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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.

Abstract Purpose No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia. Patients and methods We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery. Results Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03–1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04–4.57), septicemia (aOR = 1.31; 95% CI = 1.03–1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29–1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10–1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04–3.48), septicemia (aOR = 1.52; 95% CI = 1.28–1.82), and overall complications (aOR = 1.24; 95% CI = 1.08–1.42). Conclusions Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. Condensed abstract No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.

Background To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast‐conserving surgery and adjuvant whole breast radiotherapy. Methods and Results A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left‐sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast‐conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25–0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose–response relationship. The 5‐year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%). Conclusions Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast‐conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.

Abstract Purpose To enhance the predictive risk model for all-cause mortality in individuals with Type 2 Diabetes (T2DM) and prolonged Atherosclerotic Cardiovascular Disease (ASCVD) risk factors. Despite the utility of the Coronary Artery Calcium (CAC) score in assessing cardiovascular risk, its capacity to predict all-cause mortality remains limited. Methods A retrospective cohort study included 1929 asymptomatic T2DM patients with ASCVD risk factors, aged 40–80. Variables encompassed demographic attributes, clinical parameters, CAC scores, comorbidities, and medication usage. Factors predicting all-cause mortality were selected to create a predictive scoring system. By using stepwise selection in a multivariate Cox proportional hazards model, we divided the patients into three risk groups. Results In our analysis of all-cause mortality in T2DM patients with extended ASCVD risk factors over 5 years, we identified significant risk factors, their adjusted hazard ratios (aHR), and scores: e.g., CAC score > 1000 (aHR: 1.57, score: 2), CAC score 401–1000 (aHR: 2.05, score: 2), and more. These factors strongly predict all-cause mortality, with varying risk groups (e.g., very low-risk: 2.0%, very high-risk: 24.0%). Significant differences in 5-year overall survival rates were observed among these groups (log-rank test

Background/Objectives: Frozen shoulder is a common shoulder disorder that often places limitations on the range of motion of the shoulder. The disease may induce neck pain due to overuse of the neck muscle in an attempt to compensate for lack of shoulder movement. In clinical practice, swelling and inflammation of the scalene and levator scapulae may be detected via sonography in patients with frozen shoulder. The aim of this study was, therefore, to determine whether the involvement of the scalene complex or levator scapulae could compensate for the limited motion of the shoulder in patients with frozen shoulder. Methods: We retrospectively reviewed the medical records of 362 patients with unilateral frozen shoulder. These patients were divided into four groups depending on the involvement of the scalene complex or levator scapulae muscle. The range of motion of the shoulder—encompassing flexion, abduction, and external rotation—was measured with a goniometer. We also performed an ultrasound scan on each shoulder. The involvement of the scalene complex and levator scapulae muscle was also assessed via musculoskeletal ultrasound. Results: The range of motion of the shoulder in terms of flexion, abduction, external rotation, and total range of motion differed significantly between the four groups (p < 0.05). Patients in whom the scalene complex or levator scapulae muscle was involved demonstrated a significantly wider range of motion in different shoulder directions than patients without the involvement of those muscles (p < 0.05). Conclusions: A greater range of motion in the shoulder can be obtained through the activation of the scalene complex or levator scapulae muscle, which act to compensate for the lack of shoulder movement in patients with frozen shoulder. These two muscles showed thickening and hypoechoic changes upon sonography.

Abstract. Introduction:. This study investigates the association between chronic postsurgical pain (CPSP) and long-term postsurgical analgesic usage in patients undergoing neuraxial anesthesia, with a specific focus on the presence or absence of sarcopenia. Objectives:. To assess the rate of analgesic prescription, including opioids, at 3 and 6 months postsurgery for patients with and without preoperative sarcopenia, and to determine the impact of sarcopenia on analgesic use after neuraxial anesthesia surgery. Methods:. Patients undergoing surgery under neuraxial anesthesia were categorized into sarcopenic and nonsarcopenic groups based on preoperative diagnosis using the ICD-10-CM code M62.84. Propensity score matching in a 1:4 ratio was applied for group matching. Analgesic prescription rates were evaluated at 3 and 6 months postsurgery, and multivariable logistic regression was used to analyze analgesic use, comparing patients with and without preoperative sarcopenia. Results:. Among 3805 surgical patients, 761 had sarcopenia, while 3044 did not. At 3 months postsurgery, 62.3% of sarcopenic patients received analgesics, with 2.9% receiving opioids, compared to 57.1% of nonsarcopenic patients receiving analgesics and 0.8% receiving opioids. At 6 months postsurgery, 30.8% of sarcopenic patients received analgesics (1.7% opioids), while 26.3% of non-sarcopenic patients received analgesics (0.3% opioids). Multivariable logistic regression analysis revealed that preoperative sarcopenia was significantly associated with higher analgesic prescription rates at both 3 months (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.05–1.53) and 6 months (aOR, 1.17; 95% CI, 1.07–1.42) postsurgery. Furthermore, sarcopenic patients exhibited significantly higher opioid prescription rates at 3 months (aOR, 1.11; 95% CI, 1.05–2.45) and 6 months (aOR, 1.89; 95% CI, 1.12–4.96) postsurgery. Conclusion:. Sarcopenia emerges as an independent risk factor for prolonged analgesic use after neuraxial anesthesia surgery and significantly elevates the risk of developing CPSP.

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.

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.

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.

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

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.

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.

This is the first and largest population-based cohort study to demonstrate that influenza vaccination reduced all-cause mortality and influenza-related hospitalization in elderly individuals with a disability. Purpose: To estimate the protective effect of influenza vaccination in elderly individuals with a disability by conducting a propensity score-matched (PSM), nationwide, population-based cohort study. Methods: Data from Taiwan’s National Health Insurance Research Database were used in this study. Generalized estimating equations (GEEs) were used to compare outcomes between the vaccinated and unvaccinated cohorts. The GEE logit was used to estimate the relative risks of death and hospitalization after influenza vaccination. Adjusted odds ratios (aORs) were used to estimate relative risk. Results: The matching process yielded a final cohort of 272 896 elderly individuals with a disability (136 448 individuals in each cohort). In multivariate GEE analyses, aOR (vaccinated vs. unvaccinated) and 95% confidence interval (CI) of death were 0.70 (0.68−0.72). The aORs (95% CIs) of hospitalization for influenza and pneumonia, respiratory diseases, respiratory failure, heart disease, hemorrhagic stroke, and ischemic stroke were 0.98 (0.95−1.01), 0.96 (0.94−0.99), 0.85 (0.82−0.89), 0.96 (0.93−0.99), 0.85 (0.75−0.97), and 0.89 (0.84−0.95), respectively. The length of stay and medical expenditure exhibited greater reduction in vaccinated elderly individuals with a severe and very severe disability than in unvaccinated elderly individuals. Conclusions: Influenza vaccination reduced all-cause mortality, influenza-related hospitalization, length of stay, and medical expenditure in elderly individuals with a disability. The decrease in the length of stay and medical expenditure because of influenza vaccination was proportional to the severity of disability.

Purpose: The effects of influenza vaccines are unclear for elderly individuals with disabilities. We use a population-based cohort study to estimate the effects of influenza vaccines in elderly individuals with and without disabilities. Methods: Data were taken from the National Health Insurance Research Database and Disabled Population Profile of Taiwan. A total of 2,741,403 adults aged 65 or older were identified and 394,490 were people with a disability. These two groups were further divided into those who had or had not received an influenza vaccine. Generalized estimating equations (GEE) were used to compare the relative risks (RRs) of death and hospitalization across the four groups. Results: 30.78% elderly individuals without a disability and 34.59% elderly individuals with a disability had vaccinated for influenza. Compared to the unvaccinated elderly without a disability, the vaccinated elderly without a disability had significantly lower risks in all-cause mortality (RR = 0.64) and hospitalization for any of the influenza-related diseases (RR = 0.91). Both the unvaccinated and vaccinated elderly with a disability had significantly higher risks in all-cause mortality (RR = 1.81 and 1.18, respectively) and hospitalization for any of the influenza-related diseases (RR = 1.73 and 1.59, respectively). Conclusions: The elderly with a disability had higher risks in mortality and hospitalization than those without a disability; however, receiving influenza vaccinations could still generate more protection to the disabled elderly.

Radiation-induced fibrosis (RIF) occurs after radiation therapy in normal tissues due to excessive production and deposition of extracellular matrix proteins and collagen, possibly resulting in organ function impairment. This study investigates the effects of low-molecular-weight fucoidan (LMF) on irradiated NIH3T3 cells. Specifically, we quantified cellular metabolic activity, fibrosis-related mRNA expression, transforming growth factor beta-1 (TGF-β1), and collagen-1 protein expression, and fibroblast contractility in response to LMF. LMF pre + post-treatment could more effectively increase cellular metabolic activity compared with LMF post-treatment. LMF pre + post-treatment inhibited TGF-β1 expression, which mediates negative activation of phosphorylated Smad3 (pSmad3) and Smad4 complex formation and suppresses downstream collagen I accumulation. In addition, LMF pre + post-treatment significantly reduced actin-stress fibers in irradiated NIH3T3 cells. LMF, a natural substance obtained from brown seaweed, may be a candidate agent for preventing or inhibiting RIF.

Background: Betel nut chewing involves the chewing of areca nuts or betel quid (areca nuts wrapped in betel leaves), which is associated with an increased risk of esophageal squamous cell carcinoma (ESCC). Statins have anticancer properties. We investigated the association between statin use and ESCC risk in betel nut chewers. Methods: The study included 105 387 betel nut chewers matched statin users and nonusers. Statin use was defined as the use of =28 cumulative defined daily doses (cDDDs) of statin. The primary outcome was incidence of ESCC. Results: The incidence rate of ESCC was significantly lower in statin users than in nonusers (2.03 vs. 3.02 per 100 000 person-years). Statin users had a lower incidence rate ratio of 0.66 for ESCC (95% confidence interval [CI]: 0.43-0.85) relative to nonusers. After potential confounders were adjusted for, statin use was determined to be associated with a reduced risk of ESCC (adjusted hazard ratio [aHR], 0.68; 95% CI: 0.51-0.91). A dose-response relationship was observed between statin use and ESCC risk; the aHRs for statin use at 28-182 cDDDs, 183-488 cDDDs, 489-1043 cDDDs, and > 1043 cDDDs were 0.92, 0.89, 0.66, and 0.64, respectively. Conclusion: Statin use was revealed to be associated with a reduced risk of ESCC in betel nut chewers. [ABSTRACT FROM AUTHOR]

The effects of clinically relevant concentrations of lidocaine on epithelial-mesenchymal transition (EMT) and associated lung cancer behaviors have rarely been investigated. The aim of the present study was to assess the impact of lidocaine on EMT and its related phenomena, including chemoresistance. Lung cancer cell lines (A549 and LLC.LG) were incubated with various concentrations of lidocaine, 5-fluorouracil (5-FU) or both to test their effects on cell viability. Subsequently, the effects of lidocaine on various cell behaviors were assessed in vitro and in vivo using Transwell migration, colony-formation and anoikis-resistant cell aggregation assays, and human tumor cell metastasis in a chorioallantoic membrane (CAM) model quantitated by PCR analysis. Prototypical EMT markers and their molecular switch were analyzed using western blotting. In addition, a conditioned metastasis pathway was generated through Ingenuity Pathway Analysis. Based on these measured proteins (slug, vimentin and E-cadherin), the molecules involved and the alteration of genes associated with metastasis were predicted. Of note, clinically relevant concentrations of lidocaine did not affect lung cancer cell viability or alter the effects of 5-FU on cell survival; however, at this dose range, lidocaine attenuated the 5-FU-induced inhibitory effect on cell migration and promoted EMT. The expression levels of vimentin and Slug were upregulated, whereas the expression of E-cadherin was downregulated. EMT-associated anoikis resistance was also induced by lidocaine administration. In addition, portions of the lower CAM with a dense distribution of blood vessels exhibited markedly increased Alu expression 24 h following the inoculation of lidocaine-treated A549 cells on the upper CAM. Thus, at clinically relevant concentrations, lidocaine has the potential to aggravate cancer behaviors in non-small cell lung cancer cells. The phenomena accompanying lidocaine-aggravated migration and metastasis included altered prototypical EMT markers, anoikis-resistant cell aggregation and attenuation of the 5-FU-induced inhibitory effect on cell migration. [ABSTRACT FROM AUTHOR]

Purpose To elucidate the association of presurgical sarcopenia and long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia. Methods We conducted this population-based propensity score matched to investigate the effects of sarcopenia and long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia between 1 October 2016 and 31 December 2019 from Taiwan's National Health Insurance Research Database. Sarcopenia is a disease and coded as M62.84 in the International Classification of Diseases, 10th Revision, Clinical Modification. The primary outcome was the combined rate of the long-term use of all non-opioid analgesics or opioids over 3 and 6 months after elective surgery. By performing a logistic regression analysis, we calculated the adjusted ORs (aORs) with 95% CIs to identify the independent predictors for long-term non-opioid analgesic and opioid use after surgery. Results In total, 2860 patients underwent elective surgery. The 3-month non-opioid analgesic and opioid use rates were respectively 49.7% and 1.8% in the sarcopenia group and 37.9% and 0.9% in the non-sarcopenia group; by contrast, 6-month non-opioid analgesic and opioid use rates were respectively 31.6% and 1.2% in the sarcopenia group and 17.2% and 0.3% in the non-sarcopenia group. Moreover, presurgical sarcopenia increased the risk of long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia (aORs for non-opioid analgesic use over 3 and 6 months after surgery: 1.17 (95% CI 1.05 to 2.23) and 1.26 (95% CI 1.04 to 1.45), respectively; aORs for opioid use over 3 and 6 months after surgery: 1.17 (95% CI 1.07 to 2.21) and 1.23 (95% CI 1.10 to 3.64), respectively). Conclusion Sarcopenia is associated with higher rates of long-term non-opioid analgesic and opioid use after elective surgery under general anesthesia. Summary The aim of this study was to compare the long-term use of non-opioid analgesics and opioids after elective surgery under general anesthesia between patients with and without sarcopenia. Results suggest that patients with sarcopenia are more likely to have increased use of non-opioid analgesics and opioids after surgery. Further research is needed to determine if sarcopenia can be modified prior to surgery and if this impacts the need for long-term pain management with these medications. [ABSTRACT FROM AUTHOR]

Taiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin-angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients.Of 248,797 patients who received a hypertension diagnosis in Taiwan during 2001-2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose-response relationship, we categorized only statin or RASI use into four groups in each cohort: 365 cumulative defined daily doses (cDDDs).In the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50-0.65), 0.72 (0.53-0.98), and 0.47 (0.41-0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54-0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used.Statins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis risk.

Purpose: Radiotherapy is a crucial treatment approach for many types of cancer. Radiation pneumonitis (RP) is one of the major complications in chest irradiation. Fucoidan is a sulfated polysaccharide found mainly in various species of brown seaweed. Recent studies have demonstrated the anti-inflammatory effects of fucoidan. However, no study has reported a well-established prophylactic agent for RP. Therefore, we investigated the effects of fucoidan on RP and radiotherapy (RT)-induced lung fibrosis. Materials and Methods: We compared RP and RT-induced fibrosis in lung tissue specimens obtained from irradiated (10 Gy/shot) C57BL/6 mice with or without fucoidan administration (200 mg/kg/day, oral gavage for 14 days). The expression patterns of cytokines in the pleural fluid were determined using a cytokine array and confirmed through enzyme immunoassays. Results: Fucoidan administration attenuated RP and RT-induced fibrosis in lung tissues. Decreased neutrophil and macrophage accumulation was observed in irradiated lung tissues, and radiation-induced lung fibrosis, as demonstrated by Masson trichrome staining, was attenuated. We investigated the expression patterns of inflammatory cytokines in the irradiated lung pleural fluid through the protein array; results revealed that fucoidan administration changed the expression patterns of inflammatory cytokines in irradiated lung tissues. Furthermore, the expression levels of TIMP-1, CXCL1, MCP-1, MIP-2, and interleukin-1Ra were substantially enhanced in the pleural fluid, but fucoidan administration significantly reduced their expression. Conclusions: Fucoidan changes the expression patterns of inflammatory cytokines, which may consequently attenuate RP and RT-induced lung fibrosis.

Lysophosphatidic acid (LPA) is a multi-function glycerophospholipid. LPA affects the proliferation of hepatocytes and stellate cells in vitro, and in a partial hepatectomy induced liver regeneration model, the circulating LPA levels and LPA receptor (LPAR) expression levels in liver tissue are significantly changed. Liver sinusoidal endothelial cells (Lsecs) play an important role during liver regeneration. However, the effects of LPA on Lsecs are not well known. Thus, we investigated the effects of LPA on the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs.Mouse Lsecs were isolated using CD31-coated magnetic beads. The mRNA expression levels of LPAR's and other target genes were determined by quantitative RT-PCR. The protein levels of angiogenesis factors, cytokines, and chemokines were determined using protein arrays and enzyme immunoassay (EIA). Critical LPAR related signal transduction was verified by using an appropriate chemical inhibitor.LPAR1 and LPAR3 mRNA's were expressed in mouse LPA-treated Lsecs. Treating Lsecs with a physiological level of LPA significantly enhanced the protein levels of angiogenesis related proteins (cyr61 and TIMP-1), cytokines (C5/C5a, M-CSF, and SDF-1), and chemokines (MCP-5, gp130, CCL28, and CXCL16). The LPAR1 and LPAR3 antagonist ki16425 significantly inhibited the LPA-enhanced expression of cyr61, TIMP-1, SDF-1, MCP-5, gp130, CCL28, and CXCL16, but not that of C5/C5a or M-CSF. LPA-induced C5/C5a and M-CSF expression may have been through an indirect regulation mechanism.LPA regulated the expression profiles of angiogenic factors, cytokines, and chemokines in Lsecs that was mediated via LPAR1 and LPAR3 signaling. Most of the factors that were enhanced by LPA have been found to play critical roles during liver regeneration. Thus, these results may prove useful for manipulating LPA effects on liver regeneration.

Condensed abstract: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). This is the first head-tohead propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18FDGPET- CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era. Purpose: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects. Patients and methods: We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. Results: We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively). Conclusions: Pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT. [ABSTRACT FROM AUTHOR]

This study aimed to examine the association between the use of H1-antihistamines (AHs) and head and neck cancer (HNC) risk in patients with type 2 diabetes mellitus (T2DM). Data from the National Health Insurance Research Database of Taiwan were analyzed for the period from 2008 to 2018. A propensity-score-matched cohort of 54,384 patients each in the AH user and nonuser groups was created and analyzed using Kaplan-Meier method and Cox proportional hazards regression. The results showed that the risk of HNC was significantly lower in AH users (adjusted hazard ratio: 0.55, 95% CI: 0.48 to 0.64) and the incidence rate was also lower (5.16 vs. 8.10 per 100,000 person-years). The lower HNC incidence rate in AH users (95% CI: 0.63; 0.55 to 0.73) suggests that AH use may reduce the risk of HNC in T2DM patients. [ABSTRACT FROM AUTHOR]

Here, dual-sensitive fluorescent branched alginate-polyethyleneimine copolymer (bAPSC) nanogels were synthesized from thiolated alginate and stearoyl-derivatized branched polyethyleneimine. The formation of bAPSC conjugates was confirmed through proton nuclear magnetic resonance and Fourier transform infrared spectroscopy, whereas dynamic light scattering was used to measure the particle size and ζ potential of the nanogels. The fluorescent properties of the nanogels were confirmed through fluorescent spectroscopy and microscopy. In addition to the excitation-dependent fluorescence behavior, the fluorescence emission intensity of bAPSC was altered by both pH and γ-irradiation. This intensity was higher at a lower pH than at a higher pH, and it slightly decreased after γ-irradiation. The drug loading and encapsulation efficiency of bAPSC were 25.9% and 11.2%, respectively. An in vitro drug release study revealed that the synthesized nanogels release their doxorubicin (Dox) contents in a time-dependent manner, and the drug release was higher after 96 h of incubation. Approximately 43.74% and 88.36% of Dox was released after 96 h of incubation at pH 5.5 in the absence and presence of glutathione (GSH), respectively. However, relatively lower drug release, approximately 21.6% and 16%, was observed in the presence and absence of GSH at pH 7.4, respectively. Fluorescence microscopy confirmed that Dox-loaded bAPSC nanogels were internalized by HeLa cells, and drug distribution was easily tracked using fluorescent materials without additional probing agents. Moreover, cellular cytotoxicity and hemolysis results revealed less cytotoxicity and hemocompatibility of the synthesized nanogels, confirming that they are the most favorable alternative drug carriers for drug delivery systems. [ABSTRACT FROM AUTHOR]

Immune interferon (IFN), also known as IFN-γ, promotes not only immunomodulation but also antimicrobial and anticancer activity. After IFN-γ binds to the complex of IFN-γ receptor (IFNGR) 1-IFNGR2 and subsequently activates its downstream signaling pathways, IFN-γ immediately causes transcriptional stimulation of a variety of genes that are principally involved in its biological activities. Regarding IFN-γ-dependent immunosurveillance, IFN-γ can directly suppress tumorigenesis and infection and/or can modulate the immunological status in both cancer cells and infected cells. Regarding the anticancer effects of IFN-γ, cancer cells develop strategies to escape from IFN-γ-dependent cancer immunosurveillance. Immune evasion, including the recruitment of immunosuppressive cells, secretion of immunosuppressive factors, and suppression of cytotoxic T lymphocyte responses, is speculated to be elicited by the oncogenic microenvironment. All of these events effectively downregulate IFN-γ-expressing cells and IFN-γ production. In addition to these extrinsic pathways, cancer cells may develop cellular tolerance that manifests as hyporesponsiveness to IFN-γ stimulation. This review discusses the potential escape mechanisms from IFN-γ-dependent immunosurveillance in tumorigenesis. [ABSTRACT FROM AUTHOR]

Abstract Purpose To investigate the dose-dependent protective effects of statins, specific classes of statins, and different intensities of statin use on sepsis risk in patients with type 2 diabetes mellitus (T2DM). Methods We included patients with T2DM aged ≥ 40 years. Statin use was defined as the use of statin on most days for > 1 months with a mean statin dose of ≥ 28 cumulative defined daily doses (cDDDs) per year (cDDD-year). An inverse probability of treatment-weighted Cox hazard model was used to investigate the effects of statin use on sepsis and septic shock while considering statin use status as a time-dependent variable. Results From 2008 to 2020, a total of 812 420 patients were diagnosed as having T2DM. Among these patients, 118,765 (27.79%) statin nonusers and 50 804 (12.03%) statin users developed sepsis. Septic shock occurred in 42,755 (10.39%) individuals who did not use statins and 16,765 (4.18%) individuals who used statins. Overall, statin users had a lower prevalence of sepsis than did nonusers. The adjusted hazard ratio (aHR) of statin use was 0.37 (95% CI 0.35, 0.38) for sepsis compared with no statin use. Compared with the patients not using statins, those using different classes of statins exhibited a more significant reduction in sepsis, with aHRs (95% CIs) of sepsis being 0.09 (0.05, 0.14), 0.32 (0.31, 0.34), 0.34 (0.32, 0.36), 0.35 (0.32, 0.37), 0.37 (0.34, 0.39), 0.42 (0.38, 0.44), and 0.54 (0.51, 0.56) for pitavastatin, pravastatin, rosuvastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin use, respectively. In the patients with different cDDD-years of statins, multivariate analysis indicated a significant reduction in sepsis, with aHRs of 0.53 (0.52, 0.57), 0.40 (0.39, 0.43), 0.29 (0.27, 0.30), and 0.17 (0.15, 0.19) for Q1, Q2, Q3, and Q4 cDDD-years (P for trend

Abstract Purpose No large-scale prospective randomized study with a long-term follow-up period has evaluated the survival outcomes of preconcurrent chemoradiotherapy (CCRT) 18-fluorodeoxyglucose positron emission tomography–computed tomography (18FDG PET–CT) in patients with non–human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Patients and Methods We included patients with stage I–IVA p16-negative OPSCC receiving definitive CCRT and categorized them into two groups according to pre-CCRT 18FDG PET–CT and compared their outcomes: the case group consisted of patients who underwent pre-CCRT 18FDG PET–CT, whereas the comparison group consisted of patients who did not receive pre-CCRT 18FDG PET–CT. Results The final cohort consisted of 3942 patients (1663 and 2279 in the case and comparison groups, respectively). According to multivariable Cox regression analysis, pre-CCRT 18FDG PET–CT was not a significant prognostic factor for overall survival in patients with stages I–II of p16-negative OPSCC receiving standard CCRT. The adjusted hazard ratio (95% confidence interval) of all-cause death for the patients with advanced stages (III–IVA) of p16-negative OPSCC receiving pre-CCRT 18FDG PET–CT was 0.75 (0.87–0.94, P = 0.0236). Conclusions Routine use of pre-CCRT 18FDG PET–CT is not necessary for each patient with p16-negative OPSCC. Pre-CCRT 18FDG PET–CT is associated with improved survival in patients with stage III–IVA p16-negative OSCC, but might be not in those with stage I–II p16-negative OPSCC. Condensed abstract No large-scale prospective randomized study with a long-term follow-up period has evaluated the survival outcomes of preconcurrent chemoradiotherapy (CCRT) 18-fluorodeoxyglucose positron emission tomography–computed tomography (18FDG PET–CT) in patients with p16-negative oropharyngeal squamous cell carcinoma (OPSCC). Our study is the first, largest, homogenous modality study on PET–CT including a long-term follow-up cohort to examine the survival outcomes of pre-CCRT 18FDG PET–CT or non-pre-CCRT PET–CT for patients with p16-negative OPSCC receiving standard CCRT stratified by different clinical stages. Routine use of pre-CCRT 18FDG PET–CT is not necessary for each patient with p16-negative OPSCC. Pre-CCRT 18FDG PET–CT is associated with improved survival in patients with stage III–IVA p16-negative OPSCC, but might be not in those with stage I–II p16-negative OPSCC.

Abstract Background The study aims to clarify the association of sarcopenia with perioperative and postoperative complications in oral cavity squamous cell carcinoma (OCSCC) patients undergoing curative surgery and to understand the reasons causing the poor oncologic outcomes for OCSCC. Methods We conducted a propensity score matching study to investigate the association of perioperative and postoperative outcomes in OCSCC patients with sarcopenia and without sarcopenia. A retrospective analysis of a large national data set from the Taiwan Cancer Registry Database was conducted. At least two claims for patients with a principal diagnosis of sarcopenia within the 12‐month preoperative period were defined as the criteria for sarcopenia diagnosis (ICD‐10‐CM code M62.84). Sarcopenia was diagnosed through the measurement of low muscle strength and low muscle mass by any one of the patient's attending orthopaedic physician, rehabilitation physician, family medicine specialist or geriatrician. A multivariate logistic regression model was used to calculate the perioperative, and postoperative major complications. Results Our final cohort included 16 293 patients with OCSCC (10 862 and 5 431 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for further analysis. The sarcopenia group was 10.40% female and 89.60% male, and the nonsarcopenia group was 9.74% female and 90.26% male. The mean age ± standard deviation (SD) were 56.44 ± 11.14 and 56.22 ± 11.29 for sarcopenia and nonsarcopenia groups. OCSCC patients with sarcopenia undergoing curative surgery had a significantly higher blood transfusion rate and volume; longer intensive care unit (ICU) stay, and hospital stay; higher postoperative 30‐day mortality (adjusted odds ratio [aOR]: 1.12, 95% confidence interval [CI] [1.07, 1.56]) and rates of pneumonia (aOR: 1.34, 95% CI [1.20, 1.50]), acute renal failure (aOR: 1.45, 95% CI [1.12, 1.87]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]); higher postoperative first‐year mortality (aOR: 1.18, 95% CI [1.13, 1.51]) and rates of pneumonia (aOR: 1.43, 95% CI [1.30, 1.56]), acute myocardial infarction (aOR: 1.52, 95% CI [1.06, 2.18]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]). Conclusions OCSCC patients with sarcopenia might exhibit more perioperative and surgical complications than those without sarcopenia.

Background/Purpose: Accurate staging is the first step for optimal treatment selection in patients with nasopharyngeal carcinoma (NPC). In this propensity-score-matched, population-based cohort study, we investigated the survival effects of pretreatment 8-fluorodeoxyglucose positron emission tomography–computed tomography (18FDG-PET–CT) on patients with NPC. Methods: We included patients with stage I–IVA NPC receiving radiotherapy or concurrent chemoradiotherapy and categorized them into two 1:1 propensity score–matched groups according to whether or not they underwent pretreatment 18FDG-PET–CT and compared their outcomes. Results: Of the 10,756 patients, propensity score matching yielded 4366 patients in each group. According to multivariable Cox regression analyses, the most prominent correlation between pretreatment 18FDG-PET–CT and all-cause death was observed in patients with stage II NPC (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.60–0.90; P = .0433), followed by patients with stage III NPC (aHR, 0.81; 95% CI, 0.69–0.94; P = .0071) and patients with stage IVA NPC (aHR, 0.88; 95% CI, 0.79–0.97; P = .0091). This association was not significant in patients with stage I NPC (aHR, 1.20; 95% CI, 0.75–1.93; P = .4426). Conclusion: Pretreatment 18FDG-PET–CT is associated with longer survival in patients with clinical stage II–IVA NPC but not in stage I NPC.

Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer characterized by drug resistance and distant metastasis. Cancer stem cells (CSCs) are considered a major contributor to TNBC's drug resistance. Thus targeting and eliminating CSCs have been vigorously researched. However, the precise targetable molecular networks responsible for CSC genesis remain unclear; this conundrum is mainly due to the high heterogeneity of the TNBC tumor microenvironment (TME). The cancer-associated fibroblasts (CAFs) are one of the most abundant cellular components of the TME. Emerging studies indicate that CAFs facilitate TNBC's progression by establishing a pro-tumor TME. Hence, identifying the molecular networks involved in CAF transformation and CAF-associated oncogenesis are essential areas to be explored. Through a bioinformatics approach, we identified INFG/STAT1/NOTCH3 as a molecular link between CSCs and CAF. DOX-resistant TNBC cell lines showed increased expression of INFG/STAT1/NOTCH3 and CD44 and were associated with increased self-renewal ability and CAF-transformative ability. Downregulation of STAT1 significantly reduced the tumorigenic properties of MDA-MB-231 and −468 cells and their CAF-transforming potential. Our molecular docking analysis suggested that gamma mangostin (gMG), a xanthone, formed complexes with INFG/STAT1/NOTCH3 better than celecoxib. We then demonstrated that gMG treatment reduced the tumorigenic properties similarly observed in STAT1-knocked down conditions. Finally, we utilized a DOX-resistant TNBC tumoroid-bearing mouse model to demonstrate that gMG treatment significantly delayed tumor growth, reduced CAF generation, and improved DOX sensitivity. Further investigations are warranted for clinical translation.

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

Background: Patients with end-stage renal disease (ESRD) undergoing hemodialysis are at an elevated risk of developing dementia, potentially linked to the high prevalence of vitamin D deficiency in this population, which may contribute to cognitive impairment. Nevertheless, the impact of vitamin D supplementation on the risk of dementia in hemodialysis patients remains uncertain, necessitating further investigation to elucidate the potential benefits of vitamin D intervention in this vulnerable group. Methods: In this propensity-score-matched comparative cohort study, we sought to assess the impact of vitamin D supplementation on the occurrence of dementia in patients with end-stage renal disease (ESRD) undergoing hemodialysis. A total of 1424 patients were included and matched 1:1 using propensity scores. The study population was divided into two groups: those receiving vitamin D supplementation at a dose of ≥70 μg/week and those without any supplementation. The primary outcome of interest was the incidence of dementia. We calculated adjusted hazard ratios (aHRs) to examine the association between vitamin D supplementation and the risk of dementia while controlling for relevant covariates. Results: The adjusted hazard ratio (aHR) comparing vitamin D supplementation to no supplementation was 0.44 (95% CI 0.29–0.69; p < 0.0001), demonstrating a significant decrease in the risk of dementia associated with vitamin D supplementation. The aHRs for vitamin D supplementation at different dose ranges (70–105, 106–350, 351–1000, and >1000 μg/week) were 0.51, 0.49, 0.43, and 0.41, respectively (p for trend < 0.0001). These findings suggest a potential dose-dependent relationship between vitamin D supplementation and the reduction of dementia risk. Conclusions: In our study, we found that vitamin D supplementation at doses of ≥70 μg/week significantly reduced the risk of dementia in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Furthermore, our results indicated a dose-dependent effect, with higher doses of supplementation correlating with a greater reduction in dementia risk. These findings underscore the potential of vitamin D supplementation as a preventive approach for cognitive impairment in this high-risk population.