OBJECTIVE:Traditional Sudanese gold mining poses serious health challenges to workers and communities. This issue requires early detection of at-risk populations using affordable, non-invasive sputum cytology. Thus, the present study aimed to evaluate the proliferative activity of lung epithelial cells in Sudanese individuals associated with traditional gold mining. MATERIALS AND METHODS:This study is a cross-sectional, descriptive, clinic-based pilot investigation conducted in El-Obeid, North Kordofan State, Sudan. Participants in the study are individuals actively involved in traditional gold mining. The selection of candidates was based on their willingness to participate in the study, independent of demographic characteristics. Lung cytology was performed, and the results were categorized as normal, metaplasia, cytological atypia, and cellular degenerative changes. RESULTS:Squamous metaplasia was identified in 17 out of 109 individuals (15.6%). Mild cytological atypia was identified in 3.7% of individuals. All four smears with cytological atypia showed squamous metaplasia of the lung. The risk of cytological atypia among individuals with respiratory squamous metaplasia is represented by the Odds Ratio (OR) and the 95% confidence interval (95% CI), which are OR = 28.3 (2.9333 to 273.1792) and p = 0.0038. CONCLUSIONS:Pulmonary squamous metaplasia was common and linked with cytological degeneration and inflammation. Mild cytological atypia was infrequent and only linked with respiratory metaplasia. A substantial link exists between inflammatory state, particularly CICI, and respiratory metaplasia (OR = 5.4; p < 0.003).
OBJECTIVE:First-line treatment of HER2-positive metastatic breast cancer (HER2+MBC) has recently evolved with the introduction of trastuzumab deruxtecan-based regimens. We performed an indirect comparative analysis to evaluate the relative efficacy of currently available first-line treatments using reconstructed individual patient data (IPD). MATERIALS AND METHODS:A systematic PubMed search identified phase III randomized controlled trials evaluating first-line therapies for HER2+MBC with progression-free survival (PFS) reported through Kaplan-Meier curves. Reconstructed IPD were generated using the IPDfromKM method after digitization of published curves. Three trials were included: DESTINY-Breast09, EMERALD, and CLEOPATRA. Trastuzumab plus pertuzumab plus taxane (THP) was adopted as the common comparator. Treatment effects were estimated using a Cox proportional hazards model and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Heterogeneity across pooled control groups and proportional hazards assumptions were also assessed. RESULTS:The combination of trastuzumab deruxtecan plus pertuzumab demonstrated the most favorable PFS profile among the evaluated regimens. Compared with pooled THP controls, this regimen significantly reduced the event risk (HR 0.49; 95% CI 0.40 to 0.60). In contrast, trastuzumab plus pertuzumab plus eribulin showed PFS outcomes substantially overlapping with THP (HR 0.96; 95% CI 0.77 to 1.20). Reconstructed HR estimates were highly consistent with those reported in the original trials, confirming the reliability of the IPDfromKM approach. CONCLUSIONS:Indirect comparisons based on reconstructed patient-level data suggest that trastuzumab deruxtecan plus pertuzumab currently represents the most effective first-line strategy for HER2+MBC in terms of PFS.
OBJECTIVE:Pregnancy after breast cancer (BC) is possible and does not have a negative impact on prognosis, even in hormone receptor-positive or BRCA1/2-mutated patients. Despite this, the estimated pregnancy achievability in BC survivors is significantly inferior when compared to that of women who did not have cancer. MATERIALS AND METHODS:This study investigated pregnancies after BC in 18 women monitored at the Oncofertility Center of the Italian Sandro Pertini Hospital. We compared maternal, fetal, and neonatal outcomes against general population data. Then, we evaluated the impact of chemotherapy on feto-maternal outcomes. RESULTS:Compared to findings from the general population, our results show that pregnancy after BC may have more obstetrical complications, such as premature delivery and cesarean section; in addition, our research showed a possible correlation between the occurrence of gestational diabetes and previous chemotherapy treatment. The rate of breastfed survivors appeared lower than that of women in the general population, as summarized in the article's main findings. CONCLUSIONS:Based on our data, pregnancy after BC is safe for both mother and fetus/newborn but requires strict follow-up in referral centers to best manage possible obstetric complications, particularly in women who have undergone chemotherapy.
OBJECTIVE:Ischemic heart disease is a leading cause of morbidity and mortality. In this study, we assessed the efficacy of intracoronary stem cell transplantation on left ventricular function (LVEF) in acute myocardial infarction, chronic ischemic heart disease, and severe ischemic heart failure. MATERIALS AND METHODS: We conducted a meta-analysis of randomized trials from 2002 to 2025. Mean difference in LVEF between treated and control patients at 6-months after infusion was calculated according to analysis of covariance. Heterogeneity among studies was assessed by the Cochrane's Q, Tau2, and I2 statistics. The primary outcome was the LVEF difference at follow-up. Secondary outcomes were comparisons among the type and number of transplanted stem cells. RESULTS:The analysis included 82 randomized controlled trials totaling 5,781 patients (3,048 treated and 2,733 controls) affected by acute myocardial infarction (AMI, n. 70), chronic ischemic heart disease (CIHD, n. 5), and ischemic heart failure (IHF, n. 7). Stem cells were bone marrow, mesenchymal, peripheral blood, and cardiac stem cells in 58, 15, 6 and 3 studies, respectively. Median infused cells were 100 x 106. LVEF increased 3.3% overall and 8.2%, 5.3% and 2.7% in CIHD, IHF and AMI, respectively. LVEF increased 2% per each 109 cells. CIHD improved from mild (46%) to normal (54%) and IHF from severe (30%) to moderate (38%) functional class. Study heterogeneity decreased over publication year, and there is evidence for publication bias, although the Egger's test resulted in a non-significant result. Intracoronary stem cells induced a significant decrease in mean New York Heart Association (NYHA) functional class from baseline to 6 and 12 months after transplant (2.6, 1.8, and 1.9, respectively; t-test p = 0.002) in ischemic heart failure patients. CONCLUSIONS: Intracoronary stem cell transplantation improves LVEF in acute and chronic ischemic heart disease and is associated with a reduction of functional class severity. The intracoronary route may be taken into consideration in future trials of stem cell therapy for ischemic heart disease due to its relative manageability and simplicity.
Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes, characterized by the lack of actionable molecular targets, pronounced intratumoral heterogeneity, and a highly dynamic tumor microenvironment (TME). RNA-based therapeutics, including messenger RNA (mRNA), small interfering RNA (siRNA), antisense oligonucleotides, and non-coding RNAs, represent a promising strategy for modulating gene expression and targeting previously undruggable pathways. Nevertheless, their clinical application in TNBC remains limited. This review aims to critically evaluate the main biological and technological barriers to RNA therapeutics in TNBC and to highlight emerging strategies to enhance their translational potential, with particular emphasis on advanced preclinical models and artificial intelligence (AI). The limited clinical success of RNA therapeutics in TNBC is primarily due to intrinsic RNA instability, rapid nuclease-mediated degradation, suboptimal and heterogeneous tumor delivery, and sequence-dependent off-target effects. Traditional two-dimensional in vitro models inadequately reproduce tumor architecture and TME complexity, resulting in poor predictive value. In contrast, advanced preclinical platforms-including three-dimensional spheroids, patient-derived organoids, organ-on-chip systems, and patient-derived xenografts-better recapitulate tumor biology, cell-microenvironment interactions, and interpatient variability. Concurrently, AI and machine learning approaches are increasingly employed to optimize RNA sequence design, predict off-target effects, improve nanoparticle-based delivery systems, integrate multi-omics and spatial transcriptomics data, and support patient stratification. The integration of physiologically relevant preclinical models with AI-driven approaches represents a promising strategy to overcome current limitations in RNA-based therapeutics for TNBC. This multidisciplinary framework may enhance delivery efficiency, reduce attrition rates, and accelerate the development of RNA-based precision oncology strategies in TNBC.
OBJECTIVE:Asprosin is a recently identified adipokine secreted predominantly by white adipose tissue and is implicated in energy homeostasis, insulin resistance, and inflammatory pathways. Emerging evidence suggests a close association between asprosin and obesity-related metabolic disturbances. This study aimed to investigate the relationship between serum asprosin levels and obesity- and metabolism-related parameters, including body mass index (BMI), visceral adiposity index (VAI), anthropometric measurements, and biochemical markers. MATERIALS AND METHODS: This retrospective cross-sectional study was conducted using data from patients who attended the Internal Medicine and Obesity Outpatient Clinics of Gazi Yaşargil Training and Research Hospital between January 2022 and December 2023. Participants were categorized into normal-weight (n = 55), overweight (n = 40), and obese (n = 60) groups according to BMI. Laboratory parameters, including serum asprosin levels, lipid profile, HbA1c, and VAI, were analyzed using previously collected fasting serum samples. RESULTS: Serum asprosin levels differed significantly among BMI groups and were higher in overweight and obese individuals compared to normal-weight participants (p < 0.001). Asprosin levels showed significant positive correlations with BMI, VAI, triglyceride levels, and platelet count, and a significant negative correlation with high-density lipoprotein (HDL) cholesterol. No significant associations were found between asprosin levels and HbA1c, low-density lipoprotein (LDL) cholesterol, aspartate aminotransferase (AST), or alanine aminotransferase (ALT). CONCLUSIONS:Serum asprosin is closely associated with adiposity and lipid-related metabolic alterations, suggesting its potential role as a biomarker in obesity-related metabolic disorders. However, further longitudinal studies are required to clarify its clinical utility.
The article "Can the endometrioma be an obstacle to complete oocyte retrieval in IVF cycles? A retrospective study" by G.M. Baldini, A.S. Laganà, A. Mastrorocco, A. Malvasi, D. Baldini, D. Ferri, R. Sciorio, G. Trojano, published in Eur Rev Med Pharmacol Sci 2024; 28 (7): 2827-2836-DOI: 10.26355/eurrev_202404_35911-PMID: 38639522, has been retracted by the Publisher and the Editor in Chief. Following concerns raised on the study data and ethics issues, the journal initiated an editorial investigation in accordance with journal policies and COPE guidelines. The authors were contacted and provided a reply to the issues raised, but were unable to provide the original data due to a technical failure that resulted in the loss of access to the underlying files, nor the original ethics committee approval document. The journal has therefore reassessed the manuscript based on the information provided. The external evaluation identified significant concerns regarding the study's reporting, transparency, and verifiability. Consequently, the concerns raised during the post-publication evaluation could not be satisfactorily resolved, and the reliability of the reported findings and conclusions could not be verified. In light of these issues, the Editor-in-Chief has concluded that the article is retracted. The authors have been informed of this decision and do not agree with the retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause.
The article "A multicenter clinical study with myo-inositol and alpha-lactalbumin in Mexican and Italian PCOS patients" by I. Hernandez Marin, O. Picconi, A.S. Laganà, L. Costabile, V. Unfer, published in Eur Rev Med Pharmacol Sci 2021; 25 (8): 3316-3324-DOI: 10.26355/eurrev_202104_25743-PMID: 33928619, has been retracted by the Publisher and the Editor in Chief. Following concerns raised by a whistleblower regarding ethics approval issues, statistical analysis, the reliability of the reported results, and potential conflicts of interest, the journal initiated an editorial investigation in accordance with journal policies and COPE guidelines. The authors were contacted and provided a response as well as the original data. An independent statistical expert was appointed to reassess the manuscript. The evaluation identified insufficient documentation of ethics approval across all participating centers and unresolved methodological and statistical concerns, which together limit the reliability and interpretability of the reported findings. In light of these issues, the Editor-in-Chief has concluded that the article's results and conclusions are compromised. The article is therefore retracted. The authors have been informed of this decision and do not agree with the retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause.
The article "Oxycodone inhibits myocardial cell apoptosis after myocardial ischemia-reperfusion injury in rats via RhoA/ROCK1 signaling pathway" by Y. Xie, C.-L. Ge, Z.-Y. Zhang, G.-X. Fei, published in Eur Rev Med Pharmacol Sci 2020; 24 (11): 6371-6379-DOI: 10.26355/eurrev_202006_21535-PMID: 32572934, has been retracted by the Publisher and the Editor in Chief. Following publication, concerns were raised by a third party regarding the integrity of several figures. An editorial assessment revealed multiple instances of image duplication within the article and image duplication with previously published articles by different authors. The authors have been contacted and were asked to provide the original data; however, they did not respond to the journal's correspondence. As a result, the Editor-in-Chief has lost confidence in the reliability of the data presented in this article and has decided to retract it. This article has been retracted. The Publisher apologizes for any inconvenience this may cause.
BACKGROUND:Isaac's syndrome, or neuromyotonia, is a rare autoimmune neuromuscular disorder characterized by continuous muscle fiber activity due to peripheral nerve hyperexcitability. Clinical features include persistent muscle stiffness, cramps, fasciculations, delayed muscle relaxation, and myokymia. These symptoms are often associated with autoantibodies targeting voltage-gated potassium channels (VGKCs) or related proteins such as CASPR2. Conventional treatment typically involves immunosuppressive agents and symptomatic medications, but therapeutic responses can be incomplete or transient. CASE REPORT:We report the case of a 43-year-old woman with a long-standing diagnosis of Isaac's syndrome who experienced limited benefit from prolonged immunosuppressive and symptomatic therapies. The patient presented with disabling motor symptoms, pain, and reduced quality of life. She was treated with major autohemotherapy using an oxygen-ozone (O₂-O₃) protocol. Within two months, notable clinical and electrophysiological improvements were observed, including the resolution of neuromyotonia and significant gains in daily functional abilities. These improvements, assessed via the Barthel Index, remained stable over a three-year follow-up period, indicating sustained autonomy and pain control. The patient also carried MTHFR C677T and A1298C polymorphisms, which may have contributed to the autoimmune disease and influenced treatment response. CONCLUSIONS:This case highlights the potential role of oxygen-ozone therapy as a complementary non-pharmacological approach in refractory autoimmune neuromuscular disorders. The sustained clinical benefit observed suggests that ozone therapy may contribute to immune modulation, redox balance, and restoration of mitochondrial function. Further studies are warranted to evaluate personalized ozone-based protocols in the management of immune-mediated neuromuscular conditions.
Background: Bariatric surgery remains the most effective treatment for severe obesity and obesity-associated metabolic disorders. However, substantial interindividual variability exists in postoperative weight loss and type 2 diabetes mellitus remission. Increasing evidence suggests that gut microbiome-derived metabolites may influence metabolic responses after bariatric surgery. Objective: This narrative review synthesizes current evidence regarding the predictive role of gut microbiomederived metabolites, particularly short-chain fatty acids, bile acids, and tryptophan-derived metabolites, in bariatric surgery outcomes. Methods: A narrative literature review was conducted using PubMed, Web of Science, Embase, and ClinicalTrials. gov to identify studies published through May 2026. Studies examining associations between microbiomederived metabolites and postoperative bariatric outcomes were reviewed and narratively synthesized. Results: Available evidence suggests that higher preoperative levels of beneficial microbiome-derived metabolites are associated with improved postoperative weight loss, enhanced insulin sensitivity, and greater likelihood of type 2 diabetes mellitus remission. Short-chain fatty acids appear to influence satiety and glucose metabolism, bile acids regulate metabolic signaling through farnesoid X receptor and Takeda G protein receptor 5 pathways, and tryptophan metabolites modulate inflammation and gut-brain communication. Nevertheless, findings remain inconsistent because of methodological heterogeneity, limited cohort sizes, and differences in metabolomic profiling techniques. Conclusion: Gut microbiome-derived metabolites represent promising candidate biomarkers for predicting bariatric surgery outcomes. However, large-scale longitudinal studies using standardized metabolomic approaches are required before clinical implementation can be achieved.
Acute kidney injury (AKI) is a major clinical and economic challenge worldwide. Furthermore, early identification of AKI remains difficult given that traditional biomarkers like serum creatinine and urine output (UOP) have shown to have limitations since they reflect later stages of injury and are unable to detect the initial cellular damage in AKI. This issue creates an important gap in diagnosis given that early diagnosis could prevent worsening conditions. More research is focusing on non-invasive novel biomarkers options for early and accurate detection of AKI. Urinary exosomes are emerging as a valuable source of kidney-specific biomarkers. These nanovesicles come from all nephron segments, encapsulating intracellular components and providing a unique view of kidney health. Activating transcription factor 3 (ATF3), a transcriptional regulator induced by stress conditions, has emerged as a promising candidate for early detection of AKI. Studies in animals and humans have found that ATF3 is encapsulated and released in urinary exosomes in response to kidney injury, appearing much earlier than traditional biomarkers. This review mainly examines ATF3's role as a new biomarker for the early detection of AKI, it discusses the current understanding of ATF3's molecular role in kidney disease, evaluates the evidence for its use as a biomarker, and outlines a plan for future research and development to realize its full clinical potential.
Measurement errors may be constant, change in predictable, systematic ways, or vary randomly and unpredictably. When discussing measurement errors, the distinction between systematic and random errors is often poorly characterized. Both systematic and random errors can occur at any stage of the testing process. Errors that occur during the measurement phase can be formally evaluated and quantified, for example, using CLSI evaluation protocol guidelines. Here, we assert that the assignment of measurement error labels, random and systematic, depends on the perspective of the observer and the availability of information. Random errors are usually quantified as imprecision or measurement uncertainty (MU), whereas systematic errors that remain approximately constant over time are quantified as biases. As more information becomes available, errors that were previously perceived as random may become predictable and thus considered systematic. Manufacturers/ developers, users, and regulators of measurement procedures (MP) can have very different perspectives, including different levels of available knowledge, and these differences can affect perceptions of which errors are predictable. Therefore, whenever a bias is reported or discussed, its scope must be clearly stated. Similarly, whenever an imprecision or an uncertainty is stated, the sources of variation included in the estimate must also be detailed. Determining whether a source of error is systematic or random in each scenario ensures it can be meaningfully quantified and expressed.
Background: Exosomal microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for hepatocellular carcinoma (HCC). Nevertheless, the overall diagnostic performance of exosomal miRNAs in HCC was still less reported. Therefore, this meta-analysis aimed to systematically assess the pooled diagnostic efficacy of exosomal miRNAs for HCC. Methods: A literature search was performed in accordance with the PRISMA guidelines, utilizing the PubMed, Web of Science, EMBASE, and CNKI databases up to December 22, 2024. The quality of the included studies was evaluated using the QUADAS-2 tool. A random-effects model was applied to calculate the pooled sensitivity and specificity. The overall diagnostic performance was assessed by generating a summary receiver operating characteristic (sROC) curve and calculating the area under the curve (AUC). All statistical analyses were conducted using Meta-Disc (version 1.4) and STATA (version 16). Result: A total of 1442 HCC patients, 761 health controls (HC), and 1091 chronic liver disease (CLD) were identified in 18 individual publications. The sROC analysis showed that the pooled AUC, sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) with 95% confidence interval (CI) were 0.89 (0.86, 0.91), 0.84(0.80, 0.88), 0.79(0.71, 0.86), 4.1(2.8, 5.9), 0.20(0.15, 0.27), 21(11, 37), respectively. Conclusion: This meta-analysis confirms that exosomal miRNAs represent promising novel, non-invasive biomarkers for HCC screening. Furthermore, exosomal miRNAs demonstrate superior diagnostic accuracy in HCC patients with HBV or HCV infection compared to those with other etiologies.
BACKGROUND:PET-CT is widely used to determine whether solid malignant tumors have metastasized. However, its significant limitations, such as high radioactivity, high cost, and the risk of allergic reactions to contrast agents, have clearly restricted its application. There is an urgent need to find a convenient, economical, and non-invasive diagnostic method to replace PET-CT for diagnosing cancer metastasis. The purpose of this study is to evaluate the diagnostic value of five YiDiXie™ tests in determining the metastatic status of multiple cancers. MATERIALS AND METHODS:A total of 2276 subjects were ultimately included in this study (preoperative metastatic group, n = 102; preoperative non-metastatic group, n = 1875; postoperative metastatic group, n = 24; postoperative non-metastasis group, n = 275). Residual serum samples of the subjects were collected and tested using the YiDiXie™ all-cancer detection kit to evaluate the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of YiDiXie™-48, YiDiXie™-32, YiDiXie™-30, YiDiXie™-47, and YiDiXie™-41, respectively. The receiver operating characteristic (ROC) curve analysis was incorporated in this study. RESULTS:In the preoperative group, YiDiXie™-48, YiDiXie™-32, and YiDiXie™-30 were unable to distinguish the metastatic group from the non-metastatic group due to their low specificity. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of YiDiXie™-47 were 97.1%, 82.9%, 5.7, and 0.04, respectively. The specificity of YiDiXie™-47 decreased as the stage of the non-metastatic group increased, and it had high sensitivity and high specificity for various cancer types. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of YiDiXie™-41 were 75.5%, 95.1%, 15.4, and 0.26, respectively. The specificity of YiDiXie™-41 decreased as the stage of the non-metastatic group increased, and it had high sensitivity and high specificity for various cancer types. Therefore, YiDiXie™-47 and YiDiXie™-41 can well distinguish the metastatic group from the non-metastatic group in the preoperative group. All five YiDiXie™ tests effectively distinguished the metastatic group from the non-metastatic group in the postoperative group. CONCLUSION:The combined application of YiDiXie™-47 and YiDiXie™-41 shows considerable effectiveness in diagnosing multiple cancer metastases before surgery, while the combined application of YiDiXie™-30 and YiDiXie™-41 demonstrates considerable effectiveness in monitoring cancer metastases after surgery. The combined application of YiDiXie™-47 and YiDiXie™-41 is expected to serve as a non-invasive alternative or complementary tool to PET-CT for preoperative diagnosis of multiple cancer metastases, and the combined application of YiDiXie™-30 and YiDiXie™-41 can effectively monitor cancer metastases after surgery. REGISTRY:Chinese Clinical Trial Resgistry. CLINICAL TRIAL REGISTRATION:ChiCTR2200066840. Date of Registration:2022-12-19.
OBJECTIVE:Immune thrombocytopenia (ITP), which is caused by immune-mediated platelet loss, is the most common cause of acquired thrombocytopenia in pediatric patients. In addition to evaluating treatment approaches and outcomes within a single-center cohort, this study aimed to evaluate the clinical and laboratory characteristics of juvenile ITP. MATERIALS AND METHODS:Out of 296 patients with thrombocytopenia, 135 children (ages 0-18) with acute ITP were included in this retrospective analysis. We reviewed clinical observations, laboratory results, therapeutic modalities, length of hospital stay, demographic data, and treatment outcomes. RESULTS:Out of 296 patients, 161 (54.4%) had secondary thrombocytopenia, and 135 (45.6%) had ITP. 51.1% of the population was female, and the average age was 5.5±3.97 years. The most common symptoms were petechiae (40%) and ecchymosis (46.7%). 83.7% of patients received intravenous immunoglobulin (IVIG), resulting in a 91.2% response rate after a single dose. 14.1% of patients received corticosteroids, and most of them achieved platelet counts ≥30,000/mm³. In 15.6% of cases, bone marrow aspiration was performed prior to the start of steroid treatment. Splenectomy was required in 0.7% of cases, and rituximab in 1.5%. There was no discernible variation in the treatment response between the modalities (p=0.34). Secondary thrombocytopenia (n=161) was primarily caused by infection (64.5%), with Epstein-Barr virus being found in 3.7% of cases. CONCLUSIONS:IVIG promoted rapid platelet recovery with high responder rates. Overall, the results were favorable, and there were no discernible differences between the treatment plans.
OBJECTIVE:Chronic pain affects approximately one quarter of the Italian adult population and represents a major public health burden, significantly impairing quality of life and functional capacity. When first-line analgesics are insufficient, opioid combinations such as oxycodone/paracetamol (OXY/PAR) are recommended. The effervescent formulation of OXY/PAR was developed to improve administration and acceptability, particularly in frail patients or those with swallowing difficulties. The FirAlgos study evaluated its real-world effectiveness and patient-reported acceptability. MATERIALS AND METHODS:This retrospective observational study included adult patients treated with effervescent OXY/PAR for moderate-to-severe pain (NRS >5) at a tertiary Pain Therapy Center (2022-2023). Assessments were performed at baseline (T0), Day 7 (T1), and Day 14 (T2). Outcomes included pain intensity (Numeric Rating Scale, NRS), pain interference (Brief Pain Inventory, BPI), Patient Global Impression of Change (PGIC), and treatment satisfaction. Longitudinal changes were analyzed using Friedman's Chi-Square test with Wilcoxon post-hoc correction. RESULTS:Ninety-four patients were included (mean age 69.3 ± 13.3 years; 59.6% female; 75.5% non-oncologic pain). Significant reductions in NRS scores were observed between T0 and T1 across all pain dimensions in both oncologic and non-oncologic groups (p < 0.05), with stabilization at T2. PGIC scores showed a rapid upward shift toward higher perceived improvement categories, maintained at follow-up. BPI analyses demonstrated significant early improvements in functional domains, particularly general activity, mobility, and work capability, with sustained benefit over time. CONCLUSIONS:In real-world clinical practice, the effervescent OXY/PAR formulation provided rapid, clinically meaningful, and sustained pain relief, with parallel improvements in functional outcomes and patient-perceived benefit. Its high acceptability supports its use in patients requiring flexible and easily administrable analgesic options for moderate-to-severe pain.
OBJECTIVE:Persistent Human Papillomavirus (HPV) infection causes 84% of cervical cancers (CC) worldwide. The current gold standard, Pap smear, has a high false-negative rate, highlighting the need for a specific and sensitive molecular method for early diagnosis. T cell receptor (TCR)-like antibodies offer a promising platform for cancer immunodiagnostics and immunotherapy. MATERIALS AND METHODS:Using the phage display technique, a monoclonal TCR-like antibody (16 Ab) against HPV 16 oncoprotein E7 for human leukocyte antigen (HLA)-A2 was produced in this study. 16 Ab was selected from a single-domain antibody (sDAb) library via biopanning, an affinity-selection method. Once the clone of 16 Ab was selected, it was sequenced, and the result was analyzed using IMGT/V-Quest and VBase2 databases before proceeding with 16 Ab protein expression and purification. The purified 16 Ab was evaluated for its binding capability towards its target peptide-major histocompatibility complex (pMHC) by Western blot and Enzyme-Linked immunosorbent assay (ELISA). RESULTS:A target pMHC complex was generated and panned against a phage display library. Highly enriched antibody phages from the 3rd biopanning round were chosen for phage ELISA analyses. Of the nine clones selected and sequenced, only two had proper sequences, and 16 Ab was chosen for the downstream process because it shows higher specificity for the target pMHC complex than the other clones. The dot blot showed that the soluble protein from 16 Ab was successfully expressed. The binding of 16 Ab towards the target pMHC complex (OD405 nm: 1.06) significantly differs from the non-target pMHC complex (OD405 nm: 0.09). CONCLUSIONS:This study demonstrates the potential of 16 Ab as a companion diagnostic to reduce the rate of false-negative Pap smears. Further research is needed to assess its therapeutic potential, expand coverage to all HPV variants and HLA types, and evaluate its performance in cervical cancer cell lines before clinical testing.
Acute myeloid leukemia (AML) is a diverse and complex haematological cancer that cannot be fully characterized, even with the combination of morphology and cytogenetics. As a result, molecular biomarkers have become the focus of diagnosis, risk stratification, therapeutic planning and monitoring of disease. Of these, FLT3 mutations have been identified as being clinically relevant, clinically important, and easily detected during various phases of AML care. This review examines the diagnostic, prognostic, predictive and monitoring role of FLT3 mutations in AML, with a focus on the clinical applications in the laboratory. We review the evidence for FLT3 internal tandem duplication (FLT3-ITD) and FLT3 tyrosine kinase domain (FLT3-TKD) mutations, their association with relapse risk, remission duration, survival, response to FLT3 inhibitors and measurable residual disease testing. The impact of allelic burden, variant allele frequency, insertion site, structural characteristics, co-mutational background, interpretation of FLT3 results in ELN 2022, and treatment exposure help clarify the clinical significance of FLT3 results. A particular focus is placed on laboratory assay implementation, including PCR-based assays, fragment analysis, next-generation sequencing and droplet digital PCR, as well as assay sensitivity, mutation quantification, structural annotation, and inter-platform standardization. FLT3 should be used as an integrated clinical laboratory biomarker and not a simple mutation-positive or mutation-negative result. Its mutation subtype, molecular context, treatment setting, assay performance and standardized reporting determine its diagnostic, prognostic, predictive and MRD-related value. This review offers a clinical laboratory perspective on how to interpret FLT3 mutations as actionable biomarkers in AML.
Diabetic kidney disease is a complication of inadequately controlled diabetes of any type. It is the main reason for end-stage renal disease and the need to start dialysis, leading to a great burden for health care systems. Moreover, it strongly diminishes the quality of life and shortens life expectancy. The pathophysiology, diagnostics and treatment methods of diabetic kidney disease are not yet fully understood. This complication is underestimated and most often diagnosed in an advanced stage of renal deterioration. However, the sooner the disease is detected, the better the chance to slow down its progression. Patients with type 1 diabetes are especially vulnerable to the development of diabetic kidney disease mainly because they become diabetic in their early childhood. So, it seems to be extremely important to prevent kidney damage in these patients, or at least to diagnose this complication as soon as possible and to undertake appropriate medical intervention. In this article, we describe the current state of knowledge about diabetic kidney disease and its diagnostics. We also propose new biomarkers for the early recognition of diabetic kidney disease in patients with type 1 diabetes. These biomarkers appear to have very promising properties: they are detectable in blood and/or urine samples earlier than traditional markers, and they also seem to be more sensitive and specific biomarkers of diabetic kidney disease.
