and cholesterol in control subjects. The HbA1c level was significantly higher in patients with the FTO “CC” genotype. The study recommends confirming the obtained results on a larger sample and examining the association of other gene polymorphisms with T2DM in the Palestinian population.
Clinicopathologic Features of Uterine Fibroids in a Private Gynecologic Setting in Calabar, Nigeria
Authors: Ekanem Ima-Obong , Ekanem Ima-Obong , Ekanem Odudu , Ekanem Chinweoke
Published: September 2019

Introduction

Uterine fibroid is a common gynecologic problem among adult females in Nigeria with variable clinical presentations. Unfortunately, these patients often seek medical attention very late after having consulted nonorthodox and/or traditional health practitioners.

Objectives

To assess the clinical outcome of patients diagnosed with uterine fibroids and review the pathologic features of specimens obtained from such patients managed over a 48-months period at Davis Medical Centre, a specialist gynecologic private health facility in Calabar, Nigeria.

Methods

This retrospective study was conducted at Davis Medical Centre, located in a semirural community in Calabar Municipality. It involved the extraction of data from case notes of patients and review of laboratory reports and H&E-stained histopathologic slides of surgical specimens removed from patients who presented with abdominal mass/swelling, heavy menstrual bleeding, abdominal pain, and inability to get pregnant having excluded other causes of infertility and ultrasonographic features suggestive of leiomyoma.

Results

A total of 82 patients aged between 26 and 54 years (mean age 36 ± 2 SD) were seen, giving an annual rate of about 20 cases yearly in the 4-year period (2015-2018) studied. Forty-eight (58.5%) had giant uterine fibroids with uterine size between 16 and 28 weeks. Myomectomy was the mainstay of treatment in 93.9% while 6.1% had abdominal hysterectomy. Histologically, the number of fibroid nodules ranged from 1 to 60 nodules with the largest weighing 4,097 g. All had the typical whorled grayish-tan gross appearance of leiomyoma uteri with a large proportion histologically showing degenerative changes of the hyaline type (39%) and few having features suggestive of adenomyosis.

Conclusion

Despite the grotesque, unusual macroscopic and characteristic microscopic findings, timely and careful surgical intervention can remedy the reproductive outcome and save lives of the affected patients when seen and managed by an experienced specialist gynecologist.
Bridging the Gap With Choosing Wisely Recommendations: What Laboratory Topics Matter Most to Other Medical Specialty Societies?
Authors: Caldwell Barbara
Published: September 2019

Introduction

This study sought to evaluate the nature and frequency of laboratory recommendations made by medical societies other than ASCP.

Methods

Review of all 2012 to 2018 ABIM Choosing Wisely (CW) non-ASCP laboratory recommendations and categorization of recommendations per topic area.

Results

There are 107 total recommendations made by other medical specialties that involve laboratory medicine. The most common recommendations are (1) Transfusion Medicine: to minimize transfusion of PRCs (19 recommendations, 18%); (2) Women’s Health: Pap smear testing, other women’s health testing (18 recommendations, 17%); and (3) General Laboratory: reducing repetitive routine laboratory tests (10 recommendations, 9%). Most (64, 60%) recommendations addressed screening while 29 (27%) focused on treatment and 14 (13%) were related to monitoring disease.

Conclusion

Almost one-half (44%) of all recommendations fell into three common areas and there were more recommendations related to screening for disease than for treatment or monitoring. For Choosing Wisely to achieve increasing success, increasing efforts are needed to disseminate this information, promote multidisciplinary effective test utilization, and encourage continued laboratory medicine recommendations from all medical stakeholders.
Observational Study of Tissue Acquisition Turnaround Time for Commercial Comprehensive Genomic Profiling in Solid Tumors
Authors: Krigsfeld Gabriel , Roth Aleeza , Cooper Maureen , Smith Liisa , Iyer Radhika , Brown Adam , Pratt James , Truesdell John , Schwartz Joshua
Published: September 2019

Introduction

Increased development and use of next-generation sequencing in clinical diagnostics has revolutionized precision medicine. Steps prior to a specimen arriving at a diagnostic facility, including pathological evaluation, are crucial parameters determining specimen quality and success of comprehensive genomic profiling (CGP). This observational study identified factors that may influence tissue acquisition for commercial CGP in clinical oncology.

Methods

Data were collected from deidentified patients (n = 63) from select US pathology labs enrolled in a Foundation Medicine (FMI) early access program for the CGP test FoundationOne CDx (Foundation Medicine). A representative substudy cohort (n = 20) with qualitative information available was selected. Lab visit frequency by FMI was monitored for 42 cases. Tissue acquisition turnaround time (TA-TAT) was separated into stages: (1) tissue request to pathology lab acknowledgment, (2) pathology lab acknowledgment to tissue pathology review, (3) tissue pathology review to packaging, and (4) packaging to tissue arriving at FMI.

Results

Median TA-TAT for the total population was 5.0 days (range, 0-27.0) and 3.5 days for the substudy cohort (range, 1.0-11.0). The duration of each TA-TAT stage was evaluated separately and varied between labs (0%-71.4% of total TA-TAT). TA-TAT was longer for unstained slides compared with formalin-fixed, paraffin-embedded (FFPE) tissue blocks. There was a trend for decreased TA-TAT when stages 1 and 2 occurred on the same day versus different days. For the cases with lab-visit frequency reported, those with biweekly visits had shorter TA-TAT (biweekly: n = 12, median = 2.0, 2.5th-97.5th percentile range, 0.3-5.7 days; single visit: n = 30, median = 5.5, 2.5th-97.5th percentile range, 0.7-13.1 days).

Conclusions

Understanding and optimizing the tissue acquisition workflow may reduce TA-TAT, thereby facilitating report delivery and subsequent treatment guidance to patients.

Funding

Bristol-Myers Squibb. Professional medical writing and editorial assistance was provided by Katerina Pipili, PhD, and Jay Rathi, MA, of Spark Medica Inc, funded by Bristol-Myers Squibb.
The Utilization of JAK2 Molecular Testing at the University of Minnesota Medical Center
Authors: Mroz Pawel , Arries Cade
Published: September 2019

Objectives

JAK2 gene mutation status is included in the 2017 WHO diagnostic criteria of a myeloproliferative neoplasm (MPN) and therefore indicated in the diagnostic workup. Overutilization and inappropriate testing, however, can cause harm and lead to medical errors, and most importantly, it can significantly drive up the costs of patients’ care. Here we report an attempt to evaluate the success rate and the associated costs of JAK2 testing as well as to correlate it with clinical indications and patient presentation.

Methods

We conducted the analysis of next-generation testing orders/results performed at out institution between 9/2/2015 and 7/13/2018. We reviewed the rate of positive results as well as the type of order submitted to laboratory and compared the costs of individual tests.

Results

We analyzed 3,474 NGS orders/results performed at our institution. Of those, 1,203 were submitted for JAK2 testing, making this the most commonly ordered NGS test. Out of 1,203 results, there were 820 unique patient specimens and 118 tested positive (15%). The JAK2 testing was primarily ordered as part of the NGS MPN panel, which includes JAK2, CALR, and MPL mutation hotspots (70%), the custom panel (23%), JAK2 single gene (5%), or as part of comprehensive myeloid panel (2%). The mutation detection rate was 15%, 12%, 11%, and 15%, respectively.

Conclusion

Testing for JAK2 gene mutation status is the most commonly ordered NGS test in our laboratory. The detection rate for pathogenic mutation, irrespective of the type of genetic panel ordered, was 11% to 15%. Our analysis of the JAK2 ordering and reporting suggests that the JAK2 testing may be somewhat overutilized at our institution. An ongoing analysis of clinical indications, patient presentation, and associated costs will help to fully elucidate the true utility of this testing and will be included in the poster presentation.
An Integrated Approach to Genetic Test Stewardship: The Role of Laboratory Genetic Counselors in Test Preauthorization and Ordering
Authors: Conta Jessie , Sternen Darci , Stasi Shannon , Candadai Sarah Clowes , Wellner Monica , Dickerson Jane
Published: September 2019

Introduction

The complexity and relative high cost of genetic tests combined with stringent administrative and medical coverage policies can negatively impact test accessibility and, ultimately, patient care. The burden of test preauthorization typically falls on the ordering provider and team, and is particularly cumbersome for specialists that do not have genetics expertise. As part of the Seattle Children’s laboratory stewardship program, we integrated laboratory genetic counselors (GCs) in a hospital-wide genetic test preauthorization and order review process to support efficient test authorization and ensure appropriate genetic test utilization.

Methods

A rotating team of laboratory GCs reviews all genetic test requests at the time of preauthorization for medical necessity, optimal test selection, and CPT coding. This information is triaged to our centralized insurance processing department for submission to payers. Lab GCs review test orders for the same elements, preauthorization status, and supporting paperwork.

Conclusions

The 7,889 preauth requests and 7,177 test orders have been reviewed in our institution since implementing this two-phase review process in January 2016. Twenty-eight percent of requests were modified or cancelled at the time of preauth review, with the majority of modifications related to test optimization and improved necessity documentation. Additionally, 21% of requests were modified or cancelled when reviewed at the time of order. The intervention resulted in $1.5M cost-avoidance accrued since 2016. A recent provider survey revealed that 90% of providers are neutral, very, or extremely satisfied with the genetic test authorization process and support provided by the laboratory GC team. By integrating a laboratory GC case review process, we supported effective genetic test utilization at our institution, reduced collective provider and staff time and rework related to insurance authorization, and reduced financial liability for the patient/family and institution.
Laboratory Test Utilization in an Expanding Regional Laboratory Network: Past Successes and Future Opportunities
Authors: Paczos Tamera , Bell Phoenix
Published: September 2019

Introduction

The University of Rochester Medical Center developed a reference test utilization program implemented in 2011 to tackle increasing test volumes and costs. There was an initial >7,000 decrease in test volumes, which equated to >$1,000,000.00 in savings by year end 2012. Despite this, by the end of 2018, testing volumes had increased 34% and the cost had climbed 36%. Here we would like to discuss the methods implemented for initial success, potential reasons for continued increases in volumes and costs, and ideas to mitigate this trend in the future.

Methods

In 2010, the University of Rochester formed a laboratory diagnostics committee, which successfully decreased reference testing volumes and costs in both the inpatient and outpatient settings. They did this by developing a formulary for reference tests, which was divided into three tiers based on clinical utility and cost: tier 1 tests, unrestricted and available to all providers to order; tier 2 tests, restricted with only board-certified, subspecialty-trained physicians able to order; and tier 3 tests, off formulary and not available to order. The resident physician staff was also no longer allowed to order any reference testing on inpatients. Despite initial gains costs and volumes have climbed >36% and 34%, respectively, since implementation. Possible explanations for this include the addition of regional affiliate hospitals and reference clients that are not following these protocols, increased testing volumes, and increasing use of molecular testing.

Conclusion

Despite successful implementation of a reference test utilization program, close monitoring and adaptations are necessary in our continuously changing health care environment to remain effective. Implementation of the program at the regional affiliate hospitals and a more robust molecular testing menu in-house are potential options to control rising costs while providing high-quality patient care.
Blood Utilization at Regional Hospitals
Authors: Demkowicz Ryan , Dermawan Josephine , Shetty Sindu , Scarborough Richard , Lu Haiyan , Sardina Luis , Chong Yap-Yee
Published: September 2019

Introduction

Transfusion medicine is unique to lab medicine. While it still involves testing and reporting of results, it is one of the few areas where the laboratory is providing treatment. The risk of providing a blood product must be weighed against the benefit before the decision is made to transfuse a patient. Our study looked at blood utilization at our regional hospitals to assess if there were areas where we need to improve this decision process.

Methods

Chart reviews were performed for patients who received packed red blood cells (RBCs) in the regional hospitals over a 2-month period. Using the AABB and Choosing Wisely recommendations, we created two screening criteria: hemoglobin (Hb) >8 g/dL or greater than 1 unit RBC ordered when Hb is >6 g/dL to screen for outliers among RBC orders. A more in-depth chart review including information on clinical diagnosis, indications, bleeding status, and blood loss during surgery was performed on cases that met these criteria. Using this information, a decision was made on the appropriateness of the transfusion.

Results

In total, 1,592 RBC units were screened at eight regional hospitals. Sixty-eight (4%) were flagged as inappropriate, 57 (83.8%) due to multiple units, and 11 (16.2%) for an Hb >8 g/dL. The percentage of inappropriate transfusions at a hospital ranged from 5.2% to 13.6%. However, all hospitals except one were under 5.5%.

Discussion

In general, regional physicians are transfusing RBCs appropriately. When a unit is ordered inappropriately, it is most likely due to ordering multiple units upfront. To further improve blood utilization, these data were presented to hospital administration and a new alert in the EMR was created. A repeat study will be performed to see if the alerts and awareness of these data has had an effect on blood utilization.
Diagnosis of Rare Antibody Anti-Ata in Pregnancy: A Case Report
Authors: Taherian Mehran , Liu Zhonghua , Petras Melissa
Published: September 2019

Background

Anti-Augustine antigen (Ata) is a high-prevalence RBC antigen, and anti-Ata is an extremely rare RBC alloantibody. Anti-Ata is usually produced by an Ata (–) individual after alloimmunization by transfusion or during a pregnancy and is associated with immediate or delayed hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We report the detection of a unique antibody to an antigen of high incidence, the anti-Ata.

Case Presentation

The patient was a 26-year-old African American pregnant female G7P2042 with a medical history of beta-thalassemia trait, presented at her second trimester for evaluation of abdominal cramping. The patient has had two prior ectopic pregnancies, managed surgically, and two healthy children delivered vaginally with no obstetric or congenital complications. She was treated for a pulmonary embolism a few months before while she was on OCPs. She had no prior transfusions. She also had anemia (RBC 4.1 × 1012/L, Hgb 9.7 g/dL, Hct 29.6%, MCV 72.2 fL). The patient’s blood sample was sent for type and screen, and it came positive for anti-Ata antibody. This test was performed at Memorial Blood Centers (a reference lab) and Kaleida Health Laboratories. The phenotype of our patient was c+ E+ e+ k+ Kpb+ Jsb+ Jka+ M+ N+ s+ U+ Lub+. The baby was followed with serial fetal middle cerebral arterial (MCA) Doppler assessment, without evidence of fetal anemia. The term infant was delivered by cesarean section without complications. Currently, both mother and baby are doing well.

Conclusion

Although anti-Ata is unlikely to cause hemolytic disease of the newborn, it is important to ensure that compatible blood is available should the mother require transfusion postdelivery.
Cryoprecipitate Usage and Cost at a Tertiary Care Hospital Between 2010 and 2017
Authors: Serei Virian , Wong Cecilia , Tenorio Grace
Published: September 2019

Introduction

Cryoprecipitate (CRYO), a blood product prepared from FFP, is rich in fibrinogen, von Willebrand’s factor, and factors VIII and XIII. ​The major indication for CRYO transfusion is fibrinogen deficiency with increased risk of bleeding when fibrinogen is <100 mg/dL, a transfusion trigger rarely followed by the house staff or other clinicians. To limit wastage, Transfusion Services issue them as pools of five individual CRYO units. The use of CRYO at Robert Wood Johnson University Hospital (RWJUH) has significantly risen since 2010, so we conducted a study to identify the factors leading to increased CRYO transfusions.

Methods

Data on CRYO transfusions from 2010 to 2017 were obtained and analyzed for trends in overall usage and by nursing unit/departments. Cost-analysis was performed to determine the cost of CRYO usage.

Conclusion

Overall, CRYO usage has risen since 2010, with a sharp increase between 2015 and 2017 attributed to increased transfusions in the operating room (OR), surgical intensive care unit, and hematology-oncology units. There was a sixfold rise in transfusions in the hematology-oncology units. During this time, the lower limit of the fibrinogen reference range decreased from 234 to 190 mg/dL along with a drop in the number of trauma alerts. Values less than the lower reference range were used as the transfusion trigger by some overzealous hematology fellows. Cost-analysis showed that RWJUH lost 75% revenue per patient based on Medicare reimbursement despite efforts to limit wastage and lowering purchasing cost per unit by changing to a new blood supplier. The major determinants of intensified CRYO transfusions at RWJUH are (1) changes in the fibrinogen reference range concomitant with enhanced awareness, monitoring, and early treatment of hypofibrinogenemia, particularly in hematology-oncology units and (2) the complexity of surgical procedures (ie, VAD procedures) requiring more CRYO transfusions rather than the number of trauma alerts.
Correlating Transfusion Medicine In-Service Examination Scores With Outcomes of the American Board of Pathology Transfusion Medicine Subspecialty Certifying Examination
Authors: Peedin Alexis R , Genzen Jonathan R , Karp Julie K
Published: September 2019

Objectives

The Transfusion Medicine In-Service Examination (TMISE) is offered twice a year to transfusion medicine (TM) fellows. We examined the relationship between TMISE scores and outcomes of the American Board of Pathology (ABP) TM subspecialty certifying examination (TM boards).

Methods

TM fellowship programs were contacted to provide anonymous data about TM fellows, their scores on TMISE, and outcome of TM boards.

Results

Of 48 TM fellowship programs contacted, 24 (50%) responded with data for 170 fellows. Average TMISE score of fellows who passed their first TM boards attempt was 71.3, while the average TMISE score of fellows who failed their first TM boards attempt was 64.3 (P = .009).

Conclusions

TMISE scores correlated with passing TM boards on the first attempt. Fellows who took the TM boards the same year that they graduated from TM fellowship had a significantly higher first-time pass rate than fellows who delayed taking TM boards.
An Exploration of the Impact of Non-Dependent Parental Drinking on Children
Authors: Bryant Lucy , MacKintosh Anne Marie , Bauld Linda
Published: September 2019

Aims

To examine the impact of non-dependent parental drinking on UK children aged 10–17.

Methods

Cross-sectional survey of UK parents and their children in 2017 (administered to one parent in a household, then their child, totaling 997 adults and 997 children), providing linked data on parental drinking from parent and child perspectives. The survey included measures of parents’ alcohol consumption and drinking motivations (both reported by parents) and children’s exposure to their parent’s drinking patterns and children’s experiences of negative outcomes following their parent’s drinking (both reported by children), plus sociodemographic measures.

Results

Logistic regression analysis indicates a significant positive association between parental consumption level and children reporting experiencing negative outcomes. Witnessing a parent tipsy or drunk and having a parent who reported predominantly negative drinking motives were also associated with increased likelihood of children reporting experiencing negative outcomes. Age was also associated, with older children less likely to report experiencing negative outcomes following their parent’s drinking.

Conclusions

Findings suggest levels of and motivations for parental drinking, as well as exposure to a parent tipsy or drunk, all influence children’s likelihood of experiencing negative outcomes.
A novel molecular representation with BiGRU neural networks for learning atom
Authors: Lin Xuan , Quan Zhe , Wang Zhi-Jie , Huang Huang , Zeng Xiangxiang
Published: September 2019

Molecular representations play critical roles in researching drug design and properties, and effective methods are beneficial to assisting in the calculation of molecules and solving related problem in drug discovery. In previous years, most of the traditional molecular representations are based on hand-crafted features and rely heavily on biological experimentations, which are often costly and time consuming. However, recent researches achieve promising results using machine learning on various domains. In this article, we present a novel method named Smi2Vec-BiGRU that is designed for learning atoms and solving the single- and multitask binary classification problems in the field of drug discovery, which are the basic and also key problems in this field. Specifically, our approach transforms the molecule data in the SMILES format into a set of sample vectors and then feeds them into the bidirectional gated recurrent unit neural networks for training, which learns low-dimensional vector representations for molecular drug. We conduct extensive experiments on several widely used benchmarks including Tox21, SIDER and ClinTox. The experimental results show that our approach can achieve state-of-the-art performance on these benchmarking datasets, demonstrating the feasibility and competitiveness of our proposed approach.
Regional Variation of Bitter Taste and Aftertaste in Humans
Authors: Higgins Molly J , Hayes John E
Published: September 2019

Despite widespread and persistent myths of a tongue map, all 5 prototypical taste qualities are sensed over the entire tongue. However, modern psychophysical data also suggest there may be more nuanced differences in suprathreshold intensity across oral loci, especially for bitterness. Here, we test whether bitter stimuli matched for whole-mouth intensity differ in perceived intensity across regions of the oral cavity in 2 experiments. Experiment 1 consisted of a whole-mouth sip and spit approach and Experiment 2 consisted of a spatial taste test using cotton swabs. In Experiment 1, participants (n = 63) rated overall intensity of 3 bitter solutions at 5 different loci (front, middle, back of tongue; roof of mouth; and lip). Temporal effects were explored using in-mouth and aftertaste ratings. In Experiment 2, participants (n = 48) rated the intensity of quinine and Tetralone solutions after solutions were painted on fungiform, circumvallate, and foliate papillae with a swab. After the spatial taste test, participants completed a questionnaire on self-reported beer intake. Analysis of variance results of both experiments show a significant locus by stimulus interaction, suggesting different bitterants were perceived differently across the various loci. This result was apparently driven by low-intensity ratings for Tetralone on the anterior tongue. Aftertaste ratings in Experiment 1 also revealed significant temporal effects: ratings on the anterior tongue decreased for all bitterants and ratings for quinine decreased at all loci. Reasons for these effects are not known but may suggest differential expression of bitter taste receptors or differences in bitter agonist-receptor binding affinity across tongue regions.
Transcriptomic Analysis and High-dimensional Phenotypic Mapping of Mononuclear Phagocytes in Mesenteric Lymph Nodes Reveal Differences Between Ulcerative Colitis and Crohn’s Disease
Authors: Chapuy Laurence , Bsat Marwa , Rubio Manuel , Harvey François , Motta Vinicius , Schwenter Frank , Wassef Ramses , Richard Carole , Deslandres Colette , Nguyen Bich N , Soucy Geneviève , Hacohen Nir , Fritz Jorge , Villani Alexandra-Chloé , Mehta Heena , Sarfati Marika
Published: September 2019

Background and Aims

Crohn’s disease [CD] and ulcerative colitis [UC] are distinct forms of inflammatory bowel disease. Heterogeneity of HLA-DR+SIRPα + mononuclear phagocytes [MNPs], including macrophages [MΦ], monocyte-derived [Mono] cells, and dendritic cells [DCs], was reported in gut tissue but not yet investigated in mesenteric lymph nodes [MLNs] of IBD patients. We here compared the phenotype, function, and molecular profile of HLA-DR+SIRPα + MNPs in CD and UC MLNs.

Methods

Cell distribution, morphology, immune function, and transcriptomic [bulk RNAseq] and high-dimensional protein expression profiles [CyTOF] of HLA-DR+SIRPα + MNPs were examined in MLNs of UC [n = 14], CD [n = 35], and non-IBD [n = 12] patients.

Results

Elevated frequencies of CD14+CD64+CD163+ [Mono/MΦ-like] MNPs displaying monocyte/MΦ morphology and phagocytic function were a distinct feature of UC MLNs. In CD, the proportion of CD14-CD64-CD163- [DC-like] cells was augmented relative to Mono/MΦ-like cells; DC-like cells drove naïve T cell proliferation, Th1 polarisation, and Th17 TCM plasticity. Gene expression profile corroborated the nature of DC-like cells, best represented by BTLA, SERPINF, IGJ and, of Mono/MΦ-like cells, defined by CD163, MARCO, MAFB, CD300E, S100A9 expression. CyTOF analysis showed that CD123+ plasmacytoid cells predominated over conventional DCs in DC-like cells. Four CD163+ clusters were revealed in Mono/MΦ-like cells, two of which were enriched in MARCO-CD68dimHLA-DRdim monocyte-like cells and MARCOhiCD68hiHLA-DRhi Mɸ, whose proportion increased in UC relative to CD.

Conclusions

Defining the landscape of MNPs in MLNs provided evidence for expansion of CD163+ Mono/MΦ-like cells in UC only, highlighting a distinction between UC and CD, and thus the potential contribution of monocyte-like cells in driving colitis.
Non-pigmented rapidly growing mycobacteria smooth and rough colony phenotypes pathogenicity evaluated usingin vitroand experimental models
Authors: García-Coca Marta , Aguilera-Correa John-Jairo , Ibáñez-Apesteguía Arancha , Rodríguez-Sevilla Graciela , Romera-García David , Mahíllo-Fernández Ignacio , Reina Gabriel , Fernández-Alonso Mirian , Leiva José , Muñoz-Egea María-Carmen , Del Pozo José Luis , Esteban Jaime
Published: September 2019

Non-pigmented rapidly growing mycobacteria (NPRGM) are widely distributed in water, soil and animals. It has been observed an increasing importance of NPRGM related-infections, particularly due to the high antimicrobial resistance. NPRGM have rough and smooth colony phenotypes, and several studies have showed that rough colony variants are more virulent than smooth ones. However, other studies have failed to validate this observation. In this study, we have performed two models, invitro and in vivo, in order to assess the different pathogenicity of these two phenotypes. We used collection and clinical strains of Mycobacteriumabscessus, Mycobacterium fortuitum and Mycobacteriumchelonae. On the invitro model (macrophages), phagocytosis was higher for M. abscessus and M. fortuitum rough colony variant strains when compared to smooth colony variants. However, we did not find differences with colonial variants of M. chelonae. Survival of Galleriamellonella larvae in the experimental model was lower for M. abscessus and M. fortuitum rough colony variants when compared with larvae infected with smooth colony variants. We did not find differences in larvae infected with M. chelonae.Results of our in vivo study correlated well with the experimental model. This fact could have implications on the interpretation of the clinical significance of the NPRGM isolate colonial variants.
A Question of Norton–Sullivan in the Analytic Case
Authors: Wang Jian , Yang Hui
Published: September 2019

In 1996, A. Norton and D. Sullivan asked the following question: If $f:\mathbb{T}^2\rightarrow \mathbb{T}^2$ is a diffeomorphism, $h:\mathbb{T}^2\rightarrow \mathbb{T}^2$ is a continuous map homotopic to the identity, and $h f=T_{\rho } h$, where $\rho \in \mathbb{R}^2$ is a totally irrational vector and $T_{\rho }:\mathbb{T}^2\rightarrow \mathbb{T}^2,\, z\mapsto z+\rho $ is a translation, are there natural geometric conditions (e.g., smoothness) on $f$ that force $h$ to be a homeomorphism? In [ 22], the 1st author and Z. Zhang gave a negative answer to the above question in the $C^{\infty }$ category: in general, not even the infinite smoothness condition can force $h$ to be a homeomorphism. In this article, we give a negative answer in the $C^{\omega }$ category (see also [ 22, Question 3]): we construct a real analytic conservative and minimal totally irrational pseudo-rotation of $\mathbb{T}^2$ that is semi-conjugate to a translation but not conjugate to a translation.
Effective Equidistribution of the Horocycle Flow on Geometrically Finite Hyperbolic Surfaces
Authors: Edwards Samuel C
Published: September 2019

We prove effective equidistribution of the horocycle flow in the unit tangent bundle of infinite-volume geometrically finite hyperbolic surfaces.