Addressing Low Scholarly Output in Residency With a Resident-Led Society for Innovation and Research.

PROBLEM: Research activity in residency develops skills essential for the practice of medicine and has many benefits for residents, residency programs, the community of medicine, and patients. However, resident participation in research and innovation remains limited, with several barriers that are difficult to address without significant overhead or changes to curriculum. APPROACH: In September 2021, the Society for Innovation and Research (SIR), a resident-led organization dedicated to promoting and supporting resident achievement in research and innovation, was founded. Using only 1 hour of protected didactic time a month, SIR workshops provide critical mentoring and feedback to make resident research a success as well as education on various topics of interest to residents. In addition, SIR celebrates and publicizes resident research success and lays the groundwork for interested residents to participate in innovation. OUTCOMES: The authors analyze the success of SIR in increasing resident research productivity by analyzing PubMed-indexed publications for 11 semesters from fall 2018 to fall 2023. After the launch of SIR, the mean (SD) total number of publications increased from 5.3 (2.4) to 13.3 (1.6) (P = .01), the total mean (SD) number of residents publishing increased from 3.7 (1.3) to 10.0 (1.2) (P = .009), and the mean (SD) total number of coauthored articles increased from 0.1 (0.3) to 2.8 (1.3) (P = .007). NEXT STEPS: The skill set acquired from participation in research during residency is more critical than ever in the wake of the COVID-19 pandemic. SIR initiatives are generalizable to most residency programs in most specialties and require little overhead in terms of physical space, digital resources, and staffing. The authors are currently exploring expanding the SIR program to other residencies at U.S. institutions and have set up processes for the mantle of SIR leadership to be passed down among the pathology resident body.

Application of the newly published International System for Reporting Serous Fluid Cytopathology in atypical and suspicious diagnosis: a four-year retrospective analysis.

INTRODUCTION: Serous fluids offer crucial diagnostic insights, but inconsistent analysis hampers reporting quality, especially in indeterminate (ID) categories like atypia of undetermined significance (AUS) and suspicious for malignancy (SFM). The 2020 International System for reporting Serous Fluid Cytopathology (TIS) aims to standardize communication and reduce reporting disparities. This study evaluates TIS's role in AUS and SFM categories within our institution. MATERIALS AND METHODS: A 4-year retrospective search of cytopathology reports from December 2015 to December 2019 for AUS and SFM diagnoses in pleural, ascitic, pericardial fluids, and peritoneal washings was performed and results reclassified using TIS definitions. The risk of malignancy (ROM) was calculated for existing and reclassified diagnoses. RESULTS: Over 4 years, we received 2998 serous fluid specimens. AUS constituted 2.3% (70 cases), while SFM constituted 0.5% (16 cases). Excluding repeats, 80 cases were TIS-reviewed. Sixteen cases of ID diagnoses were reclassified. Two cases of AUS were changed to negative for malignancy (NFM) and 12 to SFM. Two SFM cases were upgraded to malignancy. ROM shifted from 63% to 60% for AUS and 100% to 85% for SF (TIS's ROM range: AUS: 66% ± 10%; SFM: 82% ± 4.8%). CONCLUSIONS: This institution's ID diagnosis rate is low. AUS ROM is challenging but aligns with TIS, primarily favoring benign. All SFM diagnoses are highly suspicious but quantitatively inadequate for definitive malignancy, explaining the elevated ROM. AUS rate should gauge quality, not serve as a catch-all category. Algorithmic cytology with cell blocks and ancillary studies aids reclassification. TIS is user-friendly and is a consistent methodology for standardized reporting. Further studies are needed to evaluate ROM and define reproducible diagnostic criteria for each category for better system utilization.

Disparate outcomes in Hispanic patients with metabolic dysfunction-associated steatotic liver disease/steatohepatitis and type 2 diabetes: Large cohort study.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are a growing health burden across a significant portion of the global patient population. However, these conditions seem to have disparate rates and outcomes between different ethnic populations. The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma (HCC), and Hispanic patients experience the greatest burden, particularly those in South Texas. AIM: To compare outcomes between Hispanic and non-Hispanic patients in the United States, while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic consideration. METHODS: This cohort analysis was conducted with data obtained from TriNetX, LLC ("TriNetX"), a global federated health research network that provides access to deidentified medical records from healthcare organizations worldwide. Two cohort networks were used: University of Texas Medical Branch (UTMB) hospital and the United States national database collective to determine whether disparities were related to geographic regions, like Southeast Texas. RESULTS: This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC, type 2 diabetes mellitus, and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino groups. All-cause mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB cohort. CONCLUSION: This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.

Heterogeneity in intrahepatic macrophage populations and druggable target expression in patients with steatotic liver disease-related fibrosis.

Background & Aims: Clinical trials for reducing fibrosis in steatotic liver disease (SLD) have targeted macrophages with variable results. We evaluated intrahepatic macrophages in patients with SLD to determine if activity scores or fibrosis stages influenced phenotypes and expression of druggable targets, such as CCR2 and galectin-3. Methods: Liver biopsies from controls or patients with minimal or advanced fibrosis were subject to gene expression analysis using nCounter to determine differences in macrophage-related genes (n = 30). To investigate variability among individual patients, we compared additional biopsies by staining them with multiplex antibody panels (CD68/CD14/CD16/CD163/Mac387 or CD163/CCR2/galectin-3/Mac387) followed by spectral imaging and spatial analysis. Algorithms that utilize deep learning/artificial intelligence were applied to create cell cluster plots, phenotype profile maps, and to determine levels of protein expression (n = 34). Results: Several genes known to be pro-fibrotic (e.g. CD206, TREM2, CD163, and ARG1) showed either no significant differences or significantly decreased with advanced fibrosis. Although marked variability in gene expression was observed in individual patients with cirrhosis, several druggable targets and their ligands (e.g. CCR2, CCR5, CCL2, CCL5, and LGALS3) were significantly increased when compared to patients with minimal fibrosis. Antibody panels identified populations that were significantly increased (e.g. Mac387+), decreased (e.g. CD14+), or enriched (e.g. interactions of Mac387) in patients that had progression of disease or advanced fibrosis. Despite heterogeneity in patients with SLD, several macrophage phenotypes and druggable targets showed a positive correlation with increasing NAFLD activity scores and fibrosis stages. Conclusions: Patients with SLD have markedly varied macrophage- and druggable target-related gene and protein expression in their livers. Several patients had relatively high expression, while others were like controls. Overall, patients with more advanced disease had significantly higher expression of CCR2 and galectin-3 at both the gene and protein levels. Impact and implications: Appreciating individual differences within the hepatic microenvironment of patients with SLD may be paramount to developing effective treatments. These results may explain why such a small percentage of patients have responded to macrophage-targeting therapies and provide additional support for precision medicine-guided treatment of chronic liver diseases.

A Rare Case of Erosive Esophagitis Due to Sarcina Ventriculi Infection.

Sarcina ventriculi is a Gram-positive anaerobic coccus found in soil that is a rare cause of inflammatory infections of the GI tract. This bacterium has a propensity for causing gastritis in patients with delayed gastric emptying. Of the 66 reported cases in the literature, 10 involved the esophagus. Symptoms of an esophageal infection are non-specific and may be mistaken for long-standing gastroesophageal reflux. We present a case of a 67-year-old female with chronic dysphagia and reflux diagnosed with erosive esophagitis caused by Sarcina ventriculi. Treatment strategies documented in the literature are reviewed.

Under Disguise: A Concealed Case of Acute Hepatitis A Infection.

Acute hepatitis A virus infection is routinely identified through a thorough patient history in conjunction with liver chemistries and viral serologies. The diagnosis has the potential to be delayed when the clinical picture is obscured with another, seemingly more urgent presenting pathology with overlapping features. Here, we describe the case of a young female who presented with acute calculous cholecystitis with concurrent acute hepatitis A virus infection.

Nephrogenic Adenoma Arising From a Female Urethral Diverticulum: A Case Report and Potential Diagnostic Pitfalls.

Nephrogenic adenoma is a benign lesion of the urothelial tract characterized by tubules surrounded by thick, hyalinized basement membranes. There is a great variety of architectural patterns within nephrogenic adenomas, including patterns that mimic malignancy, such as focal clear or hobnail cells, areas of significant nuclear atypia, mitosis, and isolated cystic changes. This represents a diagnostic pitfall, where a malignant lesion can be mistaken for a nephrogenic adenoma, leading to a delay in diagnosis and treatment that adversely affects the outcome. In this case report, we describe a nephrogenic adenoma arising in a female urethral diverticulum and discuss the differential diagnosis, which includes clear cell carcinomas, microcystic variant urothelial carcinomas, and Skene's gland cysts.

Patients with fibrosis from non-alcoholic steatohepatitis have heterogeneous intrahepatic macrophages and therapeutic targets.

Background and Aims: In clinical trials for reducing fibrosis in NASH patients, therapeutics that target macrophages have had variable results. We evaluated intrahepatic macrophages in patients with non-alcoholic steatohepatitis to determine if fibrosis influenced phenotypes and expression of CCR2 and Galectin-3. Approach & Results: We used nCounter to analyze liver biopsies from well-matched patients with minimal (n=12) or advanced (n=12) fibrosis to determine which macrophage-related genes would be significantly different. Known therapy targets (e.g., CCR2 and Galectin-3) were significantly increased in patients with cirrhosis.However, several genes (e.g., CD68, CD16, and CD14) did not show significant differences, and CD163, a marker of pro-fibrotic macrophages was significantly decreased with cirrhosis. Next, we analyzed patients with minimal (n=6) or advanced fibrosis (n=5) using approaches that preserved hepatic architecture by multiplex-staining with anti-CD68, Mac387, CD163, CD14, and CD16. Spectral data were analyzed using deep learning/artificial intelligence to determine percentages and spatial relationships. This approach showed patients with advanced fibrosis had increased CD68+, CD16+, Mac387+, CD163+, and CD16+CD163+ populations. Interaction of CD68+ and Mac387+ populations was significantly increased in patients with cirrhosis and enrichment of these same phenotypes in individuals with minimal fibrosis correlated with poor outcomes. Evaluation of a final set of patients (n=4) also showed heterogenous expression of CD163, CCR2, Galectin-3, and Mac387, and significant differences were not dependent on fibrosis stage or NAFLD activity. Conclusions: Approaches that leave hepatic architecture intact, like multispectral imaging, may be paramount to developing effective treatments for NASH. In addition, understanding individual differences in patients may be required for optimal responses to macrophage-targeting therapies.

Cholesterol Granuloma: An Unusual Presentation Within the Mandible of a Pediatric Patient.

Cholesterol granulomas, while a common pathological finding, are rarely reported within the mandible. Herein, we report the case of a pediatric patient who presented with a cholesterol granuloma within a periapical cyst, extending from the inferior aspect of tooth #31 to the mandibular condyle, with no prior history of infection or trauma to the region and underwent successful marsupialization of the lesion.

Cutting-Edge Platforms for Analysis of Immune Cells in the Hepatic Microenvironment-Focus on Tumor-Associated Macrophages in Hepatocellular Carcinoma.

The role of tumor-associated macrophages (TAMs) in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. Most studies rely on platforms that remove intrahepatic macrophages from the microenvironment prior to evaluation. Cell isolation causes activation and phenotypic changes that may not represent their actual biology and function in situ. State-of-the-art methods provides new strategies to study TAMs without losing the context of tissue architecture and spatial relationship with neighboring cells. These technologies, such as multispectral imaging (e.g., Vectra Polaris), mass cytometry by time-of-flight (e.g., Fluidigm CyTOF), cycling of fluorochromes (e.g., Akoya Biosciences CODEX/PhenoCycler-Fusion, Bruker Canopy, Lunaphore Comet, and CyCIF) and digital spatial profiling or transcriptomics (e.g., GeoMx or Visium, Vizgen Merscope) are being utilized to accurately assess the complex cellular network within the tissue microenvironment. In cancer research, these platforms enable characterization of immune cell phenotypes and expression of potential therapeutic targets, such as PDL-1 and CTLA-4. Newer spatial profiling platforms allow for detection of numerous protein targets, in combination with whole transcriptome analysis, in a single liver biopsy tissue section. Macrophages can also be specifically targeted and analyzed, enabling quantification of both protein and gene expression within specific cell phenotypes, including TAMs. This review describes the workflow of each platform, summarizes recent research using these approaches, and explains the advantages and limitations of each.

Primary Hepatic Mesothelial Cyst: A Rare Entity to Be Considered in the Differential Diagnosis of Neonatal Cystic Lesions.

We report two cases of primary hepatic mesothelial cysts in neonates previously identified during perinatal imaging. Both neonatal cases were reimaged in the postnatal period, demonstrating the persistence of these cystic hepatic lesions. In both instances, the decision was made to treat with surgical resection and both patients tolerated the surgery well with no significant postoperative complications. Histopathological examination of these lesions discovered a cuboidal lining that was calretinin and WT1 positive and CD31 negative, indicating the diagnosis of a mesothelial cyst of hepatic origin. These cases bring attention to the broad differential diagnosis of congenital primary hepatic cystic lesions, as well as the diagnostic pathway to confirm a primary hepatic mesothelial cyst.

Multisite biologic tissue SARS-CoV-2 PCR testing in kidney transplantation from a COVID-positive donor.

With a high community transmission rate, SARS-CoV-2 has profoundly exacerbated the shortage of organs. Although the risk of donor-recipient transmission of SARS-CoV-2 is anecdotally low, an organ-specific infection analysis of procured organs from SARS-CoV-2 positive donors has yet to be established. Using a combination of clinically available and research-only polymerase chain reaction methods, organ preservation fluid and renal parenchymal tissues were tested for SARS-CoV-2 from the kidney of a SARS-CoV-2-positive donor prior to transplantation. The recipient has remained SARS-CoV-2 negative and clinically well, with excellent graft function 120 days post-transplantation.

Effects of Intraoperative Continuous Renal Replacement Therapy on Outcomes in Liver Transplantation.

BACKGROUND: Intraoperative continuous renal replacement therapy (CRRT) may need to be indicated for liver transplant recipients who show renal dysfunction. We aimed to investigate effects of intraoperative CRRT on outcomes after liver transplant. MATERIAL AND METHODS: This study included all adult patients who underwent liver transplant between January 2005 and May 2017 and were found to have renal dysfunction, which was defined as glomerular filtration rate < 30 mL/min at transplant. The patients were divided into 3 groups for outcome analysis: elective CRRT group (renal replacement therapy was already introduced pretransplant, group 1, n = 70), urgent CRRT (intraoperative CRRT was indicated because of unexpected renal dysfunction, group 2, n = 15), and no CRRT group (no intraoperative CRRT even with renal dysfunction, group 3, n = 57). Post-transplant outcomes were analyzed to determine effects of CRRT. RESULTS: Postoperative complication rates were similar in the 3 groups (P = .056). Group 1 showed the highest rate of postoperative renal replacement therapy (86.4% in group 1 vs 66.7% and 10.7% in groups 2 and 3, P < .001). Long-term renal function (at 3, 6, and 12 months post transplant) was similar among the 3 groups (P = .50, .77, and .52, respectively). Group 1 showed a higher risk of 1-year graft loss (hazard ratio, 2.55; P = .03) and mortality (hazard ratio, 2.71; P = .03) than group 3, whereas groups 2 and 3 were similar. CONCLUSION: CRRT used in the urgent setting did not show obvious benefit. Hence, its application should be carefully considered in those who unexpectedly present with acute kidney injury at the time of transplant.