Changhua Christian Hospital

Obstructive sleep apnea (OSA) is characterized by pharyngeal collapse, hypoxia, and hypercapnia. However, the impact of coronary heart disease (CHD) severity on OSA development has been rarely explored. This study aimed to evaluate the correlation between CHD severity and OSA incidence. This retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD). Patients with CHD were categorized into three groups: those with severe CHD who underwent percutaneous coronary intervention (PCI), those with CHD without PCI, and those receiving medical treatment. The primary outcome was the development of OSA at least six months after CHD onset. Cox proportional hazards regression was used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for OSA across the different CHD groups. A total of 5,193 and 8,313 OSA events were recorded in the CHD-PCI and CHD groups, respectively. After adjusting for multiple confounders, the incidence of OSA was significantly higher in the CHD-PCI group than in the CHD group (aHR: 1.267, 95% CI: 1.220–1.315, P = 0.0135). Subgroup analyses showed that the association between severe CHD with PCI and OSA was more pronounced in older CHD patients (P < 0.05). The cumulative incidence of both OSA and severe OSA was significantly higher in the CHD-PCI group than in the CHD group (both P < 0.001). Severe CHD requiring PCI is associated with a higher incidence of subsequent OSA compared to mild CHD. This association is particularly significant in patients older than 70 years.

Peripheral nerve injury (PNI) commonly leads to motor or sensory dysfunction, with nerve grafts being the standard treatment for neurorrhaphy. Despite advancements in biomaterials for nerve-tissue engineering, the rate of nerve regeneration remains slow. Therefore, this study aims to improve further the understanding of the impact of syndecan-3 (SDC3)-modified small intestine submucosa (SIS) on nerve reconstruction by employing two advanced approaches: cation recruitment and local growth factor delivery. Immunofluorescence staining confirmed the presence of SDC3 conjugated on the SIS. The enzyme-linked immunosorbent assay measured sustained glial cell line-derived neurotrophic factor (GDNF) levels in the SDC3-coated SIS. In vitro studies showed that SDC3-coated SIS retained GDNF in a dose-dependent manner, significantly enhancing Schwann cell proliferation compared with basal conditions. RSC96 cells proliferated most effectively on SDC3-coated SIS loaded with GDNF, and neuro-2A neurites were significantly longer on this material at 48 hours. One-month post-neurorrhaphy, morphological analysis revealed a 1.6 ± 0.02-fold increase in the number of β3-tubulin-positive axons in the GDNF+SDC3-coated SIS group compared to the SIS group. CMAP amplitude increases in the GDNF+SDC3-coated SIS group as more functioning motor axons are connected to the target muscle of ESN rats. This study provides valuable insights into the development of customized SDC3-coated SIS for promoting nerve tissue regeneration and accelerating rehabilitation.

A BSTRACT Objectives The objective of this study was to investigate the role of type I insulin-like growth factor receptor (IGF-1R) in pemetrexed-resistant lung cancer cells and its interaction with B lymphoma Mo-MLV insertion region 1 homolog (BMI1), previously identified as a key resistance gene. Materials and Methods The study started with the analysis of the activation of IGF-1R in pemetrexed-resistant A549 (A400) lung cancer cells by Western blot analysis of its form of phosphorylation. Cancer stem cell (CSC) activity was assessed by tumor sphere culture. IGF-1R inhibition was performed by picropodophyllin (PPP), an IGF-1R inhibitor, or by shRNA-mediated RNA silencing. A Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse xenograft model was used to access in vivo pemetrexed sensitivity. To further understand the relationship between IGF-1R and BMI1, both BMI1 knockdown and overexpression experiments were performed to assess IGF-1R phosphorylation by western blot. Results Increased IGF-1R phosphorylation was found in A400 cells, and subsequent IGF-1R inhibition resulted in a reduction in CSC activity in these resistant cells. In the in vivo studies, PPP treatment effectively suppressed tumor growth and reduced BMI1 expression in A400 tumor tissue. Further investigation showed that BMI1 knockdown in A400 cells resulted in decreased IGF-1R phosphorylation, whereas BMI1 overexpression in A549 cells resulted in increased IGF-1R phosphorylation, indicating an interaction between these two proteins. Conclusion A novel reciprocal regulatory relationship between IGF-1R and BMI1 has been identified in lung cancer cells, suggesting potential therapeutic strategies to combat pemetrexed resistance in lung cancer patients.

Background/Aims Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C virus (HCV) infection. The long-term hepatic and extrahepatic outcomes of DAAs in chronic hepatitis C (CHC) patients receiving curative antivirals are elusive. Methods CHC patients were retrieved from two phase III sofosbuvir-based clinical trials conducted from 2013–2014. Patients who achieved a sustained virological response have been followed prospectively for 5 years since 2016. A propensity score-matched interferon-based historical control with a 1:3 ratio was used for comparison. Quality of life (QoL) was measured by the SF-36, liver fibrosis was measured by electrography, and fibrosis-related markers were followed annually in the prospective cohort. Results A total of 160 DAA- and 480 interferon-treated patients were enrolled. Twenty-eight patients developed hepatocellular carcinoma (HCC) over a follow-up period of 4424 person-years (annual incidence: 0.6%). The incidence of HCC did not differ significantly between the DAA cohort and interferon-treated patients (P = 0.07). Cox regression analysis revealed that FIB-4 was the only factor independently associated with HCC development (hazard ratio [HR]: 95% confidence interval [CI] 3.59/1.68–7.66, P = 0.001). The incidence of newly developed cardio-cerebrovascular disease was 13.8 per 1000 person-years and 0.9 per 1000 person-years in interferon-treated patients and the DAA cohort, respectively (P < 0.001). Interferon-based patients had a significantly greater incidence of cardio-cerebrovascular disease (HR/CI 3.39/1.28–8.96, P = 0.014). There was a substantial decrease in liver stiffness (Ptrend = 0.08) and M2BPGi (Ptrend = 0.05) and a significant reduction in LOXL2 (Ptrend = 0.02) over 5 years. A significant decrease in QoL was observed in role limitations due to physical health and emotional problems, whereas the other parameters were maintained consistently throughout the 5 years of follow-up. Conclusions HCV eradication by DAAs improved liver- and non-liver-related outcomes, constantly promoted liver fibrosis regression, and maintained quality of life after HCV cure. Clinical Trial Number NCT03042520.

Intrahepatic bile duct (IHBD) dilatations are a rare disease and can lead to the formation of intrahepatic stones, cholangitis, and even cholangiocarcinoma. Surgical resection of the affected segments has traditionally been considered the only effective approach in symptomatic patients. Here, we present the successful chemical ablation of the IHBD using ethanol through percutaneous transhepatic cholangial drainage in an 82-year-old patient who is at high risk for surgery.

This retrospective cohort study investigated whether Paxlovid (nirmatrelvir/ritonavir) use during the acute phase of mild‐to‐moderate COVID‐19 reduces the risk of ischemic or hemorrhagic stroke occurring more than 3 months post‐diagnosis, a condition classified as long COVID. Utilizing TriNetX electronic health records comprising 118 million patients in the United States, adults aged 18 years or older with confirmed COVID‐19 diagnoses from 2022 to 2023 were categorized into Paxlovid (administered within 5 days of diagnosis) and non‐Paxlovid groups. Exclusion criteria included prior cerebrovascular disease, mortality within 3 months, use of specific antivirals, and severe clinical conditions such as ICU admission, intubation, mechanical support, SpO₂ < 90%, respiratory rate > 30/min, sepsis, systemic inflammatory response syndrome, and acute respiratory distress syndrome. The index date was the initial COVID‐19 diagnosis. Propensity score matching in a 1:1 ratio controlled for confounding factors, and stroke (ischemic or hemorrhagic) and mortality were analyzed using Kaplan–Meier survival curves and Cox proportional hazards models. Among 181 992 matched pairs, Paxlovid use was associated with a significantly reduced risk of ischemic and hemorrhagic stroke (hazard ratio [HR] 0.85; 95% confidence interval [CI]: 0.80–0.89) and all‐cause mortality (HR 0.68; 95% CI: 0.63–0.73) during the long COVID period, defined as more than 90 days post‐diagnosis. Subgroup analyses demonstrated consistent protective effects across age, sex, BMI, comorbidities such as hypertension, diabetes, and hyperlipidemia, and vaccination status. Notably, older adults (HR 0.81; 95% CI: 0.76–0.86) and individuals with metabolic conditions, including obesity (HR 0.86; 95% CI: 0.78–0.96), exhibited pronounced benefits, and the protective effects were observed irrespective of vaccination status. These findings highlight that Paxlovid use during the acute phase of COVID‐19 significantly reduces the risk of long‐term cerebrovascular events and mortality, emphasizing its critical role in mitigating long‐term complications associated with COVID‐19.

Background To perform a systematic review and meta-analysis that assesses the diagnostic performance of deep learning algorithms applied to breast MRI for predicting axillary lymph nodes metastases in patients of breast cancer. Methods A systematic literature search in PubMed, MEDLINE, and Embase databases for articles published from January 2004 to February 2025. Inclusion criteria were: patients with breast cancer; deep learning using MRI images was applied to predict axillary lymph nodes metastases; sufficient data were present; original research articles. Quality Assessment of Diagnostic Accuracy Studies-AI and Checklist for Artificial Intelligence in Medical Imaging was used to assess the quality. Statistical analysis included pooling of diagnostic accuracy and investigating between-study heterogeneity. A summary receiver operating characteristic curve (SROC) was performed. R statistical software (version 4.4.0) was used for statistical analyses. Results A total of 10 studies were included. The pooled sensitivity and specificity were 0.76 (95% CI, 0.67–0.83) and 0.81 (95% CI, 0.74–0.87), respectively, with both measures having moderate between-study heterogeneity (I ² = 61% and 60%, respectively; p < 0.01). The SROC analysis yielded a weighted AUC of 0.788. Conclusion This meta-analysis demonstrates that deep learning algorithms applied to breast MRI offer promising diagnostic performance for predicting axillary lymph node metastases in breast cancer patients. Incorporating deep learning into clinical practice may enhance decision-making by providing a non-invasive method to more accurately predict lymph node involvement, potentially reducing unnecessary surgeries.

Background: Both glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) improve cardiovascular (CV) outcomes in people with type 2 diabetes (T2D) and CV or chronic kidney disease (CKD). However, there are limited data about the effect of combining these agents on CV and safety outcomes. Methods: The SOUL trial (NCT03914326) randomised 9650 participants with T2D and atherosclerotic CV disease and/or CKD to oral semaglutide or placebo. As prespecified, participants were analysed according to baseline use of SGLT2i (Yes: n=2596, No: n=7054) and, subsequently for any use of SGLT2i during the trial (Yes: n=4718, No: n=4932). The primary outcome was time to first major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. Safety was evaluated by comparing the incidence of serious adverse events. Results: Over a mean follow-up of 47.5±10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide vs placebo (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.77; 0.96). In those taking SGLT2i at baseline, there were 143/1296 (semaglutide) versus 158/1300 (placebo) primary outcome events (HR 0.89; 95% CI 0.71; 1.11); and 436/3529 versus 510/3525, respectively, in participants not taking SGLT2i at baseline (HR 0.84; 95% CI 0.74; 0.95; P -interaction 0.66). An analysis of MACE by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar. Conclusions: Oral semaglutide reduced MACE outcomes independently of concomitant SGLT2i treatment and this combination appeared to be safe.

Nasopharyngeal cancer with central nervous system metastases is rare. True metastasis to the distal regions of the central nervous system, especially the spinal cord, is incredibly uncommon, although tumor invasion to intracranial locations through the skull base can be prevalent. We report on a 45-year-old male who had been suffering from progressive unsteady gait and numbness of lower limbs for 3 weeks. The numbness eventually ascended to the thigh area and the patient required a wheelchair. His muscle power was normal. Magnetic resonance imaging showed multiple enhancing nodular lesions in the thoracolumbar spinal cord with mild mass effect, causing diffuse syringomyelia and cord edema. Metastasis was confirmed by pathology after tumor excision. The patient underwent concurrent radiotherapy and steroid therapy, after which he eventually could walk with crutches. Due to the complexity and rarity of such case, the standard treatment for this type of disease is unclear. Management should be individualized and multidisciplinary.

Background and Aims Dye‐based chromoendoscopy (DCE) has been the preferred method for colonoscopy surveillance in patients with inflammatory bowel disease (IBD). However, with advances in endoscopy, virtual chromoendoscopy (VCE) techniques have emerged. This network meta‐analysis evaluates the effectiveness of different endoscopy techniques for IBD patient surveillance. Methods Sixteen randomized controlled trials involving 2514 patients were included in the analysis, comparing endoscopy techniques in IBD patient surveillance: DCE, high‐definition white light endoscopy (WLE), standard‐definition WLE, i‐scan, narrow band imaging (NBI), flexible spectral imaging color enhancement (FICE), and autofluorescence imaging (AFI). We assessed the per patient neoplasia detection rate, positive predictive value (PPV), and withdrawal time between different endoscopy techniques. Moreover, subgroup analysis was conducted to investigate the neoplasia detection rate according to endoscopy techniques using various biopsy protocols. Results Comparing neoplasia detection rates revealed that only DCE (OR: 2.56 [1.17–5.59]) significantly increased the neoplasia detection rate compared with standard‐definition WLE. The subsequent rankings were high‐definition WLE, NBI, FICE, i‐scan, and AFI. Moreover, the PPVs of DCE, VCE, and high‐definition WLE showed no significant difference compared with that of standard‐definition WLE. However, DCE required a significantly longer withdrawal time. Subgroup analysis showed that DCE with random biopsy or target biopsy and high‐definition WLE with target biopsy had superior neoplasia detection rates than standard‐definition WLE with random biopsy. Conclusion DCE significantly outperforms standard‐definition WLE in neoplasia detection rates, with random biopsy providing additional benefits. Although DCE does not lower PPV, it requires more withdrawal time. If DCE‐based surveillance is not feasible, high‐definition WLE with targeted biopsy should be considered as other VCE techniques offer no significant advantages.

Unconventional genetic subtypes of B‐cell precursor acute lymphoblastic leukaemia (B‐ALL) were analysed to compare their frequency and their impact on outcomes between children and young adults in Taiwan. Unconventional subtypes were found in 23.0% of 456 paediatric B‐ALL and 24.5% of 139 young adult B‐ALL. The most frequently unconventional subtype both in children and young adults was BCR::ABL1‐like, which could be subdivided into different kinase‐altering aberrations in 67.3% of children and 78.6% of young adults. CRLF2‐R was more frequent in children, while IL7R mutations were more common in young adults. In children, favourable outcomes were observed in patients with DUX4‐R and PAX5alt, whereas those with BCR::ABL1‐like and MEF2D‐R had inferior outcomes. BCR::ABL1‐like and MEF2D‐R were also the independent predictors of inferior event‐free survival in children. Conversely, most unconventional subtypes in young adults were associated with adverse outcomes except for DUX4‐R. We found a lower incidence of BCR::ABL1‐like and a better prognosis for paediatric PAX5alt in Taiwan compared to the West. Additionally, genetic differences were identified between paediatric and young adult BCR::ABL1‐like subtypes. The extremely poor prognosis for unclassified young adults highlights the potential use of further subdivision of unfavourable genetic subtypes in refining risk classification and treatment optimization.