Margin-to-depth ratio as an independent prognostic factor in resected oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: The prognostic significance of margin-to-depth ratio (MDR) in oral cavity squamous cell carcinoma (OCSCC) remains unclear, particularly in comparison to traditional margin status. We aimed to examine the association between MDR and clinical outcomes in a large Taiwanese cohort. METHODS: A total of 18,324 patients with first primary OCSCC were categorized by margin status: positive (1013), <5 mm (8371), and ≥ 5 mm (8940). Disease-specific survival (DSS) and overall survival (OS) served as the main outcome measures. RESULTS: After excluding patients with positive margins (MDR = 0), the optimal MDR cutoff value for DSS and OS was 0.6. Patients with MDR > 0.6 showed significantly better 5-year DSS and OS rates (87 %, 81 %) compared to those with MDR ≤ 0.6 (71 %, 63 %) and MDR = 0 (53 %, 43 %). Multivariable analysis identified MDR ≤ 0.6 as independently associated with both DSS and OS in the entire cohort (hazard ratio [HR] = 1.34/1.32). This finding was consistent in the subgroups with surgical margins < 5 mm (HR = 1.39 for DSS and 1.38 for OS) and margins ≥ 5 mm (HR = 1.21 for both DSS and OS). In subgroups with surgical margins < 5 mm and ≥ 5 mm, an MDR > 0.6 was associated with better survival outcomes. CONCLUSIONS: An MDR (cutoff: 0.6) is independently associated with prognosis in OCSCC, offering improved risk stratification compared to margin status alone. While MDR may guide surgical margin modification, further research is needed to determine whether MDR could serve as a postoperative indicator for adjuvant therapy in patients with close or clear margins.

Cutaneous T-cell lymphoma: Consensus on diagnosis and management in Taiwan.

Cutaneous T cell lymphomas (CTCLs), with mycosis fungoides (MF) and Sézary syndrome (SS) as the classic types, are the commonest group of primary cutaneous lymphomas. The diverse clinical manifestation and non-specific histologic findings of early lesions in CTCLs render diagnosis challenging. Treatment modalities also vary and include topical and oral medications, chemotherapy, phototherapy, and radiation therapies. Local dermatological, hemato-oncologic and radiotherapeutical experts in Taiwan convened meetings in 2023 to review and discuss the latest evidence and updates regarding diagnosis and management of CTCLs. A consensus was developed with the aim to raise awareness and understanding, provide practical guidance for early diagnosis and appropriate management, and ultimately optimize care to maximize benefits of patients.

Association between Semaglutide and Non-Arteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Real-World Study.

OBJECTIVE: To investigate whether semaglutide increases the risk of non-arteritic anterior ischemic optic neuropathy (NAION) in the general population. DESIGN: This retrospective cohort study utilized a de-identified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024. PARTICIPANTS: This study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight loss medications other than glucagon-like peptide receptor agonists. METHODS: Patient data were obtained from 160 healthcare organizations across 21 countries. Outcomes were evaluated at one, two, and three years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). MAIN OUTCOME MEASURES: The occurrence of NAION. RESULTS: The final analysis included 37,245 participants with T2DM-only, 33,537 participants with obesity-only, and 64,989 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1 year follow-up: HR, 2.32; 95% CI, 0.60-8.97; 2 years: HR, 2.31; 95% CI, 0.86-6.17; 3 years: HR, 1.51; 95% CI, 0.71-3.25), the obesity-only group (1 year follow-up: HR, 0.25; 95% CI, 0.03-2.28; 2 years: HR, 0.44; 95% CI, 0.09-2.21; 3 years: HR, 0.44; 95% CI, 0.09-2.21), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42-1.57; 2 years: HR, 1.2; 95% CI, 0.74-1.94; 3 years: HR, 1.19; 95% CI, 0.78-1.82). CONCLUSIONS: The findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted, as its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks.

Estimating Costs Associated with Adverse Events in Patients with Advanced Lung Cancer.

Purpose: This study aimed to estimate the costs associated with adverse events (AEs) in advanced lung cancer patients treated with first-line therapies. Subjects and Methods: All patients with advanced lung cancer diagnosed between 2011 and 2019 were identified from the Taiwan National Cancer Registry. First-line treatment was defined as a therapy that began within 30 days before and 90 days after the diagnosis. We defined a newly-developed AE as one established after first-line treatment had commenced, with the contingency that the patient had not been diagnosed with the AE within one year prior to the outset of therapy. One patient with a specific AE was matched on age, sex, and regimens with four patients without the AE. Payments incurred over the same period of time in the two groups were compared to estimate the AE-related costs. Results: A total of 27,376 patients receiving first-line targeted therapy, immunotherapy, or chemotherapy were identified. Clinical characteristics of 15,454 treatment episodes with a specific AE and 61,816 treatment episodes without the AE were well balanced. The costliest AEs of any severity were sepsis/septicemia, neuropathy, and acute kidney injury, with the respective average incremental costs of 10101, 9982, and 7839 USD. The costliest severe AEs requiring hospitalization were sepsis/septicemia, interstitial lung disease/pneumonitis, and neuropathy, with mean incremental costs of 22483, 10645, and 10120 USD, respectively. Conclusion: Costs associated with AEs in advanced lung cancer patients treated with first-line therapies were substantial. These estimates could be adopted for future cost-effectiveness analyses of new lung cancer treatments.

Long-term analysis of infections and associated risk factors in patients with multiple sclerosis treated with ocrelizumab: pooled analysis of 13 interventional clinical trials.

Background: Patients with multiple sclerosis (PwMS) have an increased risk of infections. Objectives: To characterize incidence, clinical characteristics, outcomes and risk factors of infections, and serious infections (SIs) in ocrelizumab (OCR)-treated PwMS. Design: Post-hoc analysis of pooled data from 6155 patients in 13 clinical trials. Methods: Descriptive analyses of clinical characteristics and outcomes were reported over ⩽14 years. A Poisson Generalized Estimating Equation model was constructed to examine risk factors in a subgroup of patients with longer exposure to OCR (n = 2092). Results: Over a median (max) treatment period of 3.7 (13.9) years, 420/6155 patients (6.8%) experienced 583 SIs, excluding coronavirus disease 2019. Incidence rates in relapsing multiple sclerosis (RMS; 1.50 per 100 patient years [95% confidence interval (CI): 1.34-1.68]) and progressive multiple sclerosis (PMS; 3.70 [95% CI: 3.27-4.17]) remained stable over this period. Lower respiratory tract, urinary tract, abdominal and gastrointestinal, and skin infections were the most commonly reported SIs. Most SIs (~90%) resolved, and treatment with OCR was continued in >80% of cases. The presence of 1 or ⩾2 comorbidities (rate ratio = 1.66, 2.73, respectively), recent relapse activity (2.06), and Expanded Disability Status Scale (EDSS) score ⩾6.0 (2.02) were significant risk factors for SIs in patients with RMS treated over a median (max) period of 8.3 (11.2) years. In patients with primary PMS treated over a median (max) period of 7.1 (11.8) years, an EDSS score ⩾6.0 was associated with the greatest risk of SIs, a 4-fold increase (rate ratio, 4.31), followed by abnormal immunoglobulin (Ig)M levels (1.89), the presence of ⩾2 comorbidities (1.80), and having overweight/obesity (1.46). Time on OCR and abnormal IgG levels were not significantly associated with an increased SI risk. Conclusion: Continuous long-term treatment with OCR is associated with a manageable infection risk profile. Optimal disease control and addressing modifiable risk factors may reduce the risk of infections.

Is continued treatment with ocrelizumab associated with a higher risk of infections and serious infections in patients with multiple sclerosis? Patients with multiple sclerosis (PwMS) are at an increased risk of infections compared with the general population. Infections are also among the most frequently reported side effect in PwMS treated with ocrelizumab. Initial analyses have shown that serious infection (SI) rates in PwMS treated with ocrelizumab were stable over 6 years, but there is concern that this rate may increase with continued treatment. This study aimed to describe infections and SIs in PwMS treated with ocrelizumab and look into factors that increase patients' susceptibility to infections. We analyzed the largest population of PwMS ever treated with ocrelizumab, including 6155 patients from 13 clinical trials. Some of these patients received ocrelizumab for as long as 14 years. Approximately 7 out of every 100 patients experienced SIs, excluding COVID-19 infections, with no increase in yearly rates of SIs over time. Pneumonia and urinary tract infections were the most common SIs. Almost all patients recovered from their infections (>9 out of 10 cases), and continued treatment with ocrelizumab (>8 out of 10 cases). When looking at factors that made PwMS more prone to SIs, we found that patients with relapsing MS had an increased risk if they had experienced recent MS relapses, severe walking difficulties, or other health conditions like diabetes and bladder problems. Patients with primary progressive MS (PPMS) with severe walking difficulties were four times more likely to have SIs. Having other health conditions like heart or bladder problems, low levels of immunoglobulin M, or excess weight also increased the risk of SIs in patients with PPMS. In conclusion, continued treatment with ocrelizumab did not increase the risk of SIs, and most of those infections resolved without stopping ocrelizumab treatment. Addressing certain health conditions and achieving a good control of the MS disease may help to reduce the risk of SIs.

Methanolic Extract of Cimicifuga foetida Induces G1 Cell Cycle Arrest and Apoptosis and Inhibits Metastasis of Glioma Cells.

BACKGROUND: Glioblastoma multiforme (GBM) is among the most aggressive and challenging brain tumors, with limited treatment options. Cimicifuga foetida, a traditional Chinese medicine, has shown promise due to its bioactive components. This study investigates the anti-glioma effects of a methanolic extract of C. foetida (CF-ME) in GBM cell lines. METHODS: The effects of CF-ME and its index compounds (caffeic acid, cimifugin, ferulic acid, and isoferulic acid) on GBM cell viability were assessed using MTT assays on U87 MG, A172, and T98G cell lines. The ability of CF-ME to induce cell cycle arrest, apoptosis, and autophagy and inhibit metastasis was evaluated using flow cytometry, Western blotting, and functional assays. Additionally, the synergistic potential of CF-ME with temozolomide (TMZ) was explored. RESULTS: CF-ME significantly reduced GBM cell viability in a dose- and time-dependent manner, induced G1 phase cell cycle arrest, promoted apoptosis via caspase activation, and triggered autophagy. CF-ME also inhibited GBM cell invasion, migration, and adhesion, likely by modulating epithelial-mesenchymal transition (EMT) markers. Combined with TMZ, CF-ME further enhanced reduced GBM cell viability, suggesting a potential synergistic effect. However, the individual index compounds of CF-ME exhibited only modest inhibitory effects, indicating that the full anti-glioma activity may result from the synergistic interactions among its components. CONCLUSIONS: CF-ME exhibited potent anti-glioma activity through multiple mechanisms, including cell cycle arrest, apoptosis, autophagy, and the inhibition of metastasis. Combining CF-ME with TMZ further enhanced its therapeutic potential, making it a promising candidate for adjuvant therapy in glioblastoma treatment.

Prognostic factors and risk-stratification model of recurrent or metastatic head and neck squamous cell carcinoma treated with cetuximab containing regimen.

BACKGROUND: In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population. METHODS: This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS. RESULTS: A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 - 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44-13.61), 7.5 months (95% CI 7.33-8.17), and 4.01 months (95% CI 3.94-4.08), respectively, with a log-rank test p-value < 0.001. CONCLUSION: This study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.

Application of deep learning reconstruction in abdominal magnetic resonance cholangiopancreatography for image quality improvement and acquisition time reduction.

PURPOSE: To compare deep learning (DL)-based and conventional reconstruction through subjective and objective analysis and ascertain whether DL-based reconstruction improves the quality and acquisition speed of clinical abdominal magnetic resonance imaging (MRI). METHODS: The 124 patients who underwent abdominal MRI between January and July 2021 were retrospectively studied. For each patient, two-dimensional axial T2-weighted single-shot fast spin-echo MRI images with or without fat saturation were reconstructed using DL-based and conventional methods. The subjective image quality scores and objective metrics, including signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of the images were analysed. An explorative analysis was performed to compare 20 patients' MRI images with site routine settings, high-resolution settings and high-speed settings. Paired t tests and Wilcoxon signed-rank tests were used for subjective and objective comparisons. RESULTS: A total of 144 patients were evaluated (mean age, 62.2 ± 14.1 years; 83 men). The MRI images reconstructed using DL-based methods had higher SNRs and CNRs than did those reconstructed using conventional methods (all p < 0.01). The subjective scores of the images reconstructed using DL-based methods were higher than those of the images reconstructed using conventional methods (p < 0.01), with significantly lower variation (p < 0.01). Exploratory analysis revealed that the DL-based reconstructions with thin slice thickness and higher temporal resolution had the highest image quality and were associated with the shortest scan times. CONCLUSIONS: DL-based reconstruction methods can be used to improve the quality with higher stability and accelerate the acquisition of abdominal MRI.

Resurgence of influenza and enterovirus infections in Taiwan post-COVID-19: A nationwide surveillance study.

BACKGROUND: The global impact of COVID-19 has prompted profound shifts in public health policies. The epidemiology of respiratory infectious disease may change in the post-covid era. This study investigates the repercussions of these policies on respiratory infectious diseases, specifically the resurgence of severe influenza and enterovirus infections in the post-COVID-19 era. METHODS: Examining the period from January 2020 to December 2023, our nationwide study analyzes data from the Taiwan Centers for Disease Control and Our World in Data. Two distinct phases, containing (Week 1, 2020, to Week 43, 2022) and coexisting (Week 44, 2022, to Week 50, 2023), are scrutinized, emphasizing policy changes and their potential impact on epidemiology. RESULTS: Epidemiological trends reveal a decline in COVID-19 and all-cause pneumonia during the co-existing period but a notable rise in severe influenza and enterovirus infections. Interrupted time series analysis confirms the surge in severe influenza and enterovirus cases post-restriction ease. CONCLUSION: The post-COVID-19 era introduces challenges with the resurgence of traditional respiratory diseases, necessitating continuous surveillance, timely non-pharmaceutical interventions, and vaccination as crucial strategies. Vigilance and targeted measures by policymakers and healthcare providers are imperative to navigate the evolving landscape of respiratory infectious diseases in the aftermath of the pandemic.

Efficacy and safety of videolaryngoscopes for transesophageal echocardiography probe insertion: A trial sequential meta-analysis.

OBJECTIVE: This meta-analysis aimed to compare videolaryngoscope (VL)-assisted transesophageal echocardiography (TEE) probe insertion with conventional methods in terms of efficacy and safety. METHODS: Several major databases such as Medline and Embase were systematically searched to identified relevant studies from inception to June 2024. The primary outcome was complication rate, defined as the proportion of patients experiencing complications related to TEE probe insertion. Injuries at specific sites (e.g., posterior hypopharyngeal wall) from both groups were also analyzed. The secondary outcomes included the first-attempt success rate and total insertion time of VL and conventional methods. RESULTS: Seven trials involving 716 participants were identified. The use of VL was found to significantly reduce the complication rate (risk ratio[RR]:0.28, 95% confidence interval[CI]:0.17-0.46, P < 0.00001) and increased the first-attempt success rate [FASR] (RR:1.33, 95%CI: 1.10-1.60, P = 0.003) compared with conventional methods. These findings were confirmed by trial sequential analysis. No significant difference was found in the TEE insertion time among the two techniques (mean difference: -2.94s, 95%CI: -10.28-4.4, P = 0.43). VL significantly reduced the risk of trauma to the hypopharyngeal wall but showed no significant benefits in other areas (e.g., pyriform sinus). The certainty of evidence was moderate for the complication rate, very low for the FAS rate, and low for the TEE insertion time. CONCLUSION: The use of VL for TEE probe insertion is associated with a significantly lower complication rate and higher FAS rate than conventional methods. These findings suggest that VL enhances patient safety and improves the efficiency of TEE probe insertion.

Prognostic significance of adjuvant therapy and specific radiation dosages in Taiwanese patients with oral cavity cancer and extra-nodal extension: a nationwide cohort study.

BACKGROUND: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. METHODS: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. RESULTS: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578). CONCLUSIONS: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.

Postradiotherapy Response Assessment Using 18F-FDG PET/CT in Salivary Gland Carcinoma-A Multicenter Study.

PURPOSE: This multicenter study investigates the efficacy of 18F-FDG PET/CT in postradiotherapy (post-RT) response evaluation in salivary gland carcinoma (SGC). METHODS: We retrospectively reviewed 115 SGC patients who underwent definitive or adjuvant RT followed by 18F-FDG PET/CT between 2004 and 2021. Most tumors were parotid gland malignancies (50%). The most common histological subtypes were adenoid cystic (29%) and mucoepidermoid carcinomas (18%). RESULTS: The median follow-up was 65 months. Post-RT anatomic images (CT/MRI) revealed complete response (CR) in 51 patients (44%). Among 53 patients with partial response or stable disease, only 17 (32%) patients experienced locoregional recurrence, with a 5-year locoregional control rate of 69%. Post-RT 18F-FDG PET/CT documented metabolic CR in 81 patients (70%). Metabolic complete responders had significantly higher 5-year locoregional control (90% vs 43%), distant metastasis-free survival (80% vs 48%), progression-free survival (76% vs 24%), and overall survival rates (89% vs 42%) compared with non-complete responders (all P < 0.001), as confirmed in both univariate and multivariate analyses. It identified additional viable tumors in 18 cases (16%) and facilitated salvage local therapies in 7 patients (6%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of post-RT 18F-FDG PET/CT were 63%, 91%, 70%, 88%, and 84%, respectively, in predicting locoregional recurrence. 18F-FDG PET/CT showed significantly higher sensitivity (88% vs 36%, P = 0.011) in tumors with pre-RT SUVmax ≥7.39 compared with those with SUVmax <7.39. CONCLUSIONS: Post-RT 18F-FDG PET/CT demonstrates high negative predictive value and specificity, with metabolic CR predicting excellent outcomes. Additionally, it exhibits higher sensitivity for high-SUVmax SGC, facilitating early detection of viable tumors.

Exploring possible causes of lower-than-expected suicide rates in Taiwan and South Korea during the 2020-2021 COVID-19 pandemic: a time trend analysis by sex, age, and method.

AIMS: Decreases in suicide rates during the coronavirus disease 2019 (COVID-19) pandemic were found in several countries, including Taiwan and South Korea. We investigated the pattern of the reduction in suicide by sex, age, method, and outbreak period in the two countries. METHODS: Suicide data for Taiwan (2015-2021) and South Korea (2017-2021) stratified by sex, age, method, and month were extracted from national mortality data files in the two countries. Negative binomial regression was used to estimate suicide rate ratios and 95% confidence intervals across outbreak and inter-outbreak periods during the pandemic, relative to that expected based on pre-pandemic trends, and their associations with economic and outbreak control stringency indicators. RESULTS: There were fewer-than-expected suicides in Taiwan (7%-16% fewer suicides over outbreaks and inter-outbreaks) and South Korea (17% fewer suicides in outbreaks III and IV). Fewer-than-expected suicides were found primarily in the working-age populations aged 25 to 64 years in Taiwan and those aged 45 to 64 years in South Korea. In both countries, fewer-than-expected suicides by charcoal burning during the pandemic were consistently found; the greatest reduction occurred when the outbreak control measures were most restricted. Increased time at residence was associated with decreased suicide rates in South Korea. CONCLUSION: Taiwan and South Korea showed reduced suicide rates during the COVID-19 pandemic in 2020-2021. Potential reasons for the decrease in suicides may include reduced access to suicide means during outbreaks in the two countries.

Synergistic effect of concurrent high molecular risk mutations and lower JAK2 mutant variant allele frequencies on prognosis in patients with myelofibrosis-insights from a multicenter study.

In addition to high-molecular risk (HMR) mutations (ASXL1, EZH2, SRSF2, IDH, and U2AF1Q157), lower JAK2V617F variant allele frequencies (VAF) have been demonstrated to be associated with poor prognosis of myelofibrosis (MF) patients. Nevertheless, the relationship between JAK2V617F VAF and HMR mutations remains inconclusive. To address this, we analyzed the mutation status of 54 myeloid neoplasm-relevant genes using targeted next-generation sequencing in 124 MF patients. Three cohorts from multiple international centers were analyzed for external validation. Among JAK2-mutated patients, the presence of HMR mutations drove poor prognosis in patients with lower JAK2V617F VAF but not in those with higher JAK2V617F VAF. Survival analyses showed consistent results across validation cohorts. In multivariable analysis, concurrent HMR and a lower JAK2V617F VAF was identified as an independent adverse prognostic factor for survival, irrespective of age, MIPSS70, MIPSS70 + v2, and GIPSS risk groups. Mutation co-occurrence tests revealed no shared mutational pattern over different cohorts, excluding potential confounding effect from other concurrent mutations. Importantly, the integration of HMR/JAK2V617F VAF (≤50%) status significantly enhanced existing prognostic models, as evidenced by higher c-indexes and time-dependent ROC analyses. Single-cell studies with sequential follow-ups are warranted to decipher the clonal evolution of MF and how it relates to JAK2V617F VAF dynamics.

Age- and gender-dependent impact of titanium vertebral augmentation implants combined with cementing on subsequent vertebral fracture incidence: A comparative study with cementing alone.

PURPOSE: To compare vertebroplasty (VP) and kyphoplasty (KP) with a titanium implantable vertebral augmentation device (TIVAD) in symptomatic subsequent vertebral compression fracture (SVCF) incidence among osteoporotic vertebral compression fracture (OVCF) patients stratified by age and sex. METHODS: This retrospective cohort study involved OVCF patients aged ≥ 50, who underwent KP with TIVAD or VP in our hospital from 2014 to 2019. Subgroup analysis was conducted to evaluate the efficacy of KP with TIVAD and VP in patients stratified by age and sex. RESULTS: The study included 472 patients (VP group: 303; TIVAD group: 169). SVCF incidence rates were 15.2% for VP group and 14.8% for TIVAD group (P = 0.87). In subgroup analysis, TIVAD group showed significantly lower SVCF incidence than VP group in women aged 50-70 (2.1% vs 14.3%; P = 0.03) and had significantly higher SVCF incidence than VP group in women aged > 70 (24.2% vs 13.1%; P = 0.02). In men, adjacent SVCF incidence was significantly lower in TIVAD group than VP group (0% vs 14.1%; P = 0.03). CONCLUSION: Compared to VP, TIVAD is associated with lower symptomatic SVCF rate in men and younger women aged 50-70 but not in older women aged > 70. Age and gender may influence SVCF incidence. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Epigenomic biomarkers insights in PBMCs for prognostic assessment of ECMO-treated cardiogenic shock patients.

OBJECTIVE: As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited. METHODS: Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan-Meier survival analyses. RESULTS: The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p < 0.05, log-rank test). CONCLUSIONS: This study identifies DNA methylation features in PBMCs as potent prognostic markers for ECMO-treated CS patients. Demonstrating significant predictive accuracy for in-hospital mortality, these markers offer a substantial advancement in patient stratification and might improve treatment outcomes.

Tricuspid valve maladaptation in sheep with biventricular heart failure: The posterior and septal leaflets.

Tricuspid valve leaflets are dynamic tissues that can remodel in response to altered biomechanical and hemodynamic loads. The anterior, posterior, and septal leaflets exhibit distinct morphology, composition, and mechanical properties, resulting in varying in vivo strains. We hypothesized that these differences would result in leaflet-specific remodeling changes in a sheep model of biventricular heart failure. Previously, we reported significant maladaptive changes in the anterior leaflet (Meador et al., 2020b). Here, we extended the analysis to the posterior and septal leaflets and observed a lesser but notable remodeling response. Both the diseased posterior and septal leaflets showed increased free edge thickness and valvular interstitial cell activation. However, only the posterior leaflet exhibited increased circumferential stiffness and collagen content. In contrast, only the septal leaflet increased in area and displayed signs of endothelial-to-mesenchymal transition. These findings emphasize the importance of considering leaflet-specific remodeling when developing computational models or targeted treatment strategies for tricuspid valve disease.