Search Results (175)

Background/Objectives: Pancreatic cancer (PC) is a diagnosis with a poor prognosis which can be associated with significant distress and may hinder a patient’s ability to understand treatment details. Educating patients based on their learning preferences (LPs) and emotions may allow for personalized, enhanced care. Methods: This prospective project enrolled patients with non-metastatic PC. Phase 1 utilized the Learning Preference Barometer (LPB) and Emotional Journey Barometer (EJB), which are digital instruments co-designed by CANCER101 (C101) and the Health Collaboratory, to assess patient LPs and emotional states. Phase 2 provided information prescriptions aligned with LPs through C101’s Prescription to Learn^® (P2L) platform. Collected data included demographics, treatment, LPs (auditory, kinesthetic, linguistic, visual), patient engagement with P2L, and patient emotional states with qualitative verbal validation. Descriptive variables were used to report outcomes. Results: Primary LPs in the 47 participating patients were as follows: linguistic 45%, visual 34%, auditory 11%, and kinesthetic 9%, with secondary preferences in the majority (53%). Those patients (66%) who accessed P2L had linguistic and visual preferences; the majority accessed 1- 2 resources out of the 25 provided. Resources accessed aligned to 88% of patient LPs. The majority of patients (60%) initiated treatment prior to initial EJB, and 40% were treatment naive. Common baseline emotions were optimistic (47% vs. 36%, respectively), satisfied (11% vs. 25%), acceptance (11% vs. 11%), and overwhelmed (5% vs. 11%). Conclusions: Assessing LPs and emotional state allows for personalized patient education and clinical encounters for PC patients. Future work includes examining the effects of personalized approaches on patient satisfaction, decision-making, health outcomes, and the overall patient–clinician relationship. Full article

Background: Lung cancer remains one of the leading causes of cancer-related mortality worldwide. While most diagnoses occur in outpatient settings, a subset of cases are incidentally identified during emergency department (ED) visits. The clinical characteristics and treatment decisions of these patients, particularly in relation to social background factors such as living situation and access to primary care, remain poorly understood. Methods: We conducted a retrospective study of patients diagnosed with malignancies in the ED of a single institution between April 2018 and December 2021. Patients diagnosed with lung cancer within 60 days of an ED visit were included. Data on demographics, disease status, treatment decisions, and background factors—including whether patients lived alone or had a primary care physician (PCP)—were extracted and analyzed. Results: Among 32,108 patients who visited the ED, 148 were diagnosed with malignancy within 60 days; 23 had lung cancer. Of these, 69.6% had metastatic disease at diagnosis, and 60.9% received active treatment (surgery or chemotherapy). No significant associations were observed between the extent of disease and either living arrangement or PCP status. However, the presence of a PCP was significantly associated with the selection of best supportive care (p = 0.023). No significant difference in treatment decisions was observed based on age (cutoff: 75 years). Conclusions: Although social background factors such as living alone were not significantly associated with cancer stage or treatment choice, the presence of a primary care physician was associated with a higher likelihood of best supportive care being selected. This may indicate that patients with an established PCP have more clearly defined care goals at the end of life. These findings suggest that primary care access may play a role in shaping end-of-life care preferences, highlighting the importance of personalized approaches in acute oncology care. Full article

Introduction: This study aimed to assess the accuracy of real-time polymerase chain reaction (PCR) as a diagnostic tool for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients and evaluate the applicability of quantification cycle (Cq) data for PCP diagnosis. Methods: Clinical and laboratory data were collected from medical records of 96 immunocompromised patients hospitalized at the Hadassah hospital from 2018 to 2022, for lower respiratory tract infection. PCP diagnosis was independently categorized by two infectious disease specialists, blinded to PCR results, as either “definite” (confirmed by microscopic identification of P. jirovecii) or “probable” (compatible clinical data and negative microscopy). Clinical characteristics, PCR test performance, and Cq values were then compared between these PCP diagnostic groups and a control group of 85 patients who underwent bronchoscopy for indications unrelated to P. jirovecii infection. Results: The PCR test was found to be highly reliable for diagnosing PCP, with high sensitivity and specificity (93.1%, 98.7%, respectively), a positive predictive value (PPV) of 96.4%, a negative predictive value (NPV) of 97.1%, a negative likelihood ratio of 0.71, and a positive likelihood ratio of 46.5. A Cq cutoff value of 21.89 was found to discriminate between probable PCP and definite PCP. In addition, patients with probable PCP had lower in-hospital mortality than those with definite PCP or no PCP. Conclusions: PCR offers a promising approach for diagnosing PCP in immunocompromised patients with negative respiratory microscopy results. While further research may be warranted, its use may allow for more timely treatment and potentially improved outcomes. Full article

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental condition typically requiring information from multiple informants for accurate diagnosis. However, the consistency and diagnostic value of reports from teachers, parents, primary care providers (PCPs), and other professionals remain debated. This study aimed to examine the role and diagnostic accuracy of different informants in the referral and diagnostic process for ADHD in children aged 3–11. Methods: This retrospective study analyzed data from 120 children referred for suspected ADHD. Initial reports were obtained from teachers, parents, PCPs, and other professionals, and final diagnoses were determined through comprehensive neuropsychiatric evaluations. Diagnostic concordance and informant-specific contributions were assessed. Results: Of the 120 children, 64 (53.3%) received an ADHD diagnosis. Teachers were the most frequent informants, followed by parents, with fewer referrals from PCPs and other professionals. No significant differences in diagnostic accuracy were found among informants, aligning with previous studies suggesting that no single informant is superior in identifying ADHD. Notably, over 93% of referred children were diagnosed with a neuropsychiatric disorder, though not necessarily ADHD. Conclusions: The findings underscore the importance of combining reports from parents and teachers to capture symptom expression across different environments, which is essential for accurate ADHD diagnosis. Enhanced training for informants and a multidisciplinary approach is recommended to improve diagnostic accuracy and support early identification and intervention efforts. These results support nuanced evaluation strategies that account for informant variability and help mitigate potential misinterpretations of ADHD symptoms. Full article

Background/Objectives: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [¹¹¹In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [^99mTc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. Methods: CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed ex vivo by Western blotting. Results: In vitro studies showed similar target-specific binding and internalization of [¹¹¹In]In-RM2 and [^99mTc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, in vivo imaging showed negligible tumor uptake in xenografts of the transduced cell lines. Ex vivo analysis indicated a loss of the respective biomarkers in the xenografts. Conclusions: Although the technical feasibility of a dual-tracer SPECT imaging approach using ¹¹¹In and ^99mTc has been demonstrated, the potential of [^99mTc]Tc-PSMA-I&S and [¹¹¹In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The in/ex vivo experiments indicated that results from an in vitro model may not necessarily be successfully transferred to an in vivo setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized in vivo models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches. Full article

Background/Objectives: Intrauterine growth restriction (IUGR) is a pathological condition defined by a reduced fetal ability to achieve the genetically expected growth potential during gestation. It affects 5–10% of all pregnancies and it is a leading cause of perinatal morbidity and mortality. During the initial phases of placentation, complex interlinked processes including cell proliferation, differentiation, apoptosis and the invasion of trophoblasts occur. Alterations in the regulation of these processes lead to placental dysfunction. Survivin, a member of the inhibitor of apoptosis (IAP) family, plays an important role in cell proliferation balance and apoptosis, thus leading to proper placental development. This study aimed to evaluate survivin expression in placentas from IUGR and healthy pregnancies to explore its potential as a biomarker for the early diagnosis, prevention, and treatment of IUGR. Methods: Survivin presence was determined in 153 archival formalin-fixed and paraffin-embedded placental tissues from IUGR (N = 122) and uncomplicated (N = 31) term pregnancies. Tissue microarrays (TMAs) were constructed, and survivin expression was assessed using immunohistochemistry (IHC). Survivin levels were quantified using positive cell proportion (PCP) scores and immunoreactive scores (IRS), with statistical significance determined using mean values, standard deviation (SD), standard error, and Student’s t test in instances of normal distribution, and when this was not the case, the Mann–Whitney test. Chi-square tests, Fisher exact tests, and t-tests (p < 0.05) were used to compare categorical variables. Results: Our results suggested the significantly higher expression of survivin validated with PCP (p < 0.001) and IRS (p < 0.002) in placentas with IUGR compared to placentas from non-complicated term pregnancies. Conclusions: Increased survivin expression in IUGR placentas points to its potential role as a key indicator of placental dysfunction. By signaling early pathological changes, survivin may offer a valuable tool for the early detection of IUGR, potentially allowing for timely clinical interventions that could reduce the risk of serious outcomes, including stillbirth. To fully establish survivin’s clinical value, further research is needed to validate its diagnostic accuracy and to explore its involvement in molecular pathways that may be targeted for therapeutic benefit. Full article

While multi-parametric magnetic resonance imaging (mpMRI) is known to be a specific and reliable modality for the diagnosis of non-metastatic prostate cancer (PC), positron emission tomography (PET) using ⁶⁸Ga labeled ligands targeting the prostate-specific membrane antigen (PSMA) is known for its reliable detection of prostate cancer, being the most sensitive modality for the assessment of the extra-prostatic extension of the disease and the establishment of a diagnosis, even before biopsy. Background/Objectives: Here, we compared these modalities in regards to the localization of intraprostatic cancer lesions prior to local HDR brachytherapy. Methods: A cohort of 27 patients received both mpMRI and PSMA-PET/CT. Based on 24 intraprostatic segments, two readers each scored the risk of tumor-like alteration in each imaging modality. The detectability was evaluated using receiver operating characteristic (ROC) analysis. The histopathological findings from biopsy were used as the gold standard in each segment. In addition, we applied a patient-based “congruence” concept to quantify the interobserver and intermodality agreement. Results: For the ROC analysis, we included 447 segments (19 patients), with their respective histological references. The two readers of the MRI reached an AUC of 0.770 and 0.781, respectively, with no significant difference (p = 0.75). The PET/CT readers reached an AUC of 0.684 and 0.608, respectively, with a significant difference (p < 0.001). The segment-wise intermodality comparison showed a significant superiority of MRI (AUC = 0.815) compared to PET/CT (AUC = 0.690) (p = 0.006). Via a patient-based analysis, a superiority of MRI in terms of relative agreement with the biopsy result was observed (n = 19 patients). We found congruence scores of 83% (MRI) and 76% (PET/CT, p = 0.034), respectively. Using an adjusted “near total agreement” score (adjacent segments with positive scores of 4 or 5 counted as congruent), we found an increase in the agreement, with a score of 96.5% for MRI and 92.7% for PET/CT, with significant difference (p = 0.024). Conclusions: This study suggests that in a small collective of low-/intermediate risk prostate cancer, mpMRI is superior for the detection of intraprostatic lesions as compared to PSMA-PET/CT. We also found a higher relative agreement between MRI and biopsy as compared to that for PET/CT. However, further studies including a larger number of patients and readers are necessary to draw solid conclusions. Full article

Background: Parathyroid neoplasia is a heterogeneous group of tumors, including parathyroid adenoma (PA), atypical parathyroid tumors (aPTs), and parathyroid carcinoma (PC). Differential diagnosis, especially preoperatively, between parathyroid carcinoma and the other two entities is challenging. The purposes of this study were to highlight the main differences between different parathyroid tumors and to evaluate how combined PC suspicion and intraoperative adjuncts can influence surgical decision-making and outcome-related issues. Methods: We performed a retrospective study of a database of patients diagnosed with parathyroid tumors who underwent surgical treatment at our endocrine surgery referral center between June 2019 and July 2024. Demographic, clinical, biochemical, imaging, intraoperative, immunohistochemical, and follow-up data were analyzed. Results: A total of 83 cases were included in our study, divided for analysis into PA (n = 67), aPT (n = 9) and PC (n = 7) subgroups. The clinical profile of the cohort showed a significant difference (p < 0.05) between the PA, aPT, and PC subgroups regarding the presence of palpable tumors (0% vs. 11.11% vs. 14.29%), both bone and kidney involvement (14.93% vs. 44.44% vs. 85.71%), and extensive disease beyond bone and kidney involvement (4.48% vs. 44.44% vs. 71.43%). PTH levels over five times the normal value were present at significantly different rates (p < 0.001), with higher rates in the aPT and PC subgroups (55.56% and 85.71%, respectively) compared with the PA subgroup (7.46%). Also, a significant difference (p < 0.001) was observed when analyzing extreme albumin-corrected serum calcium elevations over 14 mg/dL, with much higher rates in the PC subgroup (71.43%) compared to PA (1.49%) and aPT (33.33%). On preoperative ultrasonography, a significantly higher number of PCs presented diameters ≥ 3 cm (p < 0.001), depth-to-width ratios (D/W) ≥ 1 (p = 0.003), suspicious delineation (p < 0.001), and suspicious echotexture features (p < 0.001), compared to PAs. On preoperative US performed by the surgeon, suspicious features for thyroid cancer were identified in five more patients compared to the four identified by the initial US evaluation, and all (10.84% of all patients) were confirmed on final histopathology as papillary thyroid cancers. Intraoperatively, a significant difference (p < 0.001) regarding parathyroid macroscopic suspicious features, including adhesions to the thyroid gland, was seen between subgroups. When analyzing only cases with en bloc resection, we found that, in all PC cases, a combined preoperative suspicion was present, and in five cases an intraoperative suspicion was raised. Immunohistochemical data showed significantly different median Ki-67 indices between subgroups (1, 2, and 5; p = 0.008) and a different parafibromin staining profile between PC and aPT. Regarding intraoperative neuromonitoring use, a significantly lower incidence of voice changes related to the external branch of the superior laryngeal nerve was observed in the monitoring vs. non-monitoring group (57.14% vs. 12.5%, p = 0.019). Conclusions: Our findings confirm that, in a multimodal and combined diagnostic approach, early pre- and intraoperative PC suspicion can be raised in order to optimize surgical treatment and, thus, favorably influence the outcome. Utilizing all resources available, including intraoperative parathormone determination, laryngeal nerve neuromonitoring, and immunohistochemistry staining, can bring extra benefit to the management of these challenging cases. Full article

Background: The role and underlying mechanisms of synaptophysin-like-1 (SYPL1), a neuroendocrine-associated protein, in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study aims to assess the diagnostic potential of SYPL1 as a serum biomarker for both resectable PDAC (rPDAC) and metastatic PDAC (mPDAC) located at the head of the pancreas. Additionally, the SYPL1 levels were monitored in PDAC patients who underwent surgical resection, with follow-up measurements taken 6 months postoperatively. Method: We analyzed serum SYPL1 in healthy controls (n = 67), rPDAC patients (n = 39), mPDAC patients (n = 22), and rPDAC patients (6-month postoperative) (n = 20) (due to factors such as relocation or death, 20 patients were included instead of 39 patients) by ELISA. Results: The SYPL-1 levels showed significant differences across the groups (controls: 7.43 ± 3.32, PC: 15.89 ± 2.00, mPDAC: 20.01 ± 4.03, p < 0.001). Both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were significantly greater in cancer groups compared to the healthy group. In patients who underwent surgical resection, the SYPL-1 levels showed a significant decrease 6 months after surgery (p < 0.001). Strong correlations were observed between tumor markers, with CA19-9 showing a positive correlation with CEA in both rPDAC (r = 0.550, p < 0.001) and mPDAC (r = 0.623, p = 0.002), while SYPL-1 demonstrated a negative correlation with CEA (r = −0.530, p = 0.009) in mPDAC. Receiver operating characteristic (ROC) analysis revealed excellent diagnostic performance for SYPL-1 in distinguishing both rPDAC (AUC = 0.965) and mPDAC (AUC = 0.985) from healthy controls, achieving superior accuracy compared to conventional markers CEA and CA19-9. Conclusions: Serum SYPL-1 emerges as a promising biomarker for the diagnosis and monitoring of rPDAC and mPDAC. Its significantly elevated levels in cancer groups, coupled with its marked decrease following surgical resection, suggest that SYPL-1 could play a critical role in both initial diagnosis and post-treatment surveillance. The strong correlations observed between SYPL-1, CEA, and CA19-9 further support its potential utility in a multi-marker panel. Notably, SYPL-1 demonstrated superior diagnostic accuracy compared to conventional markers, with high AUC values indicating its excellent ability to distinguish rPDAC and mPDAC from healthy controls. These findings highlight the need for further investigation to validate SYPL-1 as a reliable, non-invasive biomarker that could enhance early detection, prognosis, and treatment monitoring in rPDAC. Full article

Objective: The objective of this study was to calculate the epidemiological impact of metabolic dysfunction associated with fatty liver disease (MAFLD) and hepatic fibrosis in primary care (PC). Secondarily, we assessed the correlation between serological markers (FIB-4, ELF test), abdominal ultrasound, and transient elastography in the early detection of MAFLD. Methods: An observational prospective study was designed to determine the prevalence of MAFLD and to assess the correlation between complementary tests. Patients were recruited from five health centres. Eligible participants were adults aged between 18 and 70 years with at least one metabolic risk factor, including being overweight (BMI 25–29.9 kg/m²) or obese (BMI > 30 kg/m²), or diagnosed with type 2 diabetes mellitus (T2DM), dyslipidemia, or metabolic syndrome. The prevalence of MAFLD was calculated. Correlations between diagnostic tests were evaluated using Pearson’s correlation coefficient. Results: A total of 98 patients was included. Using CAP (controlled attenuation parameter) measurements, the prevalence of MAFLD was found to be 67.7%, and the prevalence of hepatic fibrosis was 6.5%. The correlation between conventional ultrasound and CAP from FibroScan^® for the diagnosis of MAFLD was low and not statistically significant (0.160 [95% CI: −0.100; 0.400], p = 0.226). In contrast, the diagnosis of hepatic fibrosis using FibroScan^® in PC showed a high correlation with diagnoses performed in gastroenterology department (0.942 [95% CI: 0.844; 0.979], p < 0.001). The correlation with biochemical markers was low and not statistically significant for both FIB-4 (0.125 [95% CI: −0.129; 0.363], p = 0.334) and the ELF test (0.159 [95% CI: −0.111; 0.407], p = 0.246). Conclusions: Two out of three patients with metabolic risk factors were diagnosed with MAFLD, while hepatic fibrosis diagnoses were uncommon. These results reinforce the validity of using FibroScan^® in PC. Full article

Background and Objectives: In light of the growing need to incorporate primary care physicians (PCPs) in the complex care system for autistic patients, this study aims to assess the level of physicians’ knowledge of the autism spectrum in Poland. Materials and Methods: After a literature review, an online survey consisting of 20 items assessing the knowledge of autism etiology, diagnosis criteria, and patient support was developed. Of 250 invitations, 166 physicians filled out the form (a 66.4% response rate). For the statistical analysis, the normal distribution was excluded for all data based on the Shapiro–Wilk test. The U-Mann–Whitney test was performed for two variables to verify the comparison of variables. The threshold of statistical significance was at the level of p = 0.05. Results: Correct responses regarding autism etiology, diagnosis, and support were 37.95%, 42.69%, and 70.05%, respectively. Female physicians presented a higher level of knowledge regarding all categories. The level of general knowledge is statistically higher in pediatricians than in general practitioners, and the knowledge of physicians in training is higher in contrast to specialists. The knowledge of physicians from small towns, as well as physicians with more clinical experience, was low. Conclusions: This study revealed an insufficient level of knowledge relating to autism spectrum disorder among primary care physicians, which is similar to the findings of other studies conducted in different regions of the world. The lack of knowledge is especially evident in the theoretical preparation of physicians regarding ASD. Full article

A commercially available loop-mediated isothermal amplification assay (LAMP) for the detection of Pneumocystis jirovecii (P. jirovecii) has been evaluated for the diagnosis of Pneumocystis pneumonia (PcP) in critically ill patients. Altogether, 109 lower respiratory tract specimens from 95 patients with a positive P. jirovecii test in routine diagnostics were collected from five distinct university hospitals in Germany. All samples were tested with a qPCR and eazyplex^® LAMP assay. qPCR was set as the gold standard and was evaluated beforehand with samples from 100 patients categorized to have proven, probable, and possible PcP according to the EORTC/MSGERC guidelines. The sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the LAMP were assessed. Sensitivity was 68%, specificity was 86%, and PPV and NPV were 99% and 16%, respectively. All patients with proven PcP were positive in the LAMP. There was a weak correlation between the time to positivity and the fungal load (squared Pearson correlation coefficient (r²) = 0.5653). A positive result in the LAMP indicates a PcP. Because of the low sensitivity, negative results do not rule out an infection and should be clarified with further molecular methods. The LAMP should be used in patients in whom a PcP is expected, not for screening only. Full article

Background/Objectives: Syphilis diagnosis in Armenia is unreliable due to inconsistent testing methods, limited access to confirmatory tests, and the underutilization of healthcare services due to stigma and lack of awareness. In 2022, 29% of cases were latent, 8.1% were late latent, 21% were secondary, and 1% were congenital. We assessed primary care physicians’ (PCPs) knowledge, attitudes, and practices regarding syphilis diagnosis and prevention to improve early detection. Methods: Between December 2023 and February 2024, we conducted a cross-sectional survey among outpatient physicians. We randomly selected 24 clinics in six regions. In each clinic, we randomly selected respondents from employee registries. We assigned one or two points to correct answers and zero points to incorrect or unknown answers; scores were categorized as Poor (0–<30%), Moderate (30–<70%), and Good (>70%). We used non-parametric tests to compare groups. Results: Of the 413 physicians contacted, 345 (83%) responded; 74% were female; the median age was 46 years; 54% had > 16 years work experience; and 47% worked as general practitioners. The respondents had moderate knowledge of risk groups (56%) and symptoms (49%) and poor knowledge of disease transmission (8%). As for practices, the respondents expressed difficulty in prescribing additional laboratory tests based on clinical symptoms (51%) and struggled with reporting diagnosed syphilis cases (66%); moderate opinions on pregnancy termination decisions (65%) were conveyed. The respondents’ knowledge did not correlate with their practice (r = 0.23) and attitude (r = 0.25) scores. Conclusions: PCPs’ knowledge was not positively associated with improved practices and attitudes regarding syphilis diagnosis and prevention. This highlights the need to improve healthcare workers’ post-graduate education and implement an efficient screening program to detect and treat asymptomatic, late latent, and congenital infections, as well as to prevent complications, transmission, and reinfection. Full article

High-grade B-cell lymphoma (HGBL), not otherwise specified (NOS), is a rare entity within the spectrum of B-cell lymphomas. HGBL, NOS remains a diagnosis of exclusion with limited data available on the optimal clinical approach. We report a case of a 67-year-old man with HGBL, NOS with a germinal center B-cell (GCB) immunophenotype. The disease was characterized by an aggressive clinical course, refractory to multiple lines of cytotoxic chemotherapy, immunotargeted treatment, therapy with a PD-1 inhibitor, and haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Ultimately, the disease progression led to the patient’s death nine months post-diagnosis. A FISH assay identified a sole genetic rearrangement: BCL2/IGH. Whole-exome sequencing revealed a number of significant somatic mutations, such as TP53 p.C238G, B2M p.L12R, STAT6 p.D419G, STAT3 p.S614R, TREX1 p.T49fs, and CREBBP p.C367Ter, as well as a high focal amplification of the MUC3A gene and the deletion of the short arm of chromosome 17 (del(17p)). An inactivating somatic mutation in the TREX1 gene (p.T49fs) has not been previously described in patients with non-Hodgkin lymphomas. Additionally, our analysis uncovered a key cancer hallmark: tumor genomic instability, manifested as a high tumor mutational burden, which likely contributed to the aggressive disease course. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death. Its poor prognosis is closely related to late-stage diagnosis, which results from both nonspecific symptoms and the absence of biomarkers for early diagnosis. MicroRNAs (miRNAs) exert a regulatory role in numerous biological processes and their aberrant expression has been found in a broad spectrum of diseases, including cancer. Cancer stem cells (CSCs) represent a driving force for PDAC initiation, progression, and metastatic spread. Our previous research highlighted the interesting behavior of miR-216a-5p and miR-125a-5p related to PDAC progression and the CSC phenotype. The present study aimed to evaluate the effect of miR-216a-5p and miR-125a-5p on the acquisition or suppression of pancreatic CSC traits. BxPC-3, AsPC-1 cell lines, and their CSC-like models were transfected with miR-216a-5p and miR-125a-5p mimics and inhibitors. Following transfection, we evaluated their impact on the expression of CSC surface markers (CD44/CD24/CxCR4), ALDH1 activity, pluripotency- and EMT-related gene expression, and clonogenic potential. Our results show that miR-216a-5p enhances the expression of CD44/CD24/CxCR4 while negatively affecting the activity of ALDH1 and the expression of EMT genes. MiR-216a-5p positively influenced the clonogenic property. MiR-125a-5p promoted the expression of CD44/CD24/CxCR4 while inhibiting ALDH1 activity. It enhanced the expression of Snail, Oct-4, and Sox-2, while the clonogenic potential appeared to be affected. Comprehensively, our results provide further knowledge on the role of miRNAs in pancreatic CSCs. Moreover, they corroborate our previous findings about miR-216a-5p’s potential dual role and miR-125a-5p’s promotive function in PDAC. Full article