bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent Plasma Cell Myeloma with Intracytoplasmic Auer Rod-like Inclusions after Autologous Hematopoietic Stem Cells Transplantation
Authors: Niu C , Tran T , Gamayo A , Zhao X , Rezk S , Brem E
Published: October 2024

Introduction/Objective

Plasma cell myeloma (PCM) is a bone marrow based neoplastic disorder of plasma cells (PCs). The detection of intracytoplasmic Auer rod-like inclusions (ARLI) is rare in PCM. The correlation between the ARLI and the diagnosis, recurrence, prognosis of PCM remains unknown.

Methods/Case Report

Retrospective comparison of pathological findings between two separate bone marrow biopsies of a recurrent kappa-restricted, IgA-positive PCM with intracytoplasmic ARLI before and after autologous hematopoietic stem cell transplantation (HSCT) with a 7-year observation. A detailed review of all the published cases of PCM with intracytoplasmic ARLI.

Results (if a Case Study enter NA)

The neoplastic PCs exhibited anaplastic features in the original diagnosis but became relatively mature in the recurrence after the autologous HSCT. The intracytoplasmic ARLI were found in both cases and tended to increase in the recurrence. The patient’s renal function was within normal range at the first diagnosis and during the recurrence. To the best of our knowledge, about 41 cases have been published since the first description of ARLI in 1940 including 16 females (age of onset: 38 to 72 years, mean: 57.7 y), and 25 males (age of onset: 34 to 79 years, mean: 58.2 y). The lysosomal origin of ARLI with the predominance in kappa-restricted, IgG- producing PCM and possible correlation with adult Fanconi syndrome were described. Only 7 kappa-restricted, IgA- producing PCM with ARLI were among them.

Conclusion

Our case is the first recurrent kappa-restricted IgA PCM with ARLI after autologous HSCT. The morphologies of the neoplastic PCs have changed from anaplastic to relatively mature and more have ARLI in the recurrence. However, the correlation with the adult Fanconi syndrome is not observed in our case. The average age at diagnosis is similar between male and female and might be younger than the average age (69 years) at diagnosis for all PCM.
HUMAN IMMUNODEFICIENCY VIRUS’ EXPOSED UNINFECTED NEWBORNS: A VULNERABLE POPULATION WITH SOME DEFECTIVE IMMUNE SYSTEM ELEMENTS AT BIRTH IN YAOUNDE-CAMEROON, CENTRAL AFRICA
Authors: Touangnou Chamda S , NJIKI BIKOÏ J , MEMBANGBI A , MBAGA D , ELANG F , RIWOM S , MAKUE NGUIFFO E , BATOUM V M , NZUNO M , MBONGUE MIKANGUE C , BODA M , MASUMBE NETONGO P
Published: October 2024

Introduction/Objective

The reduction in vertical transmission of human immunodeficiency virus (HIV) in Cameroon, thanks to the success of Option B+ prevention measures, has favored the increase in the rate of HIV exposed uninfected (HEU) infants. The latter, however, present a threefold higher morbidity and mortality than their HIV unexposed and uninfected (HUU) counterparts. With multiple causes, a dysfunction of the immune system would be incriminated but the evidence to demonstrate this and to advocate for a specific follow-up is lacking. This study objective was to determine the effect of in utero exposure to HIV-1 on certain immune elements of HEU newborns.

Methods/Case Report

A Case-control study was carried out in three reference hospitals in Yaounde. From June 2022 to July 2023, demographical characteristics of 62 HEU newborns of positive parturients with undetectable viral load who gave their consent (cases), and 65 HUU (controls) were taken. Then samples of umbilical cord blood were collected under ethical authorization no. BTC-JIRB2022-021. Then, blood count and differential leukocytes count were performed using DF55 DEMIND and May-Grünwald Giemsa Kit. Excel 2007 and R v4.1.3 softwares were used to record and analyze the data, with significance level for a p-value < 0.05.

Results (if a Case Study enter NA)

The average APGAR vitality score (appearance, pulse, grimace, activity, respiration) at 1, 5 and 10 min of life was reduced, but not significantly (p = 0.3) in the HEU (8/10, 9/10 and 10/10), compared to the HUU (9/10, and 10/10); as well as head circumference: (33.16 ± 1.64) cm and (34.8 ± 1.52) cm (p = 0.8) respectively. Unlike leukopenia (p=0.24), umbilical monocytosis (p=0.04) and lymphopenia (p=0.001) were significantly linked to HIV exposure in HEU, signs of inflammation from birth.

Conclusion

HIV exposed uninfected newborns present a drop in immunity and an inflammatory sign at birth, materialised clinically and biologically with a highly significant lymphopenia.
A success story in a low-resource setting: Advancing cancer diagnostics in underserved region
Authors: Abdou B A , Ghaleb F , Gabr A A , Eliraqy M R
Published: October 2024

Introduction/Objective

Shefaa Al Orman Hospital (SOH) is the first oncology hospital in Luxor. Since its inception in 2016, the hospital has served approximately 45,000 patients from Luxor and other governorates. The hospital’s lab provides excellent routine laboratory services.

However, there is a pressing demand for molecular genetics and cytogenetics, that is necessary for diagnosis of hematological malignancies.

This strategic expansion faced several challenges: lack of expertise and the need for special expensive equipment and reagents.

Methods/Case Report

The project started with collaboration with oncologists to convene on a simplified panel with the aim of prioritizing clinically relevant tests.

At first, these investigations were referred to a specialized oncology hospital in Cairo. This entailed 2 problems: transport of samples led to deterioration of the quality of some samples and delay in results reporting.

In the second phase, experienced consultants from Cairo were enlisted to provide training and mentorship to local staff. Infrastructure setup included the allocation of dedicated laboratory space and the procurement of specialized equipment.

Test method selection was used to achieve successful transition. In cytogenetics, we started with FISH technique which, while more expensive, gave rapid and reliable results. After gaining experience, the technique of conventional karyotyping was established. On the other hand, in molecular genetics, we resorted to custom made reagent mix preparation, instead of commercial kits. This approach, while more laborious, is less expensive.

Results (if a Case Study enter NA)

With the gradual successful in-house setup of these tests, there has been a notable reduction of out-sourced samples to 5%. This has led to shorter result turnaround times. Cytogenetics and FISH improved from 4 to 1 week, while molecular genetics decreased from 4 to 2 weeks.

Moreover, the local processing of samples has minimized the risk of sample damage during transportation, ensuring the integrity of test results.

Conclusion

The establishment of the Molecular Genetics and Cytogenetics Laboratory at SOH represents a significant milestone. The hospital has successfully overcome logistical challenges and enhanced diagnostic capabilities for hematological malignancies, contributing to better patient outcomes and satisfaction. Moving forward, the continued investment in infrastructure, personnel training, and quality assurance measures will further strengthen the hospital’s capacity to provide high-quality cancer care to the community.
Critical Result Notifications: What Do Providers Really Think?
Authors: Kavuri S , Okorodudu A
Published: October 2024

Introduction/Objective

Timely communication of critical test results, those that are significantly outside expected ranges and potentially life-threatening, is crucial in patient care. The Joint Commission and other regulatory bodies, such as CMS, CAP, mandate that hospitals have an alert system for reporting critical values. Traditionally, our hospital system communicates these results through phone calls to the responsible licensed provider, a system that has remained unchanged despite the rise of electronic health records. To assess the perception of this system and providers’ readiness to utilize new communication methods, we conducted a survey among healthcare professionals in our institution.

Methods/Case Report

We sent a survey to all providers via broadcast email. It contained 10 questions, some with free-text input, others with categorical or multiple-choice responses. The survey was open for 4 weeks with 2 reminder emails. Of 544 providers who opened the survey, 191 completed it (35.1% completion rate). The majority (84%) of respondents were physicians, with a smaller portion (15%) identifying as advanced practitioners.

Results (if a Case Study enter NA)

Most providers reported using multiple modes to check critical results and did not rely solely on lab notifications, though a minority (7%) depended on phone calls. Only 2 respondents used the smartphone app (EPIC Haiku) for checking results. Notably, over 67% of providers were unfamiliar with different methods of critical result notification, yet nearly 82% indicated they were open to adopting a new system.

A significant proportion (more than a third) felt that phone calls distracted from patient care, suggesting that alternate methods of communication could be beneficial. Despite this, 62% of respondents found these calls useful. However, more than a third did not find the calls helpful, indicating a possible need for improved communication methods.

Conclusion

The survey indicates that while the current system of critical result notifications is useful to many providers, there are clear opportunities for improvement. Implementing secure, smart systems and increasing awareness of these new communication modalities may help reduce distractions and streamline critical result communication. This could also offer providers a customizable approach to receiving notifications, enhancing both patient care and workflow efficiency.
The Decline of Medicare Reimbursement in Clinical Pathology
Authors: Miskiel S , Khreshi S , Bombonati A , Pagliaro A , Khraishi R
Published: October 2024

Introduction/Objective

Access to clinical pathology services nationwide is threatened by the lack of an annual inflationary update for physician reimbursement from the Centers for Medicare & Medicaid Services (CMS). Most recently, the 2024 Medicare Physician Fee Schedule (MPFS) implemented an overall 2.0% reduction in pathology reimbursement. The effects of recent inflationary trends on clinical pathology physician reimbursement are unknown. Thus, our study sought to analyze trends in Medicare reimbursement rates from 2004 to 2024 for clinical 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. A subset analysis was conducted to assess physician pathology clinical consultation services average annual and total percent change in reimbursement pre- and post- 2022 MPFS Update. 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 decreased by 6.8% from 2004 to 2024 for included clinical pathology CPT codes. After adjusting for inflation, the average physician reimbursement decreased by 44.0% for included CPT codes. The greatest decrease in reimbursement observed from 2004 to 2024 was for flow cytometry interpretation, 2-8 minutes at 69.5% ($114.44 to $34.95) followed by flow cytometry interpretation, 9-15 minutes at 57.8% ($142.77 to $60.25) and flow cytometry interpretation, >16 minutes at 56.6% ($188.05 to $81.55). The average CAGR was -2.86%. Prior to adjusting for inflation, the average physician reimbursement for clinical pathology consultation services pre-2022 decreased by 0.9%, and when adjusted for inflation, decreased by 30.0%. Post-2022 MPFS revision, the average physician reimbursement for clinical pathology consultation services decreased by 3.5%, and when adjusted for inflation, decreased by 12.2%. The average CAGR pre-2022 was -2.0% and post-2022 was -4.3%.

Conclusion

Medicare physician reimbursement for common clinical pathology procedures is decreasing at an untenable rate annually. It is critical that policymakers understand these trends to ensure continued access to quality clinical pathology care at healthcare institutions.
Challenges of Conducting Point-Of-Care Testing Operations In The Municipal Public Health System Based Ambulatory Care Clinics In New York City
Authors: Sherpa T , Ahmad S , Huq Ronny F M
Published: October 2024

Introduction/Objective

Our New York City Municipal Public Health System- based multisite ambulatory clinics that offer various waived POCT (point of care tests) and provider-performed microscopy (PPM) to our communities, ensure standardization and quality of POC testing across our health system. Our laboratory service conducts system-wide centralized implementation, monitoring and oversight of the POCT operations regarding regulatory compliance, test performance, quality control and training. With our day-to-day POCT operations, like all other clinical laboratories, our ambulatory care clinics encounter various hurdles and challenges. Here we elaborated on the issues we encounter and how we manage to overcome them.

Methods/Case Report

We identified and stratified the challenges that affect our managerial as well as field-level laboratory operations and devised ways to deal with those POCT operational issues.

Results (if a Case Study enter NA)

Among the staffing issues, rapid staff turnover causes significant delays or cessation of POCT operations in our ambulatory care clinics, due to orientation, re-education and ensuring competency to the staff, that conducts POCT in our clinics. Besides, supply shortages, staff shortages and absences due to illness and overwork are the issues, noted at the laboratory field operational level. Delays in the processing of paperwork and new staff recruitments and in the laboratory supply chains are notable management issues.

Conclusion

Even though the vastness and complexity of our multisite ambulatory care network sometimes affect our ambulatory care clinic POCT operation in various challenging way, our timely, planned and coordinated intervention, close monitoring and communication and rapid initiatives handle those issues very effectively to ensure the quality of POC testing for the patient safety and care across our health system, which is one of the largest municipal-based public health care, in the country.
Integrating Biomarker Testing into EHR Systems: Implications for the Laboratory Based on Findings from a Multistakeholder Summit
Authors: Offit C , Emara R , Alvarez B , Lile A , Plotkin E , Starks R , Schiller M , McNair C , Kim J , Waugh W , Huelsman K , Kurtin S , Yu P , Martin N
Published: October 2024

Introduction/Objective

Guideline-driven tumor biomarker testing remains standard of care for precision oncology due to the increasing number of treatment decisions that can be made based on tumor-specific alterations. However, most electronic health record (EHR) systems lack bidirectional interfaces with labs that enable computerized order entry and tumor biomarker testing results. Without these integrations, cancer centers may experience delays in test ordering and resulting, manual data entry errors, and operational inefficiencies that impact patient care and survival outcomes.

Methods/Case Report

To explore how cancer centers, hospitals, oncology practices, and labs integrate EHRs to streamline cancer biomarker testing processes, the Association of Cancer Care Centers (ACCC), in partnership with LUNGevity, convened a multistakeholder summit on Oct. 4, 2023. The summit brought together clinicians, pathologists, genetic counselors, and administrators to discuss practical solutions to issues surrounding interoperability, clinical workflows, and access to clinical data.

Results (if a Case Study enter NA)

Key findings from the summit include:

-EHR-integrated orders and results save time, reduce errors, and streamline clinical workflow. These electronic interfaces enable clear communication between multidisciplinary teams system-wide and ensure that required patient information is readily available at the time of therapy planning.

-Standardized workflows that define test ordering, tracking, and resulting protocols for in-house and send-out testing offer important downstream benefits. Staff should clearly understand how specimens are handled for in-house and send-out testing.

-Integrations should be planned and built based on the EHR/laboratory information systems (LIS) in place can incorporate solutions to integrate with reference labs using HL7 standards and/or add-on modules to enable discrete genomic data elements.

Conclusion

Clinicians, pathologists, and administrators should prioritize EHR/LIS integrations to enable more effective cancer biomarker test ordering and resulting. These pre/post-analytic processes have significant implications for patient care. Findings from this summit can enable cancer programs and labs to evaluate current processes, work collaboratively to build integrations, and streamline biomarker testing workflows to enhance the quality and efficiency of delivering precision oncology.
Utility of digital cell imaging as an aid to enhance pathologist peripheral blood smear review for routine and on call practice: A verification study
Authors: Torres Y , Ourfali M , DiGiuseppe J , Johari V
Published: October 2024

Introduction/Objective

Microscopic examination of peripheral blood smear (PBS) provides important information to support the diagnosis of hematological diseases. However, manual microscopic examination of PBS is labor-intensive and cannot be done remotely. CellaVision is digital cell imaging technology that provides pre-classification and digital imaging of the red blood cells (RBCs), white blood cells (WBCs), and platelets, myeloid, lymphoid and erythroid precursors. Several studies have evaluated the performance of this technology in the hematology laboratory as tool to assist laboratory technologists; our study evaluates its use for pathologist review of peripheral blood smears both during routine and on call practice.

Methods/Case Report

Our study included 30 PBS and two hematopathologists with greater than 10 years’ experience in performing PBS review. We compared pathologist’s own impression of microscopic PBS review to their own impression using CellaVision software (intraobserver comparison). Additionally, pathologist to pathologist impression was compared for both methods (interobserver comparison). All 30 cases revealed abnormal findings including, but not limited to: pancytopenia, leukocytosis, leukopenia, anemia, thrombocytopenia, and thrombocytosis. Of the 30 cases, 5 “on-call” were cases when the pathologist had to come on–site for pathologist PBS review.

Results (if a Case Study enter NA)

The pathologists own PBS interpretation (intraobserver) by microscopy and CellaVision had a concordance of 96.7%. The pathologist to pathologist interpretation of both methods had a concordance of 96.7%.The one discrepant case was a smear with platelet clumping and normal platelet count. On chart review of this case, this discrepancy would have minimal impact on patient care.

Conclusion

Pathologist use of CellaVision in their routine practice may result in speedier PBS review, particularly in cases with leukopenia, and better communication with laboratory technologists. CellaVision is less reliable in identifying platelet clumps and should not be used in isolation in evaluating thrombocytopenia. Used with other relevant data, CellaVision has the potential to preempt in person microscopic review of PBS when on-call in certain situations.
African American Females are More Vulnerable to Develop Biliary Injury in NAFLD (Nonalcoholic fatty liver disease) Patients – A Single Institute Experience
Authors: Xue Y , Bach K , Yan S , Yin X
Published: October 2024

Introduction/Objective

Chronic alcohol exposure alone may take decades to induce severe liver disease, yet when combined with elements such as the Western diet, liver pathogenesis accelerates, resulting in earlier symptoms.

Identifying the specific contributions of alcohol, diet, and other factors to liver disease is challenging, despite the availability of diagnostic tools like patient histories, liver enzyme tests, imaging, and biopsies.

Methods/Case Report

This study seeks to detail the liver disease profile of patients who underwent liver biopsies in 2022. Comprehensive profiles were created by retrieving liver biopsy specimens and associated diagnostic data from electronic medical records. Two independent pathologists analyzed the biopsy slides, looking for liver damage associated with alcohol consumption and Western diet influences. We employed enhanced staining techniques to better associate specific types of liver damage with demographic variables. The data analysis was conducted using GraphPad Prism 9 for robust statistical evaluation.

Results (if a Case Study enter NA)

The research included 88 participants—41 males and 47 females, with average ages of 56 and 62 respectively. The predominant diagnosis was fatty liver disease, with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) accounting for 26% of cases, and alcoholic liver disease (ALD) making up 10%. The NAFLD/NASH group (n=23) consisted mainly of African Americans (n=15) and Caucasians (n=8). Among these, African Americans showed a significantly greater ductular reaction and portal inflammation (p<0.05). Conversely, no notable differences in portal fibrosis and bile stasis were observed between these groups. Notably, African American females (n=11) demonstrated more severe pathological features compared to Caucasian females (n=6), including elevated levels of ductular reaction, fibrosis, portal inflammation, and bile stasis (p<0.05), suggesting a higher vulnerability to biliary injuries.

Conclusion

The study highlights the complex interplay between lifestyle factors and liver disease development and emphasizes the need for precise diagnostic strategies that consider these multifactorial influences. Additionally, it reveals ethnic disparities in the pathology of NAFLD, advocating for further research into their causes and implications for clinical management. Future investigations should focus on race and gender-specific factors and adapt local healthcare strategies to effectively manage the escalating burden of liver disease.
Analyzing Antibiotic Resistance: A Comparative Study of E. coli Isolates from Wastewater and Clinical UTI Samples at a University Community in Grenada, West Indies
Authors: Matthew-Bernard M , Dolphin-Bond G , Farmer-Diaz K , Macpherson C , Ramos- Nino M , Cheetham S , Mitchell K
Published: October 2024

Introduction/Objective

The rise of antibiotic resistance poses a significant global health threat, needing a robust monitoring system to track its emergence and spread. However, most developing countries lack the infrastructure to monitor such resistance effectively. Wastewater-based epidemiology (WBE) has been proven effective in surveilling various outbreaks and offers a promising method for monitoring antibiotic resistance at the community level. This study aims to assess and compare the antibiotic resistance of Escherichia coli isolated from raw wastewater with those isolated from clinical urinary tract infection (UTI) samples from the same community.

Methods/Case Report

Conducted from January 2022 to October 2023, this study analyzed antibiogram data from eighty-six Escherichia coli isolates sourced from wastewater and thirty-four isolates derived from clinical urinary tract infections (UTIs). The clinical samples were obtained and processed at the Clinical Microbiology Laboratory of a university campus. The isolates were evaluated against the eleven most prescribed antibiotics for UTIs in the University Clinic including: Amoxicillin/Clavulanic Acid, Ampicillin, Cefazolin, Cefoxitin, Ceftriaxone, Cefuroxime, Ciprofloxacin, Gentamicin, Nalidixic Acid, Nitrofurantoin, and Sulfamethoxazole-trimethoprim.

Results (if a Case Study enter NA)

Explaining the observed trends in both wastewater and clinical samples from the perspective of AWaRE-WHO classification (Access, Watch, Reserve), we see similar trends of resistance in both data sets. A) The antibiotics used in the Access category (Empiric first or second choice for treatment of most common infections) demonstrates similar resistance patterns for both wastewater and clinical isolates except for Nitrofurantoin.

B) The antibiotics used in the Watch category (Antibiotics that have higher toxicity issues and higher potential to negatively impact AMR) resistance pattern shows negligible risk in the university community evaluated.

Conclusion

It is recommended that the university clinic prescribe Nitrofurantoin as the last antibiotic from the Access list to the university community to treat UTI patients. Furthermore, WBE is a useful tool to determine patterns of resistance under the studied settings.
Urogenital schistosomiasis, a leading cause of bladder squamous cell carcinoma
Authors: Johal J J , Hassan A , Movchan T , Omoscharka E
Published: October 2024

Introduction/Objective

Schistosoma, genus of trematodes, commonly known as blood flukes are parasitic flatworms responsible for a group of infections in humans termed schistosomiasis and hundreds of millions of people are infected worldwide. In areas where Shistosoma is not endemic to the region most cases of bladder malignancy are of urothelial origin. In areas where Shistosoma is endemic bladder malignancy is more commonly squamous cell carcinoma. However, with increased travel, migration and tourism it is important to potentially consider Shistosoma infection in areas that are not typically considered endemic regions.

Methods/Case Report

A 62-year-old male presented to our hospital and revealed through an interpreter he has had 1.5 years hematuria with “pieces of meat or brown dirt”. Cystoscopy was performed and showed a large necrotic mass. CT scan showed an 8.2 cm exophytic bladder dome mass. TURBT was performed and a diagnosis of invasive high-grade urothelial carcinoma with squamous differentiation and with multiple Schistosoma organisms identified.The patient received Schistosoma treatment and was scheduled for radical cystectomy and ileal conduct. A few days before the scheduled procedure the patient presented to our emergency department with acute abdominal pain. He was subsequently diagnosed with progressive bladder cancer with new left malignant ureteral obstruction, which lead to hydronephrosis, DVT, abdominopelvic ascites and intraperitoneal bladder perforation. Abdominal fluid cytology showed atypical keratinizing squamous cells suspicous for malignancy and marked acute inflammation. Patient underwent cystectomy with ileal conduit and the specimen was sent to pathology for examination.

Results (if a Case Study enter NA)

NA

Conclusion

Gross examination showed an irregular perforated bladder. Microscopic examination showed a high grade urothelial carcinoma with squamous and sarcomatoid differentiation with detrusor muscle invasion. Additionally, Schistosoma organisms with a terminal spine and calcified eggs were identified. Some of the calcified egg material was engulfed by giant cells. The organisms are surrounded by a prominent eosinophilic infiltrate. Lymphovascular invasion is also noted.

Schistosomiasis is associated with the development of squamous cell carcinoma of the bladder. It is important to maintain high oncological alertness for squamous cell carcinoma, particularly for patients arriving from endemic areas. Such as in our case, a patient from Somalia living in Kansas City.
Does the Third Sputum Exam has an Added Value in the Diagnosis of Pulmonary Tuberculosis?
Authors: tesfay E G
Published: October 2024

Introduction/Objective

Introduction: Current practice of examining three sputum for the diagnosis of pulmonary tuberculosis (PTB) has tended to overburden the already scarce human resources in all-purpose laboratories, and to increase the turn- around- time for patients seeking treatment. Therefore, assessing the added value of the third sputum in the diagnosis of PTB in resource-limited country with less functional External Quality Assurance (EQA) system is critical.

Methods/Case Report

Materials and methods: Data on patients diagnosed with smear-positive PTB during 2012- 2016 was collected retrospectively from laboratory register of nine hospitals in Eritrea. The data was extracted and analyzed for incremental yield of three sputum samples.

Results (if a Case Study enter NA)

Results: Data from 2,484 microscopically confirmed acid-fast bacilli (AFB) smear positive PTB patients were reviewed. AFB was detected in the first sputum in 87.5% of patients, and 99.1% for the combined first and second sputum specimens. The incremental yield of the third sputum specimen as a diagnostic value was only 0.9%. No significant variation was detected by region, residence, gender or HIV.

Background information Number of cases Percent Region Maekel 649 26.10%

Anseba 293 11.80%

Gash-Barka 815 32.80%

Debub 297 12.00%

Northern Red Sea 337 13.60%

Southern Red Sea 93 3.70% Sex

Male 1,251 50.40%

Female 1,233 49.60%

Residence

Urban 1,296 52.20%

Rural 1,188 47.80%

Age group

<15 35 1.40%

15 + 2,449 98.60%

Total 2,484 100

Conclusion

Conclusion: The added value of the third sputum is so minimal that its omission will reduce patient visits, workload and cost for patients and health services. Therefore, even countries like Eritrea, with limited EQA, should consider limiting the number of sputum examinations to improve quality.
Red herrings and zebras and TB, oh my! Unexpected bone marrow presentation of Mycobacterium tuberculosis
Authors: Martinez R M , Dhesi M S
Published: October 2024

Introduction/Objective

Epithelioid granulomas are uncommon and non-specific findings in bone marrow samples, and should prompt additional testing for appropriate diagnosis and treatment, especially in the immunocompromised patient. The differential diagnosis for bone marrow granulomas includes infections, neoplasia, autoimmune disease, sarcoidosis, and drug/therapy reaction. Although bone marrow workup to delineate the cause of granulomas should include staining to rule out both infection and lymphoma, morphologic review is often inconclusive. Final diagnosis requires clinical consultation and additional testing.

Methods/Case Report

A 76-year-old male was admitted to the hospital from the emergency department for a level 2 trauma after being found on the ground ~3 hours after a fall. The patient reported a recent increasing frequency of falls with associated weakness, as well as an almost 30 lb weight loss over the last 3.5 months and low grade fevers over several weeks. His past medical history was significant for treatment for urothelial carcinoma with transurethral resection and BCG therapy, hypertension, coronary artery disease, and peripheral vascular disease. Imaging showed hepatosplenomgaly, suspicious for early cirrhosis, and mild peripancreatic lymphadenopathy. Initial laboratory abnormalities demonstrated mild anemia, low albumin, and mild increase in ALT, AST, and alkaline phosphotase.

Initial Infectious Diseases workup was negative for causative etiology (blood cultures, tick-borne parasites, and respiratory pathogens). Patient symptoms did not improve and cytopenias worsened. A bone marrow biopsy showed multiple non-necrotizing epithelioid granulomas. Despite low clinical concern for infectious etiology, mycobacteria blood culture isolated Mycobacterium tuberculosis complex. Final results were available 112 days after specimen collection.

Results (if a Case Study enter NA)

NA

Conclusion

Although tuberculosis is commonly associated with granulomatous pathology, infection is very uncommon in North American patients who have not traveled and alternative diagnoses might initially be favored. A high suspicion for mycobacterial infections is essential for diagnosis even in low-incidence populations with no known exposure or risk factor(s).
Modulating Microbial Resistance: Transcription Factor Regulation of Antibiotic Resistance in Escherichia coli
Authors: Long T J
Published: October 2024

Introduction/Objective

Antibiotic resistance is a global health emergency, with resistance detected to all antibiotics currently in clinical use and only a few novel drugs in the development pipeline. Antibiotics target key biological processes in bacteria, such as protein synthesis, cell wall synthesis, DNA replication and protein translation. Cells tightly control their internal states in different environments by regulating their transcriptional program through the activity of transcription factors (TFs) that control the expression of multiple downstream effector genes. We hypothesized that efficacy of specific antibiotics can be adjusted by altering the transcriptional states of bacteria prior to treatment, using TF knockout (KO) and over- expression (O-E) strains.

Methods/Case Report

Aim: Calculate the IC50 of 9 TF KO strains and 9 TF O-E strains across across a panel of representative antibiotics. A previous barcode screen study had identified TF KOs which were associated with antibiotic resistance/susceptibility. A serial antibiotic dilution was prepared in M9 media. E. coli TF KO and O-E strains were cultured for 24 hours in M9 media+Antibiotic (37°C, shaking). Each strain/antibiotic combination contained a technical replicate. Growth was measured by OD, allowing for calculation of growth curves, drug response curves, IC50, and EC50. Strain-specific IC50 and EC50 were compared to wild-type (WT) IC50 and EC50 as a measure of drug resistance/susceptibility.

Results (if a Case Study enter NA)

Experiments demonstrated consistent, TF-specific patterns of drug susceptibility. Compared to WT, TF KO strains demonstrated altered antibiotic IC50s (drug susceptibility). Compared to WT, TF O-E strains also demonstrated altered antibiotic IC50s (drug susceptibility).

Conclusion

Hypothesis Weakly Supported – TF states affect IC50s (Abx resistance). The relationships outlined in initial screen were consistently represented in experimental trials. Strain resistance/susceptibility is directly related to TF system and drug mechanism of action. For example, drugs that inhibited ribosomal function demonstrated greater effectiveness against KO/O-E strains that relied more heavily on protein synthesis pathways. Drug resistance is not binary but is shaped by a number of internal cellular factors, including gene regulation by TFs.
Unusual Presentation of Tuberculosis in the Lungs and Lymph Nodes
Authors: Gardner S , Omoscharka E , Benton A , Barua P , Sun A
Published: October 2024

Introduction/Objective

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis mainly affecting the lungs. Despite treatment advancements, TB remains a major cause of morbidity. This report presents a patient with active pulmonary and lymph node TB.

Methods/Case Report

The patient is a 41-year-old male from Bangladesh admitted for worsening cough and shortness of breath. Earlier, he had a cough and right cervical lymphadenopathy with lymph node biopsy demonstrating noncaseating granuloma and a positive Quantiferon-Gold. Outpatient workup included negative sputum TB PCR with negative cultures. The patient was febrile, tachycardic, and oxygenating normally. D-dimer was 1484. CT angiography was negative for emboli and showed mediastinal and right hilar lymphadenopathy. Imaging was otherwise non-indicative of active TB. We started rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy with bronchoalveolar lavage for additional sputum sampling and excisional lymph node biopsy to rule out malignancy. Workup for autoimmune disease and sarcoidosis was negative. An acid-fast bacilli stain of the biopsy was positive, indicating active TB. The patient was discharged on RIPE with outpatient follow-up.

Results (if a Case Study enter NA)

NA

Conclusion

Histological findings of TB demonstrate caseating granulomatous lesions. Sarcoidosis can be considered in patients with hilar or mediastinal lymphadenopathy with noncaseating granulomatous lesions. However, both active and inactive TB should be considered in the differential diagnosis with biopsy results indicating noncaseating granuloma, as infected tissues can lack the central necrosis to produce caseation. Common chest radiographic findings in TB include pulmonary consolidation, hilar and mediastinal lymphadenopathy, disseminated miliary disease, and a normal chest radiograph. Our patient had just hilar and mediastinal lymphadenopathy. While a common finding in tuberculosis, this is also present in other inflammatory pathologies, emphasizing the importance of keeping a broad differential even in settings where initial biopsy and imaging results may indicate latent infection or other diagnoses.

We utilized the expertise of pathologists to identify lymph nodes with active TB infection in a patient who previously had inconsistent pathological and radiological findings. Without the help of the pathologists in this case, diagnosing and treating this patient would not have been possible, showing the necessity of histopathological correlation with clinical and radiologic findings.
The potential role of Circular RNA New biomarkers for the prognosis of hepatocellular carcinoma
Authors: Fyala A S , Sultan A
Published: October 2024

Introduction/Objective

Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer with related deaths worldwide. The non-coding RNAs as the functions of circRNAs in tumor progression have attracted great attention to the clinicopathological characteristics of HCC.

Methods/Case Report

The present study was conducted to investigate and evaluate the expression level of hsa_circ_2124, and hsa_circ_4018 downstream target gene pathways related to clinico-pathological parameters of HCC. Cell proliferation was examined by West-1 assay and protein expression levels by using western blotting analysis.

Results (if a Case Study enter NA)

The hsa_circ_2124 expression level was up-regulated in HepG2 and Hep3B cells, respectively compared to normal liver cells. Furthermore, hsa_circ_4018 was down-regulated in two HCC cell lines compared to the normal cell line (LO2 cells), demonstrating the heterogeneity characteristics of the circRNA expressions in different HCC cell lines. Our data showed a significant inhibition of hsa_circ_4018 in HCC cell lines which in turn inhibited cell proliferation and migration. Besides, there is an inhibition in cell proliferation after hsa_circ_2124 knockdown in the tested cell lines. In addition, our data reported that the Knockdown of hsa_circ_2124 reduced the expression of ERK, c-Myc, and β-catenin expression in Hep-G2 cells. Furthermore, hsa_circ_4018 showed significant inhibition in β-catenin and c-Myc expression levels in Hep3B cells compared to the control. The knockdown of hsa_circ_2124 induced G1-phase arrest in HepG2 cells compared to control, suggesting the role of hsa_circ_2124 in the inhibition of HCC progression.

Conclusion

All in all, our data revealed that hsa_circ_2124 or hsa_circ_4018 plays a role in the regulation of MAPK and Wnt/β-catenin signaling pathways, which might be potential therapeutic biomarkers for HCC.
Familial adenomatous polyposis gene MUTYH mutations are identified in anaplastic thyroid carcinoma
Authors: Kovalenko M , Xiaoming Z , Jansen S , Hammer R , Pavlick D C , Hiemenz M , Dougherty K C , Dooley L M , Chen N
Published: October 2024

Introduction/Objective

Anaplastic thyroid carcinoma (ATC) is a rare aggressive disease unresponsive to treatment. Next-Generation Sequencing (NGS) allows identification of targets for precision therapies, such as BRAF, with implications in treating ATC. Our prior work identified ATC clusters with characteristic gene mutations and multiple previously unreported mutations. One of these is MUTYH, which is associated with colon (CRC), ovarian, breast, bladder, and duodenal carcinomas in MUTYH-associated polyposis (MAP). Its association with ATC is not defined.

Methods/Case Report

Exploratory analysis of pathogenic mutations in 727 ATC cases using a 324-gene panel (FoundationOneCDx) and an interactive visualization of association rules was conducted for informative maximal frequent patterns among mutated gene combinations to identify gene clusters including genes not commonly associated with ATC. TCGA database was reviewed for frequency of MUTYH mutations. My Cancer Genome and the Drug-Gene Interaction Database were used to identify potential targeted drugs for MUTYH gene-mutated cancers.

Results (if a Case Study enter NA)

NGS showed MUTYH short-variant mutations in 17 cases (2.34%). Germline MUTYH variants incidence is 1.43% in normal samples. 5 cases harbored only Y165C and 7 had only G382D, with 1 case having both Y165C and G382D. The other 4 cases contained sporadic truncating events in MUTYH. All instances of Y165C and G382D were predicted to be germline. 6 patients (35%) had BRAF co-mutations, correlating with expected frequency of ATC thought to transform from papillary carcinoma (PC). One case had only MUTYH mutation while a second had MUTYH with TERT and TP53. TCGA database contained 6(0.2%) cases of PC with MUTYH mutations (total 2871 MUTYH-mutated carcinomas), but no cases of ATC or other thyroid tumors were described.

Conclusion

MUTYH is a DNA repair enzyme linked to CRC and other cancers. MUTYH mutations occur in 6.7% of MAP patients and 1–2.2% of sporadic CRC cases that are mutually exclusive of BRAF mutations. While MAP increases the lifetime risk of CRC by over 60%, the link of MUTYH mutations to PC has only been observed in MAP and not been described outside of it. To our knowledge this is the first description of MUTYH mutations in ATC, especially without concurrent BRAF mutation (11 cases), suggesting MUTYH may independently contribute to pathogenesis of ATC. PARP inhibitors, PD-1/PD-L1 inhibitors, and ATR inhibitors demonstrate promising results in clinical trials of MUTYH-mutated cancers, warranting further research.
Development of drug resistance in cancer cells
Authors: Farrell C , Caswell-Rios H
Published: October 2024

Introduction/Objective

The purpose of this study was to evaluate omeprazole treament in cancer cells.

Methods/Case Report

The colorectal cancer cell line, CACO2, was treated with omeprazole at two different concentrations and methotrexate as a positive control for 3-4 months. Using exon-spanning primers for the ABCG2 and ABCB1 genes, qPCR was used to monitor changes in mRNA expression of the efflux pumps, Breast Cancer Resistant Protein (BCRP) and P-glycoprotein (Pgp). Upregulation of BCRP and Pgp was observed through the western blot assay. Once overexpression of BCRP was confirmed, the omeprazole-treated and methotrexate-treated cells were tested for chemotherapy-resistance using the Prestoblue proliferation assay and were compared to the untreated cells. The omeprazole treatments were repeated for reproducibility using two esophageal cancer cell lines. The treated cells were also studied for expression changes of possible drug resistant and cancer genes using RNASeq analysis.

Results (if a Case Study enter NA)

N/A

Conclusion

Esophageal cancer patients, who are treated for acid reflux, may be at higher risk for developing chemotherapy-resistant/multidrug resistance (MDR) tumor cells prior to chemotherapy treatment. Esophageal cancer patients with MDR tumors will have lower chance of survival compared to patients who are responsive to chemotherapy treatment. By identifying the overexpression of BCRP in the tumor cells of cancer, oncologists will be able to use a better treatment plan with more effective chemotherapy drugs.
Introduction to the Principles of Artificail Intellengence: Bias and Ethical Considerations
Authors: Furth E E
Published: October 2024

What evidence demonstrates a need for this educational session among pathologists and/or laboratory professionals? (1,250 character limit): n/a
Sevelamer Treatment for Hyperphosphatemia in a Saudi Arabian Chronic Renal Disease Patient
Authors: Abdelmonem M , Wasim H , Hammad A , Abdelmageed M , Abdelhai A , Abdelmonem M , Hemdan A , Abo Amer S
Published: October 2024

Introduction/Objective

Introduction: Patients with advanced chronic kidney disease (CKD) often require phosphate binders to manage elevated serum phosphorus levels due to phosphorus-restricted diets being insufficient. This study aimed to assess the safety and efficacy of sevelamer in lowering serum phosphorus and improving the serum lipid profile in a hemodialysis patient.

Methods/Case Report

A prospective study was conducted on a 59-year-old hemodialysis man with CKD. Sevelamer was administered orally as 800 mg tablets, with the dosage adjusted based on washout serum phosphorus levels (WSPL). Blood samples were collected every two weeks before dialysis, and all samples were analyzed using standard clinical laboratory methods.

Sevelamer treatment resulted in a significant reduction in serum phosphorus levels from 6.9 mmol/l to 4.3 mmol/l. No major adverse events were observed during the trial period, and there was no evidence of negative consequences associated with sevelamer therapy. Additionally, sevelamer treatment led to a decrease in hemoglobin levels to 10.5 g/dl and a substantial reduction in total cholesterol concentration from 5.22 mmol/l to 4.26 mmol/l.

Results (if a Case Study enter NA)

NA

Conclusion

Conclusion: Sevelamer, a non-absorbable aluminum and calcium-free phosphate binder, effectively lowered serum phosphorus levels in dialysis patients while improving lipid profiles. It was well tolerated with no instances of hypercalcemia and resulted in significant reductions in intact parathyroid hormone (PTH) and total and LDL cholesterol. Sevelamer may serve as a valuable therapeutic option for managing hyperphosphatemia in patients with CKD.