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1.
Arch Pathol Lab Med ; 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37852170

ABSTRACT

CONTEXT.­: Transition from pathology trainee to independent pathologist is stressful. No study has examined junior pathologists' challenges and concerns during this transition. OBJECTIVE.­: To identify challenges and concerns of junior pathologists. DESIGN.­: Junior pathologists were defined as those who had been practicing independently for up to 5 years after completion of residency/fellowship. An institutional review board-approved electronic survey was created and distributed to recent pathology graduates of MD Anderson Cancer Center (Houston, Texas) and MedStar Georgetown University Hospital (Washington, District of Columbia). The survey was open from October 13, 2022, to January 31, 2023. The survey included 16 multiple-choice and free-text questions. RESULTS.­: Responses were received from 39 junior pathologists. Participants working in academic settings indicated independence, work-life balance, and professional identity formation as challenges; those in nonacademic settings indicated pathology reporting, efficiency, and administration as challenges. Areas where participants wished they received more guidance differed by practice setting: participants in academic settings more often chose effective time management and importance of turnaround time (35% [7 of 20] versus 0% [0 of 14], P = .03) and tumor board conference presentation skills (25% [5 of 20] versus 0% [0 of 14], P = .06), while those in nonacademic settings more often chose current procedural terminology (CPT) coding, billing, and cost-effective patient care (79% [11 of 14] versus (35% [7 of 20]; P = .02). More female than male participants indicated that they wished they had received more guidance in leadership and soft skills (79% [11 of 14] versus 28% [5 of 18]; P = .01). CONCLUSIONS.­: This study identified challenges experienced by junior pathologists. Collective efforts from training programs, experienced pathologists, and professional organizations can explore ways to improve the transition experience.

2.
Arch Pathol Lab Med ; 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37639451

ABSTRACT

CONTEXT.­: To provide high-quality, safe training during the COVID-19 pandemic, our anatomic pathology fellowship program implemented a hybrid virtual/in-person training model with supplemental digital material. OBJECTIVE.­: To evaluate the impact of this model. DESIGN.­: We examined Accreditation Council for Graduate Medical Education survey results and board pass rates for fellows before the pandemic (group 1); during the pandemic peak (group 2); and early and late after the pandemic peak (groups 3 and 4). Additionally, we distributed an online survey including questions related to performance as attending physicians and fellowship experience to recent graduates. RESULTS.­: Information loss during handover, supervision and teaching by faculty, and having at least 4 free days a month exhibited the greatest score declines between group 1 and groups 2, 3, and 4 on the Accreditation Council for Graduate Medical Education surveys. No differences were seen in board passing rates between groups. The groups did not differ in responses regarding preparation for role as attending, confidence in role as attending, or overall impression of the fellowship program. The pandemic-affected groups responded more positively on the perceived utility of supplemental digital material, impact of digital pathology on quality of education, and impact of supplemental digital material on familiarity with digital pathology. The difference was particularly large between group 1 and combined groups 3 and 4. CONCLUSIONS.­: Despite the limitations noted, the hybrid training model was effective and successfully prepared fellows for their role as attending physicians. Similar studies can be informative for the implementation of similar programs or for the meaningful integration of digital pathology into training curricula.

3.
Front Immunol ; 13: 898799, 2022.
Article in English | MEDLINE | ID: mdl-36148239

ABSTRACT

Type 1 Natural Killer T-cells (NKT1 cells) play a critical role in mediating hepatic ischemia-reperfusion injury (IRI). Although hepatic steatosis is a major risk factor for preservation type injury, how NKT cells impact this is understudied. Given NKT1 cell activation by phospholipid ligands recognized presented by CD1d, we hypothesized that NKT1 cells are key modulators of hepatic IRI because of the increased frequency of activating ligands in the setting of hepatic steatosis. We first demonstrate that IRI is exacerbated by a high-fat diet (HFD) in experimental murine models of warm partial ischemia. This is evident in the evaluation of ALT levels and Phasor-Fluorescence Lifetime (Phasor-FLIM) Imaging for glycolytic stress. Polychromatic flow cytometry identified pronounced increases in CD45+CD3+NK1.1+NKT1 cells in HFD fed mice when compared to mice fed a normal diet (ND). This observation is further extended to IRI, measuring ex vivo cytokine expression in the HFD and ND. Much higher interferon-gamma (IFN-γ) expression is noted in the HFD mice after IRI. We further tested our hypothesis by performing a lipidomic analysis of hepatic tissue and compared this to Phasor-FLIM imaging using "long lifetime species", a byproduct of lipid oxidation. There are higher levels of triacylglycerols and phospholipids in HFD mice. Since N-acetylcysteine (NAC) is able to limit hepatic steatosis, we tested how oral NAC supplementation in HFD mice impacted IRI. Interestingly, oral NAC supplementation in HFD mice results in improved hepatic enhancement using contrast-enhanced magnetic resonance imaging (MRI) compared to HFD control mice and normalization of glycolysis demonstrated by Phasor-FLIM imaging. This correlated with improved biochemical serum levels and a decrease in IFN-γ expression at a tissue level and from CD45+CD3+CD1d+ cells. Lipidomic evaluation of tissue in the HFD+NAC mice demonstrated a drastic decrease in triacylglycerol, suggesting downregulation of the PPAR-γ pathway.


Subject(s)
Fatty Liver , Reperfusion Injury , Acetylcysteine/pharmacology , Animals , Cytokines , Fatty Liver/drug therapy , Interferon-gamma , Ligands , Mice , Mice, Inbred C57BL , Peroxisome Proliferator-Activated Receptors , Phospholipids , Reperfusion Injury/etiology , Triglycerides
4.
Front Immunol ; 13: 899525, 2022.
Article in English | MEDLINE | ID: mdl-35833123

ABSTRACT

Innate lymphoid cells (ILCs), the most recently described family of lymphoid cells, play fundamental roles in tissue homeostasis through the production of key cytokine. Group 1 ILCs, comprised of conventional natural killer cells (cNKs) and type 1 ILCs (ILC1s), have been implicated in regulating immune-mediated inflammatory diseases. However, the role of ILC1s in nonalcoholic fatty liver disease (NAFLD) and ischemia-reperfusion injury (IRI) is unclear. Here, we investigated the role of ILC1 and cNK cells in a high-fat diet (HFD) murine model of partial warm IRI. We demonstrated that hepatic steatosis results in more severe IRI compared to non-steatotic livers. We further elicited that HFD-IRI mice show a significant increase in the ILC1 population, whereas the cNK population was unchanged. Since ILC1 and cNK are major sources of IFN-γ and TNF-α, we measured the level of ex vivo cytokine expression in normal diet (ND)-IRI and HFD-IRI conditions. We found that ILC1s in HFD-IRI mice produce significantly more IFN-γ and TNF-α when compared to ND-IRI. To further assess whether ILC1s are key proinflammatory effector cells in hepatic IRI of fatty livers, we studied both Rag1-/- mice, which possess cNK cells, and a substantial population of ILC1s versus the newly generated Rag1-/-Tbx21-/- double knockout (Rag1-Tbet DKO) mice, which lack type 1 ILCs, under HFD IRI conditions. Importantly, HFD Rag1-Tbet DKO mice showed significant protection from hepatic injury upon IRI when compared to Rag1-/- mice, suggesting that T-bet-expressing ILC1s play a role, at least in part, as proinflammatory effector cells in hepatic IRI under steatotic conditions.


Subject(s)
Non-alcoholic Fatty Liver Disease , Reperfusion Injury , Animals , Cytokines , Homeodomain Proteins , Immunity, Innate , Killer Cells, Natural , Mice , Mice, Knockout , Reperfusion Injury/prevention & control , Tumor Necrosis Factor-alpha
5.
BMJ Case Rep ; 14(8)2021 Aug 19.
Article in English | MEDLINE | ID: mdl-34413046

ABSTRACT

We describe an unusual case of membranous nephropathy precipitated by syphilis infection in a patient without systemic lupus erythematosus (SLE). A previously healthy 20-year-old man presented with leg and facial swelling. Laboratory investigation revealed nephrotic range proteinuria, acute kidney injury, hypocomplementaemia and a highly positive rapid plasma reagin. Kidney biopsy showed membranous nephropathy with 'full-house' immunofluorescence (IgG, IgA, IgM, C1q and C3), mimicking lupus nephritis class Vb. However, the patient had no features of SLE and had negative antinuclear and anti-double-stranded DNA antibodies. He was treated with high-dose methylprednisolone and mycophenolate mofetil for lupus nephritis and with penicillin for syphilis. After 2 months of therapy, his proteinuria resolved, and his renal function and C4 level normalised. This case illustrates that syphilis infection can be a mimicker of lupus nephritis. A literature review suggests that ful-house nephropathy may occur independently of lupus nephritis and may or may not develop into SLE.


Subject(s)
Glomerulonephritis, Membranous , Lupus Erythematosus, Systemic , Lupus Nephritis , Syphilis , Adult , Antibodies, Antinuclear , Glomerulonephritis, Membranous/diagnosis , Glomerulonephritis, Membranous/drug therapy , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/complications , Lupus Nephritis/diagnosis , Lupus Nephritis/drug therapy , Male , Young Adult
6.
J Cutan Pathol ; 48(4): 526-534, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32564423

ABSTRACT

Cutaneous carcinosarcomas are rare biphenotypic tumors that simultaneously show epithelial and mesenchymal differentiation. The most common carcinomatous components in skin carcinosarcomas are basal cell carcinoma and squamous cell carcinoma; adnexal carcinomas are rarely encountered. We report a case of an adnexal carcinoma with ductal and squamous differentiation and spindle cell component, which is interpreted as carcinosarcoma. Loss of immunohistochemical expression of E-cadherin and ß-catenin detected in the sarcomatous component suggested epithelial mesenchymal transition (EMT). RNA sequencing analysis identified several gene mutations and alterations such as translocations and upregulations/downregulations, either shared by the two components of the tumor or differentially present in the carcinoma or the sarcoma parts. Thus, mutations in genes, such as TP53, were found in both components of the tumor while mutations in PDGFRA and RB1 (a pathogenic missense mutation) were exclusively present in the sarcomatous areas, further supporting EMT. EMT is a dynamic process by which tumors acquire mesenchymal phenotype while simultaneously losing epithelial properties. Although the pathways involved in EMT have been extensively studied, this phenomenon still needs to be investigated in cutaneous tumors of adnexal origin for a better understanding of their pathogenesis. These molecular changes may represent promising targets for personalized therapies.


Subject(s)
Carcinosarcoma/diagnosis , Epithelial-Mesenchymal Transition/genetics , Neoplasms, Adnexal and Skin Appendage/pathology , Skin Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Cadherins/metabolism , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/ultrastructure , Carcinosarcoma/genetics , Carcinosarcoma/radiotherapy , Carcinosarcoma/surgery , Female , Genes, p53/genetics , Humans , Immunohistochemistry/methods , Male , Middle Aged , Mutation , Neoplasm Recurrence, Local/secondary , Sequence Analysis, RNA/methods , Vimentin/metabolism
7.
Arch Pathol Lab Med ; 145(1): 22-31, 2021 01 01.
Article in English | MEDLINE | ID: mdl-32937659

ABSTRACT

CONTEXT.­: As teaching hospitals institute social distancing and defer nonemergent procedures to cope with the coronavirus disease 2019 pandemic, the need for daily on-site presence, unless necessary, has been reduced for all medical staff, including trainees. Pathology training programs must adapt to these changes to ensure overall safety without significantly compromising training and the educational mission of the institution. OBJECTIVE.­: To describe the hybrid on-site and remote anatomic pathology training model in response to the coronavirus disease 2019 pandemic that was implemented in our pathology department and report the clinical fellows' responses to the survey about their experiences. DESIGN.­: The hybrid model was implemented March 25, 2020. Fellows alternate weekly between working on site and working remotely. On site, fellows wear personal protective equipment and maintain social distancing. Remotely, fellows use digital pathology to review cases and supplement with online educational activities. Virtual "coffee breaks," meditation, and exercise are part of the curriculum. Online platforms, including WebEx, Google Classroom, and Canvas, are used to continue educational activities. The survey was open May 19 through June 8, 2020. RESULTS.­: Twenty-eight of the 29 clinical fellows (96%) responded. Many of the respondents indicated substantial increase in their skill with using digital pathology and online platforms during the pandemic. The top most helpful resources were the United States and Canadian Academy of Pathology interactive microscopy courses (found very or somewhat helpful by 22 of 23 clinical fellows; 96%), ExpertPath (19 of 23; 82%), the College of American Pathologists virtual learning series (18 of 23; 78%), the World Health Organization Blue Books (16 of 23; 70%), the American Society of Cytopathology webinars (14 of 23; 61%), and our institutional digital slide collection (12 of 23; 52%). CONCLUSIONS.­: Hybrid on-site and remote training can maximize anatomic pathology learning opportunities while maintaining the safety of trainees, hospital personnel, and the community.


Subject(s)
COVID-19 , Curriculum , Education, Distance/methods , Pathology, Clinical/education , Computer-Assisted Instruction/methods , Education, Distance/trends , Hospitals, Teaching , Humans , Internship and Residency , Pandemics , Physical Distancing , SARS-CoV-2 , Surveys and Questionnaires , Teleworking , Texas , Virtual Reality
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