Molar Incisor Hypomineralization (MIH) is a dynamic condition in which demarcated opacities can progress to post-eruptive enamel breakdown, increasing the risk of dental caries. This study aimed to evaluate the clinical and economic impact of late diagnosis of MIH. A total of 803 children aged 6-11years were examined, of whom 172 were diagnosed with MIH and classified into 2 groups based on age at diagnosis: early diagnosis (under 8years) and late diagnosis (8years or older). A treatment plan was developed according to the severity and clinical presentation of MIH in each child, and the associated financial costs were calculated. Children in the late-diagnosis group presented more severe MIH, with a higher prevalence of demarcated opacities, atypical carious lesions, and atypical restorations. Although the estimated overall financial cost of treatment did not differ significantly between groups, a 2-year delay in MIH diagnosis led to more severe clinical presentations and higher expenses from the more complex interventions required. In conclusion, a 2-year delay in the diagnosis of MIH was associated with a more severe clinical presentation, necessitating more complex restorative treatments and leading to increased financial costs related to these treatments.Research Ethics Committee: CAAE 12161019.2.0000.5419, date 29.04.2019.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with morbidity and mortality driven by late diagnosis, a dense desmoplastic stroma, and resistance to conventional therapies. Over sequential therapeutic eras, treatment has progressed from early cytotoxic agents to metabolism-directed strategies. A central feature of PDAC biology is extensive metabolic reprogramming, largely controlled by the Kirsten rat sarcoma viral oncogene homologue (KRAS) protein, which promotes aerobic glycolysis, glutamine utilization, and mitochondrial oxidative phosphorylation to sustain tumor growth under nutrient-limiting conditions. Accordingly, therapeutic efforts have increasingly focused on exploiting these metabolic dependencies, including inhibitors of glycolysis, glutaminase, and mitochondrial complex I, which have shown encouraging results in preclinical studies. Constitutively elevated autophagy-lysosomal flux provides PDAC cells with the capacity for nutrient recycling and supports immune evasion by promoting the neighbor of BRCA1 gene 1 (NBR1) protein-dependent degradation of major histocompatibility complex class I (MHC-I). Although inhibition of autophagy with hydroxychloroquine and related lysosomal inhibitors has provided proof of concept, their limited specificity has motivated the development of more selective approaches, such as Unc-51-like autophagy activating kinase 1 (ULK1) inhibitors and selective autophagy receptor-directed strategies. Emerging combination regimens that integrate autophagy blockade with KRAS/extracellular signal-regulated kinase (ERK) pathway inhibition, metabolic stress, or immune checkpoint blockade may help overcome chemoresistance and enhance anti-tumor immunity. Together, these advances underscore the therapeutic promise of targeting metabolic plasticity and autophagy in PDAC and lay the groundwork for rational next-generation combination strategies.

Primary leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant smooth muscle tumor, representing fewer than 1 in 100,000 adult cancers and less than 0.5% of soft tissue sarcomas. Despite its rarity, it is the most common primary tumor of the IVC and typically aff ects women in their 50s to 60s. Clinical presentation is often silent or nonspecific, resulting in late diagnosis and poor long-term outcomes. Surgical resection remains the only potentially curative treatment, and IVC reconstruction may be necessary depending on tumor location and extent. We present a video demonstrating robotic resection and reconstruction of the IVC in a 75-year-old patient with a 5.5 cm leiomyosarcoma located below the left renal vein, exhibiting both intraluminal and extraluminal growth. Patient underwent robotic en bloc resection of the tumor and a 6 cm segment of the IVC. Reconstruction was performed using a tubularized bovine pericardium graft. Total operative time was 440 minutes, with 80 minutes of IVC clamping and 180 mL of blood loss. No transfusion was required, postoperative recovery was uneventful, and the patient was discharged on postoperative day six. Imaging confi rmed graft patency, and final pathology reported high-grade leiomyosarcoma (T3N0M0). To our knowledge, this is the first reported case of robotic resection of IVC leiomyosarcoma and only the second reported robotic IVC resection and reconstruction in the English literature. This case supports the feasibility and safety of a minimally invasive robotic approach for complex vascular oncologic surgery.

The evolving HIV landscape in Central and Eastern Europe: progress, gaps, and future directions-Part I.

Racial and ethnic differences in oral cavity cancer (OCC) stage at diagnosis are substantial, but the reasons remain unclear. We assessed insurance status and social neighborhood factors as potential pathways. Using the Texas Cancer Registry, we identified adults diagnosed with OCC between 2010 and 2020. We examined the crude and multivariable associations of race and ethnicity, insurance status, and social neighborhood factors with stage at diagnosis. We investigated the mediating effects of insurance status and neighborhood-level social factors on racial and ethnic differences in stage at diagnosis using four-way decomposition with modified Poisson regression and robust standard errors. Among the 6,488 patients, 49.6% were diagnosed at a late stage. Compared to non-Hispanic White patients, non-Hispanic Black, Hispanic, and non-Hispanic Asian Americans, Native Hawaiians, and Pacific Islanders had 51% (Prevalence Ratio [PR]: 1.51; 95% confidence interval [95% CI]: 1.40, 1.63), 29% (PR: 1.29; 95% CI 1.22-1.37), and 17% (PR: 1.17; 95% CI 1.05-1.32) higher risks of being diagnosed at a late stage, respectively. For non-Hispanic Black patients, being uninsured, living in a vulnerable neighborhood, and living in a deprived neighborhood explained roughly 20%, 31%, and 15% of the disparity in late stage diagnosis, respectively. These pathways accounted for similar proportions of the disparity in stage at diagnosis among Hispanic patients. Insurance status and neighborhood-level social factors may partially account for the differences in OCC stage at diagnosis between racial and ethnic groups. Identifying these pathways may help clarify and reduce these disparities.

Review of Minimally Invasive Surgical Treatment of Gallbladder Cancer.

The aim of this study was to present three adult cases of obstructed hemivagina, and ipsilateral renal anomaly (OHVIRA) syndrome diagnosed in different gynecological centers in Poland. The clinical presentations, diagnostic imaging, surgical treatment, and outcomes were analyzed to highlight the diagnostic challenges and variability in clinical course. This retrospective case series included three female patients aged 19,20 and 30 diagnosed in adulthood with OHVIRA syndrome. All three patients were diagnosed with uterus didelphys. Two had confirmed congenital right renal agenesis, while one had undergone nephrectomy in infancy. One patient presented with severe dysmenorrhea and purulent content in the right hemivagina, initially suspected to be hematocolpos. Another patient, with a history of adolescent hematocolpos, was diagnosed postpartum during assessment following cesarean section. The third case was identified incidentally during nephrological imaging. The patient had undergone the right nephrectomy in infancy. All patients underwent resection of the vaginal septum and drainage of hematocolpos. These cases show the variable clinical presentation of OHVIRA syndrome and emphasize the importance of a detailed history and imaging evaluation. Early diagnosis remains essential to prevent complications and provide treatment.

Dual role of TRIM E3-ligases in hepatocellular carcinoma: Mechanistic insights and therapeutic perspectives.

The OET Autism Framework represents a social justice response to the diagnostic disparities of misdiagnosis, underdiagnosis, and late diagnosis experienced by adolescent and adult autistic females. The theoretical intersection of optimal distinctiveness and empowerment theories and trauma-informed care incorporates lived experience narratives to produce an intersectional, antioppressive, and strengths-based approach to holistic therapeutic assessment to inform treatment choice. The author proposes core principles that are aligned with the theoretical underpinnings of the OET Autism Framework to guide practitioners in its clinical application to foster collaborative goal setting, treatment planning, and treatment choice with this population. Seminal and present-day autism scholarship is revisited to expose the impact of gender assumptions and biases that have perpetuated harm and informed treatment choice for adolescent and adult autistic females. Accentuating the ethical responsibilities of the social work profession, the author proposes future recommendations to invite critical analysis from autism scholars to explore the efficacy of the framework and clinical assessment tool identification.

Hepatocellular carcinoma (HCC) poses a significant global health challenge due to late diagnosis and limited treatment effectiveness. Cuproptosis, a newly identified form of copper-induced mitochondrial cell death, is emerging as a promising therapeutic target, with Dihydrolipoamide S-acetyltransferase (DLAT) playing a key role in protein aggregation during this process. This study investigates the long non-coding RNA KCNQ1OT1/miR-27b-5p/DLAT regulatory axis’ involvement in cuproptosis and HCC progression, emphasizing its potential for diagnostic and therapeutic monitoring. Accordingly, a total of 180 participants were divided into three main groups: A healthy control group, untreated HCC group (naïve, NV) and treated HCC group which further subclassified into HCC patients treated with Sorafenib (Sor) or treated with Regorafenib (Rog). The regulatory axis KCNQ1OT1/miR-27b-5p/DLAT was predicted through bioinformatics analysis. Expression levels of KCNQ1OT1, miR-27b-5p, and cuproptosis-related genes (ATP7A, ATP7B, SLC31A1) were assessed using RT-qPCR. Serum DLAT was measured through ELISA technique. The NV group showed elevated serum DLAT levels, KCNQ1OT1 expression, and ATP7A/B levels, while miR-27b-5p, SLC31A1 expression, and serum Glutathione (GSH) levels were reduced, indicating impaired cuproptosis. In contrast, the treated groups (Sor & Rog) demonstrated lower DLAT, KCNQ1OT1, and ATP7A/B levels, alongside higher miR-27b-5p, SLC31A1, and GSH levels, suggesting copper accumulation and activated cuproptosis. ROC and correlation analyses indicate that KCNQ1OT1, miR-27b-5p, and DLAT constitute a regulatory axis, potentially serving as diagnostic and therapeutic monitoring biomarkers in HCC.

Background/Objectives: Cytomegalovirus (CMV) retinitis remains a significant opportunistic infection in patients with advanced human immunodeficiency virus (HIV) infection, particularly with late HIV diagnoses. This three-case series aimed to describe HIV-associated CMV retinitis in newly diagnosed advanced HIV infection with documented concurrent and/or prior infectious conditions, and to highlight the importance of bord systemic screening and multidisciplinary management. Methods: We retrospectively reviewed three male patients diagnosed with HIV-associated CMV retinitis at a tertiary ophthalmology referral center. Clinical findings, CD4-positive T-cell counts, HIV-RNA levels, aqueous humor CMV-DNA results, systemic infectious conditions, treatment and ocular outcomes were summarized. Results: All patients had marked cellular immunodeficiency, with CD4-positive T-cell counts ranging from 46 to 141 cells/µL, and CMV-DNA was detected in aqueous humor in all cases. The infectious burden was substantial: all three patients had syphilis and hepatitis B virus infection, two had oral candidiasis, and individual patients had chlamydia infection, tuberculosis, amebic colitis, or a history of herpes zoster. One patient was initially suspected of having syphilitic uveitis, which illustrates how coinfections may obscure the diagnosis of CMV retinitis. Retinal detachment occurred in two cases and was surgically repaired with anatomical recovery. Conclusions: These cases emphasize that CMV retinitis in newly diagnosed advanced HIV infection should prompt broad infection screening and multidisciplinary evaluation, particularly in the setting of delayed HIV diagnosis and severe immunosuppression. Comprehensive screening for opportunistic and sexually transmitted infections, prompt ocular virological confirmation, and multidisciplinary management are essential in patients with HIV-associated CMV retinitis.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely due to late diagnosis and the limited sensitivity of current screening biomarkers such as alpha-fetoprotein (AFP). Circulating long noncoding RNAs (lncRNAs) have recently emerged as promising, noninvasive biomarkers that may reflect the molecular mechanisms underlying hepatocarcinogenesis. This systematic review and meta-analysis aimed to comprehensively evaluate the diagnostic accuracy of circulating lncRNAs for detecting HCC. A systematic search of PubMed, Scopus, Web of Science, and Embase was performed up to March 2025 following the PRISMA-DTA guidelines. Eligible studies reporting the diagnostic performance of circulating lncRNAs for HCC were included. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model. Subgroup analyses were conducted according to sample type, detection method, and reference standard. Eighty-one studies encompassing over 6,000 participants were included. The pooled sensitivity and specificity of circulating lncRNAs were 0.83 (95% CI: 0.80-0.86) and 0.80 (95% CI: 0.75-0.84), respectively, with an area under the summary receiver operating characteristic (SROC) curve of 0.88. Serum-based assays showed slightly higher accuracy than plasma-based assays. lncRNAs also demonstrated good diagnostic performance in discriminating HCC from cirrhotic patients, as well as from patients with HBV-positive and HCV-positive status. Circulating lncRNAs exhibit high diagnostic accuracy and hold significant potential as complementary biomarkers to AFP for early HCC detection. Their mechanistic roles in tumor proliferation and immune regulation underscore their value in molecular diagnosis and personalized management of liver cancer.

A male in his 50s initially presented with left ventricular hypertrophy (LVH) identified on transthoracic echocardiogram. He was diagnosed with hypertrophic cardiomyopathy without any further investigations. He later presented in his 70s with decompensated heart failure. A cardiac MRI was performed that demonstrated extensive scarring, and the patient was labelled with a presumptive diagnosis of cardiac amyloidosis. An endomyocardial biopsy demonstrated extensive myocyte hypertrophy and fibrosis but was non-diagnostic in identifying a cause of the LVH. Genetic testing revealed that the patient had a genetic variant in the GLA gene, which encodes for the α-galactosidase A enzyme that is known to be associated with adult onset of Fabry disease. This case highlights the importance of early incorporation of genetic screening and advanced imaging modalities in patients presenting with LVH.

This study aimed to estimate the risks of AIDS progression and death among people living with HIV using left-truncated and right-censored survival methods. Competing-risk methods were used to evaluate AIDS progression in the presence of death as a competing event. A retrospective cohort study was conducted using data from Behavioral Disease Counseling Centers (BDCC) in East Khuzestan, Iran, from 2001 to 2022. Survival analyses were performed within a left-truncated and right-censored framework, in which the physician-estimated HIV infection date served as the biological time origin and HIV diagnosis was treated as delayed entry. Competing-risk methods were used to evaluate AIDS progression in the presence of death as a competing event. Late HIV diagnosis, defined as a baseline CD4 count below 350 cells/mm³, was a key variable of interest. Throughout the follow-up period, the cumulative incidence of death exceeded that of AIDS in most time intervals. Late diagnosis was associated with significantly higher hazards for both death and AIDS, with a two-fold increase in the hazard of death (HR = 2.1, p < 0.001). Other significant predictors of death included age ≥ 50 (HR = 2.4, p < 0.001), male sex (HR = 2.84, p = 0.014), and TB co-infection (HR = 2.02, p < 0.001). Accounting for left truncation and right censoring is essential when analyzing registry-based HIV cohorts. Late HIV diagnosis was strongly associated with increased risks of both AIDS progression and death, highlighting the importance of earlier testing, timely diagnosis, and prompt linkage to care. Appropriate survival methods that accommodate delayed entry and competing risks can provide more accurate estimates of disease progression and mortality in HIV populations.

Survival rates for ovarian cancer drop sharply at late-stages due to late diagnosis. Although PARP inhibitors are effective in homologous recombination-deficient (HRD) tumors, their efficacy in homologous recombination (HR)-proficient ovarian cancer remains limited, highlighting the need for novel molecular targets to inhibit tumor progression and improve patient outcomes. Differentially expressed piRNAs were screened using ovarian cancer tissues from early- and advanced-stage patients. Functional studies were performed in ovarian cancer cell lines, xenograft models, and patient-derived organoids. Molecular mechanisms were investigated using RNA pulldown, RNA immunoprecipitation, MeRIP-seq, ubiquitination assays, and DNA damage analyses. We identified piR-26681 as a piRNA significantly downregulated in advanced-stage ovarian cancer and associated with favorable prognosis. Functional assays demonstrated that piR-26681 suppressed ovarian cancer progression in cell lines, xenograft mouse models, and patient-derived organoids. Mechanistically, piR-26681 directly interacted with METTL3 and METTL14, enhancing their interaction, reducing their ubiquitination, and thereby increasing their protein stability. This stabilization promoted global m6A methylation in ovarian cancer cells. Increased m6A modification subsequently enhanced the stability of FBXO16 mRNA through the m6A reader IGF2BP2, leading to elevated FBXO16 expression. As an E3 ubiquitin ligase, FBXO16 further mediated the ubiquitination and degradation of MORF4L1, a key regulator of homologous recombination repair. Loss of MORF4L1 impaired HR repair, increased DNA damage accumulation, and sensitized ovarian cancer cells to the PARP inhibitor niraparib. Our study identifies a novel piR-26681-METTL3/METTL14-FBXO16-MORF4L1 regulatory axis that impairs DNA repair and suppresses ovarian cancer progression. piR-26681 represents a promising therapeutic target for sensitizing HR-proficient ovarian cancers to DNA-damaging therapies.

Late HIV diagnosis increases morbidity and mortality. In this retrospective cohort study on the national HIV register, we analysed risk factors for late HIV diagnosis among newly registered people living with HIV (PLWH) between 2008 and 2023, using the updated definition. Of 2683 PLWH registered, 1813 (67.6%) were newly diagnosed with CD4+ T-cell count available ≤90 days for 1572 (86.7%). Eighty-seven of the 609 (14.3%) individuals with CD4+ T-cell count <350/μL had recent infections and were reclassified as non-late. Of the newly diagnosed, 50.3% were diagnosed late. Multivariable analysis identified higher age as an independent risk factor for late diagnosis (adjusted OR 1.42 per ten years, 95% CI 1.30-1.56). Of the Finnish-born, females had lower odds than males (aOR 0.59, 95% CI 0.39-0.88). Asian-born (aOR 6.83, 95% CI 3.49-13.35) and African-born females (aOR 3.26, 95% CI 1.58-6.73) had significantly higher odds than Finnish-born females. In urban municipalities, men who have sex with men had lower odds than individuals with heterosexual transmission (aOR 0.55, 95% CI 0.40-0.76). Higher age was the most important factor for increasing the proportion of late diagnoses. We recommend enhanced testing and risk awareness for older adults and migrants from high-prevalence countries.

Despite substantial advances in radiotherapy and chemotherapy for nasopharyngeal carcinoma (NPC), a subset of patients still develops metastasis or recurrence following initial treatment. Additionally, the atypical early symptoms of NPC often lead to clinical misdiagnosis or missed diagnosis, resulting in late diagnosis and unfavorable prognosis. Thus, novel diagnostic biomarkers are urgently required. By integrating five GEO datasets and applying four machine learning models, namely LASSO, SVM-RFE, XGBOOST, and mRMR, this study identified two key NPC-related genes, BLK and OSBPL10. Bioinformatic analyses revealed that both genes are significantly downregulated in NPC, and this downregulation pattern was further validated in the GSE61218 dataset. Notably, receiver operating characteristic (ROC) curves confirmed their high diagnostic efficacy for NPC. BLK and OSBPL10 are involved in pathways such as B-cell receptor signaling and lipid metabolic regulation, respectively, and are closely associated with the infiltration of various immune cells. Immunohistochemical staining validation further confirmed that the protein expression levels of BLK and OSBPL10 are downregulated in NPC tissues compared with those in benign lesions, and their low expression is strongly associated with the poor prognosis of patients. In summary, these findings indicated that BLK and OSBPL10 may serve as candidate biomarkers for NPC diagnosis and prognosis, although further validation in independent cohorts is warranted.

Oral cancer is a significant global public health issue, with high morbidity and mortality often linked to late diagnosis. This study evaluated a 12-year oral cancer screening program in northern Portugal to characterize its implementation and outcomes, identifying predictors of lesion detection. The program's outcomes were analyzed to assess its feasibility and contribution to early detection. A retrospective analysis of screening program data from 2012 to 2024 was conducted. Participants were recruited through community outreach and selection of high-risk groups in primary care settings. A standardized oral/oropharyngeal examination protocol was used to classify lesions as benign, suspicious, or malignant based on clinical examination. Demographic data and risk factors were recorded, and individuals with suspicious or malignant lesions were referred for specialized evaluation. A total of 10 433 participants were screened (median age 63 years; 64% female). Oral lesions were detected in 16.7%, with 6.1% classified as suspicious and 0.2% malignant. Current smoking (OR = 1.65; p < 0.001), former smoking (OR = 1.27; p = 0.010), and previous oncological disease (OR = 1.74; p < 0.001) were associated with lesion detection on multivariable logistic regression. Overall, 16.4% of participants were referred for specialized consultation. This large-scale screening program successfully reached a broad population, identifying a substantial number of potentially malignant lesions. The association with known risk factors supports the need for targeted screening strategies. Further research should integrate diagnostic confirmation, evaluate long-term patient outcomes, and assess cost-effectiveness to refine oral cancer screening policies and healthcare resource allocation.

Despite advances in the management of Human Immunodeficiency Virus (HIV), delayed diagnosis remains a major public health challenge. Evidence on late HIV diagnosis in Oman and the wider Gulf region remains limited. This study aimed to identify factors associated with late HIV diagnosis among adult patients of people living with HIV (PLWH) in Oman. A 32-year ambidirectional cohort study was conducted at the Royal Hospital, a tertiary referral hospital and the national HIV referral centre in Muscat, Oman, including adults aged ≥ 18 years diagnosed with HIV between 1992 and 2024. Participants with available baseline Cluster of Differentiation 4 (CD4) count, viral load, and haemoglobin measurements were included. Late diagnosis was defined as a CD4 count ≤ 350 cells/mm³ at diagnosis. Data were extracted from electronic medical records and analysed using multivariable Poisson regression with robust variance. Adjusted relative risks (aRRs) with 95% confidence intervals (CIs) were reported. Among 549 patients, 30.1% were diagnosed late. Of those diagnosed late, 72.1% acquired HIV through sexual transmission, 64.8% were asymptomatic at presentation, and 61.8% had no comorbidities. Younger age was independently associated with higher risk of late diagnosis among individuals aged 18-27 years (aRR 5.66; 95% CI: 2.26-14.21), 28-37 years (aRR 3.25; 95% CI: 1.33-7.94), and 38-47 years (aRR 3.51; 95% CI: 1.40-8.77), compared with those aged > 47 years. Low haemoglobin (≤ 10g/dL) was associated with increased risk (aRR 3.03; 95% CI: 1.42-6.67). Heart disease (aRR 5.38; 95% CI: 1.36-21.31) and hypertension (aRR 3.34; 95% CI: 1.13-9.91) were also significant predictors. Sex, mode of HIV transmission, and reason for HIV testing were not significantly associated with late HIV diagnosis in the adjusted analysis. WHO clinical stage 2 was also not significantly associated. Late HIV diagnosis remains common in Oman and is associated with younger age, anaemia, and comorbidities. These findings highlight missed opportunities for earlier HIV testing, as a substantial proportion of late-diagnosed individuals were asymptomatic and many were young adults. Strengthening targeted testing strategies, reducing stigma, and improving early linkage to care are essential to support timely diagnosis and progress toward the UNAIDS 95-95-95 targets.

Head and neck squamous cell carcinoma (HNSCC) is a global malignancy characterised by extremely low survival rates, primarily contributed to by late diagnosis, tumour heterogeneity, and resistance to available therapies. Deciphering reliable biomarkers is crucial for early diagnosis, prognosis and personalized therapy. This review discusses the possibilities of clusterin (CLU) as an emerging biomarker in the field of HNSCC therapeutics by incorporating insights derived from preclinical, clinical and proteomic data. The expression of CLU in HNSCC cases has been found to be correlated with advanced stages of the tumour, metastatic potential higher histological grades and therapeutic resistance. Mechanistic studies demonstrate that CLU plays a dual role in enhancing tumour cell survival and facilitating apoptosis, contingent upon isoform and environmental context. Recent findings confirm the effectiveness of CLU as a biomarker for early diagnosis, risk evaluation, and forecasting therapeutic response. This review also focuses on the comparison of CLU to known HNSCC biomarkers and stresses the progress made in non-invasive screening and targeted therapies. In conclusion, CLU shows strong potential as a biomarker and therapeutic target, warranting further research for clinical application in HNSCC.