bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYOD1 c.365G&gt;T, p.L122R Variant Detection by Droplet Digital PCR (ddPCR)
Authors: Lip V , Grimmett L , Diaz C , Cantave J , Yang W , Harris H , Tsai H K , Church A J , Harris M H 
Published: October 2021

Abstract

Introduction/Objective
Rhabomyosarcomas (RMS) are a group of skeletal muscle tumors that include embryonal, alveolar, pleomorphic, spindle cell/sclerosing subtypes (SC/SRMS). Spindle cell RMS occurs in both adult and pediatric populations, and is associated with either more aggressive or better clinical outcomes respectively. A recurrent hotspot variant in MYOD1, p.L122R (NM_002478.4 c.365G&gt;T), has been described in SC/SRMS. The classification of this diagnosis is evolving, with VGLL2 and NCOA2 fusions defining the diagnosis in young children, and MYOD1 p.L122R defining the diagnosis in older children. The MYOD1 p.L122R variant seems to be associated with more aggressive disease, and may be increasingly used in risk stratification with intensification of treatment.

Methods/Case Report
A digital droplet PCR (ddPCR) assay was used to detect the MYOD1 p.L122R in DNA samples with RMS. Patients and controls were coded as positive or negative, and tested for association with clinical features and outcome.

Results (if a Case Study enter NA)
Known-positive cohort of samples was limited by the extreme rarity of this tumor. “Known-positive” status was established by confirmation of the variant with an external clinically-validated assay. The six known positive samples were assessed by ddPCR for the presence of MYOD1 L122R. The L122R variant was detected in all six variants for a sensitivity of 100%. DNA and/or TNA obtained from known wild-type FFPE and frozen material was assessed, for a total of nine unique samples (1 synthetic, 8 patient-derived). All 9 samples were wild- type, with no positive droplets detected, for a specificity of 100%.

Conclusion
Our MYOD1 c.365G&gt;T, p.L122R variant detection by droplet digital PCR (ddPCR) assay is a robust, reproducible, specific and sensitive method to detect the MYOD1 hotspot mutation.
Evaluation of the siemens N Latex free light chain assay and comparison to Binding Site Freelite™ assay
Authors: Lin H 
Published: October 2021

Abstract

Introduction/Objective
The International Myeloma Working Group (IMWG) guidelines include serum free light chain (sFLC) level and κ/λ ratio as excellent indicators of clonality. The Binding Site Freelite ™ was the first FDA approved assay for quantitative measurement of sFLC, the assay was based on a mixture of polyclonal antibodies directed against a variety of FLC epitopes. The Siemens N-Latex assay employs a probe mixture of mouse monoclonal antibodies. Both assays can be run on nephelometers. We assessed the analytical performance of the N-Latex assays and compared it with the Freelite™ assays.

Methods/Case Report
Analytical accuracy, precision, reproducibility and linearity were evaluated according to the regulatory standards. Method comparison was performed with 220 clinical samples for statistic correlation and clinical concordance analysis.

Results (if a Case Study enter NA)
The N-Latex FLC κ and λ assays had coefficient variation of 1-5% with-in run and 3-8% between run precision. Accuracy was verified using assayed controls in the duration of 21 days. Within analytical measuring range, almost perfect linearity was achieved for both κ and λ FLC assays. In comparison study to Freelite™ with 220 clinical samples, good agreement in classification was observed for κ, λ and κ/λ ratio (Cohen’s κ 0.73, 0.82 and 0.87). Pearson correlation analysis showed correlation coefficient value r &gt;0.90 for all the analytes.

Conclusion
The N-Latex FLC assay has good analytical performance, did not exhibit gross antigen excess and can be used in clinical practice. However, it showed markedly lower absolute values for κ/λ ratio compared with Freelite™. Our data demonstrated that although good clinical concordance between N-Latex and Freelite™ FLC assays was achieved, the absolute values from the two assay are not interchangeable. Further studies in modification of the assay-specific diagnostic (involved FLC/non-involved FLC) thresholds for smoldering multiple myeloma (SMM) and multiple myeloma (MM) are needed.
Initial Clinical Laboratory Response to COVID-19: A Qualitative Lookback at a Survey of Medical Laboratory Professionals
Authors: Baker D P , Jones A P , Edwardson K , Nunez-Argote L 
Published: October 2021

Abstract

Introduction/Objective
In this 2020 survey, the co-investigators of this study explored the experiences of medical laboratory professionals (MLPs) and their perceptions of the testing needs of clinical laboratories in the initial response to the COVID-19 pandemic. The responses gathered in this survey highlighted changes in the laboratory workforce and the impact on laboratory operations moving forward.

Methods/Case Report
This cross-sectional, anonymous, web-based survey of MLPs was conducted between April 29, 2020, and May 31, 2020. To recruit participants, ‘invitation to participate’ messages were posted using online forums and social media platforms (i.e. LinkedIn, Twitter). Furthermore, the survey link was shared with professional contacts and laboratory professional groups. The main source of recruitment was the membership of the American Society for Clinical Laboratory Science (ASCLS), which had more than 6,800 active members at the time of the study. Data provided from individuals who provided informed consent was included in the sample. The inclusion criteria for the survey were that participants self-identify as a current employee of a clinical laboratory whose usual employment involved participating in the diagnostic testing and providing of clinical laboratory test results using human specimens. The instrument gathered demographic data about participants and their workplace using 32 closed-ended questions with 8 questions containing branching that allowed for optional open-ended responses. This project was approved by the institutional review board at the University of Kansas Medical Center.

Results (if a Case Study enter NA)
Notably, there was an overall decrease in clinical laboratory testing and overtime work for laboratorians during the first months of the COVID-19 pandemic. Respondents noted a lack of pay increase during the pandemic; however, some received in-kind gifts and messages of support in recognition of their essential work. MLPs reported better (or unchanged) job satisfaction and morale in their respective workplaces.

Conclusion
The response to the testing needs by healthcare facilities and clinical laboratory leadership can influence the job satisfaction of MLPs, perceptions toward their work, and overall morale during the initial phase of the pandemic. Additionally, cost-reducing measures further shaped the perceptions of MLPs while impacting the operational efficiency of clinical laboratories.
Improving the pipeline for pathologists in Botswana
Authors: Kyokunda L , Souda S , Obeng R 
Published: October 2021

Abstract

Introduction/Objective
In the United States, there are approximately 39 pathologists per one million people. In contrast, there is only one pathologist per one million people in sub-Saharan Africa. This shortage of the pathologist workforce significantly impacts the quality of pathology and laboratory services that can be provided in Botswana.

Methods/Case Report
Root cause and SWOT analyses consisting of the major stakeholders including government officials and key leadership figures from the training university and national referral laboratories were conducted to identify areas within the training pipeline that can be improved. The educational structure, core competencies, clinical exposure and hands-on training, as well as retention and additional faculty were some of the areas in the pipeline identified for improvement.

Results (if a Case Study enter NA)
NA

Conclusion
The collaborative training program between Botswana and South Africa were strengthened and additional clinical training sites were incorporated into the training program. The core competencies required of residents were reviewed and additional resources were provided to current residents. The collaboration between Botswana and South Africa for residency and fellowship training was strengthened to include active participation of the head of Pathology at the University of Botswana on the educational curriculum committee. These implemented changes led to the successful advancement of four anatomic pathology residents from the didactic phase to the practical phase of their training. Furthermore, two pathologists were hired to support clinical diagnostics and the education of the pathology residents. In conclusion, a structured review of the educational pipeline and resources that included stakeholders that could effect change led to substantial improvement in the training program and workforce of pathologists in Botswana.
Multi-Health System Comparison of Outpatient Diagnostic Testing for Urinary Tract Infection
Authors: Windham A K , Whitted M , Brimhall B , Clark K , Podichetty A , Shifarraw S 
Published: October 2021

Abstract

Introduction/Objective
Comparisons of diagnostic test utilization for outpatient encounters across multiple health systems are uncommon. Such comparisons are helpful to establish baseline diagnostic testing patterns across health systems.

Methods/Case Report
Using the Vizient Clinical Database, we compared the number of clinical laboratory tests (CPT codes 80000-89999) and imaging studies (CPT codes 70000-79999) per outpatient encounter for patients with urinary tract infection (UTI, N=97,714) or dysuria (N=125,388). We employed primary ICD-10 codes for UTI (N39.0) and dysuria (R30.0, R30.9, R35.0, R39.15) to define each patient group. We measured the aggregate Clinical Resource Intensity Weight (RIW) per outpatient visit to quantify diagnostic resource consumption for each encounter. The RIW is based on the US Centers for Medicare and Medicaid Services (CMS) Ambulatory Payment Classification (APC) weights. CMS assigns an APC weight to each diagnostic test based on the geometric mean cost of each particular test. We compared diagnostic testing at 20 academically affiliated health systems across the United States (2017- 2019) with &gt;500 annual outpatient visits for UTI and dysuria. We also examined two relevant tests: urinalysis (CPT codes 8100, 81001, 81002, 81003, 81005, 81007, and 81015) and basic urine culture (CPT code 87086) testing patterns.

Results (if a Case Study enter NA)
The mean number of laboratory tests was 4.30 tests (range 3.04-5.89) and 3.01 (range 2.41-3.86) for UTI and dysuria patients, respectively. Average laboratory RIW and quantity were moderately correlated with a mean RIW of 0.50 and 0.38 for UTI and dysuria patients, respectively. The mean number of imaging studies for each group was 0.26 (range 0.08-0.46) and 0.05 (range 0.01-0.14), respectively. Average imaging RIW and quantity were more highly correlated with a mean RIW of 0.52 and 0.11 for UTI and dysuria patients, respectively. UTI encounters averaged 0.78 (range 0.38-1.28) urinalysis tests and 0.65 (range 0.39-0.86) urine cultures. Dysuria patient visits averaged 0.77 (range 0.45-1.17) urinalysis tests and 0.58 (range 0.13-0.76) urine cultures.

Conclusion
There are significant differences in diagnostic tests and resource utilization between large health systems for patients with UTI and dysuria. These differences persist with specific test comparisons for urinalysis and urine culture.
Multi-Health System Comparison of Diagnostic Testing in Hospitalized Sepsis Patients
Authors: Brimhall B , Whitted M , Windham A , Podichetty A , Shifarraw S 
Published: October 2021

Abstract

Introduction/Objective
Comparisons of diagnostic testing across multiple health systems over multiple years are uncommon. Such comparisons would quantify variations in test use between health systems.

Methods/Case Report
Using the Vizient Clinical Database, we compared clinical laboratory and imaging utilization for hospitalized adult sepsis patients (N = 69,035) over three years (2017-2019) at 19 large academic-affiliated health systems across the United States. We used Medicare Severity Diagnosis Related Groups (MSDRG), employed by the US Centers for Medicare and Medicaid Services (CMS), and identified sepsis patients (MSDRG triplet 870/871/872). We stratified hospitalized sepsis patients by severity of illness (SOI) into high severity (MSDRG 870), moderate severity (MSDRG 871), and low severity (MSDRG 872) groups. SOI further categorizes patients within a diagnostic group, quantifying the extent of comorbid conditions and complications. We measured hospital length of stay (LOS), number of laboratory tests (CPT codes 80000-89999), and number of imaging studies (CPT codes 70000-79999). We divided the number of laboratory tests and radiology studies by mean hospital LOS (in days) to calculate laboratory tests and imaging studies per hospital day.

Results (if a Case Study enter NA)
Between health systems, lowest and highest values for laboratory and imaging utilization ranged from 50.1 to 141.3 tests per hospitalization and 1.4 to 7.2 studies per hospitalization, respectively. Differences in laboratory tests between health systems persisted after adjusting for SOI with low to high laboratory tests per hospitalization ranging from 127.8 to 405.7, 51.0 to 144.7, and 31.9 to 78.2, for high, moderate, and low SOI groups. Utilization ranges were smaller for imaging studies. After adjusting for hospital LOS, laboratory testing differences between health systems were more pronounced and with low and high laboratory test per day utilization of 6.5 to 24.3, 6.1 to 18.5, and 6.0 to 17.1, for high, moderate, and low SOI groups. Differences in radiology studies were not as pronounced after adjusting for LOS.

Conclusion
There is considerable variation among health systems in laboratory and radiology resource utilization for hospitalized sepsis patients. This variation persists, especially for laboratory testing, after adjusting for SOI and LOS.
Clinical Impact of Bleeding Time and Concordance with Platelet Function Analysis at a Single Academic Institution
Authors: Ly J T , Woo J 
Published: October 2021

Abstract

Introduction/Objective
Bleeding time (BT) was historically used as a screening test to evaluate in vivo primary hemostasis. However, various disadvantages of BT and development of tests such as the platelet function analysis (PFA) contributed towards a discontinuation of its use at many hospitals. As our institution continues to offer BT, we sought to determine the concordance rate of BT with other coagulation tests and its clinical effectiveness.

Methods/Case Report
BT tests from 2014 to 2020 at our institution were evaluated. Results from BT were compared with those from concurrently ordered PFA. A chart review was performed to analyze the effect of BT on patient outcomes, defined as determiningsurgical/medical management or changing the patient’s diagnosis.

Results (if a Case Study enter NA)
From 2014-2020, there were 71 BT orders. There were 22 concurrently ordered PFAs. BT and PFA results were concordant in 14 of 22 instances with 4 of 14 being abnormal while 10 of 14 were normal. In terms of clinical outcomes, after removing five cases from analysis for lack of data, BT had a significant clinical impact in 25 of 66 cases, 20 of 25 determining surgical/medicalmanagement and 5 of 25 changing the patient’s diagnosis. After the release of ASCP’s Choosing Wisely guidance on BT in 2014, the number of BT ordered dropped from 35 in 2014 to 13 in 2015.

Conclusion
At our institution, most BT orders were ordered to assess bleeding risk prior to procedures or to find a cause for bleeding of unknown origin; however, BT affected clinical outcomes in less than half of cases. BT and PFA generally correlated well. Following guidance published by professional groups, including ASCP’s Choosing Wisely, BT utilization saw a decrease.
Secondary sclerosing cholangitis: a lesser known side effect of pembrolizumab therapy
Authors: Taylor C , Reno M , Sharma D 
Published: October 2021

Abstract

Introduction/Objective
Immune check-point inhibitors have increasingly taken hold as mainstays of various cancer treatments, revolutionizing outcomes for individuals diagnosed with terminal malignancy. Hepatotoxicity is reported to occur in 2-10% patients, predominantly manifesting as a mixed cholestatic hepatitis pattern of injury. Cholangitis is a rare immune-mediated adverse event (irAE). We present a case of pembrolizumab-induced secondary sclerosing cholangitis presenting with multiple biliary strictures. Early recognition is crucial as these cases are resistant to treatment with steroids.

Methods/Case Report
82-year-old woman with recurrent, metastatic, high grade urothelial carcinoma status post cystectomy and neoadjuvant chemotherapy, presented with new onset obstructive jaundice (alkaline phosphatase 958 U/L, aspartate aminotransferase of 331 U/L, alanine aminotransferase of 422 U/L, and total bilirubin of 19.8 mg/dL) following two weeks of pembrolizumab therapy. MRCP suggested intrahepatic biliary ductal dilation. ERCP showed multiple strictures involving hepatic bifurcation, left, right and intrahepatic ducts with beaded intrahepatic bile ducts. Liver biopsy showed expanded portal tracts with mixed inflammatory infiltrate, extensive bile duct injury, neutrophilic cholangitis, ductular proliferation, and perivenular cholestasis (10% dropout) concerning for mechanical obstruction. CK7 did not show ductopenia and immunostain IgG4 was negative. All autoimmune work-up was negative. Liver enzymes continued to rise despite multiple therapeutic stents, drains, high-dose corticosteroids, ursodiol and mycophenolate mofetil. The patient died five months later.

Results (if a Case Study enter NA)
NA

Conclusion
Pemrolizumab-induced secondary sclerosing cholangitis is a rare, hence under-recognized, adverse effect of check point inhibitor-mediated hepatotoxicity. It is important to recognize this association, as it has limited benefit from steroid therapy. Our finding of pembrolizumab-related SC adds to the growing body of literature of immune check-point inhibitor-related hepatobiliary injury and calls for further characterization of PD-1/PD-L1 inhibitor SC and its clinical implications.
Cystic angiomatosis of the bone, liver, and spleen
Authors: Fleckenstein J , Milliken John T , Lee J S , Ballentine S J 
Published: October 2021

Abstract

Introduction/Objective
Cystic angiomatosis is a very rare entity characterized by multifocal cystic angiomatous lesions of the skeletal system, occasionally involving visceral organ systems. Clinical presentation and progression are extremely variable. Cases with liver involvement are even rarer, and have been described as invariably fatal. The pathogenesis of this disorder is poorly understood, and no treatments are currently available.

Methods/Case Report
A 24 year old man with history of polysubstance abuse and untreated hepatitis C presented with acute abdominal pain. Imaging revealed hepatosplenomegaly and multiple liver, spleen, and skeletal lesions. Differential diagnoses included metastatic disease, lymphoma, and infection. Apart from known untreated chronic hepatitis C, all infectious, autoimmune and hypercoagulability work-ups were negative. Biopsies of the liver and iliac bone lesions showed areas of benign-appearing vascular proliferation in a background of fibrosis. The vascular endothelial cells were positive for CD34 and CD31 but negative for D2-40. On follow-up approximately eight months later, the patient was asymptomatic.

Results (if a Case Study enter NA)
NA

Conclusion
Liver involvement by cystic angiomatosis is exceedingly rare and has been associated with increased mortality. This case provides an example of a patient with incidentally discovered cystic angiomatosis involving liver, spleen, and bone who remains asymptomatic at follow-up. Additional cases are required to understand the pathophysiology and disease course in this group of patients, and to investigate possible therapeutic targets.
Blood Culture Contamination in a Community Hospital- less than 2% is achievable
Authors: Bedi R , Atkinson J 
Published: October 2021

Abstract

Introduction/Objective
Blood cultures are commonly obtained to evaluate the presence of bacteria or fungal infection in a patient’s bloodstream. The presence of living microorganisms circulating in the bloodstream is of substantial prognostic and diagnostic importance. A positive blood culture indicates a reason for the patient’s illness and provides the etiological agent for antimicrobial therapy. Collection of blood culture is an exact process that requires time, the proper order of draw, and following of correct protocol. The busy Emergency department that requires multiple demands for nurse’s time, turnover of staff, rushing from one task to another can result in the improper collection and false-positive blood cultures. The national benchmark is set at 3% by the American Society of Clinical Microbiology (ASM) and The Clinical and Laboratory Standard Institute (CLSI). False-positive blood culture results in increased length of stay and unnecessary antimicrobial therapy, resulting in an increased cost burden to the hospital of about $5000 per patient.

Methods/Case Report
At our 150-bed community hospital, 26 beds Emergency Department, we have come a long way in reduction of our blood culture contamination rates from upwards of 4% to less than 2%, far lower than the national benchmark.

Results (if a Case Study enter NA)
NA

Conclusion
There are multiple devices available from various manufacturers claiming to reduce blood culture contamination. These devices do reduce blood culture (BC) contamination but at an added cost of the device. The rate of BC can be reduced and less than 3% is achievable by materials available in the laboratory. We have achieved this by providing training to every new staff by demonstration and direct observation, providing everything required for collection in a kit, using proper technique, the inclusion of diversion method that involves the aseptic collection of a clear tube before collecting blood cultures, and following up monthly on any false positive blood cultures.
ABO Blood Groups and COVID-19 Infection
Authors: Petersen J M , Jhala D 
Published: October 2021

Abstract

Introduction/Objective
There exists contradictory evidence in the literature that ABO blood group may have some impact on risk of COVID-19 infection. Some argue that the blood group A may confer a higher susceptibility to infection and thus be overrepresented in those who test positive for COVID-19, though other studies in the literature do not support this. Therefore, we present a regional Veterans Administration Medical Center’s (VAMC) experience early in the pandemic to provide a reference on blood group and risk of testing positive early in the pandemic for a veteran population.

Methods/Case Report
A retrospective review of all positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) was performed for all RT-PCR tests collected at a regional VAMC from March 17th, 2020 to May 20th, 2020 was performed to collect ABO blood group information. Patients with no known ABO blood group were excluded.

Results (if a Case Study enter NA)
There were 81 patients who tested positive for SARS-CoV-2 with a known ABO blood group during the study period. This group had an age range of 45 to 99, consisted of 80 males and 1 female, and was racially proportioned at 57 African Americans (70.3%), 2 Asian Americans (2.5%), 1 Hispanic American (1.2%), 20 Caucasian Americans (24.7%), and one of unknown race (1.2%). The blood group distribution among these 81 patients was as follows: 39 were O+ (48.1%), 3 were O- (3.7%), 15 were B+ (18.5%), 3 were AB+ (3.7%), 18 A+ (22.2%), and 3 were A- (3.7%).

Conclusion
Comparison with the known distribution of ABO groups in the general population reveals that the proportion of blood groups of those testing positive are similar. This provides support to the proposition that the ABO type may not predispose significantly to COVID-19 infection.