Biofilm formation of Staphylococcus aureus on various implants used for surgical treatment of destructive spondylodiscitis.

The incidence of spondylodiscitis has witnessed a significant increase in recent decades. Surgical intervention becomes necessary in case of bone destruction to remove infected tissue and restore spinal stability, often involving the implantation of a cage. Despite appropriate treatment, relapses occur in up to 20 percent of cases, resulting in substantial economic and social burdens. The formation of biofilm has been identified as a major contributor to relapse development. Currently, there is no consensus among German-speaking spinal surgeons or in the existing literature regarding the preferred choice of material to minimize relapse rates. Thus, the objective of this study is to investigate whether certain materials used in spinal implants exhibit varying degrees of susceptibility to bacterial attachment, thereby providing valuable insights for improving treatment outcomes.Eight cages of each PEEK, titanium-coated PEEK (Ti-PEEK), titanium (Ti), polyetherketoneketone (PEKK), tantalum (Ta) and antibiotic-loaded bone cement were incubated with 20% human plasma for 24 h. Subsequently, four implants were incubated with S. aureus for 24 h or 48 h each. The biofilm was then removed by sonication and the attained solution plated for Colony Forming Units (CFU) counting. Scanning electron microscopy was used to confirm bacterial attachment. The CFUs have been compared directly and in relation to the cages surface area. The surface area of the implants was PEEK 557 mm2, Ti-PEEK 472 mm2, Ti 985 mm2, PEKK 594 mm2, Ta 706 mm2, bone cement 123 mm2. The mean CFU count per implant and per mm2 surface area after 24 h and after 48 h was calculated. Bone cement was found to have significantly more CFUs per mm2 surface area than the other materials tested. When comparing the CFU count per implant, bone cement was statistically significantly more prone to biofilm formation than PEEK after 48 h. There was no statistical significance between the other materials when comparing both CFU count per mm2 surface area and CFU count per implant. The electron microscopic analysis showed the attachment of the bacteria, as well as production of extracellular polymeric substances (EPS) as a sign for beginning biofilm formation. Antibiotic-loaded bone cement has shown statistically significantly more bacterial attachment than the other examined materials. No difference was found between the other materials regarding bacterial attachment after 24 h and 48 h. Proposed hypotheses for further studies include testing whether differences become apparent after longer incubation or with different pathogens involved in the pathogenesis of pyogenic spondylodiscitis.

Clinicopathologic Insights and Molecular Oncogenesis: Understanding Epstein-Barr Virus-Induced B-cell Lymphoproliferations.

Epstein-Barr virus (EBV) is a highly prevalent virus among adults worldwide. In an immunocompetent individual, EBV infection generally results in lifelong latency of the virus and no sequelae. However, in the setting of immune dysfunction, EBV can induce the development of autoimmune disorders, hyperplastic proliferations, and cancers, including lymphoma. Here, we explore the pathogenic and oncogenic role of EBV in Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, plasmablastic lymphoma, lymphomatoid granulomatosis, and post-transplant lymphoproliferative disorders and lymphoproliferative disorders associated with immune deficiency and dysregulation. In addition to describing general mechanisms of EBV-associated oncogenesis, we also discuss EBV-associated oncogenesis in the context of each disorder, as well as their microscopic, phenotypic, and clinical presentations.

Unveiling the Tempest: Dermal Plasmacytoid Dendritic Cell Proliferation as the Harbinger of Acute Myeloid Leukemia.

ABSTRACT: Plasmacytoid dendritic cell neoplasms are rare neoplasms originating from plasmacytoid dendritic cells (pDCs). They are subclassified into 2 types: blastic plasmacytoid dendritic cell neoplasm and mature plasmacytoid dendritic cell proliferation. Neoplastic expansion of pDCs has also been found to be associated with myeloid neoplasia. We present the diagnostically challenging case of a 62-year-old woman who presented to the emergency department with numerous hemorrhagic nodules and papules on the face and extensor surfaces near the elbows and neutropenic fevers. The patient had a history notable for lupus erythematosus and a recently performed excisional lymph node biopsy involved by a "plasmacytoid dendritic cell proliferation." A punch biopsy was performed, which showed a robust dermal infiltrate of atypical intermediate-sized mononuclear cells. The infiltrate was positive for CD4, CD43, and CD123. CD3 and CD8 highlighted background T cells. The infiltrate was negative for CD10, CD34, CD56, CD68, CD117, myeloperoxidase, lysozyme, TdT, and TCL-1. The findings favored a diagnosis of cutaneous involvement of the plasmacytoid dendritic cell proliferation. Given the association with acute leukemias, a subsequent bone marrow biopsy was recommended. The bone marrow biopsy was performed, which showed increased blasts (68% on a 500 differential cell count). Furthermore, immunohistochemical stains were performed, which highlighted the blasts to be positive for CD34 and BEST (alpha-naphthyl butyrate esterase) cytochemical stain. This diagnosis was consistent with bone marrow involvement of acute myelomonocytic leukemia. Given the overlapping presenting symptoms (skin lesions, adenopathy, marrow involvement) of pDC neoplasms and myeloid neoplasia and the possibility of presenting concurrently, increased awareness is of pivotal importance to help prevent potential misdiagnosis, missed diagnosis, and prompt investigation of possible associated neoplasms.

Navigating The 2022 International Consensus and World Health Organization Classifications of Hematopathology: A Call for Unified Diagnostic Language.

CONTEXT.­: In 2022, 2 distinct guidelines for the diagnosis of myeloid neoplasms became available: the 5th edition of the World Health Organization guideline (WHO2022) solely and the International Consensus Classification (ICC). Despite major overlap, there are important differences that can have important implications. OBJECTIVE.­: To explore the current opinions and diagnostic practices of hemato-oncologists and hematopathologists across the United States. DESIGN.­: An online anonymous survey was created using REDCap, and a secure link was shared via email to fellowship program leaderships and via posts on social media. RESULTS.­: A total of 310 responses were obtained. Only 33 of 309 respondents (10.7%) reported using solely the 2016 World Health Organization guideline to make diagnoses, whereas 167 of 309 (54%) supplemented it with other guidelines. The rest were either not sure (17; 5.5%), used WHO2022 solely (46; 14.9%), or used ICC solely (6; 1.9%). The choice of guideline was not related to region (P = .15), practice setting (P = .86), or hospital size (P = .22). More than 90% reported it is a source of confusion in clinical diagnosis, management, trial design, and other areas. CONCLUSIONS.­: Overall, our study found that having 2 distinct guidelines could be a source of confusion for physicians and calls for a unified diagnostic language.

Implementing PathElective as an organized means of supplementing pathology education in an osteopathic medical school-the New York Institute of Technology College of Osteopathic Medicine experience.

Pathology is not traditionally chosen by medical students applying to residency. In osteopathic medical schools, limited access to dedicated pathology faculty further complicates this issue. Because of a lack of pathology experiences, osteopathic medical students may not be as familiar with a pathology career. The purpose of this brief report is to describe the pilot experience of implementing a pre-existing web-based, free virtual platform for pathology education as alternative, supplemental exposure to pathology for osteopathic medical students at our institution. We began to offer the online pathology elective for Academic Year 2022-2023. Using the online free service of PathElective, this course provided a valuable exposure to pathology with multiple modules in anatomic, clinical, and digital/molecular pathology, before and after assessments, recorded videos by pathology experts, handouts, and reading assignments. During the first week, three introductory modules were required followed by weeks 2-4, in which the students would complete a total of 10 modules of their own choice. In total, 14 students participated in this virtual rotation from August 2022-May 2023. All chose cardiac pathology as the most popular module. Three of the 14 students matched into pathology residencies. This small cohort of 4th year medical students at our osteopathic medical school successfully completed a virtual elective rotation with the resources of PathElective. We report the success of this experience and hope to continue monitoring progress.

Liquid biopsy-based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results.

AIMS: Liquid biopsy (LBx)-based next-generation sequencing (NGS) of circulating tumour DNA (ctDNA) can facilitate molecular profiling of haematopoietic neoplasms (HNs), particularly when tissue-based NGS is infeasible. METHODS AND RESULTS: We studied HN LBx samples tested with FoundationOne Liquid CDx, FoundationOne Liquid, or FoundationACT between July 2016 and March 2022. We identified 271 samples: 89 non-Hodgkin lymphoma (NHL), 43 plasma-cell neoplasm (PCN), 41 histiocytoses, 27 myelodysplastic syndrome (MDS), 25 diffuse large B-cell lymphoma (DLBCL), 22 myeloproliferative neoplasm (MPN), 14 Hodgkin lymphoma (HL), and 10 acute myeloid leukaemia (AML). Among 73.4% with detectable pathogenic alterations, median maximum somatic allele frequency (MSAF) was 16.6%, with AML (36.2%), MDS (19.7%), and MPN (44.5%) having higher MSAFs than DLBCL (3.9%), NHL (8.4%), HL (1.5%), PCN (2.8%), and histiocytoses (1.8%) (P = 0.001). LBx detected characteristic alterations across HNs, including in TP53, KRAS, MYD88, and BTK in NHLs; TP53, KRAS, NRAS, and BRAF in PCNs; IGH in DLBCL; TP53, ATM, and PDCD1LG2 in HL; BRAF and MAP2K1 in histiocytoses; TP53, SF3B1, DNMT3A, TET2, and ASXL1 in MDS; JAK2 in MPNs; and FLT3, IDH2, and NPM1 in AML. Among 24 samples, the positive percent agreement by LBx was 75.7% for variants present in paired buffy coat, marrow, or tissues. Also, 75.0% of pairs exhibited alterations only present on LBx. These were predominantly subclonal (clonal fraction of 3.8%), reflecting the analytical sensitivity of LBx. CONCLUSION: These data demonstrate that LBx can detect relevant genomic alterations across HNs, including at low clonal fractions, suggesting a potential clinical utility for identifying residual or emerging therapy-resistant clones that may be undetectable in site-specific tissue biopsies.

Bacteriophage-mediated decolonization of Klebsiella pneumoniae in a novel Galleria mellonella gut colonization model with Enterobacteriaceae.

Galleria mellonella larvae have emerged as an invertebrate model for investigating bacterial pathogenesis and potential therapies, addressing ethical concerns related to mammalian models. This model has the advantage of having a simple gut microbiome, which is suitable for gut colonization studies. Intestinal colonization by Enterobacteriaceae significantly contributes to the spread of antibiotic resistance. This study aimed to establish a novel Enterobacteriaceae gut colonization larval model and assess its suitability for evaluating distinct antimicrobial efficacies. Larvae were force-fed sequentially with bacterial doses of K. pneumoniae and E. coli at 0, 24, and 48 h, with survival monitoring at 24 h intervals. Bacterial counts were assessed after 48 h and 120 h of force-feeding. Successfully colonized larvae were subjected to one-time force feeding of a bacteriophage cocktail (107 PFU/larvae) or MIC-based meropenem and ciprofloxacin. The colonized bacterial load was quantified by CFU count. Three doses of 106 CFU/larvae resulted in stable gut colonization, independent of the K. pneumoniae or E. coli strain. Compared with the control, force-feeding of the bacteriophage reduced the colonization of the strain Kp 419614 by 5 log10 CFU/larvae, while antibiotic treatment led to a 3 log10 CFU/larval reduction. This novel G. mellonella model provides a valuable alternative for gut colonization studies, facilitating proof-of-concept investigations and potentially reducing or replacing follow-up experiments in vertebrate models.

Evolving educational landscape in pathology: a comprehensive bibliometric and visual analysis including digital teaching and learning resources.

AIMS: Pathology education is a core component of medical training, and its literature is critical for refining educational modalities. We performed a cross-sectional bibliometric analysis to explore publications on pathology education, focusing on new medical education technologies. METHODS: The analysis identified 64 pathology journals and 53 keywords. Relevant articles were collected using a web application, PaperScraper, developed to accelerate literature search. Citation data were collected from multiple sources. Descriptive statistics, with time period analysis, were performed using Microsoft Excel and visualised with Flourish Studio. Two article groups were further investigated with a bibliometric software, VOSViewer, to establish co-authorship and keyword relationships. RESULTS: 8946 citations were retrieved from 905 selected articles. Most articles were published in the last decade (447, 49.4%). The top journals were Archives of Pathology & Laboratory Medicine (184), Human Pathology (122) and the American Journal of Clinical Pathology (117). The highest number of citations was found for Human Pathology (2120), followed by Archives of Pathology & Laboratory Medicine (2098) and American Journal of Clinical Pathology (1142). Authors with different backgrounds had the greatest number of articles and citations. 12 co-authorship, 3 keyword and 8 co-citation clusters were found for the social media/online resources group, 8 co-authorship, 4 keyword and 7 co-citation clusters for the digital pathology/virtual microscopy/mobile technologies group. CONCLUSIONS: The analysis revealed a significant increase in publications over time. The emergence of digital teaching and learning resources played a major role in this growth. Overall, these findings underscore the transformative potential of technology in pathology education.

Improving Transparency in the Residency Application Process: Survey Study.

BACKGROUND: Increasing numbers of residency applications create challenges for applicants and residency programs to assess if they are a good fit during the residency application and match process. Applicants face limited or conflicting information as they assess programs, leading to overapplying. A holistic review of residency applications is considered a gold standard for programs, but the current volumes and associated time constraints leave programs relying on numerical filters, which do not predict success in residency. Applicants could benefit from increased transparency in the residency application process. OBJECTIVE: This study aims to determine the information applicants find most beneficial from residency programs when deciding where to apply, by type of medical school education background. METHODS: Match 2023 applicants voluntarily completed an anonymous survey through the Twitter and Instagram social media platforms. We asked the respondents to select 3 top factors from a multiple-choice list of what information they would like from residency programs to help determine if the characteristics of their application align with program values. We examined differences in helpful factors selected by medical school backgrounds using ANOVA. RESULTS: There were 4649 survey respondents. When responses were analyzed by United States-allopathic (US-MD), doctor of osteopathic medicine (DO), and international medical graduate (IMG) educational backgrounds, respondents chose different factors as most helpful: minimum United States Medical Licensing Examination (USMLE) or Comprehensive Osteopathic Medical Licensing Examination (COMLEX) Step 2 scores (565/3042, 18.57% US-MD; 485/3042, 15.9% DO; and 1992/3042, 65.48% IMG; P<.001), resident hometown region (281/1132, 24.82% US-MD; 189/1132, 16.7% DO; and 662/1132, 58.48% IMG; P=.02), resident medical school region (476/2179, 22% US-MD; 250/2179, 11.5% DO; and 1453/2179, 66.7% IMG; P=.002), and percent of residents or attendings underrepresented in medicine (417/1815, 22.98% US-MD; 158/1815, 8.71% DO; and 1240/1815, 68.32% IMG; P<.001). CONCLUSIONS: When applying to residency programs, this study found that the factors that respondents consider most helpful from programs in deciding where to apply differ by educational background. Across all educational groups, respondents want transparency around standardized exam scores, geography, and the racial or ethnic backgrounds of residents and attendings.