bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenal Hemangioma Presenting as an Incidentaloma Clinically Suspicious for Malignancy
Authors: Toklu A , Mesa H , Collins K
Published: November 2022

Introduction/Objective

Adrenal hemangiomas are rare, benign and non-functioning tumors. Clinical diagnosis can be challenging given that the presentation is usually vague and lesions are often found incidentally during diagnostic imaging performed for other reasons.

Methods/Case Report

We report a case of a 67-year-old man with history of hypertension, hyperlipidemia, and anemia, arthralgia and joint swelling with unexplained weight loss, which prompted imaging studies. Computed tomography (CT) scan revealed a 5.4 cm mass involving the left adrenal gland. The patient had no clinical manifestations of adrenal medullary or cortical hyperfunction. Biochemical testing performed included urine and plasma metanephrines and aldosterone/renin ratio, which yielded results within normal range. The patient was taking prednisone for hand and ankle swelling, precluding assessment for Cushing’s syndrome. Given the size of the lesion, the possibility of malignancy was considered. The patient elected for a left adrenalectomy. Gross examination revealed a 4.9 cm mass, weighing 54 grams, with a tan-brown, congested cut surface and a thin rim of residual normal appearing adrenal gland parenchyma. Histologic examination of the surgical specimen showed an enlarged adrenal gland predominantly replaced by hemorrhage with foci of thick and thin walled vessels with areas of intermingled adrenocortical elements at the periphery. A diagnosis of adrenal hemangioma was made.

Results (if a Case Study enter NA)

NA.

Conclusion

Adrenal hemangioma should be considered in the differential diagnosis of adrenal tumors. Surgical resection is the mainstay of treatment for a large, isolated adrenal mass to exclude malignancy and prevent retroperitoneal hemorrhage.
A New Insight Into Ectopic Sebaceous Glands in the Vagina: A Result of Surgery?
Authors: Patel R , Sallagonda A , Florence R , West L
Published: November 2022

Introduction/Objective

Ectopic sebaceous glands with or without hair follicles are well documented in a variety of sites including the vulva, cervix, esophagus, and male genitalia. Ectopic sebaceous glands in the vagina, however, are extremely rare, with only 2 case reports and a third case described in a journal correspondence letter in the English literature.

Methods/Case Report

We present a 39-year-old patient with Laurence-Moon-Biedl syndrome with pseudotumor cerebri, retinitis pigmentosa/macular degeneration, chronic kidney disease status post renal transplant, obesity, diabetes insipidus, and a urethrovaginal fistula and hypoplastic vagina status post repair and vaginoplasty at age 3 months. High grade squamous intraepithelial lesion on a cervicovaginal Pap test prompted colposcopy, during which a confluent plaque non-staining with Lugol’s solution was noted on the right vaginal sidewall extending from the introitus to 4 cm distal to the cervix. Biopsy of this area revealed hyper- and parakeratosis along with sebaceous glands and hair follicles in the subepithelial stroma. Two theories are proposed in the literature regarding the origin of vaginal ectopic sebaceous glands/cutaneous adnexal structures. The first is a developmental anomaly with aberrant differentiation in-utero, as the lower two thirds of the vagina is normally endodermal in origin and the upper one third is derived from mesoderm, while cutaneous adnexal structures are ectodermal in origin. The second postulates sebaceous glands in the vagina arise from a metaplastic process after prolonged irritation or inflammation. We add a third possibility in this patient, that vaginal plastic surgery performed at 3 months of age involved tissue re- arrangement or grafting which introduced ectodermal structures to the vagina. The patient’s vaginal surgical records were not available for review.

Results (if a Case Study enter NA)

NA.

Conclusion

We add a fourth case of ectopic cutaneous adnexal structures in the vagina in a patient with Laurence-Moon-Biedl syndrome to the literature. The origin of these structures may have resulted from vaginal surgery as an infant rather than from a developmental anomaly or metaplasia.
Eosinophils Are a Useful Morphologic Marker to Scrutinize Plasma Cells in Endometrial Polyps
Authors: Afolayan-Oloye O , Anderson J , Zhang P
Published: November 2022

Introduction/Objective

Chronic endometritis is characterized by presence of plasma cells, which can be confirmed by immune-staining for CD138. Endometrial polyps can irritate endometrium and harbor some plasma cells. As eosinophils are much easier to be identified than plasma cells on hematoxylin and eosin stained sections, the goal of this study was to investigate if the identification of eosinophils in endometrial polyps was useful to alert us for looking for plasma cells more carefully.

Methods/Case Report

Twenty-eight (28) endometrial polyp cases were retrospectively selected and eosinophils and plasma cells were searched microscopically. Cases with eosinophils and/or plasma cells found per high power filed were further stained for CD138.

Results (if a Case Study enter NA)

There were 8 cases with positive eosinophils (eosinophil group) and 18 cases without eosinophils (negative group). Age from eosinophil group ranged from 32 to 54 years old and the negative group has ages ranged from 32 to 72 years old. In eosinophil group, six of eight (6/8) cases in eosinophil group was correlated with positive CD138 positive plasma cells (ranging from 2 to 24 per high power field), whereas 2/8 cases had 1 eosinophil without confirmed CD138+ plasma cells. Negative group without eosinophils had no plasma cells identified.

Conclusion

Our data indicate that eosinophils can be an easy target for the next step to scrutinize plasma cells in endometrial polyps, thus promoting an accurate evaluation of chronic endometritis.
A Rare Case of Non-Gestational Ovarian Mixed Intermediate Trophoblastic Tumor Associated with a Mature Cystic Teratoma
Authors: Awuku J A , Elshaikh A
Published: November 2022

Introduction/Objective

Ovarian non-gestational trophoblastic tumors are rare with only a few documented cases. We report a case of a 22-year-old non-sexually active woman who presented to the emergency department with ongoing left lower quadrant abdominal pain. Workup showed elevated Beta-human chorionic gonadotropin levels (152 mIU/mL) and a left ovarian mass. This was initially thought to be an ectopic pregnancy, however patient was non- sexually active. Patient underwent a left oophorectomy and the specimen was sent to pathology.

Methods/Case Report

Microscopic examination of the ovary revealed a mature cystic teratoma with intimately associated foci of loosely cohesive pleomorphic atypical cells. The atypical cells also replaced some of the blood vessel walls and infiltrated the residual ovarian parenchyma. Mitoses were present at (2/10hpf). No necrosis or chorionic villi were identified. Immunohistochemical stains were performed, and the atypical cells were positive for GATA3, inhibin, and human placental lactogen. These cells also showed an elevated ki67 proliferative index (15%). All these findings supported a diagnosis of a placental site trophoblastic tumor. Focally, well-defined cystic structures composed of large epithelioid cells were also noted. These epithelioid cells were positive for GATA3, inhibin, and p63. These cells were negative for human placental lactogen and showed an elevated ki67 proliferative index (12%), findings consistent with an epithelioid trophoblastic tumor component.

Ovarian intermediate trophoblastic tumors are rare and could be of gestational or non-gestational origin. To confirm a non-gestational origin, DNA genotyping was performed. Results showed identical genetic profiles in the teratoma, the intermediate trophoblastic tumor, and in the patient’s benign ovarian tissue. This finding confirmed the diagnosis of a non-gestational mixed intermediate trophoblastic tumor associated with a mature cystic teratoma. This tumor is exceedingly rare with only a few reported cases in literature.

Results (if a Case Study enter NA)

NA

Conclusion

The diagnosis of a non-gestational mixed intermediate trophoblastic tumor is exceedingly rare with only a few reported cases in literature. The combination of immunohistochemistry and dna genotyping confirmed our suspicion and yielded the correct diagnosis.
The Role of Web-Based Platforms as a Novel Approach to Tackling Diversity, Equity, and Inclusion in Pathology Education - The PathElective.com Experience
Authors: Lilley C M , Quintanilla-Arteaga A , Mirza K M , Ware A D , White M J
Published: November 2022

Introduction/Objective

Since its creation, PathElective.com has reached approximately 60,000 individuals. This web-based clinical experience has demonstrated itself to be a powerful and accessible educational tool for medical students and residents across the world. However, there is currently limited data on the inclusion and equity impact of pathology education resources. Here, we assess responses from website users to better understand our audience and how this resource impacts equity.

Methods/Case Report

We composed and administered a brief, anonymous survey to assess website user educational, ethnic, gender expression, age, and socioeconomic backgrounds. The one-time user limit survey was composed of multiple-choice, choose-all-that-apply, and short answer questions. The survey was distributed via email to users and was also available via website pop-up and banner.

Results (if a Case Study enter NA)

650 users responded to the survey. 78.9% of respondents used PathElective for <1 year with a plurality (28.2%) of respondents being users for <6 months. 94% of respondents disclosed an ethnicity, and in toto, 29 of the 37 ethnicities provided were represented. 62.9% of respondents identified as female, 35.4% as male, and 0.3% as genderqueer. When asked about sexual orientation, 83.1% responded as straight, 3.5% as bisexual, 3.1% as gay/lesbian, and 1.8% in another category. Importantly, 73.8% of respondents either agreed or strongly agreed that PathElective filled a previously unmet need and 74.4% either agreed or strongly agreed that PathElective was more accessible than other education adjuncts.

Conclusion

Data of a limited cross-section of PathElective.com users demonstrate the website provides accessible educational materials to a diverse group of pathology learners. Our users were more geographically, educationally, and sociodemographically diverse compared to the 2021 Pathology ERAS applicant pool. Moreover, the broader impact was demonstrated by learners responding that the materials filled a previously unmet need.
Intravascular large B-cell lymphoma (IVLBCL): Subtle Presentation and Challenging Diagnosis
Authors: Sham S , Hosseini H , LIN H , Morrar D , Al-Refai R , Guerrero D , Yurovitsky A , BENDARI A
Published: November 2022

Introduction/Objective

Intravascular large B-cell lymphoma (IVLBCL) is a rare, clinically aggressive lymphoma defined by the proliferation of atypical lymphoma cells in the lumen of all sized blood vessels, particularly capillaries. The reasons for this unusual neoplastic cell proliferation are still only partially understood. IVLBCL is considered stage IV lymphoma and manifests with a variety of nonspecific signs and symptoms. Patients with IVLBCL usually do not present with lymphadenopathy. The tumor cells invade the blood vessels of multiple organs such as the central nervous system, skin, lungs, kidneys, and bone marrow. Common presenting symptoms are based on the organ affected and include mental status changes and fever of unknown origin. Although immunochemotherapy has significantly improved the often-poor prognosis of this kind of lymphoma, a large percentage of patients relapse.

Methods/Case Report

We present a 63-year-old man who had been diagnosed with diffuse large B cell lymphoma in the bone marrow in March 2021 and was in remission state after completing six cycles of chemotherapy. There was no abnormal FDG uptake on a post-chemotherapy PET/CT scan. Patient presented to the ER two months later with fever and dyspnea. The entire workup was completed and showed pancytopenia and elevated ESR. While chest CT scan did not show lymphadenopathy or lesions, PET/CT scans revealed a widespread increase in FDG uptake in both the lungs and spleen. Lung biopsy revealed large atypical cells within alveolar septae and vessels.

Immunohistochemical stains demonstrated that these cells were positive for CD20 and PAX-5 and had high proliferation rate based on Ki67.

Results (if a Case Study enter NA)

NA

Conclusion

IVLBCL has a low incidence rate with non-specific clinical presentation. The diagnosis can be easily missed in both clinical, radiological and the corresponding histopathological findings . Radiological finding and CT scan are not sensitive enough and may miss the lesion. Even though the PET/CT scan is more sensitive, the definitive diagnosis of IVLBCL relies mainly on histopathology and immunohistochemistry, at which point awareness of this entity by the Pathologist is most necessary.
BTEX (benzene, toluene, ethylbenzene, and xylene) and risk of cancer - a study from Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey
Authors: Malik P , Hashim T , Varma S , Diaz L , Chowdhary A , Bapat P , Alkhatib L , Centeno L , Poursina O , Pan H , Patil A
Published: November 2022

Introduction/Objective

BTEX (benzene, toluene, ethylbenzene, and xylene) is well know for its toxicity via through environmental, occupational and recreational exposures. However, there is limited literature about the carcinogenic effect of BTEX. Hence, we aim to study the prevalence and association of cancer amongst individuals with exposure of BTEX.

Methods/Case Report

A retrospective cross-sectional study was performed between 2013 and 2018 utilizing the NHANES database. Adult individuals having data on socio-demographic questionnaires and lab findings on exposure to BTEX were included. Prevalence of cancer was identified amongst exposure to BTEX (vs no-BTEX). Univariate (chi-squre test and Mann–Whitney U test) and Multivariate (survey logistic regression) analysis was performed to evaluate the epidemiologic characteristics of individuals exposred to BTEX and association of cancer with BTEX exposure in comparison to no BTEX exposure.The p value of <0.05 considered statistically significant.

Results (if a Case Study enter NA)

124,162 participants were identified with BTEX exposure. Individuals with BTEX exposure were young (40 vs 51 year old), male (91% vs female: 87%), and Mexican American (92% vs Non-Hispanic Black: 89% vs Non-Hispanic White: 89% vs other Hispanic: 87%). Univariate analysis showed higher total prevalence of cancer in BTEX (9.3% vs. 1.3%; p<0.0001) compared to no BTEX. Individuals with BTEX exposure had higher prevalnece of blood cancer (0.47% vs 0.00; p<0.0001), leukemia (0.56% vs 0.00; p<0.001), and lymphoma (1.72% vs 0.39%; p<0.0001) in comparison with no exposure. Multivaritate analysis showed participants with BTEX exposure had 10% higher risk of cancer (aOR: 1.10; 95%CI: 1.10-1.10; p<0.0001) compared to no BTEX exposure. Additionally, exposure to individual components of benzene (aOR: 1.24; 95%CI: 1.24; p<0.0001), ethylbenzene (aOR: 1.08; 95%CI: 1.08-1.08; p<0.0001), and o-xylene (aOR: 1.19; 95%CI: 1.19-1.19; p<0.0001) had higher risk of cancer compared to no exposure participants.

Conclusion

Our study conclude higher risk of cancer among participants with exposure to benzene, ethylbenzene and o-xylene. Future studies are warranted to evaluate the association of various types of cancers in BTEX exposure.
Brown Recluse Spider Bite: A Case Report of Severe Hemolysis and Sepsis
Authors: Chinchanikar S , Khalaf Z , Mateescu V
Published: November 2022

Introduction/Objective

The brown recluse spider, Loxosceles reclusa, is commonly found in the southern and central United States and is known for its venomous bite. It has six eyes, uniformly colored abdomen and legs, is around 1 cm in length and prefers to live in warm, dark and dry places. Its bite in humans can cause skin necrosis as well as more severe manifestations including acute hemolytic anemia, disseminated intravascular coagulation (DIC), rhabdomyolysis and renal failure.

Methods/Case Report

We present a case report of a 27 year old male with no known past medical history who was referred from another medical center with a critical hemoglobin of 3.6 g/dl and acute hemolytic anemia that was not responsive to packed red blood cell transfusion and intravenous immunoglobulin treatment. He reported of having bitten by a brown recluse spider 8 days ago on the right scapular region. He started developing wound and pain in the area 2 days later when he was admitted to the hospital for a day and treated with antibiotics. His white blood cell count (WBC) at the time was mildly elevated with near normal hemoglobin and was incidentally found to have COVID 19 positivity. After being discharged, he developed fever with chills, dark urine, body ache, headache, nausea and vomiting. When presented to our hospital, laboratory review exhibited normocytic normochromic anemia with elevated bilirubin and decreased haptoglobin showing a hemolytic picture. The patient also displayed severe leukocytosis (WBC count: 53.50) with absolute neutrophilia, lymphocytosis, and monocytosis. Monocyte distribution width (MDW) was 30.02. These changes were attributed to be reactive to venom effect and sepsis. The patient showed significant improvement with plasmapheresis.

Results (if a Case Study enter NA)

NA.

Conclusion

The diagnosis of systemic loxoscelism is often difficult and delayed. Brown recluse spider bites may not always present with sharp stings to be noticed and reported by the patient. Presence of another infectious condition, like COVID 19 in this case, may divert the diagnosis. An elaborate patient history, physical examination for bite wound and patient education may help in identifying the cause early. Spider bites should be considered as a differential diagnosis in a patient with dermonecrosis and abrupt onset hemolysis or sepsis. Prompt treatment can prevent development of DIC, renal failure and life threatening conditions.
Assessment of Collagen III as a Non-Invasive Biomarker in HCV Induced Liver Fibrotic Patients
Authors: Abdelmonem M , Wasim H , Elhusseny A , Eldaly R , Abdelmageed M , Saleh Abdelfattah M
Published: November 2022

Introduction/Objective

Liver biopsy is still the gold typical for assessing hepatic fibrosis. Non-invasive serum parameters measurement leads to essential changes in diagnosis. This procedure is painful, carries a risk of bleeding and infection, and is accompanied by a high sampling error rate. New biomarkers that can accurately predict the stage of fibrosis are urgently needed.

Objectives

This study aimed to identify, characterize, and detect serum collagen III in patients with HCV-induced liver fibrosis and healthy subjects.

Methods/Case Report

The study subjects were divided into two groups; group1: included 118 patients with HCV-induced liver fibrosis (60 males and 58 females). Group2: included 50 healthy comparable control subjects (27 males and 23 females). Collagen III was identified in serum samples of group1 at 70 kDa using collagen III polyclonal antibody and western blot analysis techniques. Additionally, it was purified from serum samples using the electroelution technique from preparative slab gels. The purified antigen gives a single sharp band at 70 kDa when resolved by SDS–PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and stained with coomassie blue. The 70 kDa purified collagen III showed high reactivity towards the collagen III polyclonal antibody. We used the ELISA method to quantify the collagen III, dose-response curve for purified collagen III as a function of the concentration in serum samples of liver fibrosis patients was done.

Results (if a Case Study enter NA)

The collagen III was identified in 62% of patients, and 38 % were negative collagen III (false negative) in group one. For group two, 96% of total healthy volunteers were negative for collagen III, and 4% were positive for collagen III (false positive). The mean ± SD of serum collagen III concentration was (8.38±3.56) and (3.2±0.59) for groups 1 and 2, respectively, with (P<0.0001).

Conclusion

The non-invasive assessment of liver fibrosis by collagen III has shown promising diagnostic and prognostic potential.
COVID Cholangiopathy Can Occur Despite Mild COVID
Authors: Onuiri J , Fiel M I
Published: November 2022

Introduction/Objective

Post-COVID-19 cholangiopathy is a novel entity first noted in patients recovering from critical COVID-19 infection. Since its initial description in May 2021, all cases reported to date have been in patients with a history of critical COVID-19, defined as requiring ICU admission, the development of respiratory or circulatory failure requiring intubation or ECMO, or vasopressor support. Here we report three cases of post-COVID-19 cholangiopathy arising in patients who recovered from non-severe COVID-19.

Methods/Case Report

Six cases of COVID-19-related cholangiopathy were identified by retrospective review, three of which involved patients who verifiably did not develop critical COVID-19. Histology slides for each case were reviewed and all showed features of secondary sclerosing cholangitis. Patient 1 is a 41yo female who developed COVID-19 after liver transplant (LT). Despite administration of monoclonal antibodies, she required re-transplantation 6 weeks later. Explant histology showed bile infarcts, severe hepatocytic and canalicular cholestasis, ductular reaction, organizing portal vein thrombi, and necrotic bile ducts accompanied by bile lakes. Patient 2 is a 47yo male with alcoholic cirrhosis who was diagnosed with COVID-19 at the time of LT workup, and underwent LT 90 days later. In addition to alcohol-related cirrhosis, explant histology showed dilated bile ducts with periductal fibrosis, as well as severe ductular reaction with proliferating ductules containing thick, inspissated bile. Patient 3 is a 54yo male with history of LT for PSC who developed mild COVID-19 five years after LT. Allograft function subsequently worsened and biopsy 6 months later showed bile duct damage and loss of ~35% of bile ducts; repeat biopsy 14 months after his COVID diagnosis showed periportal fibrosis with edema, ductular reaction, marked hepatocellular and canalicular cholestasis, and ductopenia with loss of 60% bile ducts. Average time between COVID-19 diagnosis and onset of COVID-related cholangiopathy was 3 months (range: 6 weeks-6 months). These patients were also all immunocompromised with two due to prior LT and one being cirrhotic.

Results (if a Case Study enter NA)

NA.

Conclusion

Although previously reported only in patients with severe COVID-19, the cases described represent the first evidence that cholangiopathy, manifested by sclerosing cholangitis, can arise even in patients who were not critically ill, although this may require an immunocompromised state to develop.
Limited Diagnostic Utility of Alpha Defensin in the Diagnosis of Periprosthetic Joint Infection
Authors: Vasconez M M , Wolk D , Tice A , Martinez R M
Published: November 2022

Introduction/Objective

A key component of laboratory stewardship is appropriate test utilization. We evaluated the utility of alpha defensin (AD), a synovial fluid biomarker, in the diagnosis of periprosthetic joint infection (PJI). Since PJI remains a diagnostic challenge in the orthopedic community, the Musculoskeletal Infection Society (MSIS) created the PJI score, a point-based criteria to help risk stratify the likelihood of infection. The score includes AD, synovial fluid white blood cell count, synovial fluid percent neutrophils, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). AD is a specialized test which adds substantial cost to the evaluation of PJI .The purpose of this study was to investigate the diagnostic utility of the PJI score with AD and without AD (routine laboratory testing of serum and synovial fluid).

Methods/Case Report

Retrospective chart review was completed on 222 patients with suspected PJI identified at Geisinger Health between January 2019 – March 2021. Data was retrieved through Geisinger’s Phenomic and Analytics Data Core and imported into Excel and JMP v.12 for analysis. All available components of MSIS diagnostic criteria were collected for each patient.

Results (if a Case Study enter NA)

Of the 222 patients with AD testing, 81% of results were negative (n=178) and 19% results were positive (n=44). AD results corresponded with synovial fluid white blood cell count in 96 % of patients (213/ 222). All components of the PJI diagnostic criteria were collected in 69% of the patients (157/222). Diagnostic criteria calculated without AD showed 43% infected (68/157), 37% possibly infected (58/157), and 20% infected (31/157). Diagnostic criteria calculated with AD showed 43% infected (68/157), 35% possible infected (55/157), and 22% infected (34/157). PJI score including AD compared to PJI score excluding AD showed similar correlation (R2 = 0.93).

Conclusion

It was found that AD testing does not provide substantial diagnostic value in the evaluation of PJI. Synovial fluid cell count was found to directly correlate with alpha defensin suggesting it’s potential use as a surrogate marker for clinical decision making. Diagnostic criteria obtained through routine testing of serum (ESR, CRP) and synovial fluid (WBC, percent neutrophils) provides sufficient data for diagnosis.
Endometrial Cancer and Molecular Methods: A Case Study of MSI Heterogeneity based on Metastatic Location with IdyllaTM
Authors: Degner A , Nam M , Hoo-Fatt N
Published: November 2022

Introduction/Objective

MMR deficiency (dMMR) and Microsatellite Instability (MSI) are hallmarks of not only Lynch Syndrome and Colorectal Cancer (CRC), but Endometrial cancer. Endometrial cancer is the most common female gynecological cancer, yet molecular tests for MSI often focus solely on CRC validation. MSI in Endometrial cancer correlates with higher staging and more aggressive pathology, resulting in a need for reliable testing methods. Immunohistochemistry (IHC) staining is the current standard for MSI detection, due to the known association between dMMR and MSI-H. Direct detection of MSI requires molecular methods, however, there is a lack of standardization of protocol between labs. Idylla™ (Biocartis, Jersey City, NJ), an automated cartridge-based PCR assay, could help eliminate this ambiguity.

Methods/Case Report

To determine whether the Idylla™ MSI assay can be reliably used to detect MSI in Endometrial cancers, both primary and metastatic sites for two known MSI-H patients were examined using the Idylla ™ MSI assay and an IHC MMR panel (MLH1, MSH2, MSH6, PMS2).

Results (if a Case Study enter NA)

The results showed MSI-H for both patients uterine primary sites on the Idylla™. Examination of the Idylla™ results for metastatic sites found they contradicted the IHC panel results for some sites. Idylla™ produced expected results for the omentum and intestinal metastases in patient IN-20-1. The Idylla™ results for the ovarian and abdominal metastatic lesions in patient IN-15/17-2 directly contradicted the MMR findings and the MSI-H result provided for the uterine primary site.

Conclusion

This discrepancy between primary and metastatic site results is likely due to MSI heterogeneity in these metastatic lesions than test errors. At this time, it is not recommended to use the Idylla™ MSI test for Endometrial cancers, particularly those with abdominal or ovarian metastasis. Further testing will be needed to verify if intestinal metastatic sites are consistently MSI-H. IHC should remain the prime mode of detection for possible dMMR MSI-H Endometrial tumors until an assay catered specifically towards Endometrial cancers is made.
Contribution of the Hashtag #PathTweetAward to Pathology Education: From the Perspective of a Medical Student
Authors: Demirci M , Emiroğlu F , Oltulu P , Mukhopadyay S
Published: November 2022

Introduction/Objective

Pathology education reaches a wide audience through social media platforms. Sharing the findings and educational material of studies in the field of pathology with a large audience through social media will accelerate the scientific and educational progress. By utilizing social media, pathologists can increase their impact on educating other physicians along with medical students. In this study, we aimed to evaluate the contribution of the hashtag #PathTweetAward to the pathology education of medical students, pathologists, pathology residents, and physicians in other branches. We tried to measure the awareness of #PathTweetAward among people who use social media for educational purposes.

Methods/Case Report

Our population is Full-time Medical Students(63/67) and Physicians(4/67) from various medical faculties in Turkey. We applied the survey via Online Google Forms Questionnaire(47 participants) and Face- to-face Questionnaire(20 participants). We collected demographical and qualitative data for the cross-sectional study, and statistical analyses were performed by comparing/contrasting.

Results (if a Case Study enter NA)

With survey results, it is clear that using PathTwitter is a great educational tool and discussion platform. Nevertheless, it is being used for educational purposes by only 22,39% of respondents, PathTwitter had heard by only 20,90% of respondents, and the numerical value of how useful the posts shared with PathTwitter is 5,86 (1-10). Also, it should not be forgotten that the percentage of usage of Twitter by respondents is 67,69%, meaning that they are aware of and can use the platform. Most people who have used social media for educational purposes have not heard of #PathTweetAward. However, 89,55% (60/67) of respondents find #PathTweetAward helpful (with an average of 5,85/10). 50,94% (27/53) said they would use #PathTweetAward for educational purposes after hearing it for the first time(response 79,10% (53/67), average 3,48/5).

Conclusion

This study aimed to determine whether social media users were familiar with #PathTweetAward and whether they found it to be a helpful educational resource. We hypothesized that people who have used social media for educational purposes have heard of #PathTweetAward. Given these points, pathology is a field that uses Twitter best and most in education, communication, and collaboration. Although the proportion of respondents familiar with #PathTweetAward was low, the majority of those familiar with this initiative found it to be a helpful educational resource.
Monitoring Direct Thrombin Inhibitors With Calibrated Diluted Thrombin Time vs Activated Partial Thromboplastin Time in Pediatric Patients
Authors: Hasan Rida A , Pak Jennifer , Kirk Christa Jefferis , Friedland-Little Joshua M , Chandler Wayne L
Published: November 2022

Objectives

Activated partial thromboplastin time (aPTT) is the primary test used to monitor intravenous (IV) direct thrombin inhibitors (DTIs) but has many limitations. The plasma diluted thrombin time (dTT) has shown better correlation with DTI levels than aPTT. This study compared dose-response curves for dTT and aPTT in pediatric patients receiving argatroban and bivalirudin.

Methods

A retrospective review of pediatric patients treated with argatroban (n = 45) or bivalirudin (n = 14) monitored with dTT and aPTT.

Results

The dTT assay was calibrated to report DTI concentrations in µg/mL for argatroban and bivalirudin with good analytic sensitivity and specificity. The dTT was fivefold more likely to show a stable dose-response slope than the aPTT (P < .0002; odds ratio, 4.9). For patients in whom both dTT and aPTT showed a significant correlation between dose and assay results, dTT had a higher average correlation factor compared with aPTT (P = .007). Argatroban dose-response slopes showed more inter- and intrapatient variation than bivalirudin (dose-response slope coefficient of variation, 132% vs 52%).

Conclusions

The dTT assay was more likely to show a stable dose response and have a stronger correlation with DTI dose than aPTT. Argatroban shows more variation in dose response than bivalirudin.
Measurement of Prevalent Versus Incident Dementia Cases in Epidemiologic Studies
Authors: Nichols Emma , Ng Derek K , James Bryan D , Deal Jennifer A , Gross Alden L
Published: November 2022

Because dementia is progressive, incident cases are on average milder than prevalent cases, affecting the performance of cognitive tests and questions on functional limitations (i.e., cognition/functional limitation items) used for dementia assessment. Longitudinal studies assess incident cases, while cross-sectional studies assess prevalent cases, but differences are not typically considered when researchers select items to include in studies. We used longitudinal data from the Religious Orders Study and Memory and Aging Project (ROSMAP) (n = 3,446) collected between 1994 and 2021 to characterize differences in associations between items (cognition: 35 items; functional limitations: 14 items) and incident or prevalent dementia using multinomial regression models with generalized estimating equations, controlling for ROSMAP cohort (Religious Orders Study or Memory and Aging Project), age, sex, race, and education. The association between a given item and incident dementia was significantly weaker than the association between the same item and prevalent dementia for 46 of 49 items. However, there was variability, with larger differences for some items, including naming a pencil (prevalence odds ratio = 0.02 (95% confidence interval: 0.02, 0.03); incidence odds ratio = 0.10 (95% confidence interval: 0.06, 0.17); P for difference < 0.001). Important differences exist in the performance of cognition/functional limitation items for measurement of incident versus prevalent dementia. Differences can inform the choice of items for cross-sectional studies of prevalent cases or longitudinal studies of incident cases, leading to reduced misclassification and increased statistical power.
e-TSN: an interactive visual exploration platform for target–disease knowledge mapping from literature
Authors: Feng Ziyan , Shen Zihao , Li Honglin , Li Shiliang
Published: November 2022

Target discovery and identification processes are driven by the increasing amount of biomedical data. The vast numbers of unstructured texts of biomedical publications provide a rich source of knowledge for drug target discovery research and demand the development of specific algorithms or tools to facilitate finding disease genes and proteins. Text mining is a method that can automatically mine helpful information related to drug target discovery from massive biomedical literature. However, there is a substantial lag between biomedical publications and the subsequent abstraction of information extracted by text mining to databases. The knowledge graph is introduced to integrate heterogeneous biomedical data. Here, we describe e-TSN (Target significance and novelty explorer, http://www.lilab-ecust.cn/etsn/), a knowledge visualization web server integrating the largest database of associations between targets and diseases from the full scientific literature by constructing significance and novelty scoring methods based on bibliometric statistics. The platform aims to visualize target–disease knowledge graphs to assist in prioritizing candidate disease-related proteins. Approved drugs and associated bioactivities for each interested target are also provided to facilitate the visualization of drug–target relationships. In summary, e-TSN is a fast and customizable visualization resource for investigating and analyzing the intricate target–disease networks, which could help researchers understand the mechanisms underlying complex disease phenotypes and improve the drug discovery and development efficiency, especially for the unexpected outbreak of infectious disease pandemics like COVID-19.
Defining near-complete response following (chemo)radiotherapy for rectal cancer: systematic review
Authors: Custers Petra A , Geubels Barbara M , Beets Geerard L , Lambregts Doenja M J , van Leerdam Monique E , van Triest Baukelien , Maas Monique
Published: November 2022

Background

A uniform definition of a clinical near-complete response (near-CR) after neoadjuvant (chemo)radiotherapy for rectal cancer is lacking. A clear definition is necessary for uniformity in clinical practice and trial enrolment for organ-preserving treatments. This review aimed to provide an overview of the terminology, criteria, and features used in the literature to define a near-CR.

Methods

A systematic review was performed based on the PRISMA statement. PubMed and Embase were searched up to May 2021 to identify the terminology, criteria, and features used to define a near-CR after (chemo)radiotherapy for rectal cancer. Studies with no clear cut-off point between a cCR and near-CR, studies using Response Evaluation Criteria In Solid Tumours, and studies including only complete responders were excluded.

Results

A total of 1876 articles were found, of which 23 were included. Patients were managed by watchful waiting and/or additional local treatment in 11 and 17 of 23 studies respectively. Response evaluation included digital rectal examination (DRE) and/or endoscopy with MRI in 18 studies. The majority of studies used the term ‘near-complete response’. In most studies, minor irregularities or a smooth induration with DRE and a small flat ulcer on endoscopy were considered to indicate a near-CR. On MRI, five studies used features (obvious downstaging with or without heterogeneous/irregular fibrosis on T2-weighted MRI or small spot of high signal on diffusion-weighted imaging), five studies used TNM criteria (ycT2), and four used magnetic resonance tumour regression grade (mrTRG) (mrTRG1–2/mrTRG2) to describe a near-CR.

Conclusion

The terminology, criteria, and features used to describe a near-CR vary substantially, which can partly be explained by the different treatment strategies patients are selected for (watchful waiting or additional local treatment). A reproducible definition of near-CR is required.
Genome-wide contribution of common short-tandem repeats to Parkinson’s disease genetic risk
Authors: Bustos Bernabe I , Billingsley Kimberley , Blauwendraat Cornelis , Gibbs J Raphael , Gan-Or Ziv , Krainc Dimitri , Singleton Andrew B , Lubbe Steven J ,   International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: November 2022

Parkinson’s disease is a complex neurodegenerative disorder with a strong genetic component, for which most known disease-associated variants are single nucleotide polymorphisms (SNPs) and small insertions and deletions (indels). DNA repetitive elements account for >50% of the human genome; however, little is known of their contribution to Parkinson’s disease aetiology. While select short tandem repeats (STRs) within candidate genes have been studied in Parkinson’s disease, their genome-wide contribution remains unknown. Here we present the first genome-wide association study of STRs in Parkinson’s disease. Through a meta-analysis of 16 imputed genome-wide association study cohorts from the International Parkinson’s Disease Genomic Consortium (IPDGC), totalling 39 087 individuals (16 642 cases and 22 445 controls of European ancestry), we identified 34 genome-wide significant STR loci (P < 5.34 × 10−6), with the strongest signal located in KANSL1 [chr17:44 205 351:[T]11, P = 3 × 10−39, odds ratio = 1.31 (95% confidence interval = 1.26–1.36)]. Conditional-joint analyses suggested that four significant STRs mapping nearby NDUFAF2, TRIML2, MIRNA-129–1 and NCOR1 were independent from known risk SNPs. Including STRs in heritability estimates increased the variance explained by SNPs alone. Gene expression analysis of STRs (eSTRs) in RNA sequencing data from 13 brain regions identified significant associations of STRs influencing the expression of multiple genes, including known Parkinson’s disease genes. Further functional annotation of candidate STRs revealed that significant eSTRs within NUDFAF2 and ZSWIM7 overlap with regulatory features and are associated with change in the expression levels of nearby genes. Here, we show that STRs at known and novel candidate loci contribute to Parkinson’s disease risk and have functional effects in disease-relevant tissues and pathways, supporting previously reported disease-associated genes and giving further evidence for their functional prioritization. These data represent a valuable resource for researchers currently dissecting Parkinson’s disease risk loci.
Transthyretin attenuates TDP-43 proteinopathy by autophagy activation via ATF4 in FTLD-TDP
Authors: Chu Yuan-Ping , Jin Lee-Way , Wang Liang-Chao , Ho Pei-Chuan , Wei Wei-Yen , Tsai Kuen-Jer
Published: November 2022

TAR DNA-binding protein-43 (TDP-43) proteinopathies are accompanied by the pathological hallmark of cytoplasmic inclusions in the neurodegenerative diseases, including frontal temporal lobar degeneration-TDP and amyotrophic lateral sclerosis. We found that transthyretin accumulates with TDP-43 cytoplasmic inclusions in frontal temporal lobar degeneration-TDP human patients and transgenic mice, in which transthyretin exhibits dramatic expression decline in elderly mice. The upregulation of transthyretin expression was demonstrated to facilitate the clearance of cytoplasmic TDP-43 inclusions through autophagy, in which transthyretin induces autophagy upregulation via ATF4. Of interest, transthyretin upregulated ATF4 expression and promoted ATF4 nuclear import, presenting physical interaction. Neuronal expression of transthyretin in frontal temporal lobar degeneration-TDP mice restored autophagy function and facilitated early soluble TDP-43 aggregates for autophagosome targeting, ameliorating neuropathology and behavioural deficits. Thus, transthyretin conducted two-way regulations by either inducing autophagy activation or escorting TDP-43 aggregates targeted autophagosomes, suggesting that transthyretin is a potential modulator therapy for neurological disorders caused by TDP-43 proteinopathy.
Maternal Antibody Response and Transplacental Transfer Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection or Vaccination in Pregnancy
Authors: Otero Sebastian , Miller Emily S , Sunderraj Ashwin , Shanes Elisheva D , Sakowicz Allie , Goldstein Jeffery A , Mithal Leena B
Published: November 2022

Background

Pregnant persons are at increased risk of severe coronavirus disease 2019 (COVID-19) and adverse obstetric outcomes. Understanding maternal antibody response, duration, and transplacental transfer after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccination is important to inform public health recommendations.

Methods

This prospective observational cohort study included 351 pregnant people who had SARS-CoV-2 infection or COVID-19 vaccination during pregnancy. Immunoglobulin (Ig) G and IgM to SARS-CoV-2 S1 receptor binding domain were measured in maternal and cord blood. Antibody levels and transplacental transfer ratios were compared across (1) disease severity for those with SARS-CoV-2 infection and (2) infection versus vaccination.

Results

There were 252 individuals with SARS-CoV-2 infection and 99 who received COVID-19 vaccination during pregnancy. Birthing people with more severe SARS-CoV-2 infection had higher maternal and cord blood IgG levels (P = .0001, P = .0001). Median IgG transfer ratio was 0.87–1.2. Maternal and cord blood IgG were higher after vaccination than infection (P = .001, P = .001). Transfer ratio was higher after 90 days in the vaccinated group (P < .001). Modeling showed higher amplitude and half-life of maternal IgG following vaccination (P < .0001). There were no significant differences by fetal sex.

Conclusions

COVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG levels, higher cord blood IgG, and higher transfer ratio after 90 days compared with SARS-CoV-2 infection. Greater infection severity leads to higher maternal and cord blood antibodies. Maternal IgG decreases over time following both vaccination and infection, reinforcing the importance of vaccination, even after infection, and vaccine boosters for pregnant patients.
Omicron Subvariants: Clinical, Laboratory, and Cell Culture Characterization
Authors: Morris C Paul , Eldesouki Raghda E , Sachithanandham Jaiprasath , Fall Amary , Norton Julie M , Abdullah Omar , Gallagher Nicholas , Li Maggie , Pekosz Andrew , Klein Eili Y , Mostafa Heba H
Published: November 2022

Background

The variant of concern Omicron has become the sole circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant for the past several months. Omicron subvariants BA.1, BA.2, BA.3, BA.4, and BA.5 evolved over the time, with BA.1 causing the largest wave of infections globally in December 2021–January 2022. This study compared the clinical outcomes in patients infected with different Omicron subvariants and the relative viral loads and recovery of infectious virus from upper respiratory specimens.

Methods

SARS-CoV-2–positive remnant clinical specimens, diagnosed at the Johns Hopkins Microbiology Laboratory between December 2021 and July 2022, were used for whole-genome sequencing. The clinical outcomes of infections with Omicron subvariants were compared with infections with BA.1. Cycle threshold (Ct) values and the recovery of infectious virus on the VeroTMPRSS2 cell line from clinical specimens were compared.

Results

BA.1 was associated with the largest increase in SARS-CoV-2 positivity rate and coronavirus disease 2019 (COVID-19)–related hospitalizations at the Johns Hopkins system. After a peak in January, cases decreased in the spring, but the emergence of BA.2.12.1 followed by BA.5 in May 2022 led to an increase in case positivity and admissions. BA.1 infections had a lower mean Ct value when compared with other Omicron subvariants. BA.5 samples had a greater likelihood of having infectious virus at Ct values <20.

Conclusions

Omicron subvariants continue to be associated with a relatively high rate of polymerase chain reaction (PCR) positivity and hospital admissions. The BA.5 infections are more while BA.2 infections are less likely to have infectious virus, suggesting potential differences in infectibility during the Omicron waves.
Implementation of a method for sperm cryopreservation in sceloporine lizards
Authors: Sánchez-Rivera Uriel Á , Medrano Alfredo , Cruz-Cano Norma B , Alcántar-Rodríguez Alicia , Dávila-Govantes Rodrigo , Castro-Camacho Yabín J , Martínez-Torres Martín
Published: November 2022

Actual loss of lizard biodiversity continues, even with the implementation of conventional conservation programs. An approach including assisted reproductive techniques such as sperm cryopreservation may contribute to the management of endangered species. We developed a method for sperm cryopreservation in sceloporine lizards and compared the response among the studied species. Prior to the mating season, we obtained semen from adult males of Sceloporus aeneus (n = 21), Sceloporus grammicus (n = 20) and Sceloporus torquatus (n = 21) via pressure of the genital papilla. Volume and sperm concentration were measured before semen dilution in a Tris–egg yolk (TEY) medium to evaluate progressive motility, sperm viability, morphology, plasma membrane and acrosome integrity. Then, we cooled the remaining volumes to 5°C at a rate of 0.1°C per minute to incorporate glycerol (8% v/v) in two fractions. Immediately afterwards, we placed 40 μl of the mix on solid CO2 to form pellets and immersed them in liquid nitrogen for storage. We thawed the pellets at 29°C for 3 minutes and diluted them 1:1 (v/v) in TEY medium to assess sperm quality. We found a positive relationship between body weight and seminal volume in S. grammicus and S. torquatus and a negative correlation with sperm concentration in S. grammicus (P < 0.05). Moreover, we observed that the freezing–thawing process decreased sperm quality in the three species, mostly affecting motility and viability. However, S. torquatus and S. aeneus showed a higher sperm tolerance than S. grammicus.