bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticoagulant-Related Nephropathy in a Patient on Coumadin
Authors: Almukhtar R , Qu H , Alrammahi A
Published: November 2023

Introduction/Objective

Anticoagulant therapy is commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation. However, it carries the risk of bleeding and can lead to serious complications such as anticoagulant-related nephropathy (ARN), a recently described entity characterized by hematuria and acute kidney injury. This report presents a case of a 79-year-old male with a history a patient with a history of atrial fibrillation on coumadin, highlighting the importance of monitoring for anticoagulant-related complications and the need for prompt diagnosis and management to prevent further renal damage.

Methods/Case Report

The kidney biopsy showed evidence of underlying hypertensive and diabetic nephropathy, with nodular and global glomerulosclerosis, moderate to marked interstitial fibrosis, and tubular atrophy along with many red cell casts of variable ages in the tubules indicative of anticoagulant-related nephropathy. Additionally, one glomerulus had a partial cellular crescent associated with a focus of blood clot, likely related to heavy hematuria.

Patient is seronegative for ANCA. The immunofluorescence microscopy is non-contributory due to absence of glomerulus in the sample.

Electron microscopy showed diffuse foot process effacement and microvillous transformation of podocytes, increased mesangial matrix, and thickened glomerular basement membranes, but no immune complex deposits. these ultrastructural features confirm the background diabetic nephropathy.

Results (if a Case Study enter NA)

NA

Conclusion

Anticoagulant-related nephropathy (ARN) is a rare but serious complication of anticoagulation therapy that can result in hematuria and acute kidney injury. Our case highlights the importance of monitoring for anticoagulant-related complications, especially in high-risk patients with multiple comorbidities. Prompt diagnosis and management of ARN is essential to prevent further renal damage. In this case, despite initial improvement with vitamin K therapy, the patient developed severe renal dysfunction requiring dialysis and renal biopsy. This emphasizes the need for increased awareness and early recognition of ARN in patients on anticoagulant therapy.
Drug-induced thrombotic microangiopathy
Authors: Alrammahi A , Almukhtar R , Qu H
Published: November 2023

Introduction/Objective

Drug-induced thrombotic microangiopathy is observed in the patient on the new cancer therapy. It shares similar pathologic changes, as seen in conventional thrombotic microangiopathy, and is characterized by a pentad of hemolytic anemia, thrombocytopenia, renal dysfunction, fever, and neurological dysfunction. However, some patients may not have full scope of the pentad. Instead, only “diad” (hemolytic anemia and thrombopenia) exists, which could be mistakenly attributed to the drug side effect of bone marrow suppression.

Methods/Case Report

A 71-year-old white male with a history of multiple myeloma (MM) and cardiomyopathy presented with nausea and vomiting following the second round of carfilzomib and pomalidomide chemotherapy.

Laboratory tests showed anemia, thrombocytopenia, and peripheral blood abnormalities such as normocytic erythrocytes with occasional schistocytes, slight left shift in leukocytes, and decreased platelet count.

Results (if a Case Study enter NA)

The biopsy shows diffuse closure of glomerular capillaries, occasional microthrombi and fragmented red cells in glomerular capillaries. Under electron microscope, there are subendothelial space widening, mesangial interposition and wrinkling of glomerular basement membranes. These changes are consistent with acute or subacute thrombotic microangiopathy (TMA).

Conclusion

With the frequent use of advanced chemotherapy drugs, awareness of the drug-induced TMA should be emphasized. Early recognition is important to avoid development of more permanent kidney damage.
INTRAOPERATIVE FROZEN SECTION ANALYSIS OF ENDOMETRIOID OVARIAN BORDERLINE TUMOR: A DIFFICULT DIAGNOSIS
Authors: Jain D , Zaiem F , Ballouk C , Bandyopadhyay S
Published: November 2023

Introduction/Objective

Borderline ovarian tumors (BOT) comprise approximately 15% of all primary ovarian neoplasms; of these endometroid borderline ovarian tumors (EBOT) are much rarer (2-3%). BOT is often potentially misdiagnosed as a malignant tumor based on its challenging histomorphological features and thus, treated aggressively. Herein, we present an unusual case of EBOT with adenofibromatous pattern in a 50-year-old gravida 3, para 2 female diagnosed on intraoperative frozen sections (IOFS).

Methods/Case Report

Patient with history of endometriosis presented with left lower quadrant abdominal pain. MRI revealed complex bilateral ovarian masses with solid and cystic components measuring 5 cm and 6.7 cm in right and left ovary, respectively. An ovarian malignancy was suspected. Patient underwent exploratory laparotomy, total abdominal hysterectomy with bilateral salpingo-opherectomy, and omentectomy. Grossly, bilateral ovaries (BO) showed intact capsule with solid and cystic components. On IOFS, the solid areas demonstrated endometrioid glands arranged in a lobular fashion with squamous morules. The cystic component demonstrated papillary projections with squamous differentiation. Cytology is mildly atypical at best. Based on these findings, a diagnosis of EBOT was made, necessitating staging. Differential diagnoses include atypical endometriosis, endometrioid adenofibroma (EAF) and endometrioid adenocarcinoma (EA). Lack of endometrial stroma surrounding the glands ruled out endometriosis.

Presence of CC with papillary architecture ruled out EAF and lack of destructive stromal invasion with desmoplasia, confluence of glands and significant cytologic atypia ruled out EA. Final histopathological diagnosis of formalin-fixed paraffin-embedded specimen revealed EBOT, pT1bN0M0. Uterus and cervix revealed endometrial hyperplasia with atypia, adenomyosis, leiomyomas, and endocervical polyp.

Results (if a Case Study enter NA)

NA

Conclusion

The accurate diagnosis of BOT during IOFS is critical as it directs surgeons towards staging studies and in choosing conservative surgical treatment over aggressive treatment especially in cases of young women who desire future childbearing. As this is a rare entity, it serves the pathologist well to keep all relevant differential diagnoses in mind.
A rare case of poorly-differentiated endometrial carcinoma in a female-to-male transgender man on testosterone therapy
Authors: Riahi I R , Kang Y , Douglas C , Salani R , Salehiazar S
Published: November 2023

Introduction/Objective

Testosterone is commonly used as gender-affirming therapy for transmasculine individuals. The effects of testosterone therapy on endometrial tissue are complex, with some experiencing atrophy, and others with abnormal uterine bleeding (AUB). Endometrial carcinomas in transgender men are rarely reported in the literature. Here we present a case of poorly-differentiated endometrial carcinoma in a transgender man on testosterone.

Methods/Case Report

A 56 year-old female-to-male transgender man who had been on testosterone and finasteride therapy since 2015 developed vaginal discharge in 2022. No history of abnormal pap smears was noted. The patient’s pelvic ultrasound that was subsequently obtained after presenting with the vaginal discharge showed a thickened endometrium of 4 cm thickness. PET-CT revealed hypermetabolic activity corresponding to the endometrial lining of the uterus. Endometrial biopsy was notable for poorly differentiated carcinoma with retained expression of the mismatch repair proteins by immunohistochemical stains.

The patient underwent hysterectomy with bilateral salpingo-oophorectomy. Grossly, there was a 9.5 cm necrotic mass occupying the entire endometrial cavity, extending >50% into myometrium thickness and extending into the lower uterine segment, without cervical involvement. Background endometrium was inactive/atrophic. Microscopic examination of the tumor showed sheets of epithelioid tumor cells with extensive necrosis, without any glandular pattern. On immunohistochemical stains, the tumor cells were positive for pankeratin and patchy staining for keratin 7 and keratin 20, without expression of PAX8, estrogen receptor, progesterone receptor or androgen receptor.

Results (if a Case Study enter NA)

N/A

Conclusion

Gender-affirming testosterone is a common long-term treatment for transgender men. There is limited understanding of the long-term effects of testosterone therapy on endometrial pathology, particularly regarding the potential for developing malignancy. Positive staining for androgen receptor has been previously reported in endometrial malignancies, and therefore, studies on the potential effects of testosterone therapy on endometrial malignancies is warranted. This case demonstrates the importance of continued gynecologic care in female-to-male transgender individuals who have not undergone previous gender affirming gynecologic surgery.
A rare case of cervical gastric-type adenocarcinoma mimicking bilateral ovarian malignancy in a genetically confirmed Peutz-Jeghers syndrome without known polyposis
Authors: Feng Y , Angel J , Husson M
Published: November 2023

Introduction/Objective

Cervical gastric-type adenocarcinoma (GAS) is rare and accounts for 2-4% of cervical cancer. GAS is usually sporadic but can be associated with Peutz-Jeghers syndrome (PJS), a rare autosomal dominant disorder caused by germline STK11 mutations and characterized by hamartomatous polyposis in the gastrointestinal (GI) tract, mucocutaneous pigmentation, and cancer predisposition. Although cases of GAS may occur in patients with PJS associated with polyposis, our patient with GAS has an unusual and perhaps unique association with the PJS mutation that is unassociated with polyposis.

Methods/Case Report

A 33-year-old female presented with abdominal pain, abnormal uterine bleeding, vaginal discharge, weight loss, and fatigue for one year. Pigmentations were noted on lips, gum, tongue, and hands. She had a family history of maternal ovarian and pancreatic cancers. Computerized tomography revealed large bilateral multiloculated complex cystic adnexal masses, thickened endometrium extending into the endocervix, and ascites.

Tumor markers showed increased CA19-9 and CA125, suggesting either a primary ovarian malignancy or possible metastatic GI tract cancer to both ovaries. Her PAP smear demonstrated atypical glandular cells that favored endocervical origin. HPV was not detected. A cervical biopsy showed bland gastric-type glands without obvious stromal invasion. Given the clinical concern for malignancy, a cervical cone biopsy was performed, demonstrating unequivocal invasion by gastric-appearing glands. The tumor cells were positive for CK7, CEA, and PAX8, and were negative for CK20, CDX2, and p16. The pathologic diagnosis confirmed a primary GAS with a spread to bilateral ovaries. Although the upper GI tract and left colon were free of polyps or masses by endoscopic exam, the genetic evaluation revealed a germline heterozygous STK11 mutation consistent with PJS.

Results (if a Case Study enter NA)

NA

Conclusion

To our knowledge, this is the first case of occult PJS (confirmed by genetic analysis) presenting with widely advanced metastatic GAS without known polyposis.
Endometrial stromal tumor presenting as multiple endometrial polyps with limited infiltration; a novel presentation
Authors: Saikia K , Ziying Z , Wang Z B , Azordegan N , Scialla A
Published: November 2023

Introduction/Objective

The 2020 WHO classifies endometrial stromal tumors into endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma, and undifferentiated sarcoma. Minimal irregularity of the interface is allowed in ESN (up to 3 foci of <3 mm). In a small number of cases, the irregular interface exceeds the acceptable criteria for ESN but relatively limited compared to most LGESS. These cases are classified as endometrial stromal tumor with limited infiltration. These tumors may recur, and it is best managed as LGESS.

Methods/Case Report

We report a case of endometrial stromal tumor in a 42-year-old female who presented with abnormal vaginal bleeding. Imaging showed multiple fibroids. She underwent total abdominal hysterectomy and bilateral salpingectomy. On gross examination three endometrial polyps with sharp demarcation from the adjacent myometrium were identified (largest 4 cm). Histology revealed proliferation of uniform small cells with scant cytoplasm and round to oval nuclei with rare mitotic figures in a delicate network of arterioles. Immunostains showed positive staining for CD10 and estrogen receptor while negative for Caldesmon. These polyps were mainly confined to the endometrium with only small foci of irregular border with the myometrium. No vascular invasion, high grade cytologic atypia or necrosis were seen. The tumor showed JAZF1-SUZ12 gene fusion. This case was diagnosed as an endometrial stromal tumor with limited infiltration.

Results (if a Case Study enter NA)

NA

Conclusion

In conclusion, endometrial stromal tumors are commonly submucosal or intramural, we report a rare case that presented as multiple endometrial polyps, with very limited myometrium infiltration. To our knowledge, no cases have been reported so far. It is essential to be cognizant of this entity when dealing with polypoid lesions of the endometrium, they may recur and should be managed as LGESS.
Malignant Melanoma of the jaw and oral mucosa - A rare diagnosis to consider when assessing high-grade tumors on small biopsies
Authors: Tushir A , Belogrivtseva Y , Mazur I , Nobee A , Kuklani R , Proca D
Published: November 2023

Introduction/Objective

Malignant melanoma arises from neural crest-derived cells called melanocytes. These melanocytes migrate to several sites, including the skin and the mucous membranes. Oral melanoma (OM) cases account for <1% of all melanoma cases and <2% of all oral malignancies. Primary malignant melanoma of the jaw is an even rarer entity. Most OM cases arise in the palate and the maxillary alveolar gingivae. Other sites, such as mandibular gingiva and buccal mucosa, are rarely involved. The etiopathogenesis remains unclear, with stimulation of melanoblasts being one of the proposed hypotheses. The incidence is highest in the fifth and sixth decades of life and occurs more commonly in males than females. Clinically, it remains an asymptomatic pigmented growth until it reaches advanced stages. Diagnosis in advanced stages leads to OM having an overall survival (OS) rate of just 15.4% at 10 years with an abysmal prognosis. These neoplasms are highly invasive and metastasize quickly. Of mutations, KIT (14.6%), BRAF (7%) and NRAS (5.6%) were the most frequently encountered in OM cases.

Methods/Case Report

We searched for “oral melanoma” in our healthcare system for the last 10 years- from 2013 to 2022. 4 cases were selected for this case series, and pertinent information was pulled from CoPath and Epic software. The cases were then analyzed, and the results were reported.

Results (if a Case Study enter NA)

In our case series, we found the mean age to be 78.5 years, with 75% (3 of 4) of the patients being male and the rest 25% (1 of 4) female. Three cases were diagnosed with melanoma or malignant melanoma, while the 4th case had atypical melanocytic proliferation favoring malignant melanoma as the diagnosis. Regarding the tumour site, 1 case arose in the right anterior maxilla, 2 cases involved the mandible (left mandible and right anterior mandibular vestibule, respectively), and 1 case was present in the buccal mucosa. Microscopic findings and immunohistochemistry results concurred with the diagnoses.

Conclusion

Herein, we present 3 cases (out of the 4) from rarer sites, such as the mandible and oral mucosa, as opposed to the typical sites- the palate and the maxilla. Discussing rarer cases helps physicians to keep these in the differential while examining similar tumors. Additionally, having rarer cases adds to the literature and focuses attention on entities that require more study and research. Since these neoplasms are highly invasive and metastasize quickly, they necessitate an early diagnosis for effective management.
Pathologists Shortage in United States of America (USA) - How Academic Centers and Private Laboratories Can Play an Effective Role in Recruiting Qualified Future Pathology Residents from Pool of United States (US) and International Medical Graduates (IMGs)
Authors: Prajapati P R , Wells A , Tyler A , Brice J , Perkins C , Ehsan A
Published: November 2023

Introduction/Objective

Pathology training (PT) in the US requires 4 years of AP/CP training. Only 2% of any medical school class (US or IMGs) enter Pathology. However, among practicing pathologists, an estimated 20 to 30% are IMGs that are working in academia/private settings. Even with artificial intelligence (AI) and digital pathology (DP), the need for pathologists will continue to rise, especially those who will acquire AI and DP skills.

Methods/Case Report

Our facility is a private reference laboratory. About 60 to 70% of graduates after residency join private practices. We initiated an education model to offer internship opportunities mainly for IMGs who have difficulty in gaining access to US academic centers due to numerous obstacles. Our initiative also offered electives for US medical students (US-MS) exploring pathology as a career. Between 2016 and 2022, 72 IMGs (12 countries) and 18 MS (5 states) rotated with us in a structured rotation lasting 4 weeks.

Results (if a Case Study enter NA)

Most of our IMGs were not able to find access to academic centers for internship. From the pool of IMGs who rotated with us, 51/72 (70%) matched into PT. In addition, we were able to positively influence 16/18 (88%) US-MS to adopt pathology as a career.

Conclusion

1) We successfully created an educational model in a non-academic setting to mentor and prepare access to academic centers through PT as aspiring pathologists, 2) IMGs in our program excel in their respective countries; they were interviewed before being accepted into our program and committed to pathology with higher chance of matching, 3) US-MS that rotated through our program have higher rate of adopting pathology as a career when compared to traditional academic pathology rotations, and 4) more academic centers should consider allowing internships to IMGs and initiate private collaborations as an integral part of supporting the future of our profession.
Understanding cytomorphologic changes in Pap tests of transgender men on testosterone therapy
Authors: Chiang N , Shumer D
Published: November 2023

Introduction/Objective

Pap test findings in transgender men on testosterone therapy can often lead to misdiagnosis of dysplasia, especially in the setting of a positive HPV test. We reviewed relevant literature to analyze the cytomorphological nuances and applicable correlations to subsequent pathology in Pap tests of transgender men on testosterone therapy.

Methods/Case Report

We searched peer-reviewed journals on PubMed, synthesizing five articles published from 2018-2022 that specifically address cytomorphological findings on cervical Pap tests and biopsy results in transgender men on testosterone therapy.

Results (if a Case Study enter NA)

Various cytological changes, such as small parabasal-type cells and transitional cell metaplasia (TCM) can be mistaken for dysplasia in transgender men. In fact, these changes are representative of atrophy due to testosterone, as such findings have been observed in patients undergoing tamoxifen therapy. Small parabasal-type cells are described as clusters or sheets with intermittent nuclear enlargement and hyperchromatic nuclei, whereas TCM comprises flat sheets of cells with oval to spindle-shaped nuclei, powdery chromatin, and prominent nuclear grooves. Relevant clinical history can often help clarify cytologic diagnoses, as Pap tests that show atrophic changes can be misinterpreted as being abnormal. In several cases described in the literature, original diagnoses of atypical squamous cells of undetermined significance (ASCUS) were re-interpreted as atrophic changes after eliciting a history relevant for testosterone therapy. Small parabasal-type cells found on cytology have correlated with sections of the ectocervix that have groups of small hyperchromatic cells attached to the surface of atrophic cervical epithelium or areas of TCM. These cells may be mistaken for endometrial cells, especially in patients over 45 years old. Distinguishing atrophic changes from dysplasia on surgical pathology may modify cytologic diagnoses.

Conclusion

Transgender men on testosterone therapy often retain their cervix, necessitating ongoing cervical cancer screening. However, Pap test results from these individuals often exhibit atrophic changes through the presence of small parabasal-type cells and TCM. Differentiating between atrophy and dysplasia can pose a diagnostic challenge, especially in the setting of positive HPV testing or inflammation. Continued analyses into these cytomorphological nuances will assist providers in refining their diagnostic approaches and providing personalized care to transgender men.
Perception and Awareness Among Students on Bridging the Employment Gap in Clinical laboratory Sciences: A Single Center Experience
Authors: Isabella D , Carbonaro C A , Huq Ronny F M , Faisal M
Published: November 2023

Introduction/Objective

The clinical laboratories within hospitals across the United States are facing a critical and growing shortage of qualified laboratory personnel. Moreover, there has been a steady and alarming erosion in the number of students entering and graduating from medical laboratory training programs. The introduction of robotics in the clinical laboratory during the 1990’s sent the message that Medical /Clinical Technologist would have a reduced role and could, therefore be hired in fewer numbers. Programs closed and in time, resulted in personnel shortages.

With decreased awareness of the profession and increasing number of laboratory professionals retiring, it is essential to attract and retain young talents. We explored various methods used to attract students into the Clinical Laboratory Science profession.

Methods/Case Report

This qualitative study was part of our New York Medical College Master’s in Clinical Laboratory Sciences (CLS) Program recruiting sessions conducted for the undergraduate students. Our goal was to recruit biology students with no career plan after graduation. The graduate school conducted virtual and on campus information sessions for the CLS program. A total of six sessions were conducted between 2021 and 2022. Trying to increase awareness, program brochures were sent to all local colleges that offered Bachelor of Science degrees.

Tours of a hospital clinical laboratories were also offered to students.

Results (if a Case Study enter NA)

College biology and CLS students find the clinical laboratory sciences to be an interesting and exciting career prospect once they are introduced to this profession. Each session produced less than a 5% email interest among attendees. At least one applicant was received from each session. In further study, students who had entered the program in the last three years were surveyed. The majority discovered this career choice by meeting a CLS at work or through a friend or family member. A few developed an interest by seeing COVID information and a Google search for the medical laboratory science profession.

Conclusion

Increasing the visibility of the program by educating students about CLS and the high demand for laboratory professionals with its concomitant high salary is essential for recruitment. After review of these results the individual technologist has been determined to be the best recruiter, having one who speaks proudly of a career, sharing the difference made in the daily diagnosis and treatment of patients is the best recruiting method.
RET Fusion Detection Using IdyllaTM Gene Fusion Assay
Authors: Nutcharoen A , Hoo-Fatt N , Nam M
Published: November 2023

Introduction/Objective

Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancers and RET fusions are detected in 1-2% of NSCLCs, 70% medullary thyroid cancers, 20% papillary thyroid cancers, and <1% of solid tumors. Next-generation sequencing (NGS) is frequently used, taking 2-3 weeks, and requires many tissue samples (10-20 formalin-fixed paraffin-embedded, FFPE, tissue sections). The Biocartis Idylla Gene Fusion Assay (IGFA), a rapid real-time walk-away RNA-RTPCR-based system, was used to detect RET, ALK, ROS1, NTRK 1/2/3 rearrangements, and MET exon 14 skipping mutations in a single assay. We hypothesized that the Idylla Gene Fusion Assay would improve patient care by detecting fusion gene(s) with 2 slides in 3 hours.

Methods/Case Report

This retrospective study compares NGS and IGFA using FFPE tissue from The Inova Health System (10 patients total). Two unstained 4-micron-thick sections were obtained per tissue block using aseptic techniques. RET fusion results from NGS and IGFA were compared, as well as turnaround time (TAT) and tissue requirements.

Results (if a Case Study enter NA)

Patient 3 had negative RET fusion by IGFA, but positive results using NGS. Patients 4, 5, and 6 had a positive correlation between IGFA and NGS. Patients 9, 10 and 11 had negative RET results by both IGFA and NGS, however Patient 10 IGFA results detected a positive NTRK3 mutation. Patient 7 was positive for RET mutation by IGFA, but passed away while awaiting NGS results. IGFA generated results in three hours while NGS had an average TAT of 14.82 days. Patients 1, 7, and 8 had insufficient remaining tissue for IGFA. IGFA Cq values were used for quality control.

Conclusion

RET fusions can be detected using the IGFA for timely treatment with limited tissue. This assay is an easy-to-use, walk-away, stand-alone diagnostic tool that can detect gene fusions on the same day, on demand while waiting for NGS results.
Racial Disparity and Blood Group Antigens; COVID-19 High Mortality Rate in Black and Duffy Antigen
Authors: Abdelmonem M , Abdelmonem M , Wasim H
Published: November 2023

Introduction/Objective

As of March 5th, 2022, the novel coronavirus disease 2019 (COVID-19) has been confirmed in 464,809,377 people worldwide, with an approximately 1.31% mortality rate. COVID-19 infection is associated with an aggressive inflammatory response and release of a large amount of pro-inflammatory cytokines known as “cytokine storm.” Cytokine storm is the release of interferons, interleukins, tumor necrosis factors, chemokines, and several other mediators. Chemokines are small protein molecules that act as chemoattractants, leading to the migration of immune cells to an infection site so they can target and destroy invading bodies such as microbes. The Duffy antigen is a broad receptor of chemokines in human blood. Early on, it was found that the overwhelming majority of people of African descent had the erythrocyte phenotype Fy(a-b-) (henceforth Duffy (-)): 68% in African Americans and 88-100% in African people (including more than 90% of West African people).

Methods/Case Report

Subjects under study: This retrospective cohort study analyzed the data from total patients with confirmed COVID-19 infection in the US through March 5th, 2022.The US population 13.4% black, non-Hispanic, 76.3% white, non-Hispanic, Asian 5.9%, 18.5% Hispanic or Latino, and 4.3 all other races. The primary outcomes were hospitalization and in-hospital death.

Results (if a Case Study enter NA)

Results: A total of 79,555,007 patients in the US were tested Covid-19 positive and 968,839 mortalities with a death rate of 1.21%. 661,678 deaths were excluded because they did not have racial details. Among the 968,839 patients who died of Covid-19, 411,078 (62.1%) were white, 89,784 (13.6%) were black, 114,455 (17.3%) were Hispanic or Latino, 5,970(4.2%) were Asian and 7,045(4.8%) all other races. The actual death rate per 100,000 is 313 in white, 330 in black, 254 in Hispanic or Latino, 156 in Asian, and 276 in all other races.

Conclusion

Despite black Americans representing only 13.4% of the total population, they have been heavily hit by the COVID-19 pandemic. The reasons for the especially severe forms of the disease in Black Americans have not been fully uncovered. People with the Duffy (-) phenotype are a high-risk group for the Chemokine Storm. One hypothesis that arguably gives the blood group marker and chemokine decoy receptor Duffy protein plays a central role in stimulating the Chemokine Storm as present in the severe forms of the COVID-19 disease.
Impact of Implementing Point of Care Hemoglobin A1C Testing in an Obstetrics Outpatient Clinic
Authors: Weli Homayemem , Farnsworth Christopher
Published: November 2023

Hemoglobin A1C ≥ 6.0% is associated with increased risk of adverse outcomes in pregnant, diabetic patients and is recommended as a secondary measure of glycemic control in pregnant patients by the American Diabetes Association. However, the utility of A1C point of care testing (POCT) during pregnancy to facilitate rapid counseling and diabetes care, particularly in relatively low-income transient patient populations is unknown. We performed a single center, retrospective analysis of patients presenting to an out-patient obstetrics office with routine, In-lab A1C (n= 70) testing and after the implementation of POCT for A1C (n=75). Demographics, results, physician referral to a nutritionist, counseling, and outcomes were retrieved from the electronic medical record. 9% and 23% of the In-lab group and POCT respectively were referred for nutrition services (p=0.02). 22% of the In-lab group and 42% of the POCT groups received immediate counseling (p<0.01). An inverse correlation was observed between entry A1C and the weeks at delivery with a Pearson r of -0.39 (-0.58-0.16) for the In-lab group and -0.38 (-0.57--0.14) for the POCT group. In conclusion, the implementation of POC A1C testing was associated with immediate counseling and management of pregnant patients.
Evaluation of Siltuximab and Tocilizumab Analytical Interference on Interleukin 6 Measurements
Authors: Wang Qian , Kian Susan Ashrafzadeh , Deters Rebecca , Irvine Clayton , Algeciras-Schimnich Alicia , Bornhorst Joshua
Published: November 2023

Background

Interleukin 6 (IL-6) plays important roles in both innate and adaptive immunity, while dysregulated persistent production of IL-6 is involved in pathological development of various diseases associated with inflammation. Targeting the IL-6 pathway has led to many innovative treatment approaches. Siltuximab and Tocilizumab are monoclonal antibodies targeting IL-6 and IL-6 receptors respectively and have been FDA-approved for treatment of Castleman disease (Siltuximab), a rare lymphoproliferative disorder characterized by hyperproduction of IL-6 with an unknown prevalence, autoimmune diseases such as rheumatoid arthritis (Tocilizumab), and both shown potential as treatment for cytokine release syndrome in hospitalized COVID-19 patients. However, the presence of siltuximab can interfere with IL-6 assays, leading to the use of C-reactive protein (CRP) as a surrogate marker to monitor its efficacy.

Aim

To evaluate potential Siltuximab and Tocilizumab antibody interference on IL-6 measurements in three different IL-6 protein immunoassays. Method: Serum or EDTA plasma sample pools with different IL-6 concentrations ranging from low (2.3 – 11.1 pg/mL, around the reference interval cut-off for each assay) to high (18.5 – 1142 pg/mL), above reference interval cut-off for each assay) were utilized. Various concentrations of Siltuximab or Tocilizumab were spiked into the sample pools (at 10% of total volume) to achieve final concentrations up to 600 µg/mL and up to 300 µg/mL, respectively. Sample spiked with 10% saline were used as no-drug control. Three assays were used to measure IL-6 concentration: Beckman Access IL-6 assay on UniCel DxI 800 (Beckman Coulter), V-PLEX Plus human IL-6 assay on QuickPlex SQ120 (Meso Scale Diagnostics), and a Luminex cytokine panel assay developed in house (R&D systems) with upper reference interval limits of 6.4,1.8 and 5 pg/mL respectively.

Results

Siltuximab interfered with the measurement of IL-6 for all three assays. A significant interference (> 20% reduction) was observed at even a very low siltuximab concentrations in all three assays (0.05 µg/mL). In the presence of 5 µg/mL or greater Siltuximab, a maximum reduction of 93%, 83%, and 40% was observed for Beckman Access, R&D Luminex assay, and V-PLEX Plus Mesoscale assay, respectively. Tocilizumab did not interfere with the measurement of IL-6 in the three assays when serum was spiked with up to 300 µg/mL of the drug.

Conclusion

Siltuximab falsely reduce the measured IL-6 concentration on all three immunoassays tested in this study to differing degrees, whereas Tocilizumab does not. Consider the therapeutic range of Siltuximab (84 to 332 µg/mL) for treatment of Castleman disease, and a half-life of 20.6 days, measurement of IL-6 may not be useful in Siltuximab treated patients for an extended time-period.
Alternative strategies to provide actionable results when supply of urinalysis strips is unavailable
Authors: Guarner Jeannette , Smith Geoffrey , Alter David , Cole Lisa , Williams Cecellitha , Campbell Davette , Elsea Suzanne , Reynolds Stacian , Lawrence Christine
Published: November 2023

Urinalysis “dip strips” offer physicians qualitative results of 6 analytes which are immediately actionable: protein, glucose, leukocyte esterase, nitrates, blood, and ketones; however, the strips are instrument specific such that they are at the mercy of supply chain shortages. Due to vendor supply issues, we implemented a strategy that would continue to support clinical decision making in the absence of supplies for protein, glucose, white blood cells (WBC) and blood (RBC) detection. Method: In supply shortage situations, an automated algorithm triggered such that urine samples would be sent to the automation chemistry line to run quantification of protein and glucose and make sure an automated urine microscopy was performed for RBC and WBC detection. The algorithm triggered printing two labels so nursing would collect two specimens. We monitored the turn-around time from the specimen being received in the laboratory to results, made sure that the culture reflex order was triggered, and tracked complaints by physicians regarding not having all usual urinalysis results provided by the strips. Prior to implementation, correlation between sample types for protein and glucose measurement was found acceptable.

RESULTS: When we put in place the algorithm, the turn-around time of urine microscopic study was identical to that obtained when the urinalysis was done with the strips; however, the quantification of glucose and protein took approximately 30 minutes more. Urine reflex cultures were triggered correctly with the algorithm as they derive entirely from a WBC count >20. During the period we had the algorithm in place we only had one complaint by a physician wanting to have results of nitrates.

Conclusion: The successful implementation of the algorithm allowed the laboratory to provide actionable urinalysis analytes in a timely manner with minimal complaints from physicians.
An organization-wide analysis of laboratory test cost variables and costs as displayed in the electronic health record: first steps
Authors: Fang Karen , Hoffman Noah , Krumm Niklas , Mathias Patrick
Published: November 2023

Displaying the cost of laboratory tests and medications in the electronic health record (EHR) at the time of order may influence ordering practices. Our organization’s EHR was configured to display a semi-quantitative value adjacent to laboratory orders: “$” tests imply relatively little cost and “$$$$” tests imply resource intensive tests. Cost display is associated with charges from hospital or clinic fee schedules by default but can also be configured to reflect direct laboratory costs. To understand our system’s configuration and potentially improve the information being provided to our clinicians upon ordering, all the test ordering data was compiled and analyzed for all individual “orderable” tests within the year of 2021 (Jan 1st 2021 – Dec 31st 2021). Variables analyzed included frequency of test ordering, average test turnaround time, and each of the various possible measures of “cost”: direct costs based on labor and reagents/supplies (when available), reimbursement from the Clinical Laboratory Fee Schedule, and pricing from the fee schedule of the largest hospital in our organization (chargemaster). Results showed an extensive rightward skew in each of the “cost” variables, with most routine tests, like the complete blood count (CBC) or complete metabolic panel (CMP), falling in the lower price range and a number of outlier tests with much higher costs (newer forms of molecular testing). There was minimal linearity in correlations between the various price variables. Correlation between chargemaster price by quintile and actual dollar signs displayed in the EHR showed that the two often disagree. No definitive discernable logic was thus identified for the number of dollar signs shown in the EHR based on the possible “cost” variables analyzed here. Between the lab’s best estimate for direct costs and chargemaster pricing, a rough correlation with slope greater than 1 was identified, suggesting that chargemaster pricing is systematically higher than the cost of running each test. Between the cost of running each test and reimbursement via the Clinical Laboratory Fee Schedule, a rough correlation with slope less than 1 was identified, suggesting that lab costs are systematically higher than reimbursement. The current lack of strong correlations between these various “cost” variables is helpful as a first step in examining how to improve our organization’s EHR system, assessing our laboratory’s cost effectiveness, and discussing potential future considerations for hospital chargemaster pricing as well as the US system of reimbursement. Further work is needed to clarify the relationship between cost displays in EHR and physician ordering practices.
Treatment of Chin Retrusion With Botulinum Toxin Plus Hyaluronic Acid Filler in Comparison With Hyaluronic Acid Filler Alone: A Randomized, Evaluator-Blinded, Controlled Study
Authors: Guo Yanping , Wang Ji , Wei Wuhan , Zhang Aijun , Li Qiang , Tao Changbo , Shen Caiqi , Wei Hanxiao , Jin Peisheng
Published: November 2023

Background

Hyaluronic acid (HA) has already been widely administered for chin augmentation. Patients with chin retrusion frequently present with increased chin hypertonia. Monotherapy with HA falls short in addressing the multifaceted cosmetic concerns associated with chin retrusion.

Objectives

This study aimed to investigate the clinical efficacy and safety of the combination therapy involving botulinum toxin (BTX) and HA in the treatment of chin retrusion.

Methods

We enrolled patients with moderate to severe chin retrusion for 9 months of follow-up after they received either combined treatment with BTX plus HA or monotreatment with HA. We also calculated the surface-volume coefficient with 3-dimensional digital scanning technique, and evaluated outcomes based on the Allergan Chin Retrusion Scale (ACRS), the Global Aesthetic Improvement Scale (GAIS), and treatment-related adverse events (TRAEs).

Results

A total of 50 patients were recruited and randomized to the treatment group (BTX plus HA) or control group (HA alone) in a 1:1 ratio. Patients in the treatment group exhibited significantly higher surface-volume coefficients during the first 6 months (P < .05). ACRS scores and responder rates in the 2 groups remained similar throughout the follow-up (P > .05). Within the initial 3 months, the GAIS responder rate in the treatment group was significantly higher than that in the control group (P < .05). Mild TRAEs were observed in both groups, and subsided within 7 days. There was no increase in adverse effects with the combined treatment.

Conclusions

In comparison to monotherapy, the combined treatment not only improved the surface-volume coefficient of hyaluronic acid but also achieved similar ACRS scores with less HA volume. Furthermore, the combination treatment yielded superior treatment outcomes for individuals with chin retrusion.

Level of Evidence: 2
Cryolipolysis of the Arms and Inner Thighs Shows Similar Treatment Outcomes in Chinese Individuals Compared to White Individuals Treated in a Prior Study: The XinCOOL Study
Authors: Rivers Jason K , McGillivray William , Braun Martin , Bhogal Meetu , Zheng Suzanne , Hickling Matthew
Published: November 2023

Background

Studies of predominantly White participants show that cryolipolysis reduces subcutaneous fat in the arms and inner thighs, but none have specifically tested for similar outcomes in participants of Chinese descent.

Objectives

This study assessed the safety and effectiveness of cryolipolysis treatment for noninvasive subcutaneous fat reduction of arms and inner thighs in participants of Chinese descent to assess equivalence to results seen in a prior study of White participants.

Methods

Replicating a similar study design, participants of first- or second-generation Chinese descent underwent cryolipolysis treatment of arms and/or inner thighs. Effectiveness was assessed using pretreatment and posttreatment photographic review by blinded, independent experts, investigator-assessed caliper measurements, and participant satisfaction 12 weeks posttreatment. Safety was assessed throughout.

Results

Among 50 enrolled participants, 48 completed the study. The majority of participants (97.9%) were female, with a mean age of 36.0 years and mean BMI of 24.16 kg/m2 (range 19.3-29.9 kg/m2). Overall, 76.4% and 70.0% of pretreatment photographs of arms and pairs of inner thighs, respectively, were correctly identified by at least 2 of 3 reviewers. The mean reduction from baseline in caliper-measured fat thickness was 6.5 mm for arms and 6.6 mm for inner thighs, and the majority of participants (>60%) were satisfied with the treatment. No adverse events were reported.

Conclusions

Cryolipolysis is a well-tolerated, effective means of noninvasive fat reduction of arms and inner thighs in participants of Chinese descent. The results from this study show similar effectiveness and safety in Chinese participants compared with White participants treated in a prior study.

Level of Evidence: 2
Pretarsal Augmentation of the Lower Eyelids Using Fat Grafts in Asian Patients
Authors: Mizuno Tsutomu , Yamamoto Atsushi
Published: November 2023

Background

Surgical procedures are required to achieve long-term pretarsal roll fullness of the lower eyelids with a satisfactory appearance.

Objectives

To assess the efficacy of a surgical method using fat grafts for pretarsal augmentation of the lower eyelids.

Methods

We conducted a retrospective clinical study that included 12 Japanese patients (24 lower eyelids) who underwent pretarsal augmentation of the lower eyelids using fat grafts and were followed up for more than 6 months. Morphometric measurements of the projection, width, and area of the pretarsal roll fullness of the lower eyelids were performed. Additionally, surgical outcomes and complications were assessed.

Results

Pretarsal roll fullness of the lower eyelids was achieved for more than 6 months postoperatively. The surgery resulted in enlarged eyes with sufficient pretarsal roll fullness, and all patients were satisfied with the aesthetic outcomes. The mean projection (1.6 ± 1.0 vs 0.5 ± 0.6 mm), width (7.4 ± 1.5 vs 4.4 ± 3.6 mm), and area (143.5 ± 42.2 vs 32.8 ± 39.6 mm2) of the pretarsal roll fullness of the lower eyelids were significantly greater postoperatively than preoperatively (P < .05). No early postoperative complications were observed during the 6- to 12-month follow-up period. However, overcorrections were observed in 2 cases (16.7%) due to late-onset fat overgrowth, which was corrected by revision surgery.

Conclusions

Fat grafting can help achieve sufficient pretarsal roll fullness of the lower eyelids. The technique presented herein is a simple and reliable alternative surgical procedure for creating pretarsal roll fullness of the lower eyelids.

Level of Evidence: 4
An in-depth comparison of linear and non-linear joint embedding methods for bulk and single-cell multi-omics
Authors: Makrodimitris Stavros , Pronk Bram , Abdelaal Tamim , Reinders Marcel
Published: November 2023

Multi-omic analyses are necessary to understand the complex biological processes taking place at the tissue and cell level, but also to make reliable predictions about, for example, disease outcome. Several linear methods exist that create a joint embedding using paired information per sample, but recently there has been a rise in the popularity of neural architectures that embed paired -omics into the same non-linear manifold. This work describes a head-to-head comparison of linear and non-linear joint embedding methods using both bulk and single-cell multi-modal datasets. We found that non-linear methods have a clear advantage with respect to linear ones for missing modality imputation. Performance comparisons in the downstream tasks of survival analysis for bulk tumor data and cell type classification for single-cell data lead to the following insights: First, concatenating the principal components of each modality is a competitive baseline and hard to beat if all modalities are available at test time. However, if we only have one modality available at test time, training a predictive model on the joint space of that modality can lead to performance improvements with respect to just using the unimodal principal components. Second, -omic profiles imputed by neural joint embedding methods are realistic enough to be used by a classifier trained on real data with limited performance drops. Taken together, our comparisons give hints to which joint embedding to use for which downstream task. Overall, product-of-experts performed well in most tasks and was reasonably fast, while early integration (concatenation) of modalities did quite poorly.
Characterization on the oncogenic effect of the missense mutations of p53 via machine learning
Authors: Pan Qisheng , Portelli Stephanie , Nguyen Thanh Binh , Ascher David B
Published: November 2023

Dysfunctions caused by missense mutations in the tumour suppressor p53 have been extensively shown to be a leading driver of many cancers. Unfortunately, it is time-consuming and labour-intensive to experimentally elucidate the effects of all possible missense variants. Recent works presented a comprehensive dataset and machine learning model to predict the functional outcome of mutations in p53. Despite the well-established dataset and precise predictions, this tool was trained on a complicated model with limited predictions on p53 mutations. In this work, we first used computational biophysical tools to investigate the functional consequences of missense mutations in p53, informing a bias of deleterious mutations with destabilizing effects. Combining these insights with experimental assays, we present two interpretable machine learning models leveraging both experimental assays and in silico biophysical measurements to accurately predict the functional consequences on p53 and validate their robustness on clinical data. Our final model based on nine features obtained comparable predictive performance with the state-of-the-art p53 specific method and outperformed other generalized, widely used predictors. Interpreting our models revealed that information on residue p53 activity, polar atom distances and changes in p53 stability were instrumental in the decisions, consistent with a bias of the properties of deleterious mutations. Our predictions have been computed for all possible missense mutations in p53, offering clinical diagnostic utility, which is crucial for patient monitoring and the development of personalized cancer treatment.