Sarcomas with Murine Double Minute 2 (MDM2) amplification are considered potential candidates for MDM2-targeted therapy. However, the limited efficacy of MDM2 inhibitor monotherapy suggests that additional biological factors may influence tumor behavior and prognosis. This study investigated the relationship between MDM2 expression and the Complexity Index in SARComas (CINSARC) transcriptomic signature, a gene expression signature that reflects cell division and chromosomal instability in soft tissue sarcomas. In the public GSE21050 dataset comprising 310 soft tissue sarcomas, the MDM2-low/CINSARC-low subgroup showed the most favorable metastasis-free survival, whereas the MDM2-high/CINSARC-low subgroup had an unfavorable metastasis-free survival comparable to that of the MDM2-high/CINSARC-high group. Among the representative genes in the 12q13-15 region, fibroblast growth factor receptor substrate 2 (FRS2) showed a strong positive correlation with MDM2 expression, but no significant correlation with CINSARC, suggesting an association independent of proliferative capacity. These findings suggest that proliferation-based risk assessment alone may underestimate the metastatic risk of a subset of MDM2-high sarcomas, and FRS2 may present a biologically relevant marker of aggressive behavior independent of tumor proliferation.

The pathogenesis of Hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC) has not been fully elucidated at present. While METTL14 is crucial in innate immunity, its specific role in HBV-related liver disease progression is unclear. We analyzed METTL14 expression in patient tissues and bioinformatics datasets. Mouse models of HBV-related cirrhosis and HCC were established to evaluate liver injury, fibrosis, and tumorigenesis. Mechanistic studies utilized MeRIPqPCR, RIP, and Actinomycin D assays, and hepatocyte-stellate cell co-cultures to investigate METTL14's impact on cGAS mRNA stability, the cGAS-STING pathway, and IFNB1 secretion. METTL14 was downregulated in HBV infection, cirrhosis, and HCC. METTL14 knockdown aggravated liver injury, fibrosis, and tumor formation in mice. Mechanistic studies revealed that METTL14 overexpression in HBV-infected hepatocytes promoted the degradation of cGAS mRNA by increasing its m6A modification, thereby suppressing the cGAS-STING pathway activation and IFNB1 release. Consequently, METTL14 overexpression inhibited stellate cell activation, which was reversed by cGAS-STING agonists. Downregulation of METTL14 reduces the degradation of cGAS mRNA through m⁶A modification, facilitates the cGAS-STING pathway activation and IFNB1 release, thereby accelerating HBV-related cirrhosis and HCC progressions.

Background/Objectives: Periductal fibrosis (PDF) is a common hepatobiliary abnormality associated with chronic Opisthorchis viverrini infection and may represent an ultrasonographic marker of chronic biliary injury in liver fluke-endemic regions. This systematic review and meta-analysis evaluated the association between ultrasound-defined PDF and cholangiocarcinoma (CCA)-related outcomes and summarized the prevalence of overall PDF and advanced periductal fibrosis (APF) in endemic populations. Methods: PubMed, Embase, and Scopus were searched from database inception to April 2026, supplemented by manual screening of reference lists. Observational studies reporting PDF prevalence and/or the association between PDF and CCA-related outcomes were included. Pooled odds ratios (ORs) and prevalence estimates were calculated using random-effects models. Five studies met the inclusion criteria. Results: Three studies involving 758,686 participants were included in the pooled association analysis. Ultrasound-defined PDF was associated with higher odds of CCA-related outcomes, including confirmed CCA, incident CCA, and clinically suspected CCA, with a pooled OR of 2.77 (95% CI: 2.24-3.44; I² = 0%). Because outcome definitions, effect measures, adjustment status, and PDF exposure categories varied across studies, this estimate should be interpreted as a summary association rather than as a precise estimate of confirmed CCA risk. Four studies involving 759,117 participants contributed to the overall PDF prevalence analysis, whereas three studies reported APF prevalence data. Prevalence estimates varied substantially across endemic settings, with extreme between-study heterogeneity. Conclusions: Overall, ultrasound-defined PDF may help identify individuals who warrant closer surveillance or further evaluation; however, it should not be interpreted as a definitive histopathological diagnosis or a proven causal precursor of CCA. Further prospective studies using standardized fibrosis definitions, blinded ultrasonographic assessment, confirmed or incident CCA outcomes, and adjustment for O. viverrini infection-related factors and other key confounders are needed to validate the role of PDF in CCA risk stratification.

Objective: To analyze the epidemiological characteristics of incidence and mortality of esophageal cancer in Shandong Province from 2012 to 2023. Methods: Data on incidence and mortality of esophageal cancer from 2012 to 2023 were obtained from the Shandong Provincial Cancer Registry. Crude and age-standardized rates stratified by year, gender and urban-rural residence were calculated using the standardized population of China in 2000. Joinpoint Regression Program 4.8.0.1 was adopted to estimate the annual percent change (APC) and average annual percent change (AAPC). Results: Both crude and age-standardized incidence rates of esophageal cancer in Shandong Province declined remarkably from 2012 to 2023, with the AAPC of -4.59% (P<0.001) and of -7.67% (P<0.001), respectively. Males had higher crude and age-standardized incidence rates than females, and rural areas presented higher rates than urban areas. For males, the AAPCs of crude and age-standardized incidence rates were of -3.33% (P<0.001) and of -6.89% (P<0.001). For females, the values were of -6.29% (P<0.001) and of -10.73% (P<0.001). In urban areas, the AAPCs were of -4.59% (P=0.001) and of -6.68% (P<0.001), while those in rural areas were of -4.57% (P<0.001) and -8.16% (P<0.001). Crude and age-standardized mortality rates also showed a significant downward trend, with the AAPC of of -4.48% (P<0.001) and of -8.26% (P<0.001). Mortality rates were higher in males and rural populations. The AAPCs of crude and age-standardized mortality rates were of -3.70% (P<0.001) and of -5.53% (P=0.003) in males, and of -7.92% (P=0.001) and of -11.41% (P<0.001) in females. In rural areas, the corresponding AAPCs were of -4.64% (P<0.001) and of -8.49% (P<0.001). No obvious trend was observed in the urban crude mortality rate. The age-standardized mortality rate had no significant change from 2012 to 2014, and decreased significantly from 2014 to 2023 (APC= -7.68%, P<0.001). Age-specific incidence and mortality rose rapidly after 45 years and peaked in the 80-84 age group. Conclusion: The incidence and mortality of esophageal cancer have decreased significantly in Shandong Province in the past decade, with obvious gender and urban-rural disparities.

Pulmonary function tests (PFTs), particularly spirometry, are the reference standard for assessing airflow limitation in respiratory diseases such as chronic obstructive pulmonary disease (COPD) and interstitial pulmonary disease. However, spirometry requires substantial patient cooperation and may be unreliable in children, the elderly, and patients with cognitive impairment, and its use was further limited during the COVID-19 pandemic. Dynamic chest radiography (DCR), which captures sequential thoracic images during respiration at low radiation dose, has emerged as a promising modality for evaluating respiratory dynamics, but its potential to quantitatively estimate pulmonary function through radiomic analysis remains insufficiently explored.

This study aimed to determine the potential of radiomic features of the lung on DCR to predict pulmonary function (FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity) and to classify patients at high risk (FEV₁/FVC).

We retrospectively analysed data from 151 patients. The DCRs at end-inspiration (EI), end-expiration (EE), and the respiratory phase of maximum variation in the lung area from EI to EE (insp2exp_vmax) or from EE to EI (exp2insp_vmax) were defined based on the lung area. A respiratory motion map was also calculated. To combine the defined DCR and respiratory motion map, feature extraction was performed, followed by the least absolute shrinkage and selection operator (LASSO). Predictive regression and classification models with various radiomic feature combinations (nos. 1-6) were constructed for pulmonary function. Pearson's correlation coefficients (R) were calculated for FEV₁ and FVC, and the area under the curve (AUC) was calculated for FEV₁/FVC. Our predictive models were compared using the conventional formula.

We constructed a predictive regression and classification model for FEV₁, FVC, and FEV₁/FVC ratio using DCR images and a respiratory motion map. The model accuracy with DCR at each respiratory phase and the respiratory motion map-based radiomic features was better than that of the conventional method.

In this single-center retrospective study, radiomic features extracted from DCR at multiple respiratory phases combined with respiratory motion maps showed promise for estimating pulmonary function, outperforming conventional demographic-based prediction. External validation in multi-center cohorts is warranted before clinical translation.

To evaluate whether day-of-procedure ambient ozone exposure is associated with pneumothorax after CT-guided lung biopsy.

This retrospective single-centre study included 160 CT-guided lung biopsies performed between January 2018 and February 2026. Environmental data from the day of biopsy were assigned from the nearest national monitoring station. The primary outcome was any pneumothorax on post-biopsy CT; the secondary outcome was drainage-requiring pneumothorax. Multivariable logistic regression included ozone exposure, emphysema, and access route through dependent lung area (ARDA). Ozone was analysed as a continuous variable per 10 μg/m³ and, exploratorily, using a ROC-derived threshold of ≥75.8 μg/m³. Restricted cubic splines assessed nonlinearity. Sensitivity models adjusted for needle size, biopsy system, operator identity, and season. Drainage-requiring pneumothorax was analysed using Firth logistic regression.

Pneumothorax occurred after 86 of 160 biopsies (53.8%), and 13 biopsies (8.1%) required drainage. Ozone was not associated with pneumothorax when modelled linearly (OR, 1.09 per 10 μg/m³; 95% CI, 0.97-1.23; p = 0.167). In exploratory threshold modelling, ozone ≥ 75.8 μg/m³ was associated with pneumothorax (OR, 2.76; 95% CI, 1.39-5.61; p = 0.004). Emphysema increased pneumothorax odds (OR, 2.16; 95% CI, 1.03-4.68; p = 0.047), whereas ARDA was protective (OR, 0.23; 95% CI, 0.11-0.45; p < 0.001). Spline analysis supported nonlinearity (p = 0.001). For drainage-requiring pneumothorax, only emphysema was significant.

Ambient ozone showed an exploratory nonlinear association with pneumothorax after CT-guided lung biopsy, with a threshold signal around 70-80 μg/m³. ARDA was protective, whereas emphysema was associated with drainage-requiring pneumothorax.

Despite normal lung imaging and preserved pulmonary and cardiac function, many patients with long COVID continue to experience persistent respiratory symptoms. This study aimed to quantify the pulmonary blood and airway volumes in patients with long COVID compared with healthy controls and to evaluate the associations of COVID-19 vaccination with these imaging parameters.

Patients with long COVID presenting with persistent respiratory symptoms despite normal laboratory findings, pulmonary function tests, chest radiography, and chest computed tomography (CT) were prospectively enrolled. CT datasets were analyzed using functional respiratory imaging (FRI), incorporating the three-dimensional reconstruction and automated segmentation of the lungs, airways, and pulmonary vasculature. Quantitative imaging parameters were compared with those of historical healthy controls from the COPDGene study, matched for age, sex, body mass index, comorbidities, and pulmonary function test parameters.

Thirty patients with long COVID (mean 221 ± 128 days after confirmed SARS-CoV-2 infection) and 30 matched healthy controls were included. Compared with controls, patients with long COVID demonstrated significantly lower pulmonary blood volumes in small and large pulmonary vessels, together with significantly reduced intrapulmonary airway volumes. Within the long COVID cohort, full COVID-19 vaccination was associated with a significantly greater small-vessel pulmonary blood volume and lobar airway volume compared with non-vaccinated individuals.

These findings indicate that patients with long COVID exhibit persistent reductions in pulmonary blood and airway volumes despite normal conventional imaging and pulmonary function tests, suggesting the presence of subtle microvascular and small-airway abnormalities that may contribute to ongoing respiratory symptoms. The association between full COVID-19 vaccination and higher small-vessel pulmonary blood and lobar airway volumes suggests a potential protective effect on pulmonary structure and function; however, these findings require confirmation in larger, prospective controlled studies.

The COVID-19 pandemic profoundly disrupted healthcare utilization patterns at both primary care (PC) and hospital emergency department (ED) levels. This study aimed to assess the impact of the pandemic on referral patterns from PC to a hospital ED and on the resource consumption associated with those referrals.

A descriptive, retrospective, longitudinal comparative study with multivariable sensitivity analyses was conducted at a first-level hospital of Madrid (Spain). All consecutive PC-to-ED referrals received during two observation windows were included: a pre-pandemic period (1 June-31 December 2019; n=946) and a Later-Pandemic period (1 January-30 June 2022; n=1797). Sociodemographic characteristics, referral form quality, diagnostic specialty, and in-ED resource utilization variables were collected and compared using χ2, Student's t-test, and Mann-Whitney U tests as appropriate. To assess seasonal confounding, multivariable logistic and ordinal regression models adjusting for calendar season, age, and sex were performed for the primary resource-utilization outcomes.

A total of 2743 referrals were analyzed. The monthly referral rate increased by approximately 122% between periods (135/month vs. 300/month). A statistically significant but clinically negligible difference in mean age was observed (53.1±18.3 vs. 54.9±19.0 years; p=0.015); no significant sex differences were found. Referral form completion improved significantly for clinical history (94.5% vs. 98.2%; p<0.001). Orthopedics referrals nearly tripled (5.8% vs. 18.4%), while respiratory/COVID-19-related referrals represented 22.0% of the 2022 caseload. ED length of stay between 3 and 6 h increased from 13.0% to 42.8% (p<0.001), while the need for urgent blood tests fell from 68.9% to 56.0% (p<0.001), hospital admission from 68.4% to 10.9% (p<0.001), and referral to another center from 12.3% to 0.9% (p<0.001). In multivariable sensitivity analyses, the period effect remained statistically significant after adjustment for calendar season, age, and sex for hospital admission (adjusted OR =0.062; 95% CI: 0.037-0.106; p<0.001) and urgent blood test utilization (adjusted OR =0.470; 95% CI: 0.326-0.678; p<0.001), although study period and season remain partly confounded by the non-overlapping design.

During the later-pandemic period, PC-to-ED referrals increased substantially while being associated with fewer complementary investigations and fewer hospital admissions. This study documents between-period differences in referral patterns and ED resource utilization rather than causal effects; the differences persisted after adjustment for seasonality but cannot be definitively attributed to the pandemic. Future multi-center longitudinal studies are needed to confirm these trends and clarify their underlying mechanisms.

Delayed initiation of mepolizumab may influence long-term disease control and the achievement of clinical and functional outcomes in patients with uncontrolled severe asthma (SUA), but no definitive conclusions have yet been established regarding the optimal timing for biologic initiation. The aim of this study was to evaluate, in a real-world clinical setting, the effect of delayed mepolizumab initiation-from the moment patients first met EMA eligibility criteria-on the treatment response (using the EXACTO scale), clinical remission (according to SEPAR-REMAS criteria) and lung function at 12 months and 3 years after treatment initiation.

We conducted a retrospective observational cohort study including 148 patients with SUA treated with mepolizumab from January 2017 to November 2024 in our hospital. Patients were stratified into tertiles according to delay: ≤5 months, 6-19 months, and >19 months. Baseline demographic, clinical, and lung function characteristics were analyzed.

Patients with shorter delay exhibited distinct significance baseline profiles, including higher eosinophil counts, lower BMI and current smoker, and better pre-treatment lung function (p < 0.05). Shorter delay was significantly associated with higher rates of good/complete response according to the EXACTO scale at both 12 months and 3 years (p < 0.05). Clinical remission rates were numerically higher in the early-treatment group, although differences did not reach statistical significance. No significant differences in lung function outcomes were observed between delay groups at either 12 months or 3 years.

In conclusion, earlier initiation of mepolizumab after meeting EMA criteria is associated with improved clinical response, although it does not significantly influence remission rates or lung function recovery. These findings underscore the importance of timely treatment initiation and reinforce the relevance of accurate phenotypic and endotypic characterization to optimize biologic selection in SUA.

Cervical spinal cord injury (SCI) carries a significant burden in Saudi Arabia, frequently resulting in permanent ventilator dependence and high morbidity. While laparoscopic diaphragmatic pacing (DP) has emerged as an alternative to long-term mechanical ventilation (MV) globally, regional evidence regarding its application within the Middle East remains limited. This study evaluates a single-center cohort of ventilator-dependent cervical SCI patients undergoing laparoscopic DP.

We conducted a retrospective analysis of all ventilator-dependent patients with cervical SCI admitted to a tertiary hospital in Riyadh between 2012 and 2024 who underwent laparoscopic DP after failing traditional weaning attempts. Inclusion criteria required at least 3 months of MV dependence, intraoperative diaphragmatic stimulability and a minimum one-year follow-up post-implantation. Across the entire cohort, the long-term follow-up duration reached a median of 60.0 months (interquartile range [IQR]: 36.0-84.0 months; range: 12.0-120.0 months).

Out of 30 initial candidates with cervical SCI, 28 patients (22 males, 6 females; median age 24.0 years (interquartile range [IQR]: 15.0-33.0 years)) were included. Patients had been on MV for a median of 13.0 months (IQR: 10.5-16.0 months) prior to the procedure. Utilizing a combined weaning success rate (complete or partial weaning), 26 patients (92.86%; 95% CI: 77.42-98.01%) were successfully transitioned to the pacing protocol, while 2 patients (7.14%) experienced DP failure. Complete (24 h) daily MV independence was achieved by 18 patients (64.29%), and partial weaning (≥4 h/day of MV-free time) was achieved by 8 patients (28.57%). Age at the time of injury ranged from 5 to 62 years. No major intraoperative or postoperative complications occurred. Minor exit-site skin irritation was observed in 3 patients (10.71%), all of which resolved completely with conservative local care alone without requiring antibiotic therapy.

In this selected single-center Saudi cohort of ventilator-dependent cervical SCI patients, laparoscopic DP was feasible and was associated with high rates of partial or complete ventilator-free breathing. Larger prospective multicenter studies with standardized selection criteria, safety reporting, respiratory outcomes, quality-of-life measures, and longer follow-up are needed.