bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemoglobin C/Korle-Bu Identified In A Patient With A Previous Diagnosis Of Hemoglobin S/C Disease
Authors: Dolezal D , Tormey C , Rinder H , Siddon A J 
Published: October 2020

Abstract

Casestudy
Hemoglobin Korle-Bu (Hb-KB) is an uncommon Hb variant that can be mistaken for Hb-S on electrophoretic screening. While Hb-KB alone has no clinical manifestations, there are only limited case studies describing KB in combination with other Hb variants. Here we report a rare case of Hb-C/KB misdiagnosed and managed as Hb-S/C disease for over 20 years.

Results
A 21-year-old African American woman with presumed Hb-S/C disease presented with generalized abdominal pain, nausea, and vomiting. In 1999, Hb electrophoresis showed 59% of abnormal hemoglobin presumed to be HbS and 41% HbC+A2; agar/acetate gel analysis was not employed and the hemoglobinopathy remained incompletely characterized. She had a history of back, chest, abdomen, and extremity pains requiring multiple hospital admissions, with treatments including dilaudid, oxycontin, oxycodone, and hydroxyurea. Her vital signs were normal and her examination was only significant for abdominal tenderness. Imaging studies did not show any evidence vascular occlusion, avascular necrosis, or end-organ dysfunction. RBC indices were remarkable for mild borderline anemia, microcytosis, decreased MCH/elevated MCHC, and borderline elevated RDW. Peripheral smear showed microcytic red cells with anisocytosis, scattered target cells, and a notable absence of sickled cells and Hb-C-crystals. The diagnosis of Hb-S/C disease was then revisited. HPLC showed abnormal hemoglobins in the Hb-D window at 55.1% and in the Hb-C window at 40.6%, with 3.5% Hb-A2 and no normal Hb-A. Gel electrophoresis with cellulose acetate followed by citrate agar suggested Hb-C in combination with either D, G, or Korle-Bu. Definitive diagnosis was obtained by beta globin gene sequencing that demonstrated one copy Hb-C (19G&gt;A, Glu7Lys) and one copy Hb- Korle-Bu (220G&gt;A, Asp74Asn). Given the absence of Hb-S/C disease, her gastrointestinal distress and pain episodes were re-evaluated.

Conclusion
Hb-S and Hb-Korle-Bu migrate similarly in cellulose acetate electrophoresis but can be distinguished on citrate agar. Challenging beta chain variants can now be readily differentiated by complete gene sequencing. This case study emphasizes the importance of distinguishing Hb-KB from clinically-significant Hb-S.
Phosphaturic Mesenchymal Tumor; A Diagnostically Elusive Cause Of Oncogenic Osteomalacia; Case Study
Authors: Chand M , Edens J , Danforth R 
Published: October 2020

Abstract
Casestudy: Phosphaturic mesenchymal tumor (PMT) is a rare, benign neoplasm. It is associated with oncogenic osteomalacia, a paraneoplastic condition caused by secretion of a peptide hormone-like substance, fibroblast growth factor 23, which increases renal clearance of phosphate and increased mobilization of calcium and phosphate from bone. PMT is difficult to diagnose as a primary etiology because patients usually experience non- specific symptoms associated with hypophosphatemia like bone pain, muscular weakness, and pathologic fractures. Because PMT is a benign neoplasm, surgical excision is curative and rapid resolution of symptoms typically ensues. Discussed here is a case of PMT arising in the soft tissue of the medial thigh of a 65 year old man with a five year history of osteomalacia with pathologic fractures and complicated healing. Lab studies revealed hypophosphatemia, hyperphosphaturia, hypercalcemia, and elevated serum fibroblast growth factor 23 during workup for fracture. A small superficial soft tissue mass was discovered in the proximal thigh via octreotide scan which was subsequently excised. On histologic examination it was composed of an encapsulated proliferation of spindle cells in a chondromyxoid background with distinctive areas of flocculent calcification and osteoclast-like giant cells. A diagnosis of PMT was rendered. The patient’s symptoms resolved rapidly after surgery. Despite the benign characteristics and behavior of this rare neoplasm; delayed or mis-diagnosis can have severe implications for patient’s health. Interdisciplinary communication, shrewd clinical index of suspicion, and awareness of the causes of, and the tests available to diagnose oncogenic osteomalacia can speed accurate diagnosis leading to better outcomes for patients.
New Markers For Human Ovarian Cancer That Link Platinum Resistance To The Cancer Stem Cell Phenotype And Define New Therapeutic Combinations And Diagnostic Tools
Authors: Kamel Y S 
Published: October 2020

Abstract

Introduction/Objective
Ovarian cancer is the leading cause of gynecologic cancer-related death, due in part to a late diagnosis and a high rate of recurrence. Primary and acquired platinum resistance is related to a low response probability to subsequent lines of treatment and to a poor survival. Therefore, a comprehensive understanding of the mechanisms that drive platinum resistance is urgently needed.

Methods
We used bioinformatics analysis of public databases and RT-qPCR to quantitate the relative gene expression profiles of ovarian tumors. Many of the dysregulated genes were cancer stem cell (CSC) factors, and we analyzed its relation to therapeutic resistance in human primary tumors. We also performed clustering and in vitro analyses of therapy cytotoxicity in tumorspheres.

Results
Using bioinformatics analysis, we identified transcriptional targets that are common endpoints of genetic alterations linked to platinum resistance in ovarian tumors. Most of these genes are grouped into 4 main clusters related to the CSC phenotype, including the DNA damage, Notch and C-KIT/MAPK/MEK pathways. The relative expression of these genes, either alone or in combination, is related to prognosis and provide a connection between platinum resistance and the CSC phenotype. However, the expression of the CSC-related markers was heterogeneous in the resistant tumors, most likely because there were different CSC pools. Furthermore, our in vitro results showed that the inhibition of the CSC-related targets lying at the intersection of the DNA damage, Notch and C-KIT/MAPK/MEK pathways sensitize CSC-enriched tumorspheres to platinum therapies, suggesting a new option for the treatment of patients with platinum-resistant ovarian cancer.

Conclusion
The current study presents a new approach to target the physiology of resistant ovarian tumor cells through the identification of core biomarkers. We hypothesize that the identified mutations confer platinum resistance by converging to activate a few pathways and to induce the expression of a few common, measurable and targetable essential genes. These pathways include the DNA damage, Notch and C-KIT/MAPK/MEK pathways. Finally, the combined inhibition of one of these pathways with platinum treatment increases the sensitivity of CSC-enriched tumorspheres to low doses of platinum, suggesting a new treatment for ovarian cancer.
Developing The Next Generation Of Clinical Laboratory Scientist Supervisors: A Study Of Supervisory Competencies In Clinical Laboratory
Authors: Kummerfeldt V D 
Published: October 2020

Abstract

Introduction/Objective
Developing the next generation of clinical laboratory scientist (CLS) supervisors who are competent and comprehensively prepared to meet the industry’s healthcare demands can be challenging. When a CLS is promoted to a supervisory position and then found to be incompetent due to the lack of experience, skills, knowledge and/or abilities. To identify the root cause of this phenomena a comprehensive review of the literature explored management competency theories and concepts (Katz’s three-skills approach, the Peter principle, Sandwith’s competency domain model, and National Center for Healthcare Leadership’s health leadership competency model). The management competency theories provided the foundational theoretical framework for this study.

Methods
Quantitative and qualitative data was used to address the research questions. A modified Tipton’s instrument/survey was used. The survey used demographic, open-ended, and Likert-type questions.

Results
This study had a total of 247 participants, who self-identified as CLS supervisor or manager, and completed an online survey. The results showed an increased competency level due to experience, continuous learning, mentors, formal education, leadership programs and delegation of tasks. The majority of the participants did not feel that the College of American Pathologists regulatory standard of a general CLS supervisor was sufficient to produce a competent CLS supervisor. Training and education was recommended to help transition CLS practitioner into the role of CLS supervisor. Other recommendations include mentors, succession planning, career ladder/leadership programs, experience, and support.

Conclusion
In order to develop the next generation of CLS supervisors, who are comprehensively prepared to meet the industry’s healthcare demands, healthcare organizations are going to need to employ evidence-based human resource management strategies. Human resource management strategies, such as training and development programs, leadership programs, mentor programs, and succession planning, should include administrative and interpersonal domain knowledge, skills, abilities and experience
Clinically Significant Hepatopathology Detected At Cholecystectomy Dramatically Increases Billing
Authors: Rane A , Li-cheng Wu M 
Published: October 2020

Abstract

Introduction/Objective
Incidental hepatic tissue obtained via cholecystectomy is generally minute and inconsequential. For these reasons, the hepatic tissue is bundled with the gallbladder and cannot invoke additional billing. However, hepatic tissue that is very large or that harbors significant hepatopathology has clinical utility and could justify additional billing. We hypothesized that such incidental hepatic tissue would dramatically increase billing because the liver is billed at a higher level of complexity than the gallbladder and requires cytochemistry for evaluation.

Methods
We retrospectively reviewed pathology reports, slides, and codes from 9 specimens from cholecystectomy that contained hepatic tissue that was grossly evident or that demonstrated significant hepatopathology. Our billing department with decades of experience but without medical training codified the reports using the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) and Current Procedural Terminology (CPT), blinded to our study.

Results
The patients included 5 women and 4 men, ages 18 to 72 years. Five specimens contained very large pieces of liver 0.8 cm to 2.2 cm long and 0.3 cm to 1.8 cm thick. Diagnoses included nonalcoholic fatty liver disease or steatohepatitis (6 specimens), de novo alpha-1 antitrypsin deficiency (2 specimens), de novo sinusoidal amyloidosis (1 specimen), hemosiderosis (1 specimen), and obstruction (1 specimen). Some specimens demonstrated multiple diagnoses. Only ICD-10 codes K76.0 (6 specimens) and K75.81 (2 specimens) were generated, corresponding to nonalcoholic fatty liver disease and steatohepatitis, respectively. ICD-10 codes were omitted for 1 specimen. Although all specimens generated CPT codes 88312 (20 charges) and 88313 (14 charges), corresponding to cytochemistry, none generated CPT code 88307, corresponding to the liver.

Conclusion
Incidental hepatic tissue obtained via cholecystectomy dramatically increases billing, but significant hepatic findings and exceptions to coding principles must be clearly conveyed to billing departments to ensure proper coding.
Transfusion Medicine Informatics: Analysis of User Burden from Clinical Decision Support Alerts in Promoting Patient Blood Management
Authors: Tsang H C , Mathias P , Hoffman N , Pagano M B 
Published: October 2020

Abstract

Introduction/Objective
To increase efficiency of blood product ordering and delivery processes and improve appropriateness of orders, a major project to implement clinical decision support (CDS) alerts in the electronic medical record (EMR) was undertaken. A design team was assembled including hospital and laboratory medicine information technology and clinical informatics, transfusion services, nursing and clinical services from medical and surgical specialties.

Methods
Consensus-derived thresholds in hemoglobin/hematocrit, platelet count, INR, and fibrinogen for red blood cell (RBC), platelet, plasma, and cryoprecipitate blood products CDS alerts were determined. Data from the EMR and laboratory information system were queried from the 12-month period before and after implementation and the data was analyzed.

Results
During the analysis period, 5813 RBC (avg. monthly = 484), 1040 platelet (avg. monthly = 87), 423 plasma (avg. monthly = 35), and 88 cryoprecipitate (avg. monthly = 7) alerts fired. The average time it took for a user to respond was 5.175 seconds. The total amount of time alerts displayed over 12 months was 5813 seconds (~97 minutes of user time) compared to 56503 blood products transfused. Of active CDS alerts, hemoglobin/RBC alerts fired most often with ~1:5 (31141 RBC units) alert to transfusion ratio and 4% of orders canceled (n=231) when viewing the alert, platelet alerts fired with ~1:15 (15385 platelet units) alert to transfusion ratio and 6% orders canceled (n=66), INR/plasma alerts fired with ~1:21 (8793 plasma units) alert to transfusion ratio and 10% orders canceled (n=41), cryoprecipitate alerts fired with ~1:13 (1184 cryoprecipitate units) alert to transfusion ratio and 10% orders canceled (n=9). Overall monthly blood utilization normalized to 1000 patient discharges did not appear to have statistically significant differences comparing pre- versus post-go-live, except a potentially significant increase in monthly plasma usage at one facility with p = 0.34, although possibly due to an outlier single month of heavy usage.

Conclusion
Clinical decision support alerts can guide provider ordering with minimal user burden. This resulted in increased safety and quality use of the ordering process, although overall blood utilization did not appear to change significantly.
Prevalence Of Urinary Tract Infections (Utis) Among Pregnant Women Attending Antenatal Clinic At Ile –Ife, Southwestern Nigeria
Authors: Oladipo A , Onifade J A 
Published: October 2020

Abstract

Introduction/Objective
This is a prospective study that reports the prevalence of Urinary Tract Infections (UTIs) and the bacteriological causative agents among pregnant women attending antenatal clinics at a Secondary Care Hospital in Ile Ife, South western Nigeria. 335 mid-stream clean catch urine samples were collected from pregnant women between April -July 2017.

Methods
These were cultured for the presence of bacterial pathogens. All the isolates were subjected to antibiotic sensitivity testing on Mueller Hinton agar by modified Kirby-Bauer disk diffusion technique using CLSI, guidelines. Data were analysed using SPSS for Windows version 16 and WHONET 5.

Results
A total of 190 showed significant bacterial growth while 145 showed no significant bacterial growth. Bacterial agents isolated included Klebsiella spp. showing the highest occurrence of [60(31.5%) followed by Escherichia coli and Staphylococcus aureus with prevalences of [49(25.7%) and [32(16.8%) respectively. Other organisms implicated are Proteus mirabilis [20(10.5%), Coagulase Negative Staphylococci [24(12.3%) and Pseudomonas aeruginosa with the least prevalence of [5(2.6%). Resistant to antibiotics such as amoxycilin 64%, gentamicin 52.6%, erythromycin 62.5%, ceftazidime 69%, cefotaxime 74%, ceftriaxone 79.6% while a high sensitivity to tetracycline (88.5%), nitrofurantoin (96.3%), imipenem (100%) respectively.

Conclusion
This study indicated a high prevalence of UTIs (56.7%) in pregnant women though most of them showed no clinical manifestation.
Antibiotic Resistance Crisis in Urinary Tract Infections Utis in Egypt
Authors: Abdelmonem M , Wasim H , Shedid M , Hassan D M , Boraik A , Elshamsy M , Al-Shalchi N 
Published: October 2020

Abstract

Introduction/Objective
Bacterial adaptation to antibiotics has been very successful. Over the past decade, the increase in antibiotic resistance has generated considerable medical problems. UTIs are one of the most common community-onset infections. The emergence of resistance to all classes of antibiotics in previously susceptible bacterial pathogens is a major challenge to infectious disease medicine. Thus, it is important that we forcefully implement strategies to reduce the rate of appearance and spread of resistant bacteria to allow new drug discovery to catch up with bacterial resistance development. Objectives:

Methods
The aim of this study is to predict the percentage of urine cultures antibiotic resistance in patients with UTIs in Egypt. Subjects and methods: A total of 200 subjects were enrolled in this study from The Delta region in Egypt; 38% males and 62% females with a median age of 39 years and 35 years respectively. Identification of the isolated organisms was identified by the cultural characters (Morphological characters of the purified bacterial isolates were carried out according to the colony characters, Gram stain reaction and biochemical tests for each organism using a standard semi-automated technique

Results
98 cultures (49%) were observed to have resistance to 3- 5 classes of antibiotics including, 98% Cephalosporins, 85% β-lactam inhibitors and 71% fluoroquinolones; 66 females (57 gram -ve stain and 9 gram +ve stain) and 33 males (27gm -ve stain, 6gm +ve stain). 82 cultures (41%) were not resistant to any classes.; 32 males (28 gram -ve stain and 3 gram +ve stain) and 50 females (45 gram -ve stain and 5 gram +ve stain). 19 cultures (9.5%) were observed to be resistant to all antibiotics.; 12 males (11 gram -ve stain and 1 gram +ve stain) and 7 females (2 gram -ve stain and 5 gram +ve stain).

Conclusion
This study highlights the highest antibiotic resistance associated with urinary tract infection in Egypt as well as the classification of the organisms. The high resistance percentage is due to the overuse of antibiotics by public and inappropriate antibiotic prescribing. Antibiotics are unregulated and available over the counter without a prescription in Egypt which makes it easily accessible. We recommend regulating the use of antibiotics and lunch antimicrobial stewardship programs in Egypt.
Frequent Mutations in p53, CDKN2A, PTEN Genes in Lung Squamous Cell Carcinoma: A Next Generation Sequencing Study
Authors: Xu H , Wei E 
Published: October 2020

Abstract

Introduction/Objective
Targeted therapies have been successfully used for the treatment of lung adenocarcinoma but have not been implemented in the treatment of lung squamous cell carcinoma (SqCC). In order to better understand the underlying biology of SqCC, we present comprehensive Next Generation Sequencing (NGS) data via Cancerplex from SqCC. We have observed frequent mutations in p53, CDKN2A, PTEN, CDKN2B, and TGFBR2 genes together with few new rare gene mutations.

Methods
Twenty-one patients with diagnosis of Lung SqCC have been selected for Cancerplex assay (Kew, Inc., Waltham, MA). Formalin-fixed tissues from these patients were used for the assay. Neoplastic tissues with tumor content higher than 20% were micro-dissected from the blocks and NGS was performed with at least 50 ng DNA content and with a limit of detection of 10% mutant alleles. The depth of coverage was 500, and the size of the targeted region was 2.8 Mb. Results were compared with published databases.

Results
We have observed p53 mutations in 100% cases. p53 gene mutations included single point mutations with various coding protein mutations as well as splice variants. Mutations in CDKN2A is found in 47.6% of cases; PTEN mutations in 33.3% of cases; CDKN2B mutations in 28.6% of cases, and TGFBR2 in 28.6% of cases, which has been reported as actionable variants and actionable copy number variants.

Conclusion
Previous literatures have provided evidence that SqCC arising in different anatomical sites share common genomic mutation patterns. Our data partially supports this finding. We demonstrated p53, CDKN2A and PTEN are among the most commonly mutated genes in lung SqCC, while a few other genes mutations does not fit in this pattern. Apparently more studies need to be done to provide a more clear genetic landscape of SqCC, which would facilitate the development of targeted therapies.
The Wild West of Emergency Use Authorizations for SARS-CoV-2 Testing: What Could Be the True Sensitivity?
Authors: Dalal S , Patel S , Petersen J M , Jhala D 
Published: October 2020

Abstract

Introduction/Objective
SARS-CoV-2 is a pandemic that has required mobilization to meet urgent needs. In this mobilization, emergency use authorizations (EUA) have been issued by the FDA to expedite the deployment of these tests. This has led to a situation whereby sensitivity has not been rigorously studied for any of the assays with EUAs. Estimates can be extrapolated from the limited samples documented by the company in their instructions for use (IFU). Although the nationwide shortage of testing reagents prevent parallel testing of multiple platforms on all specimens, observations of repeat specimens at the Veteran Affairs Medical Center (VAMC) provides the first study in the literature of more complete data for SARS-CoV-2 nucleic acid (RT-PCR) assay on sensitivity on the Abbott (Abbott Park Ill) and Cepheid (Sunnyvale CA) assays.

Methods
A retrospective search was performed for all test results for SARS-CoV-2 by RT-PCR from 3/1/2020 to 4/14/2020 at Corporal Michael J. Crescenz Medical Center, in order to evaluate the sensitivity on Abbott m2000 and Cepheid platforms. Results across multiple reference laboratories and in-house testing platforms were collated in a table with all patients clinically requiring repeat testing recorded.

Results
114/863 patients had repeat testing. The tests were performed initially by outside reference laboratories (25 patients), on the Abbott m2000 (63 patients), and Cepheid Infinity (26 patients). 15/114 (13%) had discordant results on repeat testing. This included 1 test initially done by a reference laboratory. 8 days after the initial result from the reference lab, a positive for the same patient was identified on the Abbott platform. 11 initial Abbott results were discordant on further repeat testing on two platforms - Abbott (6 patients) and Cepheid (5 patients) 1-6 days later. In addition, 3 initial Cepheid were discordant on further repeat testing by the same Cepheid platform (1-16 days later).

Conclusion
While the instructions for use for both platforms suggest 100% sensitivity and specificity (due to the 100% positive and negative percent agreement in limited specimens), the true sensitivity is less than 100%, particularly early in the course of the infection. In our study, the positive percent agreement (surrogate for sensitivity) was 83% for initial Abbott tests, 88% for initial Cepheid tests, and 95% by Reference laboratory platform.