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Objective: To determine the pain and electromyographic (EMG) amplitude ratio of the vastus medialis oblique (VMO) to the vastus lateralis (VL) after botulinum toxin type A (BTA) was injected in the bilateral osteoarthritic knee of patients with patellar malalignment for analysis. Material and methods: A total of fifteen patients were recruited; the more symptomatic knee of each patient received a BTA injection (BTA side). The other set of patients were left untreated. In all, fifteen healthy participants comprised the control group. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and numeric rating scale (NRS) for pain were assessed. The EMG amplitude of VL and VMO activity was recorded using an isokinetic dynamometer and synchronized using the BIOPAC MP100. The data were collected before and at 4, 8, and 12 weeks post–BTA injection. Results: The EMG ratios of the patient group were lower than those of the control group at all testing velocities (p < 0.05). The VMO/VL ratio improved significantly on the BTA side only. The VMO/VL ratios on the BTA side were higher than those on the untreated side (p < 0.05). Knee pain decreased significantly after the BTA injection. The EMG ratios were negatively correlated with the NRS and WOMAC scores. Conclusion: BTA injection effectively reduces knee pain and restores the EMG ratio between the VMO and VL.

Summary: Background: Whether the route of anaesthesia is an independent risk factor for dementia remains unclear. Therefore, we conducted a propensity score–matched (PSM) population-based cohort study to compare dementia incidence among surgical patients undergoing different routes of anaesthesia. Methods: The inclusion criteria were being an inpatient >20 years of age who underwent major elective surgery, defined as those requiring GA without or with inhalation anaesthetics or regional anaesthesia, and being hospitalised for >1 day between Jan 1, 2008 and Dec 31, 2019 in Taiwan. Patients undergoing major elective surgery were categorised into three groups according to the type of anaesthesia administered: noninhalation anaesthesia, inhalation anaesthesia, and regional anaesthesia, matched at a 1:1 ratio. The incidence rate (IR) of dementia was determined. Findings: PSM yielded 63,750 patients (21,250 in the noninhalation anaesthesia group, 21,250 in the inhalation anaesthesia group, and 21,250 in the regional anaesthesia group). In the multivariate Cox regression analysis, the adjusted hazard ratios (aHRs; 95% confidence intervals) of dementia for the inhalation and noninhalation anaesthesia groups compared with the regional anaesthesia group were 20.16 (15.40–26.35; p

Abstract Background To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). Patients and methods We enrolled 646 women with left-breast IDC at clinical stages I–IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). Results In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37–0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79–0.96; P = 0.0356) and 0.89 (0.54–1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group. Conclusion Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.

PurposeTo compare acute, subchronic, and chronic complications between older patients with high-risk localized prostate cancer (HR-LPC) receiving radical prostatectomy (RP) and high-dose intensity-modulated radiotherapy (IMRT) combined with long-term hormone therapy (HT).Patients and MethodsWe recruited older patients (≥80 years) with HR-LPC from the Taiwan Cancer Registry database. After propensity score matching, logistic regression analysis was used to compare the acute, subchronic, and chronic complication rates between patients who underwent RP (the RP group) and high-dose IMRT combined with long-term HT (the IMRT+HT group).ResultsBenign prostatic hyperplasia (BPH) symptoms and urinary incontinence (UI) were the most common complications over 5 years (BPH symptoms: RP, 17.69%; IMRT+HT, 29.58%; UI: RP, 10.47%; IMRT+HT, 5.50%). Compared with the RP group, the IMRT+HT group had higher odds of BPH symptoms and lower odds of UI and hernia after the 5-year follow-up period. The impotence rates were significantly higher in the IMRT+HT group than in the RP group at 3 months and 1 year after treatment and became nonsignificant after 2 years. At 5 years after treatment, the IMRT+HT group had lower risks of UI (adjusted odds ratio [aOR], 0.50; 95% confidence interval [CI], 0.28–0.88) and hernia (aOR, 0.21; 95% CI, 0.11–0.82) and a higher risk of BPH symptoms (aOR, 4.15; 95% CI, 2.82–7.37) than the RP group.ConclusionIMRT+HT was associated with lower UI and hernia risks than RP. By contrast, RP was associated with fewer complications of BPH over the follow-up period and less impotence during the first year after treatment. Our findings provide important and valuable references for shared decision-making for optimal therapy selection among older men with HR-LPC.

PurposeFew studies have compared the long-term medical resource consumption between radical prostatectomy (RP) and intensity-modulated radiation therapy (IMRT) among old (≥80 years) patients with localized prostate cancer (LPC), particularly in those at high risk of prostate adenocarcinoma.Patients and MethodsThe propensity score matching was conducted to investigate the medical expenditure of two therapeutic modalities (RP and IMRT) in elderly patients with high-risk LPC (HR-LPC). The generalized linear mixed and logistic regression models were employed to evaluate the number of postdischarge visits and medical reimbursement for urinary diseases or complications and the number of hospitalizations for treatment-related complications over 5 years after treatment, respectively.ResultsSignificant differences were observed in the median or mean urology clinic visit numbers across the two therapeutic modalities from the first until fifth year post treatment (p < 0.0001). After adjustment for covariates, the mean difference [95% confidence interval (CI)] of urology clinic visit numbers between RP and IMRT was 13.07 (10.45–15.49, P < 0.0001), 7.47 (8.01–14.92, P < 0.0001), 8.24 (4.59–9.90, P < 0.0001), 6.63 (3.55–11.70, P < 0.0001), and 5.02 (1.12–8.73, P < 0.0001) for the first, second, third, fourth, and fifth years, respectively. In the logistic regression multivariate model with adjustment for covariates [therapy type, age, diagnosis year, income, hospital area, hospital level (academic or nonacademic), clinical and pathological T-stage, grade (Gleason score), pretreatment PSA level (ng/ml), and D'Amico risk classification], the adjusted odds ratio (95% CI) of IMRT was 2.10 (1.37–2.56, P = 0.0013), 1.55 (1.08–2.21, P = 0.0151), 1.35 (1.08–2.21, P = 0.0084), 1.24 (1.07–2.21, P = 0.0071), and 1.09 (1.02–1.81, P = 0.0379) for the first, second, third, fourth, and fifth years, respectively, compared with those of RP. The mean difference (95% CI) of total medical claims amounts of RP and IMRT between the RP and IMRT + ADT groups was 2,69,823 New Taiwan Dollars (NTD) (247,676–291,970, P < 0.0001), 40,803 NTD (17,379–54,228, P < 0.0001), 36,202 NTD (24,375–68,029, P < 0.0001), 26,708 NTD (11,179–54,595, P = 0.0321), and 12,173 NTD (17,140–41,487, P = 0.0187) for the first, second, third, fourth, and fifth years, respectively.ConclusionThe long-term medical resource consumption was higher in old men with HR-LPC undergoing IMRT than in those undergoing RP.

MAX dimerization (MXD) protein 3 (MXD3) is a member of the MXD family of basic-helix-loop-helix-leucine-zipper (bHLHZ) transcription factors that plays pivotal roles in cell cycle progression and cell proliferation. However, there is insufficient scientific evidence on the pathogenic roles of MXD3 in various cancers and whether MXD3 plays a role in the immuno-oncology context of the tumor microenvironment, pathogenesis, prognosis, and therapeutic response of different tumors through certain common molecular mechanisms; thus, we saw a need to conduct the present in silico pan-cancer study. Using various computational tools, we interrogated the role of MXD3 in tumor immune infiltration, immune evasion, tumor progression, therapy response, and prognosis of cohorts from various cancer types. Our results indicated that MXD3 was aberrantly expressed in almost all The Cancer Genome Atlas (TCGA) cancer types and subtypes and was associated with the tumor stage, metastasis, and worse prognoses of various cohorts. Our results also suggested that MXD3 is associated with tumor immune evasion via different mechanisms involving T-cell exclusion in different cancer types and by tumor infiltration of immune cells in thymoma (THYM), liver hepatocellular carcinoma (LIHC), and head and neck squamous cell carcinoma (HNSC). Methylation of MXD3 was inversely associated with messenger (m)RNA expression levels and mediated dysfunctional T-cell phenotypes and worse prognoses of cohorts from different cancer types. Finally, we found that genetic alterations and oncogenic features of MXD3 were concomitantly associated with deregulation of the DBN1, RAB24, SLC34A1, PRELID1, LMAN2, F12, GRK6, RGS14, PRR7, and PFN3 genes and were connected to phospholipid transport and ion homeostasis. Our results also suggested that MXD3 expression is associated with immune or chemotherapeutic outcomes in various cancers. In addition, higher MXD3 expression levels were associated with decreased sensitivity of cancer cell lines to several mitogen-activated protein kinase kinase (MEK) inhibitors but led to increased activities of other kinase inhibitors, including Akt inhibitors. Interestingly, MXD3 exhibited higher predictive power for response outcomes and overall survival of immune checkpoint blockade sub-cohorts than three of seven standardized biomarkers. Altogether, our study strongly suggests that MXD3 is an immune-oncogenic molecule and could serve as a biomarker for cancer detection, prognosis, therapeutic design, and follow-up.

Purpose: To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM). Patients and methods: We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis. Results: After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52–0.81, P

Purpose: To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival. Patients and methods: Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs). Results: Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2–4) or nodal (ypN2–3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03–0.81), 0.32 (0.16–0.64), 0.43 (0.23–0.79), 0.23 (0.13–0.42), 0.52 (0.20–1.33), and 0.34 (0.13–0.87) in the ypT0, ypT1, ypT2–4, ypN0, ypN1, and ypN2–3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00–4.07), 0.46 (0.26–0.83), 0.18 (0.06–0.51), 0.28 (0.06–1.34), 0.25 (0.10–0.63), 0.47 (0.23–0.88), and 0.32 in the cT0–1, cT2, cT3, cT4, cN0, cN1, and cN2–3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST. Conclusion: WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response.

PurposeWe examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.Patients and MethodsPatients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsIn the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28–0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3–4, pathological nodal (pN) stage 1, and pN stage 2–3 were 1.16 (1.04–2.08), 1.28 (1.07–2.12), 3.71 (1.82–7.59), 4.67 (1.65–13.18), 1.09 (1.02–1.21), 1.17 (1.03–2.16), 1.10 (1.03–1.33), and 1.22 (1.06–2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64–0.94) compared with that for no adjuvant RT.ConclusionPB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.

Abstract Purpose To assess the feasibility and short-term outcomes of neoadjuvant chemoradiotherapy (CCRT) followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery (TaTME-SPLS) for low-lying rectal adenocarcinoma. Methods and materials A total of 23 patients with clinical stage II-III low-lying (from anal verge 0-8 cm) rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS consecutively from December 2015 to December 2018, were enrolled into our study. Chi-squared testing and Student’s t testing were used to make parametric comparisons, and Fisher’s exact test or the Mann–Whitney U test were used to make nonparametric comparisons. Results Conversion rate in patients who underwent neoadjuvant CCRT followed by TaTME-SPLS was only 4%. The mean operation time was 366 min and the inter-sphincter resection (ISR) was done for 14 patients (60%). The mean number of lymph nodes harvested was 15. There was no surgical mortality, but the 30-day morbidity rate was 21% (5 patients were Clavien-Dindo I-II). Pathological complete response was 21.74% with 100% organ preservation and 100% clear distal margin after neoadjuvant CCRT followed by TaTME-SPLS. Conclusion TaTME-SPLS would be highly successful in lymph node negative and low T stage of low-lying rectal cancer patients who had pathological complete remission or high percentage of partial remission after neoadjuvant CCRT.

Abstract Background To estimate easily assessed preoperative factors for predicting 90‐day mortality in patients with a pancreatic head adenocarcinoma (PHA) receiving a pancreaticoduodenectomy. Methods We analyzed data from the Taiwan Cancer Registry Database of patients with a PHA who received a pancreaticoduodenectomy. Basic demographic characteristics, including gender and age, were categorized. The selection of preoperative comorbidities was based on the preoperative American Society of Anesthesiologists score and Charlson comorbidity index. Results We enrolled 8490 patients with a PHA who received a pancreaticoduodenectomy without distant metastasis. Currently, a pancreaticoduodenectomy for a PHA achieves an overall 90‐day mortality rate of 8.39%. Univariate and multivariate Cox regression analyses indicated that an older age (65‐74 and ≥75 years) and specific comorbidities (chronic obstructive pulmonary disease, chronic kidney disease, dementia, and sepsis) were significant independent prognostic factors for predicting 90‐day mortality after a pancreaticoduodenectomy. After adjustment, the adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) of subjects with middle and high comorbidity scores for 90‐day mortality in 65 to 74‐year‐old patients were 1.36 (1.05‐1.75) and 2.25 (1.03‐4.90), respectively, compared to subjects with low comorbidity scores. The aHRs (95% CIs) of subjects with middle and high comorbidity scores for 90‐day mortality in ≥75‐year‐old patients were 1.35 (1.07‐1.78) and 2.07 (1.19‐3.62), respectively, compared to those with low comorbidity scores. Conclusions Elderly patients with a PHA and moderate or high comorbidity scores have an increased risk of 90‐day mortality after a pancreaticoduodenectomy.

Purpose: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving breast conservative surgery (BCS) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints. Patients and methods: Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.67 (0.46–0.99) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3–4, pathological nodal (pN) stage 2–3, and Her-2 positivity were 1.87 (1.03–3.42), 2.31 (1.20–4.44), 1.67 (1.09–2.56), 2.43 (1.18–4.97), 1.17 (1.03–1.19), 1.28 (1.13–2.24), 1.20 (1.05–2.22), and 1.59 (1.01–2.51), respectively, compared with those for differentiation grade I, clinical stage I, pT1, pN0, and HER-2 negativity. The aHR of LRR for adjuvant radiotherapy was 0.60 (0.38–0.97) compared with that for no adjuvant radiotherapy. Conclusion: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with INHA-GA without propofol.

Purpose: The effect of sarcopenia on the survival of patients with type 2 diabetes remains unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare the patients with diabetes with or without sarcopenia. Patients and Methods: We included patients with type 2 diabetes and categorized them into two groups according to whether they had sarcopenia and compared their survival; patients in the groups were matched at a ratio of 1:2. Results: The matching process yielded a final cohort of 201,698 patients (132,805 and 68,893 in the sarcopenia and nonsarcopenia diabetes groups, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of all-cause death for the sarcopenia diabetes group compared with the control group: 1.35 (1.33–1.38; p < 0.001). The aHRs (95% CIs) of all-cause death for those aged 41–50, 51–60, and >60 years (compared with those aged ≤40 years) were 1.53 (1.48–1.60), 2.61 (2.52–2.72), and 6.21 (5.99–6.45), respectively. The aHR (95% CI) of all-cause death for the male patients compared with the female patients was 1.56 (1.54–1.60). The aHRs (95% CIs) of all-cause death for those with adapted Diabetes Complications Severity Index (aDCSI) scores of 1, 2, 3, 4, and ≥5 (compared with an aDCSI score of 0) were 1.01 (1.00–1.14), 1.38 (1.35–1.42), 1.58 (1.54–1.63), and 2.23 (2.14–2.33), respectively. Conclusion: Patients with type 2 diabetes and sarcopenia had higher mortality than did those without sarcopenia.

Purpose: The effect of pre-existing sarcopenia on patients with oral cavity squamous cell carcinoma (OCSCC) remains unknown. Therefore, we designed a propensity score-matched population-based cohort study to compare the oncological outcomes of patients with OCSCC undergoing curative surgery with and without sarcopenia. Patients and Methods: We included patients with OCSCC undergoing curative surgery and categorized them into two groups according to the presence or absence of pre-existing sarcopenia. Patients in both the groups were matched at a ratio of 2:1. Results: The matching process yielded 16,294 patients (10,855 and 5439 without and with pre-existing sarcopenia, respectively). In multivariate Cox regression analyses, the adjusted hazard ratio (aHR, 95% confidence interval [CI]) of all-cause mortality for OCSCC with and without pre-existing sarcopenia was 1.15 (1.11–1.21, p < 0.0001). Furthermore, the aHRs (95% CIs) of locoregional recurrence and distant metastasis for OCSCC with and without pre-existing sarcopenia were 1.07 (1.03–1.18, p = 0.0020) and 1.07 (1.03–1.20, p = 0.0148), respectively. Conclusions: Pre-existing sarcopenia might be a significant poor prognostic factor for overall survival, locoregional recurrence, and distant metastasis for patients with OCSCC undergoing curative surgery. In susceptible patients at a risk of OCSCC, sarcopenia prevention measures should be encouraged, such as exercise and early nutrition intervention.

In elderly patients with newly diagnosed breast cancer, clarity is lacking regarding the effects of influenza vaccines, particularly on clinical outcomes. This study conducted two nationwide, population-based, and propensity score-matched cohorts to estimate and compare the protective effects of influenza vaccine in elderly women and elderly patients with breast cancer. Data were derived from the National Health Insurance Research Database and Cancer Registry Database. Generalized estimating equations (GEEs) were used to compare outcomes between the vaccinated and unvaccinated cohorts. Adjusted odds ratios (aORs) were used to estimate the relative risks, and stratified analyses in the breast cancer cohort were performed to further evaluate elderly breast cancer patients undergoing a variety of adjuvant therapies. The GEE analysis showed that the aORs of death and hospitalization, including for influenza and pneumonia, respiratory diseases, respiratory failure, and heart disease, did not significantly decrease in vaccinated elderly patients with newly diagnosed breast cancer. Conversely, the aORs of all influenza-related clinical outcomes were significantly decreased in elderly women. No protective effects of influenza vaccination were found in the elderly patients with a newly diagnosed breast cancer. More studies focusing on identifying strategies to improve the real-world effectiveness of influenza vaccination to the immunocompromised are needed. Our clinical outcomes will be valuable for future public health policy establishment and shared decision making for influenza vaccine use in elderly patients with newly diagnosed breast cancer. According to our findings, regular influenza vaccine administration for elderly patients with newly diagnosed breast cancer may be reconsidered, with potential contraindications for vaccination. On the other hand, implementing the vaccination of close contacts of patients with breast cancer may be a more important strategy for enhancing protection of those fragile patients.

Abstract Background Chemotherapy is the main treatment for acute myeloid leukemia (AML), but the cure rates for AML patients remain low, and the notorious adverse effects of chemotherapeutic drugs drastically reduce the life quality of patients. Penfluridol, a long-acting oral antipsychotic drug, has an outstanding safety record and exerts oncostatic effects on various solid tumors. Until now, the effect of penfluridol on AML remains unknown. Methods AML cell lines harboring wild-type (WT) Fms-like tyrosine kinase 3 (FLT3) and internal tandem duplication (ITD)-mutated FLT3 were used to evaluate the cytotoxic effects of penfluridol by an MTS assay. A flow cytometric analysis and immunofluorescence staining were employed to determine the cell-death phenotype, cell cycle profile, and reactive oxygen species (ROS) and acidic vesicular organelle (AVO) formation. Western blotting and chemical inhibitors were used to explore the underlying mechanisms involved in penfluridol-mediated cell death. Results We observed that penfluridol concentration-dependently suppressed the cell viability of AML cells with FLT3-WT (HL-60 and U937) and FLT3-ITD (MV4–11). We found that penfluridol treatment not only induced apoptosis as evidenced by increases of nuclear fragmentation, the sub-G1 populations, poly (ADP ribose) polymerase (PARP) cleavage, and caspase-3 activation, but also triggered autophagic responses, such as the light chain 3 (LC3) turnover and AVO formation. Interestingly, blocking autophagy by the pharmacological inhibitors, 3-methyladenine and chloroquine, dramatically enhanced penfluridol-induced apoptosis, indicating the cytoprotective role of autophagy in penfluridol-treated AML cells. Mechanistically, penfluridol-induced apoptosis occurred through activating protein phosphatase 2A (PP2A) to suppress Akt and mitogen-activated protein kinase (MAPK) activities. Moreover, penfluridol’s augmentation of intracellular ROS levels was critical for the penfluridol-induced autophagic response. In the clinic, we observed that patients with AML expressing high PP2A had favorable prognoses. Conclusions These findings provide a rationale for penfluridol being used as a PP2A activator for AML treatment, and the combination of penfluridol with an autophagy inhibitor may be a novel strategy for AML harboring FLT3-WT and FLT3-ITD.

Background/purpose: Recurrent aphthous stomatitis (RAS) is common and associated with certain comorbidities. The aim of this study was to investigate the prevalence of selected comorbidities in patients with RAUs and to compare the risks of comorbidity between the two cohorts of patients with or without RAUs based on the Taiwanese National Health Insurance Research Database. Methods: This case–control study included patients with recurrent aphthous stomatitis (the RAS cohort) and patients without recurrent aphthous stomatitis using 1:1 matching for year of index date, age, sex, monthly income, geographical location, and urbanization level (the non-RAS cohort). We calculated the prevalence of 31 medical comorbidities based on a modified version of the Elixhauser comorbidity index within 1 year before and after the index date. Conditional logistic regression was conducted to compare the risks of each comorbidity between the two cohorts. Results: Compared with the non-RAS cohort, the RAS cohort had a significantly higher prevalence of 16 comorbidities, with 2% or higher prevalence difference for hyperlipidemia (2.9%), headaches (6.9%), liver diseases (2.8%), and peptic ulcers (5.4%). The adjusted odds ratios were >1.5 for headaches (1.92), migraines (1.62), hypothyroidism (1.50), rheumatoid arthritis (1.92), ankylosing spondylitis (1.94), systemic lupus erythematosus (1.82), liver diseases (1.51), peptic ulcers (1.69), hepatitis (1.62), depression (1.76), and psychoses (1.50). Conclusion: Patients with recurrent aphthous stomatitis were associated with increased risk of specific comorbidities. Physicians should screen for these comorbidities for early detection and treatment. Keywords: Recurrent aphthous stomatitis, Comorbidities, Case–control cohort, Prevalence, Risk

Background: Diabetic nephropathy is a common cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide and results in tremendous wastage of medical resources. Determining the indicators of diabetic nephropathy, such as sarcopenia, and implementing early interventions to prevent disease progression is crucial. Purpose: The effect of sarcopenia on the risk of severe diabetic nephropathy in patients with type 2 diabetes (T2DM) remains unclear. Patients and Methods: We recruited patients with T2DM and categorized them into two groups, propensity score–matched at a ratio of 1:1, according to whether they had sarcopenia. We subsequently compared the groups’ risk of severe diabetic nephropathy. Results: The matching process yielded a final cohort of 105,166 patients with T2DM (52,583 and 52,583 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for inclusion in subsequent analyses. According to both the univariate and multivariate Cox regression analyses, the adjusted hazard ratio (aHR) (95% confidence interval) of severe diabetic nephropathy for the sarcopenia diabetes group compared with the control group was 1.10 (1.08–1.13; p < 0.001). Conclusion: The patients with T2DM and sarcopenia were at a higher risk of severe diabetic nephropathy than were those without sarcopenia. Our results may serve as a valuable reference for relevant government authorities in establishing health policies to promote early detection of sarcopenia and exercise to help patients with T2DM overcome sarcopenia.

Purpose: Whether preexisting sarcopenia is an independent risk factor for cancer incidence remains unclear. Therefore, we performed this propensity score (PS)-matched (PSM) population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sarcopenia. Patients and Methods: The patients were categorized into two groups according to the presence or absence of sarcopenia, matched at a 4:1 ratio. Results: PS matching yielded a final cohort of 77,608 patients (15,527 in the sarcopenia and 62,081 nonsarcopenia groups) eligible for further analysis. In our multivariate Cox regression analysis, compared with the nonsarcopenia group, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for cancer risk in the sarcopenia group was 1.277 (1.10 to 1.36; p < 0.001). Furthermore, the adjusted IRRs (95% CIs) for sarcopenia patients were pancreatic cancer 3.77 (1.79 to 4.01), esophageal cancer 3.38 (1.87 to 4.11), lung cancer 2.66 (1.15 to 2.90), gastric cancer 2.25 (1.54 to 3.23), head and neck cancer 2.15 (1.44 to 2.53), colorectal cancer 2.04 (1.77 to 2.30), hepatocellular carcinoma 1.84 (1.30 to 2.36), breast cancer 1.56 (1.12 to 1.95), and ovarian cancer 1.43 (1.10 to 2.29), respectively. Conclusions: Sarcopenia might be a significant cancer risk factor for lung, colorectal, breast, head and neck, pancreas, gastric, esophageal, and ovarian cancer, as well as hepatocellular carcinoma.

Abstract Background Hepatocellular carcinoma ranks fourth in cancer‐related mortality currently lacks effective therapeutics. Fucoidan is sulfated polysaccharide that is mainly found in brown seaweeds. In this study, we investigated the effects and mechanisms of low molecular weight fucoidan (i.e. oligo‐fucoidan [OF]) preventing hepatocarcinogenesis. Methods We used [HBx,src], [HBx,src,p53−/+], and [CD36] transgenic zebrafish liver cancer model treated with OF, and performed molecular and histopathological analysis. Transcriptomic and pathways analysis was performed. Results Decreased expression of lipogenic enzymes, fibrosis markers, and cell cycle/proliferation markers by OF in [HBx,src] and [HBx,src,p53−/+] transgenic fish. Liver fibrosis was decreased as revealed by Sirius Red staining, and the liver cancer formation was eventually reduced by feeding OF. OF was also found to be capable of reducing lipid accumulation and cancer formation in non‐B non‐C Hepatocellular carcinoma (HCC) model in CD36 transgenic zebrafish. Whole‐genome expression analysis showed that 661 genes were up‐regulated, and 451 genes were downregulated by feeding OF. Upregulated genes were mostly found in protein transporter activity, and downregulated genes were enriched with response to extracellular stimulus and metal binding in gene ontology analysis. The driver gene was HNF4A revealed by NetworkAnalyst from OF differential regulated genes at various insults. OF is able to bind the asialoglycoprotein receptor (ASGR) in hepatoma cells, and increased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in both hepatoma cells and [HBx,src,p53−/+] transgenic fish liver cancer model. Using chromatin‐immunoprecipitation, we found pSTAT3 could associate with the P1 promoter of HNF4A. Knockdown of either ASGR or HNF4A reversed OF mediated anti‐cancer cell proliferation. Conclusions Taken together, we provide evidence that OF exhibits the anti‐HCC, anti‐steatosis, and anti‐fibrosis effect for liver in zebrafish models, and the anti‐cancer potential of OF attributed to the binding to ASGR and activation of STAT3/HNF4A signaling. OF might be potentially valuable for the management of HCC.

Purpose: Hepatocellular carcinoma (HCC) is a major malignancy and the common cause of cancer-related deaths. Surgical intervention provides superior long-term survival outcomes; however, perioperative mortality is a major concern for clinicians while making treatment decisions, especially for major hepatectomy. Scoring systems for predicting 90-day mortality in patients with HCC undergoing major hepatectomy are not available. Methods: This study used the Taiwan Cancer Registry Database that is linked to the National Health Insurance Research Database to analyze data of 60,250 patients with HCC who underwent major hepatectomy and determine risk factors to establish a novel predictive scoring system. By using the stepwise selection of the multivariate Cox proportional hazards model, we divided the patients with HCC undergoing major hepatectomy into four risk groups. Results: The Chang Gung-PohAi predictive scoring system exhibited significant differences in the 90-day mortality rate among the four risk groups (very low risk: 2.42%, low risk: 4.09%, intermittent risk: 17.1%, and high risk: 43.6%). Conclusion: The Chang Gung-PohAi predictive scoring system is a promising tool for predicting 90-day perioperative mortality in patients with HCC undergoing major hepatectomy.

Purpose: The impact of tramadol analgesic use before breast cancer diagnosis on survival in patients with chronic pain is unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare the breast cancer-related survival of patients with chronic pain who received long-term tramadol analgesic treatment with that of those who did not receive such treatment. Patients and Methods: We included patients with chronic pain and categorized them into two groups according to their analgesic use, comparing their breast cancer-related survival; patients with breast cancer and chronic pain who were prescribed ≥180 defined daily doses (DDDs) of tramadol analgesics per year >3 months before breast cancer diagnosis comprised the case group, and those who were prescribed non-tramadol analgesics before breast cancer diagnosis comprised the control group. Patients in both groups were matched at a ratio of 1:5. Results: The matching process yielded a final cohort of 624 patients (104 and 520 in the case and control groups, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratio for all-cause death in the case group compared with in the control group was 3.45 (95% confidence interval = 2.36–5.04; p < 0.001). Conclusion: Long-term tramadol analgesic use prior to breast cancer diagnosis might be associated with poor overall survival in patients with chronic pain compared with such patients that did not receive long-term tramadol analgesic treatment.

PURPOSE: To investigate the effects of pre-existing sleep disorders on the survival outcomes of women receiving standard treatments for breast invasive ductal carcinoma (IDC). METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received surgery for clinical stage I–III breast IDC. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching. RESULTS: In the multivariate Cox regression analysis, the adjusted hazard ratio for all-cause mortality for Group 1 compared with Group 2 was 1.51 (95% confidence interval: 1.19, 1.91; p < 0.001). CONCLUSION: Our study demonstrated that the sleep disorder group had poorer survival rates than the non-sleep disorder group in breast cancer. Therefore, patients should be screened and evaluated for pre-existing sleep disorders prior to breast surgery, with such disorders serving as a predictor of survival in patients with breast cancer. Future studies may investigate the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with breast cancer.

This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT. Background: To date, no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available for old (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS). Patients and Methods: We enrolled old (≥80 years old) and very old (≥90 years old) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We grouped them based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed. Results: Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT. In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44–0.70). The aHRs (95% CIs) of LRR and DM for adjuvant WBRT were 0.29 (0.19–0.45) and 0.45 (0.32–0.62), respectively, compared with no adjuvant WBRT. Conclusions: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.

Background: to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). Patients and Methods: we included 294 women with left-breast IDC at clinical stages IA–IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). Results: in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44–0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24–0.71; p = 0.0017) and 0.37 (0.22–0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group. Conclusion: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.

That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort study by using propensity score matching (PSM) to evaluate the clinical outcomes of RP and IMRT-ADT in relatively young patients with HR/VHR-LPC. Methods: We used the Taiwan Cancer Registry database to evaluate clinical outcomes in relatively young (aged ≤ 65 years) patients with HR/VHR-LPC, as defined by the National Comprehensive Cancer Network risk strata. The patients had received RP or IMRT-ADT (high-dose, ≥72 Gy plus long-term, 1.5–3 years, ADT). Head-to-head PSM was used to balance potential confounders. A Cox proportional hazards regression model was used to analyze oncologic outcomes. Results: High-dose IMRT-ADT had a higher risk of biochemical failure (adjusted hazard ratio [aHR] = 2.03, 95% confidence interval [CI] 1.56–2.65, p < 0.0001) compared with RP; IMRT-ADT did not have an increased risk of all-cause death (aHR = 1.2, 95% CI 0.65–2.24, p = 0.564), locoregional recurrence (aHR = 0.88, 95% CI 0.67–1.06, p = 0.3524), or distant metastasis (aHR = 1.03, 95% CI 0.56–1.9, p = 0.9176) compared with RP. Conclusion: In relatively young patients with HR/VHR-LPC, RP and IMRT-ADT yielded similar oncologic outcomes and RP reduced the risk of biochemical failure compared with IMRT-ADT.

Scarce evidence is available in Asia for estimating the long-term risk and prognostic factors of major complications such as re-rupture, vasospasm, or re-stroke for patients with aneurysmal subarachnoid hemorrhage (SAH) undergoing endovascular coil embolization or surgical clipping. This is the first head-to-head propensity score-matched study in an Asian population to demonstrate that endovascular coil embolization for aneurysmal SAH treatment is riskier than surgical clipping in terms of re-rupture, vasospasm, or re-stroke. In addition, the independent poor prognostic factors of vasospasm or re-stroke were endovascular coil embolization, male sex, older age (≥65 years; the risk of vasospasm increases with age), hypertension, congestive heart failure, diabetes, previous transient ischemic attack, or stroke in aneurysmal SAH treatment. Background: To estimate the long-term complications and prognostic factors of endovascular coil embolization or surgical clipping for patients with ruptured aneurysmal subarachnoid hemorrhage (SAH). Methods: We selected patients diagnosed with aneurysmal SAH between 1 January 2011 and 31 December 2017. Propensity score matching was performed, and Cox proportional hazards model curves were used to analyze the risk of re-rupture, vasospasm, and re-stroke in patients undergoing the different treatments. Findings: Multivariate Cox regression analysis revealed that the adjusted hazard ratio (aHR) of re-rupture for endovascular coil embolization compared with surgical clipping was 1.36 (95% confidence interval [CI]: 1.17–1.57; p < 0.0001). The aHRs of the secondary endpoints of vasospasm and re-stroke (delayed cerebral ischemia) for endovascular coil embolization compared with surgical clipping were 1.14 (1.02–1.27; p = 0.0214) and 2.04 (1.83–2.29; p < 0.0001), respectively. The independent poor prognostic factors for vasospasm and re-stroke were endovascular coil embolization, male sex, older age (≥65 years; risk increases with age), hypertension, congestive heart failure, diabetes, and previous transient ischemic attack or stroke. Interpretation: Endovascular coil embolization for aneurysmal SAH carries a higher risk than surgical clipping of both short- and long-term complications including re-rupture, vasospasm, and re-stroke.

Purpose: To investigate whether chronic obstructive pulmonary disease (COPD) and COPD severity (acute exacerbation of COPD (AECOPD)) affect the survival outcomes of patients with colon adenocarcinoma receiving standard treatments. Methods: From the Taiwan Cancer Registry Database, we recruited patients with clinical stage I–III colon adenocarcinoma who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into COPD and non-COPD (Group 1 and 2) groups through propensity score matching. Results: In total, 1512 patients were eligible for further comparative analysis between non-COPD (1008 patients) and COPD (504 patients) cohorts. In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for all-cause mortality for Group 1 compared with Group 2 was 1.17 (1.03, 1.29). In patients with colon adenocarcinoma undergoing curative resection, the aHRs (95% CIs) for all-cause mortality in patients with hospitalization frequencies of ≥1 and ≥2 times for AECOPD within 1 year before adenocarcinoma diagnosis were 1.08 (1.03, 1.51) and 1.55 (1.15, 2.09), respectively, compared with those without AECOPD. Conclusion: In patients with colon adenocarcinoma undergoing curative resection, COPD was associated with worse survival outcomes. Being hospitalized at least once for AECOPD within 1 year before colon adenocarcinoma diagnosis was an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for AECOPD within 1 year before diagnosis was associated with poorer survival. Our study highlights the importance of COPD management, particularly the identification of frequent exacerbators and the prevention of AECOPD before standard colon adenocarcinoma treatments are applied.

PURPOSE: The survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving concurrent chemoradiotherapy (CCRT) for bladder preservation is unclear. METHODS: We recruited patients with MIBUC, clinical stages IIA–IVB, who had received maximal transurethral resection of bladder tumor (TURBT) followed by CCRT from the Taiwan Cancer Registry Database. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into two groups by using propensity score matching based on the preexisting COPD status (within 1 year before CCRT) to compare overall survival outcomes: Group 1 (never smokers without COPD) and Group 2 (current smokers with COPD). RESULTS: In multivariate Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality in Group 2 compared with Group 1 was 1.89 (1.12–3.18), p = 0.017. The aHRs (95% CIs) of all-cause mortality for ≥1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT for bladder preservation were 3.26 (1.95–5.46) and 6.33 (3.55–11.281) compared with non-COPDAE patients with MIBUC undergoing CCRT for bladder preservation. CONCLUSIONS: Among patients with MIBUC undergoing TURBT followed by CCRT for bladder preservation, current smokers with smoking-related COPD had worse survival outcomes than did nonsmokers without COPD. CONDENSED ABSTRACT: This was the first study to estimate the survival impact of smoking-related chronic obstructive pulmonary disease (COPD) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy (CCRT) for bladder preservation. Smoking-related COPD was a significant independent risk factor for all-cause mortality in patients with clinical stages IIA–IVB receiving TURBT followed by CCRT. Hospitalization frequency for COPD with at least one acute exacerbation within 1 year before CCRT was highly associated with high mortality for patients with MIBUC receiving CCRT for bladder preservation. Not only all-cause death but also bladder cancer death and COPD death were significantly higher in the current-smoking COPD group than in the never-smoking non-COPD group.

Purpose: The survival effect of current smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with rectal adenocarcinoma undergoing curative resection. Methods: We recruited patients with clinical stage I–IIIC rectal adenocarcinoma from the Taiwan Cancer Registry Database who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into two groups by using propensity score matching based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD). Results: In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.25 (1.04–1.51). The aHRs (95% cis) of all-cause mortality for frequency of ≥1 hospitalizations for COPDAE or ≥2 hospitalizations within 1 year before diagnosis were 1.17 (1.05–1.51) and 1.48 (1.03–2.41) compared with no COPDAE in patients with rectal adenocarcinoma undergoing curative resection. Conclusion: In patients with rectal adenocarcinoma undergoing curative resection, being a current smoker with COPD (Group 1) was associated with worse survival outcomes than being a nonsmoker without COPD (Group 2). Being hospitalized at least once for COPDAE within 1 year before the diagnosis of rectal adenocarcinoma is an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for COPDAE within 1 year before diagnosis was associated with poorer survival.

Purpose: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments. Methods: we recruited women with clinical stage I–III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group). Results: PSM yielded 2319 patients with stage I–III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83–1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18–2.36) compared with no COPDAE. Conclusion: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I–III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.

Background: To date, no data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT). Patients and methods: We enrolled 3986 patients with clinical stage IIIA–IIIB, unresectable lung SCC, who had received standard definitive CCRT, and categorized them into two groups based on their COPD status to compare overall survival outcomes. We also examined the effects of COPD severity (0, 1, or ≥2 hospitalizations for COPDA within 1 year before CCRT). Results: In the inverse probability of treatment weighting (IPTW)-adjusted model, the adjusted hazard ratio (aHR) (95% confidence interval (CI)) of all-cause death for COPD was 1.04 (1.01, 1.16), compared no COPD in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. In the IPTW-adjusted model, the aHRs (95% CIs) of 1 and ≥ 2 hospitalizations for COPDAE within 1 year before CCRT were 1.32 (1.19, 1.46) and 1.81 (1.49, 2.19) respectively, compared with no hospitalization for COPDAE. Conclusion: COPD and its severity are significant independent risk factors for all-cause death in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. Hospitalization for COPDAE within 1 year before CCRT is the significant independent risk factor for lung cancer death in the patients with stage IIIA–IIIB lung SCC receiving definitive CCRT.

Fucoidan is an abundant marine sulfated polysaccharide extracted from the cell wall of brown macroalgae (seaweed). Recently, fucoidan has been highly involved in various industrial applications, such as pharmaceuticals, biomedicals, cosmetics, and food. However, the presence of a sulfate group (negative surface charge) in the fucoidan structure limits its potential and biological activity for use in biomedical applications during cellular uptake. Thus, we aimed to improve the uptake of fucoidan by using an L-arginine uptake enhancer within an in vitro study. A Fucoidan–L-Arginine (Fuc-L-Arg) fiber complex was prepared via α-helical electrostatic interactions using a freeze-drying technique and confirmed using field-emission scanning electron microscopy, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. In addition, fucoidan was conjugated with cyanine 3 (Cy3) dye to track its cellular uptake. Furthermore, the results of Fuc-L-Arg (1:1, 1:2.5) complexes revealed biocompatibility >80% at various concentrations (5, 10, 25, 50, 100 µg/mL). Owing to the higher internalization of the Fuc-L-Arg (1:5) complex, it exhibited