Castleman disease (CD) is a heterogeneous lymphoproliferative disorder with unicentric and multicentric forms. Multicentric CD (MCD) is etiologically classified into idiopathic MCD (iMCD), POEMS-associated MCD, and Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8)-associated MCD, and it typically presents with systemic inflammation. KSHV/HHV-8-associated MCD is most commonly seen in HIV-positive patients, although it may rarely occur in HIV-negative individuals.

We report a case of a 65-year-old HIV-negative woman diagnosed with mixed-type KSHV/HHV-8-associated MCD accompanied by Kaposi sarcoma and POEMS-like clinical features. The patient presented with generalized lymphadenopathy, splenomegaly, cytopenias, hypercalcemia, and monoclonal IgG lambda gammopathy. PET-CT revealed widespread hypermetabolic lymphadenopathy and a sclerotic bone lesion in the left humerus. Bone marrow examination was normocellular and showed polytypic plasma cell proliferation. Lymph node biopsy demonstrated HHV-8 (LANA-1) positivity consistent with mixed-type MCD and Kaposi sarcoma. HHV-8 DNA positivity was also confirmed.

The patient was treated with a regimen including daratumumab, bortezomib, cyclophosphamide, and dexamethasone, achieving a clinical and hematologic response after the third cycle. This case highlights that KSHV/HHV-8-associated MCD may occur in HIV-negative individuals and may present concurrently with Kaposi sarcoma and POEMS-like manifestations, representing a rare diagnostic challenge.

Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, underscoring the need to identify key molecular drivers. Cell division cycle 20 (CDC20), a regulator of cell cycle progression, is frequently dysregulated in malignancies. Its specific role and mechanisms in CRC pathogenesis are poorly understood, warranting investigation to uncover novel therapeutic targets. In this study, CDC20 mRNA expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR), while its protein levels were assessed using Western blotting. Cell proliferation was evaluated via the 5-Ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was analyzed by flow cytometry. Migration and invasion capabilities were examined using wound-healing and Transwell invasion assays, respectively. Angiogenesis was assessed using a tube formation assay. To investigate the in vivo effects of CDC20 knockdown, a xenograft mouse model was employed to monitor tumor growth. Flow cytometry was performed to quantify CD206( +) macrophages. Mechanistic studies included chromatin immunoprecipitation (ChIP), dual-luciferase reporter, RNA immunoprecipitation (RIP), and methylated RNA immunoprecipitation (MeRIP) assays to explore GATA binding protein 6 (GATA6) and methyltransferase-like 3 (METTL3) interactions with CDC20. The results showed that CDC20 expression at the mRNA and protein levels was significantly upregulated in CRC tissues in comparison with normal colorectal tissues. Moreover, its protein expression was higher in CRC cells than in human normal colonic epithelial cells. Its knockdown suppressed CRC cell proliferation, migration, invasion, and tube formation, while promoting apoptosis. In addition, CDC20 depletion inhibited tumor growth and immune escape. Transcription factor GATA6 directly activated transcription of the CDC20 gene. Crucially, restoring CDC20 expression counteracted the tumor-suppressive effects of GATA6 knockdown on malignant behaviors and immune escape. METTL3 stabilized CDC20 transcripts via insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)-mediated mRNA stability. Further, overexpressing CDC20 similarly reversed the inhibitory effects of METTL3 knockdown on CRC cell malignancy and immune escape. Thus, CDC20, upregulated transcriptionally by GATA6 and post-transcriptionally by METTL3, drove CRC progression, angiogenesis, and immune evasion. Targeting CDC20 or its regulators holds significant clinical promise for developing therapies in CRC patients.

Endoscopic radiofrequency ablation (RFA) has become an established minimally invasive option for patients with pancreaticobiliary tumors who are not candidates for resection or who have obstructing lesions of the bile duct or pancreas. This narrative review summarizes the devices, technique, and supporting clinical evidence for endoscopic RFA, organized by clinical indication rather than by device alone.

RFA delivers high-frequency alternating current that produces localized thermal injury and coagulative necrosis. Two endoscopic delivery routes are in use: an ERCP-guided approach, which treats intraductal lesions such as malignant biliary strictures and ampullary tumors using bipolar endobiliary catheters, and an EUS-guided approach, which uses a monopolar needle electrode to ablate pancreatic parenchymal lesions, including solid tumors, neuroendocrine tumors, and pancreatic cysts and intraductal papillary mucinous neoplasms (IPMN). Hybrid needles that combine fine-needle aspiration with ablation are an emerging, still investigational, third category.

Across the published series, technical success generally exceeds 90% for both approaches, with adverse event rates that are mostly low and dominated by self-limited abdominal pain, mild pancreatitis, or cholangitis; perforation and clinically significant bleeding are uncommon when established energy and safety-margin parameters are followed. A proposed, but still poorly characterized, immune-stimulating effect of ablation-induced tissue injury is discussed as a hypothesis rather than an established mechanism.

Taken together, the available data support endoscopic RFA as a useful adjunct in the multidisciplinary management of pancreaticobiliary disease, but most of the supporting literature consists of small, single-arm, or retrospective series. Prospective, ideally randomized, studies with standardized energy protocols and longer follow-up are needed before the technique's role in routine practice, particularly for pancreatic cystic lesions and IPMN, can be considered settled.

Oxidative stress, resulting from the disruption of redox homeostasis, is increasingly recognized as a central driver of gastric cancer pathogenesis and a critical determinant of cell fate. An imbalance between reactive oxygen species (ROS) production and cellular antioxidant defenses leads to oxidative stress, which may ultimately result in cellular oxidative death. Helicobacter pylori (H. pylori), through its virulence factors, induces a vicious cycle of oxidative stress and inflammation that collectively remodels the tumor microenvironment. Gastric cancer is molecularly heterogeneous, and ROS demonstrate profound context dependency across these different subtypes, with distinct mechanisms governing ROS generation, antioxidant defense, and redox-regulated cell death. Importantly, ROS orchestrate a diverse repertoire of cell death modalities in gastric cancer, including ferroptosis, apoptosis, necroptosis, cuproptosis, paraptosis, pyroptosis, and oxeiptosis via a regulatory network involving key molecules such as GPX4, SLC7A11, NRF2, and caspases. In-depth research into the mechanisms of cell death holds promise for developing preventive and therapeutic agents. This review summarizes the mechanisms of ROS‑regulated cell death and explores various therapeutic strategies, including the combined use of small‑molecule compounds and emerging nanomaterial‑based approaches, alongside conventional chemotherapy, immunotherapy, and radiotherapy, to target oxidative stress. It also highlights recent advances, opportunities, and challenges in translating these strategies into gastric cancer therapy. In conclusion, this review offers a mechanistically grounded framework for developing redox-targeted precision therapies in gastric cancer.

IKK_α, a key component of canonical and non-canonical NFκB signalling, is implicated in prostate cancer and bone metabolism. Here, we validated the anti-proliferative effects of selected molecules from a series of first-in-class IKK_α inhibitors against a panel of human prostate cancer models and then showed that the potent anti-tumour and highly IKK_α-selective SU¹³⁴⁹ reduced the ability of human PC3 cells to migrate and invade in vitro, induce osteolysis ex vivo, and cause trabecular bone loss in mice. Paradoxically, mice treated with SU¹³⁴⁹ exhibited cortical bone loss. Histomorphometrical in vivo and functional in vitro studies confirmed that SU¹³⁴⁹ suppressed osteoclastogenesis, but both enhanced and reduced osteoblast number and activity. Mechanistically, despite SU¹³⁴⁹ being an inhibitor with a significant selectivity for IKK_α over IKK_β, it inhibited both canonical and non-canonical NFκB signalling in PC3 cells, osteoclasts, and osteoblasts, and reduced the levels of several PC3-secreted, NFκB-regulated factors. This study suggests that IKK_α inhibitors could be of therapeutic value in the treatment of prostate cancer-induced osteolysis. However, osteoblast inhibition may limit their usefulness as osteoprotective agents.

Accurate MRI characterization of pancreatic cystic neoplasms (PCNs) is essential for risk stratification and clinical decision-making. Despite their widespread use, the reproducibility of several MRI features incorporated into international guidelines remains poorly studied, particularly in MRI-based evaluation. We evaluated interobserver agreement among fellowship-trained abdominal radiologists in assessing MRI features of PCNs according to the revised Fukuoka guidelines.

In this retrospective single-center study, three fellowship-trained abdominal radiologists (5-10 years post-fellowship experience) independently reviewed MRI/MRCP examinations of 23 patients harboring 25 PCNs. Readers were blinded to clinical data and each other's assessments. A predefined checklist based on the 2017 revised Fukuoka guidelines was used to evaluate imaging features including cyst size, location, morphology, main pancreatic duct (MPD) diameter, ductal communication, mural nodules, solid components, wall characteristics, and wall enhancement. Interobserver agreement was quantified using Fleiss' kappa for categorical variables (with pairwise Cohen's kappa), and the intraclass correlation coefficient (ICC) for continuous variables. Kappa values were interpreted using the Landis and Koch scale.

Substantial agreement was observed for lesion location (kappa = 0.75, p < 0.0001), cyst size (kappa = 0.62, p < 0.0001), and morphological form (kappa = 0.60, p < 0.0001). Moderate agreement was noted for MPD diameter (ICC = 0.52, p < 0.0001), wall thickness (kappa = 0.31, p = 0.008), and signs of chronic pancreatitis (kappa = 0.36, p = 0.002). Fair agreement was found for ductal communication (kappa = 0.18, p = 0.041) and wall enhancement (kappa = 0.20, p = 0.089), while solid components showed no agreement beyond chance (kappa = - 0.03, p = 0.812). Mural nodules showed 100% agreement attributable to their absence in this cohort.

Objective MRI features such as lesion size and morphology showed consistently good agreement between readers, supporting their use as primary criteria in clinical decision-making. However, qualitative features including ductal communication, wall enhancement, and solid components show poor reproducibility, potentially leading to inconsistent risk stratification. Our results highlight the need for standardized interpretation criteria, structured reporting templates, and quantitative imaging tools to improve diagnostic consistency in PCN evaluation.

The 2026 AHA/ACC guideline on acute pulmonary embolism introduces normotensive shock as a clinically relevant pre-cardiopulmonary failure state with implications for treatment escalation. Evidence from cardiogenic shock indicates that tissue hypoperfusion despite preserved arterial blood pressure is associated with substantial mortality, underscoring the need for early recognition. This requires reliable, rapidly obtainable, and broadly applicable criteria. As several proposed indicators are limited by delayed availability or restricted bedside use, shock assessment should integrate concordant clinical signs of tissue hypoperfusion rather than rely on a single marker. Prolonged capillary refill time and skin mottling may complement lactate as bedside markers of abnormal skin perfusion. Critical care echocardiography further supports this multimodal approach by confirming acute right ventricular pressure overload, excluding alternative causes of circulatory failure, and assessing right ventricular adaptation and right ventricular-pulmonary arterial coupling. Early recognition may identify patients at imminent risk of deterioration who could benefit from timely treatment escalation, including consideration of reperfusion therapy.

Ventilator-associated pneumonia (VAP) is a frequent and serious infection among mechanically ventilated children in pediatric intensive care units (PICUs), with oral colonization playing a key role in its pathogenesis. Effective oral hygiene measures are therefore crucial to reduce VAP incidence and improve clinical outcomes. This study aimed to compare the incidence of VAP in PICU patients receiving routine oral care versus toothbrushing with chlorhexidine, and to evaluate the impact on mechanical ventilation duration, PICU stay, and mortality with secondary outcomes including microbiological colonization, inflammatory markers, and inotropic support requirements.

A parallel-group superiority randomized controlled trial.

A randomized controlled trial was conducted on 118 children aged 18 months to 16 years, including PICU patients requiring invasive mechanical ventilation for ≥ 48 h. On admission, patients were randomly allocated into two groups: the intervention group received oral care with toothbrushing plus 0.12% chlorhexidine mouth rinse, while the control group received routine care with 0.12% chlorhexidine rinse only. Both procedures were performed three times daily. VAP was diagnosed according to CDC criteria. Quantitative and qualitative analyses assessed variables distinguishing VAP cases from controls, and multivariate logistic regression identified independent predictors of disease severity.

The results of our study revealed that VAP occurred in 31 patients (52.5%) in the control group and 25 patients (42.3%) in the intervention group, indicating a lower incidence with toothbrushing plus chlorhexidine, although this difference was not statistically significant (p = 0.36). Among all participants, 45.8% died and 54.2% were discharged. Mortality was higher in the control group (53.7%) compared with the intervention group (46.3%), while discharge rates favored the intervention group (53.1% vs. 46.9%); however, these differences did not reach statistical significance (p = 0.46). Positive sputum cultures were more frequent in the control group (55.6%) than in the intervention group (44.4%), whereas negative cultures were more common among intervention patients (54.7% vs. 45.3%), with no significant difference between groups (p = 0.268).

Although adding toothbrushing to routine chlorhexidine oral care did not produce a statistically significant reduction in VAP incidence or mortality, a consistent trend toward clinical benefit was observed across multiple outcome measures, including lower rates of positive sputum cultures, reduced inotropic support requirements, and fewer new pulmonary infiltrates. These findings highlight the potential value of enhanced oral hygiene in the PICU and support the need for larger multicenter studies to confirm its effect.

ClinicalTrials.gov, NCT07287566. Registered on November 20, 2025. Retrospectively registered at https://clinicaltrials.gov/ct2/show/NCT07287566 .

The full study protocol and the statistical analysis plan are included in this document and are available from the corresponding author upon reasonable request.

Primary acquired nasolacrimal duct obstruction (PANDO) is a common cause of epiphora in adults. Chronic inflammation has been proposed as a contributing factor, and gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) have been hypothesized to play a potential role. This study aimed to compare GERD and LPR symptoms between patients with PANDO and controls.

This retrospective case-control study included 110 patients with PANDO (previously treated PANDO group, n = 85; consecutive PANDO group undergoing DCR, n = 25) and 105 age- and sex-matched controls. The previously treated PANDO group comprised patients who had undergone external dacryocystorhinostomy over a five-year period, while the consecutive PANDO group undergoing DCR included newly diagnosed patients scheduled for surgery over one year. All participants completed the Reflux Disease Questionnaire (RDQ) and Reflux Symptom Index (RSI). Participants meeting predefined questionnaire-based criteria (RDQ score ≥ 15 or prior physician diagnosis for GERD; RSI score > 13 or prior physician diagnosis for LPR) were classified as having GERD- or LPR-related symptoms.

The prevalence of GERD-related symptoms was 33.5% in the PANDO group and 32.4% in controls (p = 0.692). LPR-related symptoms prevalence was 16.3% and 17.1%, respectively (p = 0.942). No statistically significant differences were observed between groups in total or subscale RDQ and RSI scores.

In this case-control study, reflux symptoms were not significantly more prevalent in patients with PANDO than in controls. Further studies incorporating objective diagnostic methods are warranted to clarify this relationship.

CPAP therapy is the mainstay treatment for OSA, but adherence remains challenging. This study evaluated whether CT-defined low tongue posture (LTP), operationalized as a tongue-palate air gap on sagittal CT, is associated with CPAP adherence.

Retrospective analysis of 430 adults with OSA (AHI ≥ 20) who underwent PSG, CT imaging, and CPAP initiation at our sleep center. CT-defined LTP was assessed on mid-sagittal CT. CPAP adherence at 3 months was obtained from device-recorded data. Logistic regression identified factors associated with good adherence, defined as ≥ 70% and ≥ 50% of nights with ≥ 4 h of use.

CT-defined LTP was observed in 115 patients (26.7%). Patients with CT-defined LTP had lower average CPAP adherence (39.6% vs. 54.1%, p < 0.001). In multivariate analysis, CT-defined LTP was associated with lower odds of good adherence at both the 70% (adjusted OR 0.447, 95% CI 0.272-0.734, p = 0.001) and 50% (adjusted OR 0.496, 95% CI 0.319-0.772, p = 0.002) thresholds. The model showed limited specificity at the 70% threshold (22.5%) and improved balance at the 50% threshold (specificity 68.3%).

CT-defined LTP was associated with poorer CPAP adherence. Given its non-standardized CT definition and limited specificity at the 70% threshold, it should be interpreted as an adjunctive risk marker rather than a standalone screening tool.