bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient with AIP gene mutation presenting with pituitary adenomatosis
Authors: Abu-Salah A , Vortmeyer A O , Cramer H M
Published: November 2023

Introduction/Objective

Familial isolated pituitary adenoma (FIAP) is frequently associated with germline mutation in the AIP gene. Clinically, it is characterized by the occurrence of isolated pituitary adenoma in 2 or more members of a family. In this case report, we describe a patient who presented with a pituitary adenoma and concurrent disseminated leptomeningeal adenomatosis.

Methods/Case Report

A 17-year-old female presented with amenorrhea and visual impairment. Brain MRI showed a 2.6 x 2.8 x 2.4 cm mass in the sella turcica extending to the suprasellar region. Multiple separate smaller (5-7 mm) masses in the leptomeninges of the anterior and middle cranial fossa, and small enhancing masses within the internal auditory canals bilaterally were also seen. She underwent craniotomy for resection of the pituitary tumor which was diagnosed pathologically as sparsely granulated somatotroph adenoma with co-expression of human growth hormone and prolactin. Postoperatively, she was found to have persistent hormone imbalance for which she received proton beam therapy. Genetic testing revealed mutations in the AIP gene. No mutations were detected in NF2, MEN1, and CDKN1B. At age 21, radiologic follow-up revealed recurrent pituitary adenoma, for which she underwent trans- sphenoidal resection, revealing the same histopathologic diagnosis. At age 22, MRI showed diffuse nodular enhancement throughout the subarachnoid spaces, most pronounced within the Sylvian fissures. Cytologic examination of cerebrospinal fluid (CSF) showed several loose aggregates of neuroendocrine cells, positive for synaptophysin by immunocytochemistry, consistent with the diagnosis with dissemination of pituitary adenoma cells in the leptomeninges.

Results (if a Case Study enter NA)

N/A

Conclusion

In all 136 previously reported cases, leptomeningeal dissemination of pituitary adenoma has been exclusively described in post-surgical settings or after pituitary apoplexy. To our knowledge, this is the first case of disseminated pituitary adenomatosis noted at initial clinical presentation
Tumor to Tumor Metastasis of Breast Cancer to Pheochromocytoma in a 77 Year Old Man
Authors: Addo J A , Cox B
Published: November 2023

Introduction/Objective

Male breast cancer is rare, accounting for less than 1% of all breast cancer diagnoses. The most common sites for breast cancer metastasis include bone, lung, liver and brain. Tumor-to-tumor metastasis is an unusual phenomenon where one distinct malignancy is present within the substance of another independent tumor. We present a case of a 77-year-old man with a left pheochromocytoma and a tumor to tumor metastasis (TTM) from breast cancer. To our knowledge, this is the first case of a TTM from a breast cancer to a pheochromocytoma in a man.

Methods/Case Report

The patient is a 77 year old man with a past medical history of a right pheochromocytoma resected 20 years ago and a recently diagnosed right breast cancer. PET-CT identified a left adrenal mass.

Microscopic sections of the left adrenal gland showed nests of neoplastic cells arranged in a “zellballen” pattern. Adjacent to the neoplasm was a sheet of atypical epithelioid cells with increased nuclear to cytoplasmic ratios and frequent mitoses. Immunohistochemical stains were performed, and the nests of neoplastic cells with the zellballen pattern were positive for chromogranin and synaptophysin and negative for CAM5.2. A focus of the adrenal neoplasm was negative for these stains but stained positively for CAM5.2. Due to patient’s history, additional immunohistochemical stains were performed, staining with ER, CK7, GATA3, and mammaglobin was observed.

These findings were interpreted as a tumor-to tumor metastasis of metastatic breast carcinoma to pheochromocytoma in the left adrenal gland.

Results (if a Case Study enter NA)

NA

Conclusion

Tumor-to-tumor metastasis (TTM) is an unusual phenomenon in which a primary tumor metastasizes into another tumor. Lung and breast carcinomas are the most common metastatic donors, while renal cell carcinoma and meningioma are the most common malignant and benign recipients. In patients with TTM, proper use of immunohistochemical stains and patient’s history can aid in the diagnosis of the distinct tumors.
The Carney Triad
Authors: Cao T , Abdo M E , Hamza A
Published: November 2023

Introduction/Objective

Carney triad is a multi-tumor syndrome comprising of gastrointestinal stromal tumor (GIST), extra-adrenal paraganglioma and pulmonary chondroma that was first described in 1977. The purpose of this report of this to remind the pathologists about this triad and about the fact that pathology is far beyond just giving a diagnosis on a surgical specimen.

Methods/Case Report

A 41-year-old female presented with dizziness, nausea, vomiting, weakness, early satiety, and palpitations. She was found to be pregnant, and an ultrasound showed an intrauterine pregnancy along with a large abdominal mass. A subsequent computed tomography (CT) scan demonstrated a left adrenal heterogeneous mass. CT chest was also performed which demonstrated a 0.3 cm right middle lobe pulmonary nodule, compatible with a benign tumor.

Lab work showed cortisol, dehydroepiandrosterone sulfate (DHEAS), and adrenocorticotropic hormone (ACTH) to be within normal limits, but both metanephrine and normetanephrine were elevated. The patient was treated with an alpha and beta blockade prior to undergoing an adrenalectomy. During adrenalectomy an incidental mass was found at the greater curvature of the stomach.

On gross examination, the adrenal mass was a large, encapsulated, brown-black, multi-lobulated, weighing 1,427 grams and measuring 19.8 x 13.7 x 11.6 cm. Microscopically, the mass was consistent with an extra-adrenal paraganglioma, compressing the adjacent normal adrenal gland and not invading or arising from it. The stomach mass was grossly tan-yellow, multi-lobulated, and firm. The cut sections were variegated tan, white. Microscopically, the mass was consistent with a GIST.

Results (if a Case Study enter NA)

NA

Conclusion

Individual diagnoses were rendered for the adrenalectomy and gastric mass specimens. Additionally, possibility of carney’s triad was suggested based on patient’s chest imaging findings.
Spectrum of Lymphomas involving Gastrointestinal tract in a Single Institution: A Retrospective Analysis
Authors: Huang H , Qing X
Published: November 2023

Introduction/Objective

Lymphomas affecting the gastrointestinal (GI) tract are relatively uncommon occurrences. Given that GI biopsies are primarily evaluated by pathologists specializing in GI pathology, a comprehensive understanding of GI lymphomas is essential for accurate diagnosis and appropriate referral. However, there is limited updated studies of the prevalence and distribution of GI lymphoma subtypes in diverse patient populations. Therefore, the objective of this study was to address this knowledge gap by characterizing the prevalence and distribution patterns of GI lymphoma subtypes in a diverse patient population residing in the west coast region.

Methods/Case Report

A comprehensive retrospective review was conducted on patients diagnosed with lymphomas involving GI tract between 2015 and 2023 at a single institution over 8 years. Clinical and pathological data, including age, gender, tumor locations, and histological diagnoses, were collected and analyzed.

Results (if a Case Study enter NA)

A total of 32 cases diagnosed with lymphomas involving GI tract were included in this study. The patient population consisted of 44% female and 56% male, with an average age of 61 years (range: 35 to 93 years). The most common tumor locations (figure 1) were the stomach (53%), followed by the duodenum (16%), ileum and colon (8%). The other less frequent locations such as the pancreas, jejunum, and rectum and esophagus (each 3%). Notably, 38% (12 cases) of the total cases exhibited involvement of two or more anatomical sites.

Conclusion

Our study findings are consistent with previous literature, confirming that Diffuse Large B-cell Lymphoma (DLBCL) remains the most prevalent subtype of gastrointestinal (GI) lymphoma. The high frequency of stomach involvement aligns with the recognized association between Helicobacter pylori infection and lymphomagenesis.

However, it is worth noting that the prevalence of MALT lymphoma has decreased, potentially indicating improved eradication efforts through antibiotic treatment. The observed proportion of cases with involvement of multiple anatomical sites highlights the diagnostic challenge of GI lymphomas and emphasizes the need for comprehensive evaluation.
Pre-germ cell neoplasia in-situ in a patient with complete androgen insensitivity syndrome
Authors: Muldoon J , Collins K , Ulbright T , González I A
Published: November 2023

Introduction/Objective

Complete androgen insensitivity syndrome is a disorder of sex development in 46, XY individuals with external female genitalia and undescended testes, often presenting with inguinal hernia in infancy and/or primary amenorrhea in adolescents. Given the increased risk for the development of germ cell neoplasms in the ectopic testis, early gonadectomy or orchidopexy may be indicated.

Methods/Case Report

We report a 21-year-old patient assigned female at birth (46, XY) with a history of bilateral inguinal hernia repairs (age 2) and later with lack of menarche (age 16). Additional work-up showed an elevated testosterone level (394 ng/mL) and normal luteinizing and follicle stimulating hormone values. On pelvic ultrasound, retained intraabdominal gonads were identified, but female sex organs were absent. During a gonadal relocation procedure, the gonads appeared irregular in shape with multiple cysts and small nodules, and bilateral gonadectomy was performed. Grossly, the gonads measured 4.9 and 4.3 cm with a smooth external surface and a lobulated cut surface with multiple cysts, up to 1.6 cm, containing clear, serous fluid. Histologic sections showed most seminiferous tubules were lined only by Sertoli cells with only occasional spermatogonia. Leydig cell hyperplasia and areas of ovarian-like stroma were seen. OCT4 immunostain highlighted the nuclei of individually disposed germ cells in the base of tubules (singly dispersed, non-linear pattern), raising concern for germ-cell neoplasia in-situ (GCNIS).

However, the histology and staining pattern were better interpreted as diagnostic of germ cells with delayed maturation and pre-GCNIS. Additionally, OCT4 showed rare single cells within the stroma and considered to represent residual undifferentiated gonadal tissue. After gonadectomy, the patient was started on hormone replacement therapy.

Results (if a Case Study enter NA)

NA

Conclusion

This case highlights the potential pitfalls in the interpretation of OCT4 immunostain to avoid misdiagnosis of germ cell neoplasia.
Selenium Deficiency is associated with inflammation and Cardio- metabolic dysregulation in women with Hypertensive disorders of Pregnancy
Authors: Nwadike C N , Nwanjo H U , Ikaraoha C I , Ogbuokiri A C
Published: November 2023

Introduction/Objective

Selenium (Se) deficiency has been speculated to enhance Oxidative inflammation in Pregnancy, leading to endothelial dysfunction, which has been implicated in the aetiopathogenesis of Hypertensive disorders of Pregnancy. This study aimed at evaluating the Selenium Status of pregnant women and its role in inflammation and cardio-metabolism in pregnant women with Hypertensive disorders of Pregnancy.

Methods/Case Report

The study involved 200 healthy women with Single Pregnancy who presented to Obstetrics and Gynaecology clinic of IMSUTH Teaching Hospital, Nigeria. These subjects were recruited between 10 to 15 weeks of gestation. 52 of the them who subsequently developed Hypertensive disorders ;Preeclampsia (PE)-15 and Pregnancy Induced Hypertension (PIH)- 37) were compared with their148 counterparts who remained Normotensive. The groups were matched for age, BMI, gestational age and parity. The blood Selenium levels were determined using Atomic Absorption spectrophotometer, while ELIZA was used for Markers of Inflammation and Cardio-metabolic risk (Hs Crp, Lipid profile, Insuline, MDA,TAC, GSH). P <0.05 was considered statistically significant for all variables.

Results (if a Case Study enter NA)

There was significant reduction in the mean levels of Selenium in Pregnant women with PE and PIH (52.41 μg/L, 56.02 μg/L) when compared with Normotensive (68.84 μg/L). Hs-CRP, LDL and MDA showed significant increase in the study groups (PE and PIH) against the Normotensive group (p=0.001,

0.004 and 0.001) respectively. A significant reduction was observed in the TAC and GSH in PE and PIH (p> 0.005).. There was also a significant increase in the Insulin levels of the PE group compared with the Control group. There was a negative correlation relationship between Selenium and Hs- CRP (r = -0.533, r=-601), serum lipids and Insulin and BMI in the study groups.

Conclusion

From our study, Selenium deficiency may be associated with Dyslipidemia, impaired Insulin Metabolism and may serve as a predictive Risk marker of Heart disease in women with Hypertensive disorders of Pregnancy.
Assessing the Impact of Race, Sexual Orientation, and Gender Identity on USMLE Style Questions: Preliminary Results of a Randomized Controlled Trial
Authors: Arnason T J , Mirza K M , Lilley C M
Published: November 2023

Introduction/Objective

Medical students are expected to graduate with cultural competence, which improves the quality of care of different minority groups and may help reduce health disparities. Incorporation of diversity, equity, and inclusion into medical teaching is critical to the development of culturally competent physicians; however, centuries of medical pedagogy have tied certain pathologies to racial and sexual/gender minority patients. This not only encourages stereotyping to arrive at the correct answer but also narrows the differential diagnosis developed by the future physician. We are surveying US and non-US third- and fourth-year medical students and first-year residents to demonstrate to what extent inclusion of race, sexual orientation, and gender identity data in question stems influences diagnosis and clinical decision-making.

Methods/Case Report

The survey consists of three sections. The first section collects demographic information, including age, race, gender identity, region, type of medical degree, current level of training, completion of examinations, and MCAT score. The second section presents one of two sets of twelve USMLE style questions with (experimental) or without (control) key demographic data, including race, sexual orientation, and gender identity. The third section presents four questions in order to assess participants’ understanding of the higher burden of hypertension among Black patients and attitudes regarding the role of their medical education in the development of biases. Participants were randomized to the set of twelve questions in the second section.

Results (if a Case Study enter NA)

Preliminary results from 25 medical trainees associated with Loyola University Chicago demonstrate that the presence of demographic data including race, sexual orientation, and gender identity impact answer choice on standardized questions.

Conclusion

The preliminary results of this study are significant because they suggest that race, sexual orientation, and gender identity are still being used in pathology education to highlight certain disease processes, potentially in a manner that is out of proportion to actual disease prevalence.
Systemic EBV-Positive T-cell Lymphoma of Childhood: A Case Report and Comprehensive Literature Review
Authors: Hwang C , Sae-Ow W
Published: November 2023

Introduction/Objective

Systemic EBV-positive T-cell lymphoma of childhood (SETLC) is an extremely rare disease in which most cases have been reported in Eastern Asian countries. It is characterized by a clonal proliferation of EBV- infected cytotoxic T cells that most commonly affect immunocompetent children and young adults. Patients present with systemic disease with rapid disease progression and multi-organ failure leading to death. Here, we report a case of SETLC in an 18 year old male, and review clinicopathologic features of the entity from 12 reported cases in the literature.

Methods/Case Report

A previously healthy 18 year old male presented with fever, abdominal pain, and vomiting. Clinical workup revealed elevated serum EBV viral load, hepatosplenomegaly, lymphadenopathy, pancytopenia, DIC, and multi-organ failure. Peripheral blood smear and bone marrow biopsy showed increased atypical lymphocytes with CD3+, CD8+, CD56-, TIA-1+ phenotype. In addition, prominent hemophagocytosis was noted in the bone marrow. T- cell receptor beta gene rearrangement was positive by PCR. A diagnosis of SETLC was established. Despite chemotherapy, he deteriorated rapidly and passed.

Results (if a Case Study enter NA)

NA

Conclusion

SETLC is an extremely rare disease in which most cases have been reported in Eastern Asian countries. Common clinical manifestations include fever, hepatosplenomegaly, lymphadenopathy, cytopenia, elevated LFT, coagulopathy, hyperferritinemia, hemophagocytic lymphohistiocytosis, and high serum EBV viral loads. It is a systemic disease with multiple organs involvement by EBV positive T cells. Comprehensive literature review of 12 reported cases along with our case demonstrated these neoplastic T cells were positive for CD2, CD3, CD8, TIA1 or granzyme, and EBER in situ hybridization; negative for CD56 in most cases. Hemophagocytosis was a common finding, and T cell receptor gene rearrangement confirmed clonality of the neoplastic T cells in all reported cases. Currently, there is no standard treatment. Most patient died from the disease weeks to months after disease onset.
Sclerosing Angiomatoid Nodular Transformation of The Spleen: A report of a rare entity
Authors: Raja F , Iqbal S , Hammad A , Ayub S
Published: November 2023

Introduction/Objective

Sclerosing angiomatoid nodular transformation (SANT) is a benign vascular lesion of spleen with uncertain etiology. It predominately affects women between 30 to 60 years of age. Clinically, it is asymptomatic or can cause abdominal pain, but usually discovered incidentally on imaging, which can identify a mass but may not provide a definitive diagnosis. In uncertain vascular lesions, there is always a risk of spontaneous rupture of large vessels and potential for spreading malignancy. Hence, the final diagnosis is rendered on microscopy after splenectomy

Methods/Case Report

A middle age female came to clinic complaining of abdominal pain. Radiology showed solid splenic mass and the patient underwent splenectomy. Gross examination showed a 3 cm white firm mass with focal hemorrhage. Microscopy revealed multiple nodules of variable sizes surrounded by fibrosclerotic stroma. The nodules showed round to slit-like vascular spaces with numerous red blood cells. The internodular stroma consisted of dense fibrous tissue with scattered plump myofibroblasts and lymphoplasmacytic cells. These distinctive features lead to the diagnosis of SANT

Results (if a Case Study enter NA)

SANT possessed characteristic histologic features with distinctive immunohistochemistry (IHC). IHC reveals three different types of vessels within the nodules: 1. Small veins (CD34- CD31+ CD8-); 2. Sinusoids (CD34- CD31+ CD8+); and 3. Capillaries (CD34+ CD31+ CD8-). All 3 vessels are negative for CD21/CD35 and CD68. Hemangioma and littoral cell angioma are two frequent vascular tumors in the spleen that should be differentiated. Both lesions lack microscopic features of SANT and have only a single type of vessels. The vessels in hemangioma are (CD31+ CD34+ CD8-); while in littoral cell angioma they are (CD31+ CD34- CD8- CD21+ CD68+)

Conclusion

There are no specific clinical or radiologic findings for SANT. It is important to recognize these characteristic features and to differentiate it from other benign and malignant lesions, such as angiosarcoma. A thorough histopathologic examination and IHC are helpful to make the correct diagnosis
Rapid Progression of Myelodysplastic/Myeloproliferative Neoplasm with Neutrophilia to Acute Myeloid Leukemia: A Case Report
Authors: Aljumaili Z , Wang X , Wang W , Hu Z
Published: November 2023

Introduction/Objective

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with neutrophilia, formerly atypical chronic myeloid leukemia, is a subtype of MDS/MPN that is characterized by peripheral blood neutrophilia with frequent left-shifted myeloid cells, dysplastic granulocytes, and an absence of the Philadelphia chromosome or BCR- ABL1 fusion gene. Its clinical course is variable, ranging from a chronic indolent disease to an aggressive leukemia. Herein, we report a case of who was diagnosed with MDS/MPN with neutrophilia and had rapid progression to acute myeloid leukemia.

Methods/Case Report

A 63-year-old male patient with no significant medical history presented with incidental findings of abnormal peripheral blood counts: leukocytosis of 153 × 109/L, platelets of 82 × 109/L, and Hb of 6.7g/dl.

Flow cytometry (FCM) on peripheral blood was significant for increased granulocytes and a population of aberrant blasts (~7.3%) expressing CD5, CD11c, CD13, CD34, CD38, CD56 (partial), CD117, and HLA-DR. The initial Bone marrow biopsy showed a hypercellular marrow (90-100%), 3% blasts, dysgranulopoiesis, and dysmegakaryopoiesis. Fluorescence in situ hybridization (FISH) analysis for BCR-ABL1 fusion and MPN with Eosinophilia panel, including FIP1L1-CHIC2-PDGFRA; PDGFRB/5q33; FGFR1/8p12, were all negative. Next Generation sequencing (NGS) detected at least one variant of strong clinical significance (Tier I) including: ASXL1 c.1900_1922del23, NRAS c.35G>C, U2AF1 c.470A>C, potential clinical significance (Tier II) GATA2 c.1160_1165delCCATGA and unknown clinical significance (Tier III) SETBP1 c.2620G>A. The chromosomal analysis showed trisomy 14. The patient received Decitabine for 2 months, but follow-up FCM on the subsequent bone marrow examination revealed 40% blasts, with marked erythroid hyperplasia. The patient was diagnosed with acute myeloid leukemia. Despite receiving Venetoclax and Azacitidine, the patient deteriorated and expired in 10 months after the initial diagnosis of MDS/MPN with neutrophilia.

Results (if a Case Study enter NA)

NA

Conclusion

This case highlights the poor prognosis associated with MDS/MPN with neutrophilia. Optimal management strategies for these patients are still evolving, and new targeted therapies are needed to improve outcomes.
Next-Generation Sequencing Testing and Triaging of Bone Marrow Samples: Indications, Pre-authorization and Medical Necessity for Patient Care
Authors: Haq H , Loos C , Wells A , Herschap B , Sanchez-Salazar A , Ehsan A
Published: November 2023

Introduction/Objective

Bone marrow biopsy (BMBx) is an invasive procedure and samples are usually obtained for diagnosis, staging and prognosis of hematolymphoid disorders (HDs). Given the need for WHO and ICC classification of HDs; the Next Generation Sequencing (NGS) testing (in addition to other esoteric testing) has become relevant and medically necessary. It is important to triage BMBx in real-time based on clinical indications; however, pathologists are challenged by limited published guidelines as well as need for pre-authorization (PA) thus resulting in claim denials.

Methods/Case Report

Retrospective analysis was performed (2018 to 2022) on 1610 BMBx submitted for various clinical indications. These were categorized as follows: Cytopenias 220 (MDS); Cytosis 250 (MPN); Lymphomas work-up 350 (LY), acute leukemias 440 (AL) and plasma cell disorders 350 (PCD). In addition to esoteric testing; the decision was made to perform NGS testing based on preview of aspirate slides, clinical history and CBC.

Results (if a Case Study enter NA)

Providers initially ordered NGS in 10% of cases; however, NGS was added later by pathologists in 30% of BMBx samples. Abnormal NGS results were obtained as follows: MDS (70%); MPN (75%); LY (15%); AL (90%) and PCD (40%). NGS testing provided clinically useful data for MDS, MPN and AL groups. Even though LY and PCD groups also yielded positive results; the concurrent esoteric testing (Flow, FISH and Cytogenetics) was useful thus making indication of NGS in these two subset groups less indicated.

Conclusion

Appropriate triaging of BMBx for NGS testing is medically necessary for following reasons: 1) Enables precise diagnosis in a timely manner; 2) to avoid repeat BMBx if triaging guidelines are followed; and 3) decision to order NGS is made in real-time as BMBx are time sensitive samples thus eliminating the need for PA as this study emphasize that NGS has become standard of care in the work-up of HDs.
First US Case of Vagococcus Lutrae Infection in a Human: A Case Report
Authors: Asfar M , Antoine-Reid T
Published: November 2023

Introduction/Objective

Vagococcus Lutrae is a gram-positive, catalase-negative bacterium, that has been isolated from different animal species. It is an extremely rare pathogen in humans and has been documented in only two human cases globally. We present a case of V. Lutrae infection in humans, which is the third in the world and first in the US to be documented in literature.

Methods/Case Report

Our patient was a 75-year-old male with a history of hypertension and hyperlipidemia who presented with a right groin abscess with associated skin necrosis and cellulitis. V. Lutrae was identified in the culture of the abscess fluid. The diagnosis was made after conventional biochemical tests, automated methodology, and mass spectrometry (MALDI-TOF MS). The patient underwent incision and drainage of the abscess, was treated with antibiotics, and showed improvement upon follow-up.

Results (if a Case Study enter NA)

NA

Conclusion

Our case highlights the importance of considering V. Lutrae as a potential pathogen in patients with skin infections, particularly those with a history of contact with contaminated water or soil. Further studies are needed to better understand the epidemiology and clinical manifestations of V. Lutrae infections in humans.
Viability of MDR bacteria against antibacterial biosynthesized ZnO and Au Nanoparticles
Authors: Abdelmonem M , Hammad S E , Elshikh H H , Mostafa M A , El-Rouby M N , Abdelmageed M , Wasim H , Eldaly R
Published: November 2023

Introduction/Objective: Background

Resistant strain diseases are increasing worldwide. Antimicrobials are concerned about pathogen-acquired resistance. Nanotechnology advances enable the creation of novel formulations based on various nanoparticles (NPs) with different sizes and antibacterial characteristics.

Methods/Case Report

Materials and methods

All fungi were isolated and cultivated on malt extract broth. The endophytic fungus was cultured. Zn and Au nanoparticles have been produced by adding 0.1 M, 1 mL of Zn SO4, and HAuCl4 to 10 mL of fungal filtrate. Characterization of nanoparticles by the extracts' UV-visible spectrum shows ZnO NPs and Au NPs' green synthesis. UV-Vis, HR-TEM, XRD patterns, EDX analysis, and a Zeta-sizer characterize NPs' optical properties and morphology. Using 2,3,5-triphenyl tetrazolium chloride, biosynthesized Au and ZnO NPs' MICs against bacteria were determined. The bacterial culture was cultivated until it reached an Mc-Farland standard of 0.5. After that, 10 uL of bacterial suspension was pipetted into 140 uL of nutritional broth with 0.12 to 31.25 ug/mL ZnO and Au NPs. ZnO- and Au-free nutrient broth was used as a control. Wells that didn't turn red was examined for MIC values.

Results (if a Case Study enter NA): Results

The fungal filtrate's color changed from light yellow to colorless and violet after mixing with ZnSO4 and HAuCl4, respectively, ensuring nanoparticle formation. UV-Vis spectra: ZnO NPs were confirmed by excitonic absorption peaks between 300 and 400 nm; the maximum absorbance peak was 305 nm, while Au NPs' peak was 520 nm. Results showed that Au NPs and ZnO NPs have a hydrodynamic diameter (HD) of 34.88 nm and 15.77 nm, respectively. Our EDX analysis revealed that both nanoparticles have 64.61 and 35.39 % Zn and O stoichiometric mass percent.

Energy dispersive X-rays showed a peak optical absorption band at 2.2 keV in gold nanocrystallites. Au NPs and ZnO NPs had MICs of 7.81 and 1.95 ug ml-1 against P. aeruginosa and 3.9 and 0.98 against E. coli, respectively. ZnO

NPs' MIC against E. coli and P. aeruginosa is lower than Au NPs'. ZnO NPs increased microbial cell proliferation, and its inhibition was affected by the concentrations, sizes, and forms.

Conclusion

Our study investigated that the number of pathogens Escherichia coli and Pseudomonas aeruginosa decreases as nanoparticle concentration increases. So, ZnO NPs and Au NPs can inhibit bacterial development and cytoplasmic leak contents at lower concentrations.
HIV Type-1 Genotyping in the Context of the COVID-19 Pandemic: A Critical Tool for Identifying Antiretroviral Drug Resistance and Optimizing Treatment Strategies
Authors: Simonyan H , Dabash A , Yee R
Published: November 2023

Introduction/Objective

The COVID-19 pandemic strained the healthcare system and the WHO recently reported increased rates of antibiotic resistance. Meanwhile, antiretroviral resistance can also lead to treatment failure and disease progression, especially in HIV patients. Here, we investigated the rates of HIV drug resistance (HIVDR) in our HIV population between pre and post-COVID-19 eras.

Methods/Case Report

The post-COVID-19 era began on 03/11/2020. Patients positive for HIV-1 between 01/2019- 08/2021 were included (total: 94 patients, 46 pre-COVID-19; 48 post-COVID-19). Patients’ charts were reviewed for demographics, laboratory results (including HIV-1 sequencing/genotyping (e.g., Genosure)), clinical presentation and management. Student t-test and Fisher exact test were calculated.

Results (if a Case Study enter NA)

Most patients were male (70%) and had a mean age of 49 years. 70% of patients had sufficient viral loads in samples reflexed to HIV genotyping. Post-COVID-19 patients harbored lower viral loads (1.8x105 vs. 3.4x105 copies/mL, p=0.05), CD4 counts (174 vs. 196 cells/mcL, p=0.7), CD8 counts (555 vs. 800 cells/mcL, p=0.04), and higher CD4/CD8 ratio (0.312 vs. 0.266, p=0.57). Overall, 20% of patients had HIVDR. Following COVID-19 pandemic, there was a 9% increase in HIVDR, predominantly seen in non-nucleotide reverse transcriptase inhibitors (NNRTI), although insignificant. Specifically, high resistance was documented for drugs Efavirenz (16%), Nevirapine (16%), and Rilpivirine (13%). We observed an increased prevalence of G190A, K101, K103, and E138 mutations conferring resistance to NNRTIs. Changes to therapy were observed in 47.8% (42/88) of total cases, with an increase of 12.5% in patients from post-COVID-19 era. Additionally, changes to therapy were observed more in patients with infectious diseases consultation (16% increase).

Conclusion

Increasing HIVDR was seen in our patient population post-COVID-19. Continued surveillance is critical to managing HIVDR and improving patient outcomes. The clinical utility of sequencing tests can outweigh the cost if results are appropriately acted upon which may involve the participation of other clinical teams and the antimicrobial stewardship committee.
Liquid Biopsy as a Powerful Therapeutic Tool in Veteran Patients with Prostate Carcinoma
Authors: Dalal S , Petersen J M , Jhala D , Allbee A
Published: November 2023

Introduction/Objective

The National Comprehensive Cancer Network (NCCN) guidelines currently recommend somatic tumor molecular testing for alterations in homologous recombination (HR) DNA repair genes in patients with metastatic prostate cancer, which can be performed on either the sampled tumor tissue itself or by liquid biopsy.

Particularly when the sampled tumor tissue may be limited, liquid biopsy with next generation sequencing is a recently available attractive alternative that is minimally invasive (requiring just phlebotomy). Based on the information gathered from circulating tumor cells (CTC), a tumor molecular profile can be obtained that can impact treatment, particularly if a HR DNA repair mutation is found as that may predict response to a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor such as Olaparib. However, the literature of metastatic prostate cancers targeted by liquid biopsies and the mutations found is sparse, particularly for the veteran population.

Methods/Case Report

A retrospective review was performed of all patients with a submitted liquid biopsy specimen at a Veteran Affairs Medical Center (VAMC) October 23rd, 2019, to March 3rd, 2023 to examine those patients with

metastatic prostate cancer. Information on mutations detected was collected.

Results (if a Case Study enter NA)

There were a total of 64 patient specimens with a history of metastatic prostate cancer, from which 56 had an available liquid biopsy report with the first liquid biopsy collection occurring on October 23rd, 2019. HR DNA repair mutations found included CHEK2 (6/56), ATM (4/56), and BRCA1 (1/56). Outside of HR DNA repair genes, relatively common detected mutations were found in TP53 (25/56), PTEN (6/56), BRAF (4/56), and an AR amplification (4/56). 7 of the 56 reports had no reportable genomic alterations detected.

Conclusion

Liquid biopsies continues to be a minimally invasive, highly useful powerful therapeutic tool in veteran patients with metastatic prostate carcinoma for molecular profiling. Not uncommonly in the Veteran population, these molecular findings include mutations in HR DNA repair genes that as noted by the NCCN may predict response to PARP inhibitor chemotherapy.
Genome Sequencing-Based Prognosis, Mutational Analysis, and Survival Rate of Pediatric Acute Myeloid Leukemia
Authors: Memon M D , Kazacheuskaya L , Ong M , Cotelingam J , Patil A , Centeno L
Published: November 2023

Introduction/Objective

Pediatric Acute Myeloid Leukemia (AML) is a rare diagnosis that once carried a poor prognosis, but with recent improvement, the survival rate now reaches 80%. Although studies of most genetic mechanisms of AML involved adult studies, but dissimilar mutational profiles and treatment responses in pediatric patients have become evident. Information regarding pediatric AML-specific whole genome sequencing, a prognostic prediction system, and overall survival is limited. Hence, we aimed to analyze the genomic profile, epidemiological characteristics, and overall survival of pediatric AML.

Methods/Case Report

We utilized cBioPortal cancer genomics [The Cancer Genome Atlas (TCGA) PanCancer Atlas, TCGA Firehose Legacy, and TCGA Nature 2013] to study genetic mutations associated with pediatric AML. Epidemiological characteristics and genetic profiles available on cBioportal were evaluated. Gene mutations with the most statistically significant shortest overall survival and survival in days from the samples were used for gene query, and survival rate with the most common mutations was calculated. Log-rank test and Kaplan–Meier estimators were used in analyzing the survival function. Patients with two or more overlapping mutations were excluded.

Results (if a Case Study enter NA)

We identified 899 patients with Pediatric AML, out of 886 had all demographic data available, 50.8% were males, 71.6% were Caucasian, and 11.3% were African American. 568 (63.2%) were alive, and 318 (35.4%) were deceased. 159 patients were diagnosed at less than or equal to 2 years of age, and 150 patients had 80-90% blasts in their samples. 440 (42.9%) had relapse of disease at the bone marrow, whereas 72 (7.0%) had relapse at other sites. The common mutations associated with reduced survival were C4ORF36, HERC5, GPRIN3, NFKB1, NUP88, QRFPR, SPRY1, and UNC5C. Median survival data of patients was available for GPRIN3, NFKB1, NUP88, SPRY1, UNC5C, and was 25.00, 11.00, 15.00, 59.00, and 14.00 months respectively. Comparison with the unaltered group was not available (p < 0.0001). Survival was lowest amongst NFKB1 (11.00 months), NUP88 (15.00 months), and UNC5C (14.00 months). In survival analysis, the same genes were associated with lowest survival after initial diagnosis (p = 7.301e-4).

Conclusion

Our study found that NFKB1, NUP88, and UNC5C genes were associated with the worst prognosis in pediatric AML with median survival of 11.00, 15.00, and 14.00 months. Furthermore it may result in improve the prognosis of these patients.
Invasive Pancreatic Adenocarcinoma with Squamous Differentiation Arising in an IOPN with Novel MDM2 Amplification
Authors: Wilkins R , Zee S
Published: November 2023

Introduction/Objective

Intraductal oncocytic papillary neoplasms (IOPNs) are rare pancreatic tumors that are genetically distinct from intraductal papillary mucinous neoplasms (IPMNs). Morphologic and molecular characterization of invasive adenocarcinomas associated with IOPNs remains limited due to the rarity of this entity.

Methods/Case Report

We present a 68-year-old female who initially presented with abdominal pain and jaundice. MRI revealed a 2.6 cm mass in the pancreatic head with abutment of the superior mesenteric vein and dilation of the biliary and pancreatic duct. Biopsy revealed adenocarcinoma with mucinous features. The patient was started on gemcitabine and abraxane. Her treatment course was complicated by biliary and duodenal obstruction requiring common bile duct and duodenal stenting. Surgical management with pancreaticoduodenectomy was performed six months following initial diagnosis. Gross examination revealed a 2.5 cm ill-defined tumor surrounding the main pancreatic duct adjacent to the common bile duct. Microscopy revealed an IOPN arising within the pancreatic duct exhibiting a complex papillary growth pattern. There was an associated moderately to poorly differentiated invasive carcinoma with mucinous and squamous differentiation with lymph node metastasis. Molecular testing (FoundationOne®CDx) revealed ARID1A mutation and amplification of MDM2, CDK4, and ERBB3. Patient is alive and without radiologic evidence of disease recurrence at 6 months follow-up.

Results (if a Case Study enter NA)

NA

Conclusion

To our knowledge, our case is the first report of an invasive pancreatic adenocarcinoma with squamous differentiation arising in association with an IOPN. In addition, our case showed MDM2 amplification which has not been previously identified in pancreatic adenocarcinoma arising in IOPNs. Although recent literature demonstrated that less than 30% of IOPN showed invasive disease and even fewer cases with lymph node metastasis, our case showed extensive invasion with metastases to 2 lymph nodes. This may suggest that MDM2 amplification may play a role in more aggressive disease since it is implicated with poorer outcome in conventional pancreatic adenocarcinoma. Further molecular studies of IOPN may help to identify prognostic features of this entity.
Congenital Pulmonary Airway Malformation Type 1 with Pulmonary Neuroendocrine Cell Hyperplasia in an Adult Male: a Rare Case Report
Authors: Huffman G , Xu Y
Published: November 2023

Introduction/Objective

Congenital pulmonary airway malformations (CPAM) is rare, usually diagnosed in the pediatric population, and may occur in adults. Pulmonary neuroendocrine cell hyperplasia (PNECH) mimicking diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) associated with CPAM has not been described previously. We report a case of CPAM Type 1 with PNECH.

Methods/Case Report

A 33-year-old male, with past medical history of latent tuberculosis (TB) by Quantiferon blood testing, recurrent pneumonia, recurrent lung abscesses, and lung cavitary lesion for three years, presented with fever, cough with hemoptysis, shortness of breath, and left-sided chest pain. Computerized tomography of chest displayed a 10.8 cm cavitary lesion in the left lower lobe of the lung. The patient underwent left lower lobectomy of the lung. Grossly, the lobectomy specimen revealed a 10.5 cm irregular cavity communicating to the superior segmental bronchus of the left lower lobe. Microscopically, the dominant large cyst was surrounded by lung parenchyma and small cystically dilated spaces resembling bronchioles under the fibrotic pleura. The large cyst was lined by respiratory epithelium with rare pathognomonic mucous cells in clusters. Cyst walls contained smooth muscle, small islands of cartilage, and focal intense acute and chronic inflammatory cell infiltrates with hemorrhage. There were multiple foci of proliferation of pulmonary neuroendocrine cells centered around bronchioles surrounding the large cyst. The neuroendocrine cells were arranged from individual cells and cellular aggregates to larger tumorlets, highlighted by Synaptophysin and Chromogranin immunostains. No granuloma or necrosis was present. No acid-fast bacilli or fungal microorganisms were identified by special stains. The findings are consistent with CPAM type 1, with PNECH.

Results (if a Case Study enter NA)

NA

Conclusion

Our study demonstrates a histologically diagnosed adult congenital pulmonary airway malformations type 1 with an incidental pulmonary neuroendocrine cell hyperplasia, which mimics diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. To the best of our knowledge, this is the first report of such an association.
COVID-19 Infection Can be Associated with Pauci-Immune Type of Crescentic Glomerulonephritis: A Case Report
Authors: Pokharel A , Metcalf B D , Li W , Kanaan H D , Zhang P L
Published: November 2023

Introduction/Objective

COVID-19 infection is known to cause various podocytopathies, but the pauci-immune type of crescentic glomerulonephritis (C-GN) following COVID-19 infection has only rarely been reported.

We report a case in which a positive proteinase-3 was correlated with a pauci-immune type of C-GN in a patient who contracted COVID-19 infection.

Methods/Case Report

The patient was a 56-year-old woman who had a normal baseline serum creatinine (sCr) two years ago before she developed acute respiratory failure and acute kidney injury (sCr at 1.57 mg/dl) with significant proteinuria (urine protein/creatinine ratio [UPCR] at 1.02) and 2-3+ hematuria following a COVID-19 infection. The ANCA screening tests, including a recent one, were negative several times, but her protein-3 was low positive (14) and myeloperoxidase-3 was negative recently. Her current sCr increased to 2.93 mg/dl with UPCR at 3.1 and 2+ hematuria. A renal biopsy was performed, which showed one glomerulus for light microscopy and one glomerulus for immunofluorescent studies in the absence of proliferation, crescentic formation, or necrosis. Immunofluorescent stains were all negative in the glomerulus, but the methylene-blue stained sections for electron microscopy revealed three glomeruli with cellular crescents without necrosis. The ultrastructural examination did not show additional findings. The biopsy was consistent with proteinase-3 associated C-GN, pauci-immune type. She started cyclophosphamide treatment.

Results (if a Case Study enter NA)

N/A

Conclusion

COVID-19 can be associated with the pauci-immune type of C-GN. Under this condition, the ANCA screening test can be deceiving (false negative) in ruling out C-GN, so more specific tests such as myeloperoxidase and proteinase-3 should be ordered to enhance the chances of detecting renal vasculitis.
Red Blood Cell Aliquoting: Improving O Negative Red Blood Cell Utilization in Neonate and Pediatric Inpatients at UC Davis Medical Center
Authors: Sharma N , Thomas B , Olario A , Kicin A , Padda R , McGill M , Barnhard S
Published: November 2023

Introduction/Objective

UC Davis Medical Center (UCDMC) is the Sacramento region’s only level 1 adult and pediatric trauma center. It serves a 65,000 square mile area that includes 6 million residents from 33 counties across Northern and Central California. Nearly 7000 patients are transfused annually at UCDMC. Blood supply restrictions, especially on group O negative red blood cells (RBCs), escalated by the COVID-19 pandemic, posed significant patient safety risk. We sought to mitigate this risk by employing restrictive O negative RBC transfusions as recommended by AABB Choosing Wisely, through ABO matched small volume transfusions in neonate and pediatric patients.

Methods/Case Report

We conducted monthly audits starting in January 2021 to identify trends in O negative RBC use at UCDMC. We partnered with our blood supplier, American Red Cross (ARC), to modify hospital blood inventory. In 2022, we implemented the RBC aliquoting procedure using AS-3 RBCs to facilitate ABO matched small volume transfusions in neonates and children to conserve O negative blood supply. We reviewed regulatory standards, developed standard operating procedures, performed extensive technical validations, and worked with IT to enhance laboratory information system for product manufacturing, labeling, and traceability. We developed education documents for physicians, other providers, nurses, and transfusion services staff including sustainable competency and training. We conducted audits post implementation to measure goal performance in Q4 of FY22, compared to pre- implementation baseline data from Q1 of FY22.

Results (if a Case Study enter NA)

N/A

Conclusion

We achieved 57% reduction in O negative RBC utilization post implementation of the RBC aliquoting procedure in Q4 of FY22. Overall O negative RBC use trend at UCDMC improved with a 58% reduction between January 2021 to December 2022. Subsequent reduction of orders was achieved.We conclude that ABO matched RBC aliquot transfusion in neonates and pediatrics is an effective laboratory practice to reduce O negative RBC usage.
A rare cause of Acquired Hemolytic Anemia in a child; Donath-Landsteiner antibody
Authors: Abdelmonem M , Shan H , Cai W , Roque A , Chang S , Cabungan M , Papakonstantino K , Virk M S , Yunce M
Published: November 2023

Introduction/Objective

INTRODUCTION: The Donath-Landsteiner (DL) antibody is known to cause paroxysmal cold hemoglobinuria (PCH), a rare form of intravascular hemolytic anemia which is precipitated by an IgG biphasic hemolysin with specificity to the P blood group antigen and most commonly reported in children. The DL test is a serologic test specifically examines, the biphasic nature of the antibody activity.

Methods/Case Report

CASE PRESENTATION: A 4-year-old previously healthy boy presented at an academic medical center with rhinorrhea and nasal congestion. His family reported that his urine became darker almost coke colored after his symptoms started. His initial vitals; temperature of 37.1 C, heart rate of 140, blood pressure of 122/87 and O2 saturation of 96% on room air.

Laboratory investigations showed a hemoglobin level of 4.2 g/dL, hematocrit level of 12.5%, platelets count of 229 K/uL, indirect bilirubin of 6.2mg/dL, haptoglobin <30 mg/dL, LDH >1800 U/L. Direct antiglobulin test was positive with complement only. Thermal Amplitude and indirect Donath-Landsteiner tests were both positive. Respiratory viral panel was positive for Rhinovirus.

The antibody screen was negative, and the patient was provided supportive care including as needed RBC transfusion, warming of fluids and body. By day day 9 patient Hgb stabilized, LDH, bilirubin and haptoglobin normalized and his urine turned yellow color and was discharged in stable condition.

Results (if a Case Study enter NA)

NA

Conclusion

CONCLUSIONS PCH is classified as a cold autoimmune hemolytic anemia caused by an IgG antibody that sensitizes RBCs at cold temperatures by attaching complement to the RBCs, causing intravascular hemolysis upon rewarming. The DL test for PCH involves in vitro testing for hemolysis with the patient's serum, washed group-O cells expressing the P antigen, and fresh normal serum. To prevent autoadsorption of the antibody and hemolysis, blood should be collected in prewarmed tubes that do not contain anticoagulants and kept at 37°C during the collection procedure. A high index of suspicion especially in pediatric population should be maintained after a viral infection. The treatment is usually supportive.