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Editorial on the Research Topic Value of a multidisciplinary approach for modern diagnosis of infectious diseases Editorial Infectious diseases continue to pose significant challenges to global public health, exacerbating the burden on healthcare systems worldwide (Naghavi et al., 2024; La Via et al., 2024). From advancements in rapid diagnostic assays to innovative approaches in therapeutic intervention, the contributions in this Research Topic illustrate the potential of these tools to reshape the landscape of infectious disease management. Huang et al. report the assay’s high specificity for extrapulmonary tuberculosis (EPTB), offering a non-invasive and efficient diagnostic tool that could reduce mortality, especially in settings where conventional methods fall short. [...]the development of a sandwich immunoassay targeting Francisella tularensis outer membrane protein A for tularemia diagnosis, as described by Jang et al., represents a leap forward in addressing bioterrorism-related pathogens. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The expression of programmed death-ligand 1 (PD-L1) is an established prerequisite for the administration of checkpoint inhibitor therapy and is of prognostic value in several cancer types. Data concerning the potential effect of PD-L1 on the prognosis of thyroid carcinoma are limited. Therefore, this study aimed to provide a systematic review of the published data on this topic. The literature was reviewed to gather and quantify evidence on the prognostic role of PD-L1 in follicular epithelial derived thyroid carcinomas and determine its association with clinicopathological parameters. A meta-analysis was performed using the DerSimonian-Laird random-effects model. The quality of studies was evaluated with the Newcastle-Ottawa Scale and a modified GRADE approach used to rate the quality of evidence. Out of 445 papers, 18 were included and 15 provided adequate data for meta-analysis. The quality of evidence ranged from low to high. PD-L1 expression was significantly associated with a reduced disease-free survival (DFS) (RR 1.63, CI 1.04–2.56, p = 0.03, I2 68%, τ2 0.19 and HR 1.90, CI 1.33–2.70, p< 0.001, I2 0%, τ2 0.00); however, no association was found with the overall survival (OS). Furthermore, a significant association was found with respect to underlying chronic lymphocytic thyroiditis and BRAFV600E mutation status in papillary thyroid carcinomas. In the subgroup analysis, the association of PD-L1 and DFS remained strong in papillary thyroid carcinoma when compared with dedifferentiated thyroid carcinomas (anaplastic and poorly differentiated thyroid carcinomas) that failed to demonstrate a significant association with respect to PD-L1. These findings underscore the role of PD-L1 immunohistochemistry as a potential prognostic biomarker of disease recurrence in patients with papillary thyroid carcinoma.

Objective Digital pathology (DP) is currently in the spotlight and is rapidly gaining ground, even though the history of this field spans decades. Despite great technological progress, the adoption of DP for routine clinical diagnostic use remains limited. Methods A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all published studies that encompassed any application of DP. Results Of 4888 articles retrieved, 4041 were included. Relevant articles were categorized as “diagnostic” (147/4041, 4%) where DP was utilized for routine diagnostic workflow and “non-diagnostic” (3894/4041, 96%) for all other applications. The “non-diagnostic” articles were further categorized according to DP application including “artificial intelligence” (33%), “education” (5%), “narrative” (17%) for reviews and editorials, and “technical” (45%) for pure research publications. Conclusion This manuscript provided temporal and geographical insight into the global adoption of DP by analyzing the published scientific literature.

One of the most relevant prognostic factors in cancer staging is the presence of lymph node (LN) metastasis. Evaluating lymph nodes for the presence of metastatic cancerous cells can be a lengthy, monotonous, and error-prone process. Owing to digital pathology, artificial intelligence (AI) applied to whole slide images (WSIs) of lymph nodes can be exploited for the automatic detection of metastatic tissue. The aim of this study was to review the literature regarding the implementation of AI as a tool for the detection of metastases in LNs in WSIs. A systematic literature search was conducted in PubMed and Embase databases. Studies involving the application of AI techniques to automatically analyze LN status were included. Of 4584 retrieved articles, 23 were included. Relevant articles were labeled into three categories based upon the accuracy of AI in evaluating LNs. Published data overall indicate that the application of AI in detecting LN metastases is promising and can be proficiently employed in daily pathology practice.

The transmission of cancer from a donor organ is a rare event but has important consequences. Aim of this systematic review was to summarize all the published evidence on cancer transmission in kidney recipients. We reviewed published case reports and series describing the outcome of recipients with donor-transmitted cancer until August 2019. A total of 128 papers were included, representing 234 recipients. The most common transmitted cancers were lymphoma (n = 48, 20.5%), renal cancer (42, 17.9%), melanoma (40, 17.1%), non-small cell lung cancer (n = 13, 5.6%), neuroendocrine cancers comprising small cell lung cancer (n = 11, 4.7%) and choriocarcinoma (n = 10, 4.3%). There was a relative lack of glioblastoma and gastrointestinal cancers with only 6 and 5 cases, respectively. Melanoma and lung cancer had the worst prognosis, with 5-years overall survival of 43% and 19%, respectively; while renal cell cancer and lymphomas had a favorable prognosis with 5-years overall survival of 93 and 63%, respectively. Metastasis of cancer outside the graft was the most important adverse prognostic factor. Overall reporting was good, but information on donors’ cause of death and investigations at procurement was often lacking. Epidemiology of transmitted cancer has evolved, thanks to screening with imaging and blood tests, as choriocarcinoma transmission have almost abolished, while melanoma and lymphoma are still difficult to detect and prevent.

Objectives and background: Oral squamous cell carcinoma (OSCC) is a highly malignant disease with an increasing incidence. The need to improve therapeutic strategies for patients affected by OSCC is an urgent challenge. Currently, the advent of immunotherapy represents an important step toward this aim. Programmed cell death‐ligand 1 (PD‐L1), a membrane protein that can be expressed on tumor and inflammatory cells is a key biomarker whose expression is determined by means of immunohistochemistry and is necessary for selecting patients for immunotherapy. Methods: In this study, we review the methods of PD‐L1 assessment and outcomes achieved with immunotherapy in the treatment of OSCC patients. Results: Based on a meta‐analysis we demonstrate a lack of prognostic significance of PD‐L1 in OSCC. Conclusions: We also highlight unresolved issues including difficulties in standardizing PD‐L1 evaluation and discuss future opportunities such as leveraging digital pathology.

: Up to 30% of patients with HR+/HER2-early breast cancer (eBC) may experience distant recurrence, and patients with high-risk clinical features have a higher likelihood of recurrence. For these patients, the addition of a CDK4/6 inhibitor to standard adjuvant endocrine therapy (ET) has demonstrated a significant reduction in the risk of invasive and distant recurrence. Despite that, a small subset of patients still experience distant relapse. To date, the characteristics of patients who relapse on adjuvant CDK 4/6i are not well defined. : Here we report the case of a patient with early-stage HR+/HER2- breast cancer at high risk of recurrence, who experienced distant metastatic relapse during adjuvant therapy with abemaciclib plus ET, with a shift in the tumor subtype to triple-negative. Genomic alterations associated with ET and cyclin-dependent kinase 4 and 6 inhibitor resistance were analyzed with next-generation sequencing (NGS) carried out at recurrence. Results showed P53 and PI3KCA pathway alterations, but no ESR1 mutation or RB1 mutations. The duration was 12 months for adjuvant abemaciclib, and the first-line metastatic treatment lasted less than 3 months. Conversely, T-DXd administered due to the presence of HER2-low showed excellent effectiveness. : The management of breast cancer relapse occurring during adjuvant therapy with CDK4/6 inhibitors is challenging. Performing a re-biopsy is crucial due to the possible loss of estrogen receptors, which would require a change in therapeutic strategy no longer based on endocrine therapy. In cases that remain luminal, knowledge of the mutational profile may help to offer patients novel targeted treatments.

This manuscript presents a manifesto developed by a multifaceted board of stakeholders aimed at guiding the implementation of Digital Twin (DT) technology in pathology laboratories. DTs, already transformative in other sectors, hold substantial promise for enhancing operational efficiency, diagnostic accuracy, and quality of care in pathology. We provide a comparative analysis of traditional versus DT-enhanced workflows across critical steps including accessioning, grossing, processing, embedding, cutting, staining, scanning, diagnosis, and archiving. The framework highlights measurable gains such as up to 90% reduction in labeling errors, 20–30% improvements in slide quality, and 30–50% reductions in diagnostic turnaround time. Alongside these benefits, we address key implementation challenges including upfront infrastructure costs, workforce adaptation, and data security concerns. A practical, phased deployment strategy is proposed—centered on LIS integration, IoT sensors, AI modules, and robust data governance. Estimated setup costs for a medium-sized laboratory range between USD 100,000 and USD 200,000, with a phased rollout timeline of 12–24 months. Supporting technologies like robotic process automation (RPA), collaborative robotics, and edge computing are also discussed as enablers of successful DT adoption. The manifesto closes by identifying critical research gaps, including the need for longitudinal studies evaluating DTs’ clinical and economic impacts, integration within existing hospital IT systems, and ethical implications of AI-assisted diagnostics. Through this collective vision, we provide a realistic and actionable roadmap to drive the transition toward predictive, efficient, and digitally optimized pathology laboratories.

This comprehensive review examines the unique attributes, distinctions, and clinical implications of ceftazidime–avibactam (CAZ-AVI) and meropenem–vaborbactam (MEM-VAB) against difficult-to-treat Enterobacterales infections. Our manuscript explores these antibiotics’ pharmacokinetic and pharmacodynamic properties, antimicrobial activities, in vitro susceptibility testing, and clinical data. Moreover, it includes a meticulous examination of comparative clinical and microbiological studies, assessed and presented to provide clarity in making informed treatment choices for clinicians. Finally, we propose an expert opinion from a microbiological and a clinical point of view about their use in appropriate clinical settings. This is the first review aiming to provide healthcare professionals with valuable insights for making informed treatment decisions when combating carbapenem-resistant pathogens.

Kidney transplantation is the best treatment for end-stage renal disease since it offers the greatest survival benefit compared to dialysis. The gap between the number of renal transplants performed and the number of patients awaiting renal transplants leads to a steadily increasing pressure on the scientific community. Kidney preimplantation biopsy is used as a component of the evaluation of organ quality before acceptance for transplantation. However, the reliability and predictive value of biopsy data are controversial. Most of the previously proposed predictive models were not associated with graft survival, but what has to be reaffirmed is that histologic examination of kidney tissue can provide an objective window on the state of the organ that cannot be deduced from clinical records and renal functional studies. The balance of evidence indicates that reliable decisions about donor suitability must be made based on the overall picture. This work discusses recent trends that can reduce diagnostic timing and variability among players in the decision-making process that lead to kidney transplants, from the pathologist’s perspective.