bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing HLA Laboratory Vacancy Challenges: Insights from a Survey-Based Analysis
Authors: Kudika C , Gebhart C , Hitchman K , Fisher P R
Published: October 2024

Introduction/Objective

Laboratory vacancies pose significant challenges to institutions across diverse sectors.

Understanding the landscape of these vacancies is crucial for developing effective strategies on how best to address them. The American Society of Histocompatibility & Immunogenetics (ASHI) Laboratory Professionals Recruitment Initiative (LPRI) was created to help address these issues by promoting and raising awareness of Histocompatibility and Immunogenetics (HLA) labs. This poster presents findings from a comprehensive survey conducted among various types of institutions to explore the prevailing dynamics surrounding HLA laboratory job vacancies. The primary purpose of this study is to provide a comprehensive overview of the HLA laboratory job vacancy landscape, including current vacancy rates, time taken to fill vacancies, and the perceived underlying causes attributed to these vacancies.

Methods/Case Report

The ASHI LPRI developed structured survey was administered to HLA laboratories represented in different service sectors, including hospital based, reference, organ procurement and independent laboratories. The survey collected data on the type of institution, current laboratory job vacancy rates, average time taken to fill vacancies, and perceived primary causes for vacancies. Data analysis was conducted to identify patterns and insights into the HLA laboratory vacancy challenges.

Results (if a Case Study enter NA)

The majority of respondents were from hospital-based or independent HLA laboratories, with few identifying as reference or organ procurement laboratories. Licensure or required certification was not a restricting factor in filling the vacancies. Vacancy rates for the varying institutions range between 10%- 25% with few reporting greater than 25% vacancy rate. A majority (54%) report their vacancies remain open for > 6 months. Predominant vacancy perpetuation was most attributed to lack of applicants (58%) and insufficient pay offered (41%).

Conclusion

The findings of this study offer valuable insights into the complexities surrounding laboratory job vacancies in the clinical HLA space. Understanding the underlying causes and dynamics of these vacancies is essential for developing targeted strategies to mitigate the problem. By addressing these challenges, institutions can enhance workforce stability and ensure optimal laboratory operations. This poster serves as a foundation for further research and policy interventions aimed at addressing laboratory vacancy challenges.
Severe Congenital Neutropenia with ELANE gene mutation, on G-CSF therapy; a case report
Authors: Hanan A , Altaf S , Safdar J , Khan A , Sheikh-Fayyaz S
Published: October 2024

Introduction/Objective

Severe congenital neutropenia (SCN) is a genetic syndrome characterized by a deficiency of mature neutrophils in the bone marrow and peripheral blood. The disease is caused by various gene mutations, with ELANE gene mutations accounting for 50% to 60% of cases.

Methods/Case Report

We report a case of a 12-year-old male patient with severe congenital neutropenia, positive for the ELANE gene mutation. He has a history of recurrent infections and unexplained fevers since childhood. He has been receiving G-CSF treatment for ten years but is now exhibiting a diminished response to it. Analysis of the bone marrow biopsy reveals trilineage hematopoiesis, maturing myeloid with a rise in eosinophils, maturing erythroid, megakaryocytes normal in number and morphology with significantly reduced iron reserves in normocellular bone marrow. On immunostaining, CD34, CD14, or CD117 stains were negative. Neither monocytes nor granulocytes were CD56 positive. Increased monocyte counts coincide with partial CD14 loss. Lymphocytes make up 10% of all cells and consist of Polytypic B-cells, natural killer cells, and a heterogeneous population of T-cells with a normal CD4 to CD8 ratio. Hence, myelodysplastic syndrome was ruled out.

Results (if a Case Study enter NA)

NA

Conclusion

This case report provides valuable insights into the limited knowledge of congenital neutropenia with ELANE mutation on G-CSF therapy. It highlights the importance of ruling out Myelodysplastic syndrome in patients with severe congenital neutropenia and ELANE gene mutation treated with G-CSF therapy.
Case Report: Emergence of de novo Donor-Specific HLA antibodies post Pneumococcal & Varicella Zoster Vaccinations in Waitlisted Renal Transplant Candidate
Authors: Kakodkar P , Webster D , Pearce T , Wu F , Mostafa A , Johnston B , Shekari N
Published: October 2024

Introduction/Objective

In renal transplant waitlisted patients, vaccination series remains to be the standard of care for infection prevention. There is a need to investigate if any of these vaccines or their adjuvant components can induce de novo donor-specific antibodies (dnDSA) against human leukocyte antigens (HLA). These novel anti-HLA antibodies in renal transplant waitlisted patients can result in a positive flow cell crossmatch (FCXM) associated with an increased risk of renal transplant rejection.

Methods/Case Report

We present a 59-year-old renal transplant waitlisted patient who has had multiple negative T- cell and B-cell FCXM with no detection of dnDSA at baseline. We detected de-novo anti-HLA antibodies after he received pneumococcal conjugate (Pneum-C-13) and recombinant zoster vaccine (RZV). After vaccination, FCXM was positive for both T-cells and B-cells. HLA class I antibodies (A1, 23, 24, 80; B44, 45, 76) showed a panel reactive antibody (PRA) of 51%. Epitope analysis highlighted 166DG and 166ES as shared epitopes responsible for the entire specificity. The A1 dn-DSA had a mean fluorescence intensity (MFI) of 1800 and with shared A80 epitope MFI was 15,000 contributing to the strong positivity observed in T-cell and B-cell FCXM. New onset A1, and B44 DSA predicted high risk for transplant rejection with his sibling. His planned live donor renal transplant was halted and had to instead enter the kidney-paired donor program wherein he received his transplantation after 16 months.

Results (if a Case Study enter NA)

NA

Conclusion

Allosensitization risk secondary to RZV or Pneum-C-13 vaccines or their adjuvant components in renal transplant waitlisted patients must be considered as a potential risk for transplant rejection. Future studies can utilize monitoring of HLA-specific memory B-cells to provide crucial insights into the primary mechanism of action of dn-DSA anti-HLA antibody formation and suggest interventions to mitigate this memory B-cell activation.
The Decline of Medicare Reimbursement in Anatomic Pathology
Authors: Miskiel S , Khreshi S , Khraishi R , Pagliaro A , Bombonati A
Published: October 2024

Introduction/Objective

Lack of an annual inflationary update for physician reimbursement from the Centers for Medicare & Medicaid Services (CMS) jeopardizes access to anatomic pathology services at healthcare institutions nationwide. The effects of recent inflationary trends on anatomic pathology physician reimbursement are unknown. Thus, our study sought to analyze trends in Medicare reimbursement rates from 2004 to 2024 for anatomic pathology procedures.

Methods/Case Report

The Physician Fee Schedule Look-Up Tool from the CMS was queried for the top 30 CPT codes utilized, and physician reimbursement data extracted. Monetary data was subsequently adjusted for inflation utilizing the Consumer Price Index and reported in 2024 US dollars. The average annual and total percent change in reimbursement were calculated for included procedures. The compound annual growth rate (CAGR) was calculated using 2024 and 2000 inflation-adjusted monetary data.

Results (if a Case Study enter NA)

Prior to adjusting for inflation, the average physician reimbursement increased by 9.7% from 2004 to 2024 for all included anatomic pathology CPT codes. After adjusting for inflation, the average physician reimbursement decreased by 34.2% for included CPT codes. The greatest decrease in reimbursement observed from 2004 to 2024 was for outside slide consultation at 60.5% ($330.12 to $130.49), followed by pathology consultation during surgery at 59.0% ($83.54 to $34.29). The average CAGR was -2.19%.

Conclusion

Our study demonstrates that Medicare physician reimbursement for common anatomic pathology procedures is declining annually at an unsustainable rate. This downward trend necessitates policy action to prevent access barriers to quality anatomic pathology care nationwide, especially for Medicare beneficiaries.
Identifying strengths and weaknesses at the bench, an institution’s quest to improve the Gram stain bench experience and patient care
Authors: Attaway C C , Van Huele H , Rhoads D
Published: October 2024

Introduction/Objective

The Gram stain is the first actionable result reported to guide treatment. In our laboratory, we noted instances of initial Gram stain results discrepant to subsequent cultures. In reevaluating the Gram stain bench, we devised a survey for medical laboratory scientists (MLS) to determine the strengths and weaknesses of the current workflow to search for areas of improvement. Results of the survey will help both leadership and MLS approach improving the interpretation and reporting of Gram stains.

Methods/Case Report

A 16-question survey was issued to all MLS in the microbiology lab over three weeks in January 2024 (Table 1). Questions (Q) 1 through 5 pertain to years of experience, how long it takes to review slides, and shift scheduling. Q6 through Q15 - addressing aspects of the bench including culture of the laboratory to ask for assistance, pressure to read slides, turnaround times, and confidence - were on a Likert scale from 1 to 5, 1 is strongly disagree and 5 is strongly agree; mean responses are in Table 1. Q16 was a free response question to input additional thoughts or comments. Responses were recorded on the secure local network using Microsoft Forms.

Welch’s t-test was performed on the responses for statistical analysis. Statistical significance is achieved in a p-value is < 0.05.

Results (if a Case Study enter NA)

Among the 33 respondents (Table 1), first shift has the longest MLS work experience (Q2). Third shift perceived significantly more pressure to read Gram stains correctly than first shift (Q8 2.6; 4.6), and turnaround time pressure was felt to hinder their ability to read (Q11 2.1; 3.3). Individuals who perceived the field was too large for review also took more time to review slides (Q12 2.2; 3.0). Being staffed on the Gram stain bench less frequently was associated with taking longer to interpret Gram stains.

Conclusion

Our laboratory environment is, overall, conducive to asking for assistance, there is assistance when needed, there is confidence and allotted time to read stains, and there is perceived adequate training. However, the data indicate that second and third shifts are disproportionately comprised of MLS who read the most Gram stains, have the fewest years of experience, and are least inclined to ask for assistance. This information is invaluable for redesigning the Gram stain bench in a manner that benefits and empowers MLS to maximize their expertise to read Gram stains and provide the best care for patients. Further discussion is planned to redesign the workflow using this information.
Optimization of Turnaround Time and Insufficient Quantity Frequency for Molecular Testing on FFPE Material
Authors: Tavares-Macedo R , Homsi H , Galev G , Burns B , McAfee J , Azzato E , Dermawan J
Published: October 2024

Introduction/Objective

With clinical decisions relying progressively more on molecular data extracted from formalin- fixed, paraffin-embedded (FFPE) tissue, it is pivotal to optimize the use of tissue for diagnostic and prognostic purposes. This optimization can be reached by identifying actionable instances that can decrease the turnaround time (TAT) and the rate of “quantity not sufficient” (QNS) results

Methods/Case Report

From January 2023 to December 2023, the total TAT from the time a molecular study is ordered to its delivery to the molecular lab at LL200A (Tomsich Laboratories), as well as the TAT from the time between the ordering pathologist circling the region of interest to its delivery to LL200A were broken down by subspecialty and site. In addition, the QNS results of Caris genomic profiling were evaluated considering subspecialty and site, amount of material present in the initial sample, and number of levels cut for other ancillary testing from the same material.

Results (if a Case Study enter NA)

83% of subspecialties took longer than 48 hours to have material ordered for molecular studies delivered to LL200A. The median TAT for all specialties was 58 hours (average: 71.6 hours). When examining TAT from circling to LL200A, the median time was 19 hours (average: 28.4 hours). Regarding the QNS rate of the Caris assay, most QNS cases were gastrointestinal tract specimens (27%) or specimens obtained from either CT-guided core needle biopsies (30%) or endoscopic biopsies (32%). The longest dimension of QNS cases ranged from 7.5 cm to 0.1 cm (median: 1.3cm)—the average number of slides ordered before Caris ranged from 1 to 52 (median: 12).

Conclusion

The initial results pointed towards the time from circling to LL200A as one actionable item that could improve the TAT of molecular tests. Possible solutions include enacting a dedicated tumor circling service. In addition, to decrease the rate of Caris QNS results, we propose working together with proceduralists to increase biopsy material yield and to work with pathologists to preserve limited specimens for molecular studies.
Distinct Molecular Alterations in Hepatocellular Carcinoma (HCC) Arising in a Non-Fibrotic Liver Compared to a Cirrhotic Liver
Authors: Wang L , Ramesh R G , Priore S , stashek K , Alipour Z , Furth E E , Tondon R
Published: October 2024

Introduction/Objective

HCC is known to more likely develop in a cirrhotic liver than a non-cirrhotic liver, irrespective of etiology, with TP53 and CTNNB1 being the most frequent driver mutations in this group. Whether there are distinctive molecular pathways for HCCs developing in the non-cirrhotic liver is not known. This study evaluated whether there is any difference in the mutational profile of HCCs arising in a non-fibrotic liver compared to a cirrhotic liver.

Methods/Case Report

Clinicopathologic and in-house next generation sequencing (NGS) data from HCC cases sequenced between 1/1/18-6/30/23 were reviewed. Cases from a targeted precision NGS panel were excluded. Results were correlated with publicly available data from The Cancer Genome Atlas (TCGA).

Results (if a Case Study enter NA)

29 cases were available for review; 24 patients had background cirrhosis at the time of diagnosis, while 5 patients had no evidence of fibrosis. 21 of 24 patients (88%) patients in the cirrhosis group had a variant in TP53 and/or CTNNB1 that was considered to be disease associated or probably disease associated, whereas only 1 of 5 patients (20%) in the non-fibrotic group had a variant detected in one of these genes (Fisher’s exact: p < 0.01). BAP1 and ARID1A variants were detected in two patients in the non-fibrotic group. TP53 and CTNNB1 were generally mutually exclusive (86% of cases), however, 3 patients harbored both TP53 and CTNBB1 variants; interestingly all 3 had background cirrhosis and HCV infection. All 6 poorly differentiated tumors occurred in cirrhotic livers and were found to have TP53 variants (Figure 1). TCGA data (N = 210) similarly showed that patients with intermediate fibrosis or established cirrhosis (N = 138) were more likely than patients without background fibrosis (N = 72) to harbor TP53 or CTNNB1 variants (64% vs 42%; Chi-squared: p < 0.01; Figure 2). Aside from TP53 and CTNNB1, the most common variants seen in the TCGA non-fibrotic group were in TTN (22), ALB (10), FREM2 (9), LRP1B (9), and MUC16 (9).

Conclusion

Both in-house and TCGA data showed that TP53 and/or CTNNB1 variants were more likely to be seen in HCC cases arising in a cirrhotic liver compared to a non-fibrotic liver. This data suggests there may be unique and less-well characterized molecular pathways involved in the neoplastic progression of HCC in a non-fibrotic liver.
Cervical spinal metastasis of unsuspected hepatocellular carcinoma on initial presentation
Authors: Panjshiri F , Lopez C A , moroz K
Published: October 2024

Introduction/Objective

In this case, a 66-year-old female reported to the emergency room (ER) for severe worsening neck and shoulder pain bilaterally for one month. Associated symptoms included bilateral hand weakness, swelling of the hands, inability to pick up objects, and inability to press buttons. MRI and CT scan of the spine demonstrated irregular marrow signals within C5, C6, and C7 vertebral bodies associated with anterior epidural thickening and the C6 vertebral body extending along C4-C5 nerve roots. Further imaging demonstrated a distended hepatic lesion measuring 6.3 x 6.4 x 6.9 cm. CT-guided biopsy of right hepatic lobe mass was performed. The cuboidal tumor cells showed abundant clear cytoplasm and centrally located nuclei demonstrated high nuclear:cytoplasmic ratio, and trabecular architecture. Tumor was immunoreactive to CK-7, CK-20, and Hep par 1, consistent with HCC. The Ki-67 proliferative activity is at 10%. Additionally, AFP, Napsin A, Pax 8, and RCC stains were negative. CT- guided biopsy of the longus colli muscle and anterior cervical spine at the C6 vertebrae performed at the same time demonstrated tumor positive for Hep par 1, consistent for metastatic HCC from just established liver primary. Bone metastasis of hepatocellular carcinoma (HCC) on initial presentation is rare, with an incidence rate of 0.9%. Of these cases, most incidents involve the vertebrae, pelvis, ribs, and skull, with poor patient morbidity and mortality. The thoracic and lumbar spinal locations are common in the field of view of standard abdominal imaging protocols and possibly are the most commonly reported regions of HCC spinal metastasis.

Methods/Case Report

Case report.

Results (if a Case Study enter NA)

NA

Conclusion

This case report demonstrates an unusual clinical presentation of spinal radiculopathy initially thought secondary to degenerative changes, which led to additional diagnostic imaging revealing a hepatic mass biopsied positive for hepatocellular carcinoma with metastasis to the spine.
Primary Malignant Peripheral Nerve Sheath Tumor in the Liver with Glandular Differentiation
Authors: Niu C , Ma Q
Published: October 2024

Introduction/Objective

Malignant peripheral nerve sheath tumors (MPNST) most commonly affect the proximal extremities and paraspinal region. Primary hepatic MPNST is extremely rare. Here we report a primary hepatic MPNST with heterologous glandular differentiation in a patient with Neurofibromatosis type 1 (NF1).

Methods/Case Report

Review of the clinical features and histopathological findings of the resected specimen. A review of all the published cases of primary liver MPNST.

Results (if a Case Study enter NA)

A 69-year-old male patient with a history of NF1, Gastrointestinal Stromal Tumor and treated hepatitis C without pre-existed neurofibroma presented with jaundice. Imaging revealed an ill-defied hypodense mass in the left hepatic lobe. A segmentectomy of the liver revealed an infiltrating 10 cm heterogenous yellow-white-pink slightly firm tumor with 5% necrosis. The tumor showed biphasic histology composed of predominantly spindle cells and clusters of glandular components. The spindle cells showed fascicular growth pattern with vaguely marbled appearance. Focal osteoclast-like multinucleated cells were seen. The glands were well defined, mostly appeared to be low grade, and lined by cuboidal to columnar cells, with a bile-duct and intestinal-like appearance. However, focal malignant glands with hepatic differentiation were also noted. Immunohistochemistry showed patchy loss of H3K27me3 in the spindle cells. The glandular cells were positive for AE1/AE3, CK7 and CK20. The tumor cells showed rare reactivity to TLE1 and were negative for S-100, SOX10, CD34, CD117 and DOG1.

These findings supported the diagnosis of MPNST with glandular differentiation. 13 cases of primary MPNST of liver have been reported, and only one case described epithelioid differentiation.

Conclusion

The differential diagnoses of a primary hepatic biphasic tumor include sarcomatoid carcinoma, carcinosarcoma, biphasic synovial sarcoma and MPNST. Our case illustrates a rare biphasic hepatic MPNST. The morphology and loss of H3K27me3 expression by immunohistochemistry in a patient with NF1 support this challenging diagnosis.
Metastatic Melanoma of Unknown Primary with Plasmacytoid Morphology Presenting as Acute Liver Failure
Authors: Chinchanikar S , Hassan A , Lankachandra K
Published: October 2024

Introduction/Objective

Viral hepatitis, drug toxicity, and autoimmune disorders are common etiologies of acute liver failure (ALF). Very rarely, a cause like metastatic melanoma may present as a primary driver of ALF. Malignant melanoma is histologically diverse and plasmacytoid melanoma is an unusual variant that may present as a solitary tumor or metastatic disease.

Methods/Case Report

A 48-year-old female presented with 2 weeks of right upper quadrant pain, nausea, coffee ground emesis and bleeding per rectum. She had no history of liver disease or alcohol use. On presentation, AST was 83 U/L, ALT was 29U/L, ALP was 159U/L and total bilirubin was 12.7g/dl. Viral hepatitis panel, HIV and chronic liver disease workup was negative. Esophagogastroduodenoscopy and colonoscopy showed no sources of bleeding. She was diagnosed with decompensated cirrhosis, ALF, and acute kidney injury from hepatorenal syndrome. Cirrhosis and multifocal indeterminate T1 hyper/T2 hypo intense lesions (dysplastic or regenerative nodules) were seen on MRI. Liver biopsy revealed metastatic melanoma. Almost entire liver parenchyma on biopsy was replaced by a population of neoplastic cells with plasmacytoid features. Immunostaining was positive for MART-1, HMB45 and SOX-10.

Staining for Pan Cytokeratin and CK-7 highlighted the bile ducts and negative staining was seen for CK20, CD3, CD20, PAX-8, GATA-3, CDX-2 and P63. No primary lesion was found. It was deemed unlikely that she would benefit from therapy before complications occur. She passed away in 16 days.

Results (if a Case Study enter NA)

NA

Conclusion

In most cases of ALF associated with malignant melanoma, the liver may have a seemingly normal appearance on imaging studies due to the distinctive histology of leukemoid tumor infiltration within the liver sinusoids, resulting in sinusoidal obstruction and subsequent hepatocellular dysfunction. The rapidity of liver failure in these cases is related to the replacement of liver parenchyma by malignant cells. The plasmacytoid morphology is seen in a variety of malignancies and to avoid a potential misdiagnosis of an aggressive malignant melanoma, it is imperative to perform a thorough histopathological evaluation aided with immunohistochemistry. It is important to keep in mind that the potential involvement of malignant tumor cell infiltration may cause ALF and early histological assessment with a liver biopsy may be of paramount significance and may possibly change the course of the disease.
Mycobacterium terrae Complex Associated Lymphadenitis: Negative AFB PCR
Authors: Golden K E , Doan J V , Zhang S
Published: October 2024

Introduction/Objective

Nontuberculous mycobacteria included with the Mycobacterium terrae complex (MTC) include a ubiquitous, slow-growing collection of mycobacteria known for causing severe resistant skin, joint, and bone infections. There are limited reports of M. Arupensis, included under MTC, causing human infections despite environmental ubiquity. Low sequencing sensitivity for species such as M. Arupensis may result in negative preliminary PCR speciation thus influencing the negative predictive value of this method of organism detection. No prior case reports have described MTC infection presenting as subacute lymphadenitis.

Methods/Case Report

A 48 year old El Salvadorian male with known diagnosis of HIV presented with oral thrush and significant left-sided lymphadenopathy. He was initially diagnosed with HIV in El Salvador and on ART until immigrating to the US six months prior. HIV antigen and antibody was positive with positive reflex viral PCR. QuantiFERON-TB Gold resulted positive, but CXR was without evidence of pulmonary TB. TB1, TB2, and mitogen minus NIL were negative. He was referred for fine needle aspiration and core needle biopsy of the left cervical lymph node. AFB and AFB FITE stains were performed, but no definitive mycobacteria were identified. GMS was performed and negative for fungal elements. A final histological diagnosis of necrotizing granuloma was given and the tissue was sent for bacterial, AFB, and fungal DNA PCR; no organisms were detected. A sputum sample was obtained and cultured four months after initial presentation and was positive for acid fast bacilli: Mycobacterium terrae complex, most closely resembling Mycobacterium arupensis. The Fite and AFB stains were again reviewed, revealing one single acid fast bacilli organism identified on Fite stain in the necrotizing granuloma.

Results (if a Case Study enter NA)

N/A

Conclusion

The negative AFB DNA PCR result may have been a false negative result due to poor sensitivity or selectivity for M. arupensis. There are no former reported cases of M. Arupensis associated necrotizing granulomas in lymph node. This unusual MTC infection presenting as chronic unilateral lymphadenitis underscores the importance of broadening clinical laboratory AFB DNA PCR sensitivity especially in cases of suspected AFB or modified AFB associated necrotizing granulomas.
PAS Staining Variability in Fungal Infections of Skin
Authors: Hebert A , Love G
Published: October 2024

Introduction/Objective

Developed in 1946 by J. F. A. McManus, the Periodic Acid Schiff (PAS) stain is among the most frequently used stains in histopathology as a cost-effective ancillary study for the detection of fungal organisms. Despite its wide use in dermatopathology, little research exists comparing PAS to its commonly used counterpart, Gomori methenamine silver (GMS), or to hematoxylin and eosin (H&E) alone. The variation in PAS staining between different fungi causing skin infections has been poorly studied.

Methods/Case Report

Eighteen cases of fungal skin infections from 1995-2023 were reviewed by a resident pathologist and attending medical mycologist. All eighteen cases possessed H&E, GMS, and PAS stains (staining preservation was confirmed). These cases were selected to represent the following categories of fungal skin infections: 1) superficial or cutaneous; 2) subcutaneous; and 3) systemic (including opportunistic mycoses and endemic dimorphic fungi). The following criteria were used to grade each specimen: ability of PAS to stain the organism’s cell wall; the demonstration of fungal morphology by PAS; and the ease of differentiating PAS-stained organisms from background compared to H&E alone.

Results (if a Case Study enter NA)

PAS allowed for ready visualization of fungal morphology for all organisms except for Histoplasma spp. and Blastomyces spp. in which organisms tended to blend in with background staining particularly in inflamed tissues. Both fungi were visualized better by GMS. The muriform bodies of chromoblastomycosis, while staining well with PAS, were easy to miss due to their tiny size.

Conclusion

Compared to H&E alone, PAS allowed for detection of organisms at a lower magnification (40X) for fungal infections except for those in chromoblastomycosis, histoplasmosis, and blastomycosis. PAS is a useful, cost- effective ancillary study for the detection of fungal organisms in dermatopathology; however, care must be taken when there is clinical suspicion for certain fungal organisms that are less well-visualized by PAS.
Evaluation of Electronic Hand Hygiene Monitoring Systems in UAE Hospitals
Authors: Abdelmonem M , Saleh Abdelfattah M , Alzehmi A , Alzaabi R , Alhosani H , Tanous J , Abdulrazzaq N
Published: October 2024

Introduction/Objective

Introduction: Hand hygiene (HH) compliance is pivotal in preventing infections in healthcare settings, necessitating robust monitoring systems. This abstract outlines the assessment of three electronic HH monitoring systems across four United Arab Emirates (UAE) hospitals.

Methods/Case Report

Methods: A prospective observational study was conducted in four UAE governmental hospitals, evaluating three HH monitoring systems. Sensors were strategically positioned on alcohol-based dispensers, healthcare workers’ ID badges, and patients’ beds in these systems. Additionally, a comparative analysis was performed between direct observation data and automated system data.

Results (if a Case Study enter NA)

Results: System 1 was evaluated at Hospitals A and B, revealing HH compliance rates of 65% and 46%, respectively, contrasting with direct observation rates of 88% and 80%. Hospital C assessed System 2, reporting a compliance rate of 70%, compared to direct observation’s 94%. System 3, evaluated at Hospital D, showed a compliance rate of 39%, in contrast to the 88% observed directly.

Conclusion

Conclusion: While electronic monitoring systems offer continuous surveillance and data analysis benefits, they also present limitations. These include challenges in accurately distinguishing HH indications and opportunities, identifying all required HH moments, and capturing technique nuances. Understanding these strengths and limitations is vital for healthcare institutions aiming to implement effective HH monitoring strategies to enhance patient safety and reduce healthcare-associated infections (HAI
Preparing the Laboratory for Neoadjuvant Cancer Immunotherapy: Insights from a Pathology Learning Collaborative
Authors: Schulte J J , Zhang W , Rosa M , Hernandez S A , Al Salihi S , Green L K , Ibrahim D Y , Luo W , Mettman D , Ussakli C , Kelly M , Kim J , Mani M , Jani J
Published: October 2024

Introduction/Objective

Neoadjuvant immunotherapy (NIT) is an emerging strategy to treat multiple types of early- stage resectable cancers by inducing a systemic anti-tumor immune response and increasing the likelihood of complete pathological response (pCR). The evaluation of pathological response following NIT is challenging and requires specific expertise. Traditional response criteria may be difficult to apply since immunotherapy may lead to unique changes in the tumor bed. Moreover, many laboratories may not feel prepared to evaluate pathologic response following immunotherapy given their lack of experience and the time required to accurately assess specimens and report findings.

Methods/Case Report

To explore ways to help laboratories prepare for these challenges, the American Society for Clinical Pathology (ASCP) formed an immuno-oncology learning collaborative to engage pathologists from different institutions and subspecialties. The group met over six months to review and discuss the implications of relevant literature, guideline recommendations, and emerging trends such as tumor-specific recommendations (eg, IASLC Neoadjuvant Therapy Pathologic Response Initiative) to pan-tumor immune-related pathologic response criteria (irPRC). ASCP then developed a series of educational resources based on recommendations made by the group.

Results (if a Case Study enter NA)

Members of the ASCP learning collaborative identified and prioritized several topics to help laboratories prepare and equip their teams to perform pathologic assessment after neoadjuvant immunotherapy in routine clinical practice. These included: definition and classification of pathological response criteria, assessing unique changes in the tumor bed (ie, regression bed), interpreting data from clinical trials, reporting results in routine clinical practice, organizing educational resources, and staffing workload. The group also emphasized the importance of collaborating with oncologists and surgeons and promoting communication about these topics within each institution.

Conclusion

Based on promising results from neoadjuvant immunotherapy clinical trials, we can expect more FDA approvals for neoadjuvant indications and a growing number of patients receiving this treatment. Pathologists and laboratory professionals need to prepare their institutions for a future where the assessment of pathological response in routine clinical practice will impact treatment decisions following surgical resection.
Reporting a Rare HLA Allele with Sequence Analysis Prevents Potentially Lethal Allopurinol Hypersensitivity Reaction
Authors: Patel L R , Morris A B , Achram R , Yurekci E , Sullivan H C , Bray R A
Published: October 2024

Introduction/Objective

In addition to their essential role in histocompatibility testing, human leukocyte antigen (HLA) alleles have informative pharmacogenomic and disease associations. For example, HLA-B*58:01 carriers have 100- fold greater risk of allopurinol hypersensitivity syndrome (AHS), a lethal T-cell mediated Type IV reaction with a 20- 25% mortality rate. To prevent AHS, patients are tested for carrier status before treatment.

Methods/Case Report

Patient presented for workup of intermittently flaring right knee pain and uricemia. Uric acid is elevated, plain film imaging is ordered, arthrocentesis is planned, and HLA testing is performed to inform uricemia treatment. Next generation sequencing (NGS) typing reveals the patient carries HLA-B*58:11. Sequence analysis demonstrates the allele’s open reading frame differs from HLA-B*58:01 by a single I194V substitution. Amino acid sequences of peptide binding regions (PBR) encoded by these alleles are identical. Presentation of allopurinol/oxypurinol peptides to T-cells by B*58:01 is the putative mechanism underlying AHS pathogenesis.

Identical protein sequence in the PBR of B*58:11 favors similar function. Findings are reported and treatment with allopurinol foregone.

Results (if a Case Study enter NA)

NA

Conclusion

High resolution HLA testing is essential to appropriately interpret and report results for disease risk and pharmacogenomics assessments. However, NGS detects rare alleles that have yet to be associated with a disease process. When pathogenesis is thought to be linked to the PBR, rare HLA alleles with identical or similar PBR to disease associated alleles may confer similar risk. In this case, NGS identified PBR similarity between the patient’s allele and an established AHS risk allele. Although B*58:11 has not been shown to be associated with AHS, likely due to low prevalence, the risk was deemed sufficient to select an alternative therapy and potentially prevent a lethal drug reaction.
Exploring the link between COVID-19 and gut microbiome at the community level
Authors: Li B , Terwilliger A , Maresso A , Britton R , Yousefipour Z , Donnachie E , Lyu Z
Published: October 2024

Introduction/Objective

Monitoring SARS-CoV-2 virus through wastewater has been adopted as an effective surveillance approach for combating the COVID-19 pandemic. To understand the interplay between this virus and the human microbiome, this study examined the longitudinal co-dynamics between the virus and the microbiome across various sewage samples representing diverse demographic populations in Houston.

Methods/Case Report

We collected wastewater through manholes and the viral RNA levels of SARS-CoV-2 were monitored from December 2020 to 2021. The sampling sites serve nursing homes, rehabs, and shelters across the metro Houston area, respectively. The viral load was analyzed by the gold standard RT-qPCR method, and the microbiome load and composition by qPCR and amplicon sequencing of the 16S and ITS DNA.

Results (if a Case Study enter NA)

Preliminary results on the dynamics of SARS-CoV-2 viral load indicated diverse trends among sampling sites. These viral trends could be classified into three basic categories: flat, up and down, and up, suggesting disparities in COVID-19 infections among communities. A full analysis of the microbiome is underway, but a preview of the data revealed that bacteria and fungi commonly seen in the human gut predominated the wastewater samples. This paves the way to exploring the link between COVID-19 and the gut microbiome, which could shed light on the observed COVID-19 disparities.

Conclusion

As a proof-of-concept, our sewage bio-monitoring program was able to capture COVID-19 viral, bacterial, and fungal signals longitudinally from manholes serving a wide range of communities. Because these signals are predominantly human-associated, further analysis of these signals could offer insight on COVID-19 related disparities among these communities.
DNA fragmentation of sperm and microdeletions in the long arm of the Y chromosome in male infertility patients from private fertilization units of Barquisiemto, Lara State
Authors: Alamo T G
Published: October 2024

Introduction/Objective

Figures for infertility area increasing worldwide, with a large share of causes related to the male gender. The objective of this study is to relate the frequency of abnormal sperm DNA fragmentation and the frecuency of microdeletions in the long arm of Y chromosome (Yq) in patients with male infertility from private fertilitation units of Barquisimeto, Lara, during the 2010-2012 period.

Methods/Case Report

We analyzed 38 samples of semen from infertile male patients to measure DNA fragmentation index (FI) by TUNEL technique, and 36 semen samples from patients with male infertility to measure FI employing SCD method. To dertermine the frecuency of Yq microdeletions by polymerase chain reaction (PCR), samples of peripheral blood from 33 patients with male infertility were evaluated. Among the 38 patients in whom the FI was measured by TUNEL technique, eight(8) of them were also tested for detection of Yq microdeletions, and one (1) of these patients performed SCD test for medical reasons.

Results (if a Case Study enter NA)

The frecuency of abnormal fragmentation index of sperm DNA, determined by the TUNEL technique in patients with male infertility was 47.37%. The frecuency of abnormal fragmentation index of sperm DNA determoined by SCD method in infertile male patients was 22.22%. And the frecuency of microdeletions of the long arm of the Y chromosome in patients with male infertility was 9.09%. All microdeletions were found at DAZSY208 in AZFc region and in one case there was also detected a microdeletion at DAZSY255.

Conclusion

It was also showed that, sperm DNA fragmentation is not depending on the existence of Yq microdeletions.
Exploring Molecular Signatures in Early-Stage Pancreatic Ductal Adenocarcinoma: Implications for Patient Management and Therapeutic Strategies
Authors: Mousavi S , Salehiazar S , Mirzaei Baboli K
Published: October 2024

Introduction/Objective

Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges to patient survival, predominantly due to its tendency for late-stage diagnosis and high rates of post-surgical cancer recurrence.

Therefore, a comprehensive understanding of the molecular characteristics associated with the early stages of PDAC is imperative. This understanding holds the potential to improve patient treatment strategies by enabling targeted interventions and personalized therapies.

Methods/Case Report

Initially, RNA-seq datasets of early-stage PDAC cases (stages IA, IB, IIA, and IIB, all without distant metastasis; M0) were extracted from the GEO database. Subsequently, the datasets were analyzed in four distinct groups, and differentially expressed genes were identified within each group. Group 1 compared T1T2 cases with T3 cases (T: primary tumor), irrespective of N status (N: regional lymph nodes), while group 2 compared N0 cases with N1 cases, regardless of T status. Group 3 included comparisons between T1T2N0 cases and T3N0 cases, and group 4 compared T1T2N1 cases with T3N1 cases. Utilizing a Venn diagram, commonalities between gene expression profiles were isolated. Afterward, gene ontology and signaling pathways were determined using KEGG and Enrichr. Finally, a protein network was constructed, and the proteins were evaluated using the GEPIA and TCGA clinical databases.

Results (if a Case Study enter NA)

The study encompassed a total of 43 cases, with 25 (58.1%) being male and 18 (41.9%) female. The mean age of the participants was 64.4 years. In group 1, the expression levels of MUC5AC, AKAP13, and SPG7 were significantly upregulated in T3 cases. In group 2, STAB1, PDLIM1, and MTUS1 emerged as the top upregulated genes in N1 cases. Group 3 exhibited notable upregulation of CCNL2, CEACAM6, and TSPAN3 in T3N0 cases, while group 4 demonstrated marked upregulation of LTBR, AKAP12, and BOP1 in T3N1 cases. These genes exhibited diverse functions in PDAC progression. They contributed to the regulation of gene expression and cell cycle progression, modulating cell proliferation, inhibiting tumor growth, regulating cell signaling, and were involved in cytoskeletal organization.

Conclusion

The upregulated genes in cases with the T3 and/or N1 staging components may shed light on the potential mechanisms of progression from stage IA/B to stage IIA/B in PDAC cases. Furthermore, the identified genetic alterations may hold potential therapeutic and prognostic applications for future use in the early stages of PDAC.
Social Media and Pathology: A Powerful Intersection for Visibility
Authors: Buckelew H , Crowe C
Published: October 2024

Introduction/Objective

The employment of social media usage for visibility efforts in the field of pathology is a relatively new practice, yet this strategy for both individual practitioners and departmental promotion is growing each day. Social media is being implemented for use in recruiting faculty, staff, and trainees, sharing cases and educational resources, establishing communities, and serving as a source of news for research breakthroughs and accolade recognition. A deeper look into one pathology department’s usage of social media across several platforms lends broad insight into the distinction of which forms of content perform well more consistently on each platform, and how these analytics continue to expand. The current study will examine the growth of one pathology department over the course of six months and determine which content forms made the most impact in increasing departmental visibility.

Methods/Case Report

The use of Instagram, X, LinkedIn, and Facebook is examined over the course of six months. Two reporting periods of three-month intervals are used for comparison: October–December 2023 and January–March 2024. The social media management system Sprout Social is used to gather reports of change in metrics over these periods.

Results (if a Case Study enter NA)

The audience growth rate increased 4.3% in the second reporting period (January-March 2024), with a 34.7% increase in net audience growth rate (total gained followers), an 8.6% increase in published posts, a 16.1% increase in impressions and a 55.3% increase in engagements.

Conclusion

Based on the data analysis provided above, trainee content and cases of the week perform best on X. On Instagram, reels excel in performance. On LinkedIn, faculty accolades, research news, and group photos perform best. People-centered content and educational resources increase audience, impressions, engagement, and, in turn, departmental visibility. A focus on this content and an increase in total posts is the definitive cause for growth in the second reporting period.
Comparative Study of GPT-4Vision and Convolutional Neural Networks in Histopathological Image Analysis
Authors: Koga S , Ono D , Dickson D
Published: October 2024

Introduction/Objective

Recent advancements in artificial intelligence (AI), particularly with Large Language Models like ChatGPT-4Vision (GPT-4V), have expanded the potential for automated interpretation of medical images. This study evaluates the diagnostic accuracy of GPT-4V in histopathological analysis of neurodegenerative diseases and compares its performance with traditional Convolutional Neural Networks (CNNs).

Methods/Case Report

We utilized 1515 histopathological images, including hematoxylin and eosin (H&E) staining and tau immunohistochemistry, from patients with various neurodegenerative diseases, such as Alzheimer’s disease, progressive supranuclear palsy, and corticobasal degeneration. GPT-4V’s performance was assessed through multi- step prompts to assess how textual context influences the image interpretation. In the quantitative analysis, the diagnostic accuracy of GPT-4V and the CNN-based model YOLOv8 was assessed for classifying three tau lesions—astrocytic plaques, neuritic plaques, and tufted astrocytes. The analysis used both zero-shot and few-shot learning methods, where GPT-4V and YOLOv8 were evaluated on their ability to distinguish these lesions using ten hold-out test images and 490 training images per lesion.

Results (if a Case Study enter NA)

GPT-4V accurately recognized Lewy bodies in all cases, but it showed limited accuracy in identifying neurofibrillary tangles (20%) and Pick bodies (0%) on H&E slides. Notably, GPT-4V often suggested Alzheimer’s disease as a potential diagnosis, relying more on contextual clues, such as the prevalence of certain diseases, rather than direct image analysis. In the tau immunohistochemical analysis, GPT-4V’s diagnoses were strongly influenced by additional information about staining and brain region. However, few-shot learning markedly improved GPT-4V’s diagnostic capabilities from 40% accuracy with zero-shot learning to 90% with few-shot learning, reaching best accuracy with 20-shot learning. This performance compared favorably against YOLOv8, which also achieved 90% accuracy but required 100-shot learning.

Conclusion

While GPT-4V faces challenges in independently interpreting histopathological images, few-shot learning significantly improves its accuracy. This approach is particularly promising for neuropathology, where acquiring extensive labeled datasets is challenging. The findings highlight the need for ongoing refinement of AI applications in pathology, emphasizing balanced integration of textual and visual data to optimize diagnostic efficacy and reliability.