The prevalence of high-risk human papillomavirus (HR-HPV) in cytology combined with p16/Ki67 status using limited and two types of extended HPV genotyping has not yet been described. A total of 32,724 screening tests results between 2015-2024 were included. The overall HR-HPV-positivity rate was 15.0%. The HR-HPV prevalence in limited genotyping group was 13.9%, in extended genotyping 1 (17.8%), in extended genotyping 2 (17.2%), with statistically significant difference in the proportions of positive/negative cases (p<0.0001). No statistically significant difference was noted between extended genotyping groups (p=0.706). Extended genotyping 1: the highest p16/Ki67-positivity was observed for HR-HPV 33/58 (100.0%) and 31 (58.8%), the lowest for HR-HPV 45 (18.2%), 18 (25.0%) and 59/56/66 (28.9%). Extended genotyping 2: the highest p16/Ki67-positivity was for HR-HPV 16 (66.7%) and 31/33/52/58 (58.8%). A combined approach, implementing new technologies, could help healthcare providers in more informed decisions about patient care, supporting the prevention of cervical precancer and cancer. ### Competing Interest Statement M.T. has given lectures sponsored by the Hologic company, received coverage for travel and accommodation costs. R.J. has given a lecture sponsored by the Roche company. No disclosures were reported by the other authors. ### Funding Statement This study received no external funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethics Committee of Jagiellonian University (opinion ID 118.6120.36.2023). The study was conducted in accordance with the principles of Declaration of Helsinki. Informed consent was not obtained because of the retrospective design of this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data generated in this study are available within the article. All other raw data are available upon reasonable request from the corresponding author.

This study aimed to evaluate the impact of metastatic lymph nodes (LNs) outside the extended pelvic lymph node dissection (ePLND) template on oncological outcomes, staging, grading, and concomitant parameters in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Data from 860 patients with histologically confirmed, non-metastatic PCa who underwent RP between 2012 and 2022 were retrospectively analyzed. All specimens underwent detailed histopathological examination. Preoperative and postoperative clinicopathological data were collected and analyzed. Subgroup associations were evaluated using the Mann–Whitney U test and the Kruskal–Wallis test. Kendall’s tau-b coefficient was employed to evaluate the association between two variables. All tests were performed using a two-tailed approach, with a p value of less than 0.05 considered statistically significant for differences between groups. Kaplan–Meier and Cox regression analyses assessed biochemical recurrence (BCR)-free survival based on lymph node invasion (LNI) (pN0 vs. pN1) and the presence of metastatic LNs outside the ePLND template. Of the 860 patients, 613 underwent modified-ePLND. Among them, 122 (19.9

Despite significant advancements in prostate cancer (PCa) diagnostics, it remains a challenge for accurate diagnosis and effective treatment. The aging global population and the established correlation between PCa incidence and advancing age suggest an anticipated rise in cases. Traditional clinicopathological parameters, such as prostate-specific antigen (PSA) levels, Gleason Grade Group, and pT stage, highlight the need for novel biomarkers to improve prognostic accuracy and risk assessment. The present study investigated the role of neuropilin-1 (NRP-1) in PCa progression, with a focus on lymph node metastases. Findings reveal that higher NRP-1 expression is associated with a lower percentage of metastatic lymph nodes (9.5 vs. 15.0%; P=0.027) and significantly lower postoperative PSA levels (0.02 vs. 0.21 ng/ml, P=0.039), both considered favorable prognostic factors. These observations align with prior hypotheses suggesting that NRP-1's function may depend on its ligand, semaphoring 3A (SEMA3A) or vascular endothelial growth factor (VEGF), with SEMA3A exhibiting anti-tumoral properties in hormone-sensitive PCa. However, NRP-1 expression showed no correlation with key clinicopathological parameters, such as pT stage or Gleason score, nor did it influence 5-year survival rates. These results suggest that while NRP-1 has potential as a biomarker, its prognostic utility as a standalone factor remains limited. Further studies are warranted to validate these findings in larger cohorts and to explore the molecular mechanisms underlying NRP-1's role in PCa.

BACKGROUND/AIM:Mature teratomas constitute over 95% of ovarian teratomas and account for more than 44% of all ovarian tumors and over 58% of benign ovarian lesions. The pathogenesis of these tumors is hypothesized to involve disruptions in primary germ cell development, with the PI3K/AKT signaling pathway potentially playing a crucial role. This study aimed to analyze the importance of the PTEN protein and its associated signalling pathway, particularly in relation to AKT kinase activation, in the pathogenesis of mature ovarian teratomas. MATERIALS AND METHODS:Surgical specimens from 117 patients with mature ovarian teratomas and control tissues from contralateral ovaries were analyzed. Immunohistochemical analysis was conducted to evaluate the expression of PTEN and phosphorylated AKT (P-AKT/PKB), a key component of the PI3K/AKT pathway regulated by PTEN. Expression levels were assessed using the semi-quantitative Remmele Immunoreactive Score (IRS). RESULTS:An inverse pattern was observed in PTEN expression, with a higher overall IRS score in the study group despite a lower proportion of PTEN-positive cells. The expression of P-AKT protein was elevated in the studied group, both in terms of IRS score and the percentage of P-AKT reactive cells. CONCLUSION:The study supports a potential role of the PI3K/AKT pathway in the pathogenesis of mature ovarian teratomas, as evidenced by increased P-AKT expression. The role of PTEN, however, remains unclear due to contradictory findings. Further research with larger control groups is warranted to clarify these observations.

One of the central dogmas of the Catholic Church is the belief in the Eucharistic presence of Jesus Christ, which requires no scientific confirmation because it concerns a supernatural reality. Since the early Middle Ages, however, instances have been recorded improperly referred to as Eucharistic miracles, which believers consider eyewitness testimony to a real transubstantiation. Changes in the structure, number, or an unexpected bloody red colour of the Host were often regarded as supernatural phenomena, but the Church officials themselves, aware of the possibility of a biological basis for these changes, showed far-reaching restraint. The author's team on the basis of analyses of 25 actual cases undertook to prepare research procedures that make it possible to separate phenomena that are difficult to interpret scientifically, from those associated with contamination. None of these cases revealed the actual proof of existence of human blood, human material other than single epidermal cells, and erythrocytes (probably very low-level contamination). In one case, insignificant amount of human male genetic material was observed, probably as a result of DNA transferred from a person to a host via contact with the host itself. In several specimens, a variety of microbial and fungal material was identified (Brevundimonas intermedia, Serratia marcescens, Epicoccum spp,. Fusarium spp.), including species producing reddish-pink or orange-reddish pigments (Epicoccum spp., Fusarium spp.). Based on the experience gained in this study, a complete procedure suitable for reliable examination of similar cases in the future is suggested. KEY POINTS: • The unusual appearance of the tested hosts can be explained by biological contamination. • Blood-like marks result from the presence of pigment-producing species. • A complete multidisciplinary procedure for investigating 'miracle cases' is proposed.

Colorectal carcinoma brain metastases (n = 60) were studied using next-generation sequencing and immunohistochemistry. RAS and BRAF mutations were detected in 58.2% and 7.3% of cases, respectively. Patients with RAS- and BRAF-mutant tumors could potentially benefit from the treatment with inhibitors. TP53 mutations were detected in 69.1% of metastases. Moreover, altered p53 expression was seen in 91.2% of cases. APC mutations were present in 41.8% of tumors. Diffuse nuclear accumulation of β-catenin was seen in 10.2% of metastases, although only 1 CTNNB1 mutant was identified. Nevertheless, targeting p53 and Wnt/β-catenin pathways may have potential therapeutic implications. Casein kinase 1α1 expression indicating susceptibility to protein kinase inhibitors, was seen in 95% metastases including 10 with strong immunoreactivity. The immune checkpoint marker CD276, a promising target for immunotherapy, was present on tumor cells in 50.8% of metastases and on stromal cells in almost all cases. PRAME, another immunotherapy target, was expressed in 21.7% of tumors. HER2 membrane immunostaining detected in 13.3% of cases implicated potential treatment with HER2 inhibitors. Expression of SLFN11, a predictor of response to DNA-damaging chemotherapies, and a biomarker of sensitivity to PARP inhibitors was seen in 8.3% of tumors. In 6.7% of metastases loss or partial loss of MTAP expression suggested sensitivity to PRMT5 inhibitors. CD44v5 expressed in 35% of cases indicated potential therapeutic utility of anti-CD44v5 monoclonal antibody treatment. Identification of predictive biomarkers through genomic profiling and proteomic analyses is a crucial step toward individually tailored therapeutic regimens for patients with colorectal carcinoma brain metastases.

Lymphovascular invasion (LVI) is an adverse histopathological marker in prostate cancer, associated with increased risks of disease progression and biochemical recurrence. Despite its established value as an independent predictive factor, LVI remains underutilized in clinical decision-making. In particular, LVI identified in radical prostatectomy specimens does not currently influence management strategies, even though numerous studies highlight its critical role in patient outcomes. This review synthesizes recent literature on the clinical significance of LVI in prostate cancer, emphasizing its relationship with biochemical recurrence, lymph node invasion, and survival parameters. Future directions highlight the need for larger prospective studies, standardized definitions, and AI-driven histopathological tools to enhance the detection and integration of LVI into clinical practice.

IntroductionWe report the first case of an asymptomatic woman with osteoclast-like giant cell-rich cervical squamous cell carcinoma (OGC-rich cervical SCC), where the detection of cancer was made possible only by routine cytological screening. The presence of OGCs in cervical SCCs is an extremely rare phenomenon, with only 8 cases reported to date.Case descriptionTwo consecutive liquid-based cytology revealed high-grade squamous intraepithelial lesion (HSIL). Molecular testing detected HPV 18. Colposcopic findings strongly supported the clinical diagnosis of HSIL/suspicious for invasion. Histopathological examination of biopsy samples revealed typical keratinizing-type cervical SCC morphology. The patient subsequently underwent LEEP (loop electrosurgical excision procedure). Microscopic examination of resection specimen confirmed the previous diagnosis. Moreover, groups of large multinucleated cells were observed at the periphery of some invasive nests. Most of them presented the morphology of osteoclasts, whereas some giant cells were similar to Langhans cells. All the giant cells were positive for vimentin and CD68, negative for pancytokeratin. Owing to positive margins following the LEEP procedure, the patient underwent hysterectomy via the Wertheim technique. No adjuvant treatment was applied, and after the 9-month follow-up, the patient was alive with no recurrence.ConclusionDetailed literature review revealed that our case is the first case of keratinizing-subtype cervical OGC-rich SCC. Moreover, it is the youngest (33 yo.) patient with a significantly smaller diameter than previously reported cases. Unfortunately, owing to the small number of reported cases, the analysis did not allow us to draw conclusions about the potential prognostic or predictive value of OGC-rich morphology.

This study aimed to assess the role of Diffusion-Weighted Imaging (DWI) in routine pituitary Magnetic Resonance Imaging (MRI) protocols for distinguishing sellar and parasellar tumors, addressing the lack of clear guidelines in contemporary literature. A retrospective analysis of 242 pituitary MRI scans with DWI sequences was conducted in a single-center study using a 1.5 T scanner and standard DWI sequence parameters. Measurements of both absolute and relative mean apparent diffusion coefficient (ADC) values, along with minimal ADC values within tumors, were performed. The adopted region of interest (ROI) based method used for these measurements was validated. Invasive pituitary adenomas exhibited significantly lower min ADC and min rADC than meningiomas, with optimal cut-off points of 0.64 (sensitivity 73

Background The association of Human Papilloma Virus (HPV) and Human Syncytial Virus (HSV) infection with inflammatory and potentially malignant disorders of the oral cavity (OPMD) is unknown. The aim of this cross-sectional study was to stablish the expression of the p16 INK4A and HSV proteins, to test potential correlation between those parameters in biopsies from clinically diagnosed oral lesions. Methods Immunochemical analysis of 211 formalin-fixed, paraffin-embedded (FFPE) blocks from 211 individuals was provided. The clinical diagnosis included in the research were Oral lichen planus ( N = 30), Oral Leukoplakia ( N = 13) Mucocele ( N = 25), Erosion/ulceration/ inflammation of mucosa ( N = 8), Overgrowth of mucosa ( N = 135). Results Two hundred eleven analyzed FFPE samples resulted with the median age of 58.5 years (the average age 54.0 years and SD ± 17 years). The female/male ratio was 2.3 (69.7% vs 30.3% respectively). All the samples positive for HSV also expressed p16 INK4A ( p = 0.000), that’s showed various levels of association with the diverse clinical diagnosis reaching the higher level in OM 49.1% (29 positive samples) and OLP 30.5% (18). p16 INK4A was associated with OLP at 30.5% (18), and fibroma 30.5%. HSV expression was mostly present in fibroma at 47.6% (10 positive samples). Conclusion HSV and p16 INK4A positivity in relation to diagnosis of the biopsies showed statistically most often p16 INK4A in OLP and fibroma. The results of co-expression of p16 INK4A and HSV in mucocele and fibroma in oral mucosa suggest a cooperation between the molecular alterations induced by these two viruses. Squamous papilloma samples positive for p16 INK4A were also positive for HSV, suggesting that the putative pro-oncogenic action of HSV could be an early event.

Biliary cystadenomas (BCAs), rare cystic tumors occurring in the biliary system, account for fewer than 5% of cystic lesions in the liver. This case details successful resection in a 29-year-old pregnant woman at seven weeks gestation. Urgent left hemihepatectomy and cholecystectomy removed a mucinous hepatobiliary cystadenoma. Postoperatively, a healthy newborn was delivered by cesarean section. Five-year follow-up showed no recurrence. BCAs present diagnostic challenges due to nonspecific symptoms, and surgical intervention, preferably complete resection, is recommended for potential malignancy, after weighing benefits against complications in critical hepatic vessel lesions.

Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family member A/Rho-associated coiled-coil containing kinases (RhoA/ROCK) pathway and whether previously shown downregulation of metalloproteinase 9 (MMP-9) could be associated with MLC phosphorylation. Two doses of simvastatin were administered to experimental rats with autoimmune myocarditis by gastric gavage for 3 weeks, at the stage of development of the inflammatory process. Immunohistochemical staining for RhoA and ROCK1 was evaluated semi-quantitatively with H-score. The RhoA staining showed no significant differences in expression between the groups, but the ROCK1 expression was significantly upregulated in the hearts of the EAM group and was not downregulated by simvastatin. The Western blotting analysis of the last downstream product of the RhoA/ROCK axis, phosphorylated myosin light chain (phospho-MYL9), revealed that protein content increased in EAM hearts and it was prevented by the highest dose of simvastatin. Our findings suggest that the RhoA/ROCK pathway is upregulated in EAM, and simvastatin in EAM settings inhibits the RhoA/ROCK pathway at the stage of phosphorylation of myosin light chains and provides a new insight into the molecular pathology of autoimmune myocarditis.

Background and objective: Lymphovascular invasion (LVI) is a significant histopathological feature in prostate cancer (PCa) associated with higher risk of biochemical recurrence (BCR) and other adverse outcomes. Our aim was to assess the association of LVI found in radical prostatectomy (RP) specimens with BCR and adverse clinicopathological findings. Methods: A systematic literature search was conducted using the PubMed, Embase, and Web of Science databases in July 2023, with an additional search in May 2024. We included 94 prospective and retrospective studies reporting on LVI in RP specimens and its association with the specified outcomes. Key findings and limitations: Meta-analyses revealed that LVI is significantly associated with higher BCR risk (hazard ratio 1.96, 95% confidence interval [CI] 1.73–2.21), higher pathological tumour stage (odds ratio [OR] 5.77; 95% CI 3.96–8.40), higher Gleason score (OR 5.19, 95% CI 4.12–6.54), lymph node metastasis (OR 11.52, 95% CI 7.65–17.34), distant metastasis (OR 9.10, 95% CI 5.46–15.17), positive surgical margins (OR 2.38, 95% CI 1.83–3.09), extraprostatic extension (OR 5.01, 95% CI 3.11–8.06), seminal vesicle invasion (OR 7.50, 95% CI 3.47–16.23), and perineural invasion (OR 133.71, 95% CI 65.93–271.15). Major limitations of this study include high heterogeneity of the data and the reliance on nonrandomised studies. Conclusions and clinical implications: Our findings reveal that LVI is associated with nearly twofold higher risk of BCR, highlighting its potential role as a critical prognostic marker. Patient summary: We analysed data from multiple studies to understand the impact of the spread of prostate cancer into the lymph or blood vessels, called lymphovascular invasion (LVI). We found that LVI is linked to a higher risk of cancer recurrence after surgery and other negative outcomes. Our findings highlight the importance of considering LVI in treatment decisions for better management of prostate cancer.

IntroductionLymphovascular invasion (LVI) is a pivotal histopathological parameter in prostate cancer (PCa), holding significant prognostic implications. Our study pursued a dual objective: firstly, to identify preoperative factors associated with LVI, aiming to unveil markers facilitating the recognition of patients prone to LVI during postoperative examination; and secondly, to assess postoperative outcomes correlated with LVI.MethodsWe retrospectively analyzed 861 nonmetastatic PCa patients who underwent radical prostatectomy (RP), investigating preoperative factors and postoperative outcomes. Surgical specimens were processed following established guidelines. Statistical analyses utilized non-parametric tests to assess the association between LVI and both pre- and postoperative factors. Furthermore, logistic regression analyses were utilized to develop models aimed at identifying the most significant predictors of LVI and pN1 status, respectively.ResultsNumerous preoperative factors exhibited significant correlations with LVI, offering valuable clinical insights. Logistic regression identified magnetic resonance imaging (MRI)-based clinical tumor stage (cT) 3-4, biopsy Gleason Grading Group (GGG) 3-5, preoperative prostate specific antigen (PSA) ≥20 and percentage of positive biopsy cores (PPBC) ≥50% as the strongest preoperative predictors of LVI. Additionally, the study uncovered an association between LVI and postoperative outcomes, including postoperative PSA (p value <0.001), extracapsular extension (ECE) (<0.001), positive surgical margins (PSM) (<0.001), perineural invasion (PNI) (<0.001), pathological tumor stage (pT) (<0.001), pathological lymph node status (pN) (<0.001), postoperative GGG (<0.001), and operative time (0.023). Notably, the study revealed a novel and substantial association between LVI and an increased number of positive lymph nodes in pN+ patients in the univariate analysis (<0.001). Furthermore, we have found an association between LVI and pN1 status in the logistic regression analysis (odds ratio [OR] = 23.905; p <0.001).ConclusionOur findings underscore the pivotal role of LVI in influencing the prognosis of prostate cancer (PCa). The study acknowledges the challenges associated with preoperative LVI assessment and emphasizes the need for future research to unravel the factors associated with this histopathological finding. Significantly, our research stands out as the first, to the best of our knowledge, to reveal the association between LVI and the number of positive lymph nodes in pN+ patients.

Introduction: Etiopathogenesis and the symptomatology of ureteropelvic junction obstruction (UPJO) in the pediatric population has not yet been definitely clarified, suggesting a multifactorial nature of the condition. The aim was to analyze the association between the number of Interstitial Cells of Cajal (ICCs), as well as P2X3 receptors in ureteropelvic junction (UPJ) and the pain response in pediatric patients with hydronephrosis. Methods: 50 patients with congenital hydronephrosis underwent open or laparoscopic pyeloplasty at one of two departments of pediatric surgery and urology in Poland. Patients were divided into two groups according to the pain symptoms before surgery. A total of 50 samples of UPJ were obtained intraoperatively and underwent histopathological and immunohistochemical (IHC) analysis. Quantitative assessment of ICCs was based on the number of CD117(+) cells of adequate morphology in the subepithelial layer and the muscularis propria. Expression of P2X3 receptors was evaluated as the intensity of IHC staining. Results: Patients with hydronephrosis and accompanying pain were on average 60 months older (77 vs. 17 months) than children with asymptomatic hydronephrosis (p = 0.017). Symptomatic children revealed higher numbers of ICCs in both the subepithelial layer and in the lamina muscularis propria. In particular, symptomatic patients aged 2 years or more exhibited significantly higher numbers of ICCs in the subepithelial layer. Significant differences in the distribution of ICCs between the subepithelial layer and the lamina muscularis propria were observed in both groups. Expression of P2X3 receptors was limited to the urothelium and the muscle layer and correlated between these structures. There was no relationship between pain response and the expression of P2X3 receptors. Conclusions: ICCs and P2X3 receptors may participate in the pathogenesis of UPJO and in the modulation of pain response to a dilatation of the pyelocaliceal system. Explanation of the role of ICCs and P2X3 receptors in propagation of ureteral peristaltic wave and the modulation of pain stimuli requires further studies.

Background: This study assessed the topography and lateralization of lymph node (LN) metastases in muscle-invasive bladder cancer (MIBC) patients using super-extended pelvic lymph node dissection (sePLND) with sentinel lymph node dissection (SLND). Methods: We analyzed 54 MIBC patients who underwent cystectomy with sePLND and SLND. Tumor location was classified using cystoscopy. Nanocolloid-Tc-99m was injected peritumorally. Preoperative SPECT/CT lymphoscintigraphy and an intraoperative gamma probe were used for SLN detection. Results: A total of 1414 LNs, including 192 SLNs, were resected from 54 patients. Metastases were found in 72 LNs from 22 patients (41%). The obturator fossa was the primary site for LN metastases (37.5%). SLNs were most common in the external iliac region (34.4%). In 36% of the patients with positive LNs, metastases were identified only through sePLND. In 9% of the patients, metastases were found solely in the pararectal region, identified through SLND. Tumor lateralization correlated with ipsilateral positive LNs, but 20% of the patients had contralateral metastases. Conclusions: The pararectal region may be the exclusive site for positive LNs in MIBC. The obturator fossa is the most prevalent region for LN metastases. Unilateral PLND should be avoided due to the risk of contralateral metastases. Combining sePLND with SLND improves staging.

Background/Objectives: Preferentially expressed antigen in melanoma (PRAME), a member of the cancer testis antigen family, is a promising target for cancer immunotherapy. Understanding the epigenetic mechanisms involved in the regulation of PRAME expression might be crucial for optimizing anti-PRAME treatments. Methods: Three malignancies of different lineages (sinonasal melanoma, testicular seminoma, and synovial sarcoma), in which immunohistochemical (IHC) reactivity for PRAME is a common yet variable feature, were studied. The expression of PRAME, ten-eleven translocation demethylase 1 (TET1), and DNA methyltransferase (DNMT) 3A and 3B were evaluated using immunohistochemistry. Moreover, the expression of two epigenetic marks, 5-hydroxymethylcytosine (5hmC) and histone 3 acetylation (H3ac), was tested. Results: All PRAME-positive tumors expressed medium-to-high levels of H3ac but differed considerably with respect to other markers. In seminomas, PRAME expression correlated with TET1, but in melanomas and synovial sarcomas, it correlated with both DNMTs and DNMT3A, respectively. Conclusions: PRAME expression was not determined by a balance between the global expression of DNA methylating/demethylating enzymes. However, histone acetylation may be one of the epigenetic mechanisms involved in PRAME regulation. Thus, the therapeutic combination of histone deacetylase inhibitors and PRAME immunotherapy merits further investigation.

(1) Background: Kidney transplantation is the best therapy for patients with end-stage renal disease, but the risk of rejection complicates it. Indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme involved in immune response modulation, has been suggested to play a role in transplant immunological injury. The aim of the study was to explore the expression of IDO1 in the interstitial foci of transplanted kidneys and its potential association with rejection episodes. (2) Methods: This retrospective study analysed kidney transplant biopsies from 121 patients, focusing on IDO1 expression in interstitial foci. Immunohistochemistry was used to detect IDO1, and patients were categorised based on IDO1 presence (IDO1-IF positive or negative). The incidence of rejection was compared between these groups. (3) Results: Patients with IDO1 expression in interstitial foci (IDO1-IF(+)) exhibited higher incidences of rejection 46/80 (57.5%) vs. 10/41 (24.34%) patients compared to IDO1-IF(−) patients, which was statistically significant with p = 0.0005. The analysis of antibody-mediated rejection showed that IDO1-IF(+) patients developed AMR at 12/80 (15%), while only 1 IDO1-IF(−) negative patient did (2,44%), with p = 0.035. T-cell-mediated rejection was also more common in IDO1-IF(+) patients 43/80 (53.75%) than in IDO1-IF(−) patients 7/41 (17.07%), with p = 0.0001. (4) Conclusions: IDO1 expression in interstitial foci of renal transplant biopsies is associated with a higher incidence of rejection, suggesting that IDO1 could serve as a potential biomarker for transplant rejection. These findings highlight the importance of IDO1 in immune regulation and its potential utility in improving the management of kidney transplant recipients.

Background : Major screening abnormalities in pre-colposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primary HPV-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Methods : Among 30,066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available HRHPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Results : Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher PPV for HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p<0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2,26/2,19 vs. 3,54). Only 1 HSIL+ case was missed in both triage models with DS incorporation. Conclusions : p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.