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Lattice strain engineering represents a cutting-edge approach capable of delivering enhanced performance across various applications. The lattice strain can affect the performance of electrochemical catalysts by changing the binding energy between the surface-active sites and intermediates. In this work, lattice strain is regulated through a homo/heterogeneous atomic interface merging. The strong lattice strain and electronic interactions between Ni and Mo facilitated the reaction kinetic of HER. The prepared NiMo@SSM exhibits excellent HER catalytic performance with 70 mV overpotential at the current density of 10 mA cm -2 and long-term stability. The method of controlling lattice strain through hetero/homo atom interface merging provides a new strategy for designing high-performance alkaline HER electrocatalysts., (© 2024 Wiley-VCH GmbH.)

Background: We introduced an adapted Lyman normal-tissue complication probability (NTCP) model, incorporating clinical risk factors and censored time-to-event data, to estimate the risk of major adverse cardiac events (MACE) following left breast cancer radiotherapy (RT)., Materials and Methods: Clinical characteristics and MACE data of 1100 women with left-side breast cancer receiving postoperative RT from 2005 to 2017 were retrospectively collected. A modified generalized Lyman NTCP model based on the individual left ventricle (LV) equivalent uniform dose (EUD), accounting for clinical risk factors and censored data, was developed using maximum likelihood estimation. Subgroup analysis was performed for low-comorbidity and high-comorbidity groups., Results: Over a median follow-up 7.8 years, 64 patients experienced MACE, with higher mean LV dose in affected individuals (4.1 Gy vs. 2.9 Gy). The full model accounting for clinical factors identified D 50  = 43.3 Gy, m = 0.59, and n = 0.78 as the best-fit parameters. The threshold dose causing a 50 % probability of MACE was lower in the high-comorbidity group (D 50  = 30 Gy) compared to the low-comorbidity group (D 50  = 45 Gy). Predictions indicated that restricting LV EUD below 5 Gy yielded a 10-year relative MACE risk less than 1.3 and 1.5 for high-comorbidity and low-comorbidity groups, respectively., Conclusion: Patients with comorbidities are more susceptible to cardiac events following breast RT. The proposed modified generalized Lyman model considers nondosimetric risk factors and addresses incomplete follow-up for late complications, offering comprehensive and individualized MACE risk estimates post-RT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity., Methods: We utilized the linear-quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal-tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early-stage lung cancer. Mean lung BED, Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed-rank test., Results: The transition point occurs when the tumor-to-normal tissue ratio (TNR) of the physical dose equals the TNR of α/β in the BED dose-volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all)., Conclusions: The hyperfractionated regimen has an advantage in the high-dose region of the lung but a disadvantage in the low-dose region. Further research is needed to determine the superiority between hypo- and hyperfractionation., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Vanadium-based materials, due to their diverse valence states and open-framework lattice, are promising cathodes for aqueous zinc ion batteries (AZIBs), but encounters the major challenges of in situ electrochemical activation process, potent polarity of the aqueous electrolyte and periodic expansion/contraction for efficient Zn 2+ storage. Herein, architecting vanadium nitride (VN) nanosheets over titanium-based hollow nanoarrays skeletal host (denoted VNTONC) can simultaneously modulate address those challenges by creating multiple interfaces and maintaining the (1 1 1) phase of VN, which optimizes the Zn 2+ storage and the stability of VN. Benefiting from the modulated crystalline thermodynamics during the electrochemical activation of VN, two outcomes are achieved; I) the cathode transforms into a nanocrystalline structure with increased active sites and higher conductivity and; II) a significant portion of the (1 1 1) crystal facets is retained in the process leading to the additional Zn 2+ storage capacity. As a result, the as-prepared VNTONC electrode demonstrates remarkable discharge capacities of 802.5 and 331.8 mAh g -1 @ 0.5 and 6.0 A g -1 , respectively, due to the enhanced kinetics as validated by theoretical calculations. The assembled VNTONC||Zn flexible ZIB demonstrates excellent Zn storage properties up to 405.6 mAh g -1 , and remarkable robustness against extreme operating conditions., (© 2024 Wiley‐VCH GmbH.)

Background: The literature on the association between diabetes severity and cancer risk is limited and inconclusive. The study aimed to evaluate the association between the adapted Diabetes Complications Severity Index (aDCSI) and the duration of type 2 diabetes and cancer risk., Methods: Patients ages 20 years or older with newly diagnosed type 2 diabetes between January 1, 2007, and December 31, 2011, were identified from Taiwan National Health Insurance claims data. Standardized incidence ratios (SIR) were calculated to compare cancer incidence in people with diabetes with that in the general population. Poisson regression was used to examine whether SIRs differed by age, sex, aDSCI, and duration of diabetes., Results: A total of 756,547 patients were included, with a median follow-up of 8.8 years. Excluding the first year after diagnosis, the SIR for overall cancer was 1.18 [95% confidence interval (CI) 1.17-1.19]. Higher aDCSI was associated with increased SIRs for overall [SIR ratio 1.03 (1.02-1.03) per point increase], head and neck (1.03; 1.01-1.04), liver (1.04; 1.03-1.05), pancreas (1.03; 1.00-1.05), kidney (1.13; 1.10-1.15), and leukemia (1.09; 1.06-1.13). There was no association between aDCSI and colorectal, extrahepatic biliary tract, uterus and thyroid cancer, and a negative association with breast cancer (0.97; 0.95-0.98). Type 2 diabetes duration was associated with increased SIRs for overall [1.01 (1.00-1.02) per year increase], head and neck (1.03; 1.01-1.05), and liver cancer (1.04; 1.02-1.05)., Conclusions: The heterogeneity in the association between diabetes severity and diabetes-related cancers suggests diverse underlying connections., Impact: Adopting distinct approaches in further research and prevention strategies for different kinds of diabetes-related cancers is important., (©2024 American Association for Cancer Research.)

Background: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however, no study has discussed which patients are suitable for the procedure., Methods: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk., Results: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for 1 patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images., Conclusion: Our results suggested that about half of the patients could have benefited from hydrodissection before radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article, (Copyright © 2024, the Chinese Medical Association.)

Valence modulation of transition metal oxides represents a highly effective approach in designing high-performance catalysts, particularly for pivotal applications such as the hydrogen evolution reaction (HER) in solar/electric water splitting and the hydrogen economy. Recently, there has been a growing interest in high-valence transition metal-based electrocatalysts (HVTMs) due to their demonstrated superiority in HER performance, attributed to the fundamental dynamics of charge transfer and the evolution of intermediates. Nevertheless, the synthesis of HVTMs encounters considerable thermodynamic barriers, which presents challenges in their preparation. Moreover, the underlying mechanism responsible for the enhancement in HVTMs still needs to be discovered. Hence, the universal synthesis strategies of the HVTMs are discussed, and direct Raman spectroscopic evidence for intermediates regulation is revealed to guide the further design of the HVTM electrocatalysts. This work offers new insights for facile designing of HVTMs electrocatalysts for energy conversion and storage through adjusting the reaction pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) patients who receive cancer surgeries from higher-volume providers may have better outcomes. However, the definitions of surgical volume may affect the results. We aim to analyze the effects of different definitions of surgical volume on patient outcomes. We conducted a nationwide population-based study in Taiwan that enrolled all patients who underwent definitive surgery for newly diagnosed CRC. We used three common definitions of surgical volume: total volume means the total surgical number conducted by the same provider during the study period; cumulative volume was calculated as the number of operations the surgeon performed before the index procedure; annual volume was calculated as the number of times the surgeon had been responsible for surgery during the index year. In this study, we included 100,009 newly diagnosed CRC patients, including 55.8% males, of median age 66 years at diagnosis (range 20-105 years). After adjustment for the patient and provider characteristics, we found that CRC patients receiving definitive surgery by higher-volume providers had better outcomes, especially where surgeon volume may play a more important role than hospital volume. The cumulative volume could predict the 5-year mortality of the study cohort better than the total and annual volume., (© 2024. The Author(s).)

Nickel nitride (Ni 3 N) is a promising electrocatalyst for the hydrogen evolution reaction (HER) owing to its excellent metallic features and has been demonstrated to exhibit considerable activity for water oxidation. However, its undesirable characteristics as an HER electrocatalyst due to its poor unfavourable d-band energy level significantly limit its water dissociation kinetics. Herein, the HER electrocatalytic activity of Ni 3 N was prominently enhanced via the simultaneous incorporation of bi-cations (vanadium (V) and iron (Fe), denoted as V-Fe-Ni 3 N). The optimized V-Fe-Ni 3 N displays impressive performance with an overpotential of 69 mV at 10 mA cm -2 and good stability in 1.0 M KOH, which is remarkably better than pristine Ni 3 N, V-doped Ni 3 N, and Fe-doped Ni 3 N and considerably closer to a commercial Pt/C catalyst. Based on density functional theory (DFT) studies, V and Fe atoms not only serve as active sites for promoting water dissociation kinetics but also tune the electronic structure of Ni 3 N to achieve optimized hydrogen adsorption capabilities. This work presents an inclusive understanding of the rational designing of high-performance transition metal nitride-based electrocatalysts for hydrogen production. Its electrocatalytic performance can be significantly enhanced by doping transition metal cations.

Hybrid organic/inorganic composites with the organic phase tailored to modulate the local chemical environment at the transition metal-based catalyst surface arise as an enchanting category of catalysts for electrocatalysis. A fundamental understanding of how the conductive polymers of different Lewis basicities affect the reaction path is, however, still lacking to guide rational catalyst design. Herein, polyaniline (PANI), poly(3,4-ethylenedioxythiophene) (PEDOT), and poly(vinyl alcohol) (PVA) manifesting different Lewis basicities are compared for their regulatory roles on the hydrogen evolution reaction (HER) and glycerol electrooxidation (GOR) pathways regarding local proton coverage. Concerted efforts from in situ Raman and DFT theoretical calculations unveil that conductive polymer/V 2 O 5 surface with tunable local pH regulated by Lewis acidity/basicity. As a result of the tailored chemical environment, the restructured V 2 O 5 /PANI/NF composite demonstrates a low overall potential of 1.55 V at the partial current density of 50 mA cm -2 for formate. The glycerol upgrading assisted hydrogen evolution device composed of V 2 O 5 /PANI/NF exhibits excellent electrochemical performance at a maximal Faraday efficiency of 82%, ranking among state of the art.

Background and Aims: Patients with left-sided breast cancer receive a higher mean heart dose (MHD) after radiotherapy, with subsequent risk of ischaemic heart disease. However, the optimum dosimetric predictor among cardiac substructures has not yet been determined., Methods and Results: This study retrospectively reviewed 2158 women with breast cancer receiving adjuvant radiotherapy. The primary endpoint was a major ischaemic event. The dose-volume parameters of each delineated cardiac substructure were calculated. The risk factors for major ischaemic events and the association between MHD and major ischaemic events were analysed by Cox regression. The optimum dose-volume predictors among cardiac substructures were explored in multivariable models by comparing performance metrics of each model. At a median follow-up of 7.9 years (interquartile range 5.6-10.8 years), 89 patients developed major ischaemic events. The cumulative incidence rate of major ischaemic events was significantly higher in left-sided disease (P = 0.044). Overall, MHD increased the risk of major ischaemic events by 6.2% per Gy (hazard ratio 1.062, 95% confidence interval 1.01-1.12; P = 0.012). The model containing the volume of the left ventricle receiving 25 Gy (LV V25) with the cut-point of 4% presented with the best goodness of fit and discrimination performance in left-sided breast cancer. Age, chronic kidney disease, and hyperlipidaemia were also significant risk factors., Conclusion: Risk of major ischaemic events exist in the era of modern radiotherapy. LV V25 ≥ 4% appeared to be the optimum parameter and was superior to MHD in predicting major ischaemic events. This dose constraint could aid in achieving better heart protection in breast cancer radiotherapy, though a further validation study is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Boosting oxygen evolution reaction by local surface plasmon resonance (LSPR) provides breakthrough opportunities for the promotion of solar energy conversion; the potential of LSPR, however, has rarely been tapped and investigated. Here, we report the precise regulation of commercial Au nanoparticles plasmonic nanomaterial and OER electrocatalysts, viz., the NiCoO x electrocatalytic layer with hole transport ability and photothermal effect is prepared on the surface of Au nanoparticles by photoelectrodeposition. The NiCoO x layer not only increases the transmission distance of holes generated by plasmonic Au nanoparticles, but also reduce the agglomeration of plasmonic Au nanoparticles during long-time OER reaction, which greatly improves the OER catalytic ability. The current density of NiCoO x /Au anode achieves 16.58 mA cm -2 at 2.0 V versus RHE, which is about 6.5 times of pristine NiCoO x anode (2.56 mA cm -2 ) and 47 times of pristine Au anode (0.35 mA cm -2 ). More importantly, with the LSPR and photothermal effect of plasmonic Au nanoparticles, the NiCoO x /Au anode provides additional current density of 7.01 mA cm -2 after illumination, and maintains no attenuation for more than 2000 s. Benefiting from the solution of agglomeration problem of plasmonic Au nanoparticles in the long-time OER process and the effective utilization of generated holes of plasmonic Au nanoparticles, this design can provide guidance for the application of plasmonic materials in the field of electrocatalysis., (© 2023 Wiley-VCH GmbH.)

Background: This present study investigated the incidence rates of cardiotoxicity among cancer patients treated with immune checkpoint inhibitors (ICIs) plus other anticancer drugs., Methods: This was a retrospective hospital-based cohort study using the medical records and the Cancer Registry records from the Taipei Veterans General Hospital. We enrolled patients diagnosed with cancer between 2011 and 2017, who were over 20 years old and had received ICI therapy, including pembrolizumab, nivolumab, atezolizumab, and ipilimumab. Cardiotoxicity was defined by the diagnosis of myocarditis, pericarditis, arrhythmia, heart failure, and Takotsubo syndrome., Results: We identified 407 patients who were eligible to participate in this study. We defined the three treatment groups as follows: ICI therapy, ICI combined with chemotherapy, and ICI combined with targeted therapy. Using ICI therapy as a reference group, the cardiotoxicity risk was not significantly higher compared to the ICI combined with chemotherapy group (adjusted hazard ratio 2.1, 95% confidence interval 0.2-21.1, p = 0.528] or to the ICI combined with targeted therapy group (adjusted hazard ratio 1.2, 95% confidence interval 0.1-9.2, p = 0.883). The total incidence rate of cardiotoxicity was 3.6 of 100 person-years, indicating an average incidence time of 1.0 ± 1.3 years (median: 0.5 years; range: 0.1-4.7 years) for 18 cardiotoxicity patients., Conclusion: The incidence rate of ICI-related cardiotoxicity is low. Combination of ICI with either chemotherapy or targeted therapy might not significantly increase the risk of cardiotoxicities among cancer patients. Nevertheless, it is recommend being careful in patients treated high-risk cardiotoxicity medications to avoid drug-related cardiotoxicity with a combination of ICI therapy., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: To investigate whether whole-brain radiotherapy (WBRT) decreases lymphocyte counts and evaluate the impact of treatment-related lymphopenia on survival in patients with brain metastasis., Methods: Medical records from 60 small-cell lung cancer patients treated with WBRT from January 2010 to December 2018 were included in the study. Total lymphocyte count (TLC) was obtained pre and post treatment (within 1 month). We performed linear and logistic regression analyses to identify predictors of lymphopenia. The association between lymphopenia and survival was analyzed using Cox regression analysis., Results: Thirty-nine patients (65%) developed treatment-related lymphopenia. The median TLC decrease was -374 cells/μL (interquartile range -50 to -722, p < 0.001). Baseline lymphocyte count was a significant predictor of TLC difference and percentage change in TLC. Logistic regression analysis found male sex (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.00-0.79, p = 0.033) and higher baseline lymphocyte count (OR 0.91, 95% CI 0.82-0.99, p = 0.005) were associated with a lower risk of developing ≥grade 2 treatment-related lymphopenia. Cox regression analysis showed that age at brain metastasis (hazard ratio [HR] 1.03, 95% CI 1.01-1.05, p = 0.013), ≥grade 2 treatment-related lymphopenia, and percentage change in TLC (per 10%, HR 0.94, 95% CI 0.89-0.99, p = 0.032) were prognostic factors of survival., Conclusions: WBRT decreases TLC and the magnitude of treatment-related lymphopenia is an independent predictor of survival in small-cell lung cancer patients., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant concurrent chemoradiotherapy (CRT) followed by surgical excision. Current evidence suggests a favorable prognosis for those with pathological complete response (pCR), and surgery may be spared for them. We trained and validated regression models for CRT response prediction with selected radiomic features extracted from pretreatment magnetic resonance (MR) images to recruit potential candidates for this watch-and-wait strategy., Methods: We retrospectively enrolled patients with LARC who underwent pre-CRT MR imaging between 2010 and 2019. Pathological complete response in surgical specimens after CRT was defined as the ground truth. Quantitative features derived from both unfiltered and filtered images were extracted from manually segmented region of interests on T2-weighted images and selected using variance threshold, univariate statistical tests, and cross-validation least absolute shrinkage and selection operator (Lasso) regression. Finally, a regression model using selected features with high coefficients was optimized and evaluated. Model performance was measured by classification accuracies and area under the receiver operating characteristic (AUROC)., Results: We extracted 1223 radiomic features from each MRI study of 133 enrolled patients. After tumor excision, 34 (26 %) of 133 patients had pCR in resected specimens. When 25 image-derived features were selected from univariate analysis, classification AUROC was 0.86 and 0.79 with the addition of six clinical features on the hold-out internal validation dataset. When 11 image-derived features were used, the optimized linear regression model had an AUROC value of 0.79 and 0.65 with the addition of six clinical features on the hold-out dataset. Among the radiomic features, texture features including gray level variance, strength, and cluster prominence had the highest coefficient by Lasso regression., Conclusion: Radiomic features derived from pretreatment MR images demonstrated promising efficacy in predicting pCR after CRT. However, radiomic features combined with clinical features did not result in remarkable improvement in model performance., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: Stereotactic ablative radiotherapy (SABR) is now the standard of care for patients with inoperable early-stage lung cancer. Many of these patients are elderly. EGFR (epidermal growth factor receptor) mutation is also common in the Asian population., Methods: To evaluate the effects of old age and EGFR mutation on treatment outcomes and toxicity, we reviewed the medical records of 71 consecutive patients with inoperable early-stage non-small cell lung cancer (NSCLC) who received SABR at Taipei Veterans General Hospital between 2015 and 2021., Results: The study revealed that median age, follow-up, Charlson comorbidity index, and ECOG score were 80 years, 2.48 years, 3, and 1, respectively. Of these patients, 37 (52.1%) were 80 years or older, and 50 (70.4%) and 21 (29.6%) had T1 and T2 diseases, respectively. EGFR mutation status was available for 33 (46.5%) patients, of whom 16 (51.5%) had a mutation. The overall survival rates at 1, 3, and 5 years were 97.2, 74.9, and 58.3%, respectively. The local control rate at 1, 3, and 5 years was 97.1, 92.5, and 92.5%, respectively. Using Cox proportional hazards regression we found that male sex was a risk factor for overall survival (p = 0.036, 95% CI: 1.118-26.188). Two patients had grade 2 pneumonitis, but no other grade 2 or higher toxicity was observed. We did not find any significant differences in treatment outcomes or toxicity between patients aged 80 or older and those with EGFR mutations in this cohort., Conclusion: These findings indicate that age and EGFR mutation status do not significantly affect the effectiveness or toxicity of SABR for patients with inoperable early-stage NSCLC., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: Adapted Diabetes Complications Severity Index (aDCSI) is a commonly used severity measure based on the number and severity of diabetes complications using diagnosis codes. The validity of aDCSI in predicting cause-specific mortality has yet to be verified. Additionally, the performance of aDCSI in predicting patient outcomes compared with Charlson Comorbidity Index (CCI) remains unknown., Research Design and Methods: Patients aged 20 years or older with type 2 diabetes prior to January 1, 2008 were identified from the Taiwan National Health Insurance claims data and were followed up until December 15, 2018. Complications for aDCSI including cardiovascular, cerebrovascular and peripheral vascular disease, metabolic disease, nephropathy, retinopathy and neuropathy, along with comorbidities for CCI, were collected. HRs of death were estimated using Cox regression. Model performance was evaluated by concordance index and Akaike information criterion., Results: 1,002,589 patients with type 2 diabetes were enrolled, with a median follow-up of 11.0 years. After adjusting for age and sex, aDCSI (HR 1.21, 95% CI 1.20 to 1.21) and CCI (HR 1.18, 1.17 to 1.18) were associated with all-cause mortality. The HRs of aDCSI for cancer, cardiovascular disease (CVD) and diabetes mortality were 1.04 (1.04 to 1.05), 1.27 (1.27 to 1.28) and 1.28 (1.28 to 1.29), respectively, and the HRs of CCI were 1.10 (1.09 to 1.10), 1.16 (1.16 to 1.17) and 1.17 (1.16 to 1.17), respectively. The model with aDCSI had a better fit for all-cause, CVD and diabetes mortality with C-index of 0.760, 0.794 and 0.781, respectively. Models incorporating both scores had even better performance, but the HR of aDCSI for cancer (0.98, 0.97 to 0.98) and the HRs of CCI for CVD (1.03, 1.02 to 1.03) and diabetes mortality (1.02, 1.02 to 1.03) became neutral. When aDCSI and CCI were considered time-varying scores, the association with mortality was stronger. aDCSI had a strong correlation with mortality even after 8 years (HR 1.18, 1.17 to 1.18)., Conclusions: The aDCSI predicts all-cause, CVD and diabetes deaths but not cancer deaths better than the CCI. aDCSI is also a good predictor for long-term mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Interfacial engineering and elemental doping are the two parameters to enhance the catalytic behavior of cobalt nitrides for the alkaline hydrogen evolution reaction (HER). However, simultaneously combining these two parameters to improve the HER catalytic properties of cobalt nitrides in alkaline media is rarely reported and also remains challenging in acidic media. Herein, it is demonstrated that high-valence non-3d metal and non-metal integration can simultaneously achieve Co-based nitride/oxide interstitial compound phase boundaries on stainless steel mesh (denoted Mo-Co 5.47 N/N-CoO) for efficient HER in alkaline and acidic media. Density functional theory (DFT) calculations show that the unique structure does not only realize multi-active sites, enhanced water dissociation kinetics, and low hydrogen adsorption free energy in alkaline media, but also enhances the positive charge density of hydrogen ions (H + ) to effectively allow H + to receive electrons from the catalysts surface toward promoting the HER in acidic media. As a result, the as-prepared Mo-Co 5.47 N/N-CoO demands HER overpotential of -28 mV@10 mA cm -2 in an alkaline medium, and superior to the commercial Pt/C at a current density > 44 mA cm -2 in acidic medium. This work paves a useful strategy to design efficient cobalt-based electrocatalysts for HER and beyond., (© 2021 Wiley-VCH GmbH.)

Reassessing the continuing need for and choice of antibiotics by using an antibiotic "time out'' program may reduce unnecessary treatment. This study aimed to explore the effect of an antibiotic stewardship program (ASP) on the antibiotics consumption, incidence of resistant bacterial infections and overall hospital mortality in a tertiary medical center during the study period 2012-2014. An ASP composed of multidisciplinary strategies including pre-prescription approval and post-approval feedback and audit, and a major "time out'' intervention (shorten the default antibiotic prescription duration) usage was introduced in year 2013. Consumption of antibiotics was quantified by calculating defined daily doses (DDDs). Interrupted time series (ITS) analysis was used to explore the changes of antibiotics consumption before and after intervention, accounting for temporal trends that may be unrelated to intervention. Our results showed that following the intervention, DDDs showed a decreased trend in overall (in particular the major consumed penicillins and cephalosporins), in both intensive care unit (ICU) and non-ICU, and in non-restrictive versus restrictive antibiotics. Importantly, ITS analysis showed a significantly slope change since intervention (slope change p value 0.007), whereas the incidence of carbapenem-resistant and vancomycin-resistant pathogens did not change significantly. Moreover, annual overall mortality rates were 3.0%, 3.1% and 3.1% from 2012 to 2014, respectively. This study indicates that implementing a multi-disciplinary strategy to shorten the default duration of antibiotic prescription can be an effective manner to reduce antibiotic consumption while not compromising resistant infection incidence or mortality rates., (© 2022. The Author(s).)

Background: This population-based study was to investigate the potential risk factors of cardiotoxicity among colorectal cancer (CRC) patients treated with anticancer drugs., Methods: This was a retrospective cohort study using the National Health Insurance Research Database to identify the CRC patients receiving chemotherapy (CT) alone or CT combined with targeted therapies between 2000 and 2013. The patients enrolled were those who had the first diagnosis of CRC established ≥20 years and had no cancer history three years before the incident diagnosis of CRC. The outcomes of cardiotoxicity were defined by the diagnosis of acute myocarditis, cardiomyopathy, heart failure, hypertensive heart disease, and so on., Results: A total of 11 819 CRC patients were identified and 3781 were eligible; 556 (14.7%) patients developed cardiotoxicity after receiving anticancer treatment. Patients showed a similar risk of having primary outcome (hazard ratio [HR], 0.7; p = 0.3662) between CT and CT combined with targeted therapy groups, whereas the risk of developing secondary outcome was significantly different between the two groups (HR, 0.7; p = 0.0339). The hazard was found to be increased with age (60-69, HR 2.1, p = 0.0236; 70-79, HR 3.3, p = 0.0003; and ≥80, HR 3.7, p < 0.0001). CRC patients who had a prior history of hypertension exhibited a higher risk than those without hypertension (HR 1.6, p < 0.0001). The hazard of having cardiotoxicity among patients with a prior history of severe chronic kidney disease was 2.4 times than that in those without renal dysfunction, regardless of the stage of cancer (HR 2.4, p < 0.0001)., Conclusion: CRC patients over 60 years of age run a higher risk of developing cardiotoxicity when treated with anticancer drugs. For CRC patients who have a previous history of hypertension or chronic kidney disease, physicians must be careful in evaluating the risk of anticancer drugs-related cardiotoxicity. Prescribe drugs may prevent cardiotoxicity if necessary., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Background: Cancer patients treated at higher-volume hospitals or by more experienced physicians have better outcomes. However, little is known about the effect of these provider volumes on the prognosis of patients receiving definitive radiotherapy (RT). This study aims to examine the independent association between hospital volume and physician volume in relation to the overall survival (OS) of nasopharyngeal cancer (NPC) patients after RT., Methods: Patients with newly diagnosed NPC receiving definitive RT between 2001 and 2017 were identified from Taiwan's National Health Insurance Research Database. We collected demographic characteristics of patients, physicians and hospitals, as well as cancer treatment and comorbidities. Patients were categorized into quartiles according to cumulative hospital and physician volumes of their treatment providers. The effects of hospital and physician volumes on OS was examined by the frailty Cox regression model., Results: A total of 16,315 NPC patients treated by 258 physicians in 92 hospitals were identified. When the effects of hospital volume and physician volume on survival were separately examined, both of them were positively associated with OS. In a fully adjusted model considering patient and provider characteristics, hospital volume, physician volume, and clustering effects, it showed that hospital volume significantly predicted OS, while physician volume did not. In patients treated with advanced technique RT, hospital volume was significantly associated with OS. However, volume effect was not observed in 2-D RT subgroup., Conclusions: NPC patients receiving RT at higher-volume hospitals saw better survival. Treatment for NPC should be centralized to high-volume hospitals rather than high-volume physicians., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The optimal treatment strategy for pediatric atypical teratoid rhabdoid tumor (ATRT) is inconclusive. This study evaluated the prognostic value of early radiotherapy (RT) and high-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) in pediatric ATRT., Methods: This pooled analysis included ATRT patients treated at our institution and from other studies who were identified by a search of the PubMed electronic database. The effect of patient demographics and treatment profiles on progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression., Results: Overall, 34 patients from our institution and 436 patients from 35 published studies were included. In multivariable analysis, patients with gross total resection (GTR), early RT (time to RT interval < 2 months), and HDC/ASCR had both better PFS [hazard ratio (HR) 0.46, p[Formula: see text] 0.001; HR 0.64, p = 0.011; and HR 0.51, p = 0.005, respectively] and OS (HR 0.55, p = 0.002; HR 0.48, p = 0.004; and HR 0.42, p < 0.001, respectively). For patients aged < 3 years, both RT and HDC/ASCR were significant favorable factors for PFS (HR 0.32 and 0.46, respectively) and OS (HR 0.40 and 0.36, respectively), while early RT was not prognostic. For patients aged ≥ 3 years, early RT was significantly associated with better PFS (HR 0.51) and HDC/ASCR did not affect PFS, and neither was related to OS., Conclusion: Both early RT initiation and HDC/ASCR were important components in the treatment of pediatric ATRT. However, the optimal treatment strategies might differ by age.

Aims: Patients with atrial fibrillation (AF) may be at higher risk for cancer, possibly due to the presence of coexisting risk factors. In this study, we investigate the magnitude and predictors of this potential risk within a population-based study., Methods and Results: The study cohort included 332,555 AF patients aged ≥20 years without past history of cancer. Standardized incidence ratio (SIR) was used as a measure of relative risk, comparing observed cancer incidence among patients with AF with that expected based on cancer incidence in the Taiwanese population. During the observation period, 22,911 incident cancers occurred with an incidence of 1.65%/year. Compared with the general population, AF patients had a significantly higher cancer risk with a SIR of 1.37 (95%CI = 1.36-1.39). Patients with new-onset AF had an elevated cancer risk which was highest within 1 year (SIR = 2.30; 95%CI, 2.25-2.36) and persisted beyond 10 years after AF was diagnosed (SIR = 1.18; 95%CI, 1.11-1.25). Age ≥ 65 years, male gender, hypertension, diabetes, chronic obstructive pulmonary disease (COPD) and liver cirrhosis were significantly associated with development of cancers among AF patients. The hazard ratio of cancers increased from 1.40 (95%CI = 1.28-1.53) for patients having 1 risk factor to 5.14 (95%CI = 4.03-6.06) for patients with 6 risk factors, in comparison to those without any risk factors., Conclusion: In the nationwide cohort study, we show that AF patients had a higher risk of cancer. Age, male gender, hypertension, diabetes, COPD and liver cirrhosis are important risk factors of cancer among AF patients. Prompt and detailed examinations may be considered for incident AF patients with multiple risk factors to early detect the occult malignancy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Postoperative radiotherapy for early endometrial cancer has been investigated in several randomized trials. These trials demonstrate that it reduces loco-regional recurrence, but has no impact on overall survival. The aims of this study were to better understand the role of adjuvant radiotherapy and determine predictors for loco-regional recurrence or development of distant metastasis., Materials and Methods: A retrospective medical records review was performed on patients with surgical stage I endometrial cancer treated at Taipei Veterans General Hospital between 2006 and 2013. Multivariable analysis was conducted using Cox regression for prognostic predictors., Results: A total of 337 patients were identified. The estimated five-year overall survival and loco-regional recurrence-free survival were 96.3% and 97.9% in the non-radiotherapy group, and 91.6% and 97.1% in the radiotherapy group (p = 0.06 overall survival, p = 0.956 loco-regional recurrence-free survival). Multivariable analysis revealed that elevated preoperative serum Cancer Antigen 125 (CA-125) level (hazard ratio (HR) = 2.54), age older than 60 years old (HR = 3.34), and depth of myometrial invasion > 50% (HR = 3.37) were significant factors in overall survival. Elevated preoperative CA-125 level (HR = 5.37), age older than 60 years (HR = 6.57), positive lymphovascular space invasion (HR = 50.20), and adjuvant radiotherapy (HR = 0.05) were independent predictors of loco-regional recurrence-free survival. For distant metastasis, deep myometrial invasion was a significant risk factor., Conclusions: Postoperative radiotherapy delivery is an independent predictor for loco-regional recurrence-free survival but has no impact on overall survival in this population. Preoperative CA-125 level is a risk factor for loco-regional recurrence, and deep myometrial invasion was correlated with distant metastasis., (Copyright © 2019. Published by Elsevier B.V.)

To determine whether radiotherapy (RT) can increase pelvic fracture risk in rectal cancer survivors. Rectal cancer patients who underwent curative surgery between 1996 and 2011 in Taiwan were retrospectively studied using the National Health Insurance Research Database (NHIRD) of Taiwan. ICD-9 Codes 808, 805.4-805.7, 806.4-806.7, and 820 (including pelvic, sacrum, lumbar, and femoral neck fracture) were defined as pelvic fracture. Propensity scores for RT, age, and sex were used to perform one-to-one matches between the RT and non-RT group. Risks of pelvic and arm fractures were compared by multivariable Cox regression. Of the 32 689 patients, 7807 (23.9%) received RT, and 1616 suffered from a pelvic fracture (incidence rate: 1.17/100 person-years). The median time to pelvic fracture was 2.47 years. After matching, 6952 patients each in the RT and non-RT groups were analyzed. RT was associated with an increased risk of pelvic fractures in the multivariable Cox model (hazard ratio (HR): 1.246, 95% confidence interval (CI): 1.037-1.495, P = 0.019) but not with arm fractures (HR: 1.013, 95% CI: 0.814-1.259, P = 0.911). Subgroup analyses revealed that RT was associated with a higher pelvic fracture rate in women (HR: 1.431, 95% CI: 1.117-1.834) but not in men, and the interaction between sex and RT was significant (P = 0.03). The HR of pelvic fracture increased 2-4 years after RT (HR: 1.707, 95% CI: 1.150-2.534, P = 0.008). An increased risk of pelvic fracture is noted in rectal cancer survivors, especially women, who receive RT., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: The purpose of the study is to evaluate possible prognostic factors and optimal management for pediatric atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS)., Methods: Twenty-eight pediatric patients with CNS AT/RT who were treated with radiation therapy (RT) as part of multimodality treatment regimens at a single institution (1996-2015) were reviewed. Survival outcomes were analyzed in relation to possible prognostic factors., Results: The 28 patients analyzed were followed up for a median 48-month period. Median progression-free survival (PFS) was 11 months, and overall survival (OS) was 57 months. Patients < 3 years old had RT delayed for a longer period after surgery (p = 0.04), and the mean RT dose to tumor bed was lower (p < 0.01) than in patients ≥ 3 years old. In multivariate analysis, a higher primary tumor bed RT dose was identified as a favorable prognostic factor for both PFS (hazard ratio [HR] = 0.85 per gray, p < 0.01) and OS (HR = 0.92 per gray, p = 0.02). In addition, an interval between surgery and RT initiation > 2 months, with disease progression observed before RT, as compared with an interval ≤ 2 months without disease progression prior to RT, was associated with worse PFS (HR = 8.50, p < 0.01) and OS (HR = 5.27, p < 0.01)., Conclusions: Early and aggressive RT after surgery is critical for successful disease control in AT/RT patients. Conversely, a delay in RT until disease progression is observed that leads to unfavorable outcomes.

Coordination polymers (CPs) are ideal precursors for synthesizing porous catalysts. However, the direct thermolysis of CPs is prone to generate agglomerates, greatly reducing the electrical conductivity and active sites of their derived catalysts. The construction of well-ordered CP nanostructures is a promising strategy for alleviating the above issue, but it remains challenging. Here, a facile chemical etching approach is developed for the fabrication of well-aligned three-dimensional (3D) bimetallic Prussian blue-analogue nanosheet arrays. Impressively, the derived porous metal oxide (Fe-NiO) acts as a remarkable oxygen evolution reaction (OER) catalyst, which merely requires overpotentials as low as 218 and 270 mV to achieve 10 and 100 mA cm -2 in 1.0 m KOH aqueous solution, respectively. The excellent electrocatalytic performance of Fe-NiO is ascribed to the 3D porous nanosheet array architecture, which endows the bimetallic catalyst with abundant electrocatalytic active sites, enhanced surface permeability, and high electronic conductivity. It is expected that the proposed strategy can pave a new way for fabricating highly efficient electrocatalysts for energy storage and conversion., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: To investigate second primary malignancy (SPM) risk after radiotherapy in rectal cancer survivors., Methods: We used Taiwan's National Health Insurance Research Database to identify rectal cancer patients between 1996 and 2011. Surgery-alone, preoperative short course, preoperative long course, and post-operative radiotherapy groups were defined. The overall and site-specific SPM incidence rates were compared among the radiotherapy groups by multivariate Cox regression, taking chemotherapy and comorbidities into account. Sensitivity tests were performed for attained-year adjustment and long-term survivors analysis., Results: A total of 28220 patients were analyzed. The 10-year cumulative SPM incidence was 7.8% [95% confidence interval (CI): 7.2%-8.2%] using a competing risk model. The most common sites of SPM were the lung, liver, and prostate. Radiotherapy was not associated with increased SPM risk in multi-variate Cox model (hazard ratio = 1.05, 95%CI: 0.91-1.21, P = 0.494). The SPM hazard remained unchanged in 10-year-survivors. In addition, no SPM risk difference was found between the preoperative radiotherapy and postoperative radiotherapy groups., Conclusion: In this large population-based cohort study, we demonstrated that radiotherapy had no increase in SPM., Competing Interests: Conflict-of-interest statement: None.

Background: In cancer patients, depressive disorder comorbidity is associated with greater suicide risk and poorer treatment outcomes, quality of life, and adherence to treatment. The aim of the study was to evaluate the incidence of newly-diagnosed depressive disorders after a gastric cancer diagnosis compared with a matched cohort using the National Health Insurance Research Database in Taiwan., Methods: We conducted a retrospective cohort study of 57,506 patients (28,753 patients with gastric cancer and 28,753 matched patients) selected from the National Health Insurance Research Database. Patients were observed for a maximum of 12 years to determine the incidence of newly-diagnosed depressive disorders. Also, a Cox regression analysis which included death as an independent censor was performed to identify the potentially predictive variables for developing subsequent depressive disorders following a cancer diagnosis among the patients suffering from gastric cancer., Results: The cumulative incidence of depressive disorders in the gastric cancer patients was significantly higher compared to those in the matched cohort (p < .001). The adjusted hazard ratio was 1.54 (95% confidence interval, CI = 1.39-1.70, P < .001) in the gastric cancer cohort compared with the matched cohort. Independent predictive variables for developing subsequent depressive disorders among the patients with gastric cancer included female sex and hypertension., Conclusions: In the study, higher incidence of new-onset depression, being defined by the records of the diagnostic codes combining antidepressants use in a nationwide database, was noted in the gastric cancer patients compared with the matched cohort. In addition, female sex and comorbid hypertension may be predictive variables for the subsequent depression among the patients with gastric cancer. Further clinical prospective studies were necessary to confirm these findings.

Industrial application of overall water splitting requires developing readily available, highly efficient, and stable oxygen evolution electrocatalysts that can efficiently drive large current density. This study reports a facile and practical method to fabricate a non-noble metal catalyst by directly growing a Co-Fe Prussian blue analogue on a 3D porous conductive substrate, which is further phosphorized into a bifunctional Fe-doped CoP (Fe-CoP) electrocatalyst. The Fe-CoP/NF (nickel foam) catalyst shows efficient electrocatalytic activity for oxygen evolution reaction, requiring low overpotentials of 190, 295, and 428 mV to achieve 10, 500, and 1000 mA cm -2 current densities in 1.0 m KOH solution. In addition, the Fe-CoP/NF can also function as a highly active electrocatalyst for hydrogen evolution reaction with a low overpotential of 78 mV at 10 mA cm -2 current density in alkaline solution. Thus, the Fe-CoP/NF electrode with meso/macropores can act as both an anode and a cathode to fabricate an electrolyzer for overall water splitting, only requiring a cell voltage of 1.49 V to afford a 10 mA cm -2 current density with remarkable stability. This performance appears to be among the best reported values and is much better than that of the IrO 2 -Pt/C-based electrolyzer.

Purpose: Selective internal radiation therapy (SIRT) is an effective treatment strategy for unresectable hepatocellular carcinoma (HCC) patients. However, the prognoses of patients with portal vein thrombosis, extra-hepatic metastases, or residual tumors remain poor when treated with SIRT alone. In these patients, sequential external beam radiotherapy (EBRT) may offer a chance of salvage. Here, we reported the clinical outcomes and the detailed dosimetry analysis of 22 patients treated with combination therapy., Methods: Between October 2011 and May 2015, 22 consecutive patients who underwent EBRT after yttrium-90 (90Y) SIRT were included in this study. The post-SIRT 90Y bremsstrahlung SPECT/CT of each patient was transferred to dose distribution by adopting the local deposition hypothesis. The patient-specific 3-dimensional biological effective dose distribution of combined SIRT and EBRT was generated. The overall survival and safety were evaluated. The relationship between dosimetric parameters and liver toxicity was analyzed., Results: The mean administered activity of SIRT was 1.50 GBq (range: 0.5-2.8). The mean prescribed dose of EBRT was 42.3 Gy (range: 15-63) in 14 fractions (range: 5-15) and was targeted to the residual liver tumor in 12 patients (55%), portal vein thrombosis in 11 patients (50%), and perihilar lymphadenopathies in 4 patients (18%). The overall 1-, 2-, and 3-year survival rates were 59.8%, 47.9%, and 47.9%, respectively. Overall, 8 patients (36%) developed > grade 2 liver toxicities, and the Child-Pugh score prior to EBRT strongly affected the toxicity risk. A dosimetry analysis restricted to 18 Child-Pugh A/B patients showed that the V100 (The fraction of normal liver exposed to more than 100 Gy) to V140 significance differed between patients who did or did not experience hepatotoxicity. The V110 was the strongest predictor of hepatotoxicity (18.6±11.6% vs 29.5±5.8%; P = 0.030)., Conclusion: Combined therapy is feasible and safe if patients are carefully selected. Specifically, 3-dimensional dosimetry is crucial for the evaluation of efficacy and toxicity. The normal liver V100 to V140 values of the combined dose should be as low as possible to minimize the risk of liver toxicity.

Whether age predicts treatment outcome of prostate cancer remains controversial. With the aging of the world population, properly understanding the effect of age may facilitate both treatment decision-making and defining the natural history of prostate cancer. Consecutive 581 patients with locally-confined adenocarcinoma of the prostate who received radical definitive radiotherapy(RT) (76-78 Gy) between 2004 and 2015 at a medical center in Taiwan were reviewed retrospectively. Median age was 78 years. The median follow-up was 66 months. The 5-year biochemical failure-free survival(BFFS), distant metastasis-free survival(DMFS), disease-specific survival(DSS), and overall survival(OS) rates were 84.9%, 93.8%, 97.8%, and 86.6%, respectively, for all patients. Comparing those above and below the age of 80, no difference in 5-year BFFS, DMFS, or DSS was found. Multivariate Cox regression analysis showed that tumor stage, Gleason score, initial PSA, and latency before RT were significant risk factors of BFFS. The latency before RT was significantly longer in the older group than in the under 80 group. Delay to start RT might explain the previous finding of inferior disease control in older patients in other studies. With the exception of OS, no other differences in outcomes or toxicities were observed in older patients.

Background: To evaluate the failure pattern and identify predictors of locoregional control in lateralized buccogingival cancer after postoperative radiotherapy (RT) at a single institution., Methods: We retrospectively reviewed the clinical data of 150 patients with lateralized oral squamous cell carcinoma, including carcinoma of the buccal mucosa, gingiva and retromolar trigone. All patients underwent radical surgery followed by postoperative RT with or without concurrent chemotherapy. We registered planning computer tomography images with images obtained at recurrence and categorized the failure pattern as in-field, marginal, or out-field recurrence., Results: The median follow-up duration was 47 months (range, 2-131 months). Twenty-eight patients (19%) experienced locoregional failure, including 20 local failure, 5 regional failure and 3 with both. Among the 24 patients who had image studies at recurrence, 15 patients had in-field recurrence, 5 were marginal recurrence and 4 were out-field recurrence. Seven patients (5%) had contralateral neck failure. Four of 5 patients with marginal failure had recurrent tumors in the infratemporal fossa. In multivariate analysis, extracapsular spread and positive or close surgical margin were associated with poor locoregional control., Conclusion: Local in-field recurrence is the most common failure pattern in lateralized buccogingival cancer after postoperative RT. The infratemporal fossa is a risk area for marginal failure and should be encompassed adequately in the postoperative RT field. Extracapsular spread and positive or close margin are predictors of locoregional control for lateralized oral cancer. Patients exhibiting such adverse features require more aggressive treatment., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background: The purpose of this study was to investigate the risk factors, especially the use of certain drugs and the dental procedures, for osteoradionecrosis of the jaw (ORNJ) in patients with head and neck cancer undergoing irradiation as their primary treatment., Methods: The cohort was composed of 23,527 patients with head and neck cancer. Cox proportional hazard models were used for risk factors analysis., Results: The overall incidence of ORNJ is 3.93 per 100 person-years. Buccal cancer carried the highest ORNJ risk. The use of steroids had a protective effect. Preradiotherapy extraction posed no excess risk, whereas postradiotherapy extraction was associated with gradually increased risk of ORNJ over time that peaked at 4 to 5 years., Conclusion: ORNJ warrants life-long attention for head and neck cancer survivors. The present study strongly confirms the role of preirradiation dental extractions. Meanwhile, efforts should be made to prevent posttreatment extractions, especially in the first posttreatment 4 years. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1313-1321, 2017., (© 2017 Wiley Periodicals, Inc.)

Background and Purpose: To identify the risk factors for osteonecrosis of the jaw (ONJ) in oral cancer patients after surgery with and without adjuvant therapy in a nationwide, population-based study., Material and Methods: Using the Taiwan National Health Insurance Research Dataset, we recruited patients with newly diagnosed oral cancer between 1997 and 2011. All of them underwent primary surgery. Data regarding demographic characteristics; tooth extractions; medications; and cancer treatments, including types of mandibular surgery, radiotherapy and platinum-based chemotherapy, were collected for analysis., Results: We identified 25,858 patients who suffered 2802 ONJ events. The ONJ incidence rate was 3.45 per 100 person-years. Lip cancer was associated with the highest risk of ONJ, followed by buccal mucosa, gum, mouth floor and tongue cancer. Using a time-dependent Cox regression model, multivariable analysis demonstrated that mandibulotomy (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.01-1.55; p<0.001), radiotherapy (HR, 1.39; 95% CI, 1.26-1.54; p<0.001) and platinum-based chemotherapy (HR, 1.94; 95% CI, 1.56-2.41; p<0.001) were significant risk factors for ONJ. In the subgroup analysis of patients receiving radiotherapy and patients not receiving radiotherapy, platinum-based chemotherapy remained a risk factor for ONJ., Conclusions: Mandibulotomy, radiotherapy and platinum-based chemotherapy were associated with an increased ONJ risk. Chemotherapy was a risk factor regardless of whether radiotherapy was administered., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Currently, no large study addressing the relationship between lung cancer patients with different therapies and second primary malignancies (SPMs) is available., Methods: Using the Taiwan National Health Insurance Research Database, we conducted a population-based cohort study. Patients with newly diagnosed lung cancer between 1997 and 2005 were enrolled and followed up until Dec. 31, 2011. The endpoint of the study was SPM occurrence. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort to that of the general population., Results: We identified 52,639 patients with lung cancer and excluded 34,267 patients who had expired within one year after diagnosis. The study included 18,372 subjects with a median follow-up period of 2.24 years. 590 patients developed an SPM. The overall cancer risk was significantly increased (SIR 1.33, 95% confidence interval [CI]: 1.22-1.44, p < 0.001), and there was a significant increase in the incidences of head and neck (SIR 1.60, 95% CI 1.21-2.07, p = 0.001), bone and soft tissue (SIR 2.65, 95% CI 1.27-4.87, p = 0.011), genitourinary (SIR 1.50, 95% CI 1.27-1.76, p < 0.001), and thyroid (SIR 3.85, 95% CI 2.28-6.08, p < 0.001) cancers. Importantly, after multivariate adjustment, the use of tyrosine kinase inhibitors (TKIs) statistically significantly reduced SPM incidence (HR, 0.41; 95% CI, 0.21-0.79; p = 0.008)., Conclusions: Our study indicates that lung cancer may be a risk factor for SPM. TKI use was associated with a significantly lower risk of SPM development. However, because patients with epidermal growth factor receptor mutant lung adenocarcinoma (associated with non-smokers) tend to receive TKI treatment, they might have fewer smoking-related SPMs.

Background: Recurrence of hepatocellular carcinoma (HCC) with unsatisfactory survival is common after surgical resection. Antiplatelet therapy with aspirin or clopidogrel was recently shown to prevent hepatic carcinogenesis in a murine model, but its effect in humans had not been clarified. This study aimed to investigate the association between antiplatelet therapy and the outcomes for patients with hepatitis B virus (HBV)-related HCC after liver resection., Methods: By analyzing data from the Taiwan National Health Insurance Research Database, 9461 HBV-related HCC patients who had undergone liver resection between January 1997 and December 2011 were identified. After one-to-four matching by sex, age, and propensity score, 442 patients with antiplatelet therapy and 1768 patients without antiplatelet therapy were enrolled for the analysis. The Kaplan-Meier method and modified Cox proportional hazards models were used for survival and multivariable, stratified analyses., Results: Recurrence-free survival and overall survival after resection surgery were significantly better after 5 years in the treated cohort than in the untreated cohort (52.8 vs 47.9 %; p = 0.021 and 80.3 vs 65.4 %; p < 0.001, respectively). Besides, antiplatelet therapy reduced the risk of HCC recurrence (hazard ratio [HR] 0.73; p < 0.001) and overall mortality (HR 0.57; p < 0.001) in the multivariable analysis. However, antiplatelet use significantly increased the risk of upper gastrointestinal bleeding (odds ratio [OR] 1.91; p < 0.001)., Conclusions: Use of aspirin or clopidogrel was associated with better recurrence-free survival and overall survival among patients with HBV-related HCC after liver resection. However, these agents should be used with caution due to the adverse effects of upper gastrointestinal bleeding.

Background: Patients with chronic obstructive pulmonary disease (COPD) are liable to develop significant comorbidities, including lung cancer. Whether they are at a higher risk for cancer of other types remains debatable, especially for Asians. We studied the risk of incident cancer in COPD patients using a nationwide representative database, the Taiwan National Health Insurance Research Database., Methods: From 1995 to 2008, 50,875 COPD patients who were free of antecedent malignancy were identified and followed up to development of malignancy, death or end of 2008, whichever came first. The risk of cancer was determined with the standardized incidence ratio (SIR), which is based on comparison to the national cancer incidence among the general population., Results: During a median follow-up period of 5.61 years, 3623 (7.02 %) patients developed cancer and the SIR was 1.2 [95 % confidence interval (CI) 1.16-1.24, p < 0.001]. The risk remained higher at <1, 1-5, and even ≥5 years after the diagnosis of COPD (SIR 1.83, 1.07, and 1.11, respectively). Furthermore, the risk was significantly higher for some specific types of cancer, including head and neck cancer (SIR 1.23, 95 % CI 1.08-1.39, p = 0.002), esophageal cancer (SIR 1.35, 95 % CI 1.08-1.67, p = 0.010), lung and mediastinal cancer (SIR 1.86, 95 % CI 1.74-1.99, p < 0.001), breast cancer (SIR 1.19, 95 % CI 1.01-1.4, p = 0.041), prostate cancer (SIR 1.20, 95 % CI 1.06-1.35, p < 0.001), cancer of the central nervous system (SIR 1.58, 95 % CI 1.05-2.28, p = 0.030), lymphoma (SIR 1.53, 95 % CI 1.22-1.90, p < 0.001), and multiple myeloma (SIR 1.95, 95 % CI 1.31-2.80, p = 0.001)., Conclusion: COPD patients had increased risk for incident cancers, including lung cancer and several extrapulmonary cancers.

Background: Acute lymphoblastic leukemia (ALL) is more common in children than in adults. Secondary neoplasms (SNs) in childhood ALL have been widely reported. However, only one study has demonstrated SNs in adult ALL. Because of the poorer survival of adult ALL, the incidence might be underestimated., Objective: To evaluate the incidence and risk factors of secondary solid organ neoplasms among adult and child ALL patients., Methods: Newly diagnosed ALL patients between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent or combined malignancies were excluded. Standardized incidence ratios (SIRs) were analyzed to compare the risk of our cohort to general population in the same age, sex and calendar year. Risk factors for SN development were analyzed by Cox proportional hazards models. Effects of treatments were treated as time-dependent variables., Results: The 15-year cumulative incidence of SN was 1.9% and 8.4% in 1,381 child and 2,154 adult ALL patients, respectively. The SIR was significantly increased in child ALL (SIR 6.06), but not in adult ALL (SIR 1.16). The SIRs of follow-up periods were 5.14, 2.24, .87 and .71 at ≥ 10 years, 5-10 years, 1-5 years and 0-1, respectively. Overall, 15 SNs developed, and CNS tumors (SIR 11.56) were the most common type. Multivariate analysis showed that age ≥ 20 years (hazard ratio [HR] 5.04), end-stage renal disease (HR 18.98) and cranial irradiation (HR 8.12) were independent risk factors for cancer development., Conclusions: When compared with the general population, child ALL shows a increased risk of developing SNs. CNS tumors are the most common type, and cranial irradiation is an independent risk factor. With longer follow-up, the risk of SNs increases. Hence, physicians need to pay more attention on the risk of developing SNs in long-term ALL survivors with risk factors.

Background: Several studies have reported an increase in second primary malignancies (SPMs) among gastric cancer patients., Methods: Patients who were newly diagnosed with gastric cancer between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent malignancies or gastrointestinal stromal tumor were excluded. Standardized incidence ratios (SIRs) of SPMs were calculated. Risk factors for cancer development were analyzed by Cox proportional hazards models. Effects of treatments for gastric cancer were treated as time-dependent variables., Results: During the 15-year study period, 47,729 gastric cancer patients were recruited. Overall, 2,110 SPMs developed during a total follow-up of 137,798 person-years. The SIR for all cancers was 1.46. The SIRs for specific follow-up periods were 1.43, 1.41, and 1.21 at >10 years, 5-10 years, and 1-5 years, respectively. After excluding SPMs that developed within 1 year, significantly higher SIRs were seen for cancers of the head and neck (1.34), esophagus (2.16), colon and rectum (1.37), bones and soft tissues (1.95), ovaries (2.89), bladder (1.47), or kidneys (1.44), as well as non-Hodgkin's lymphoma (5.56). Multivariate analysis showed that age ≥70 years [hazard ratio (HR) 1.19], being male (HR 1.37), diabetes mellitus (HR 1.30), chronic obstructive pulmonary disease (HR 1.17), and liver cirrhosis (HR 1.94) were independent risk factors. Radiotherapy (HR 1.24) and chemotherapy (HR 1.87) were independent risk factors, but surgery (HR 0.67) was not., Conclusions: Patients with gastric cancer are at increased risk of developing SPM. Close surveillance of patients with risk factors over a longer period should be considered.

Previous studies suggest a link between anxiety disorders and cancer. The aim of the study was to evaluate the risk of cancer among patients with obsessive-compulsive disorder (OCD) using a nationwide population-based dataset. We recruited newly diagnosed OCD patients without antecedent cancer from the Taiwan National Health Insurance Research Database between 2002 and 2011. The standardized incidence ratios (SIRs) were estimated for 22 specific cancer types among OCD patients and we determined the SIRs for subgroups according to age and sex group. In addition, because of a potential detection bias, a subgroup analysis stratified with the duration of the OCD diagnosis was carried out. Among the 52,656 OCD patients, who were followed up for 259,945 person-years (median follow-up = 4.9 years), there were 718 cases of cancer. Patients with OCD did not exhibit an increased overall cancer risk relative to the general population (SIR 1.05, 95% confidence interval [CI] 0.98-1.13). An increased SIR was observed among OCD patients only within the first year of OCD diagnosis (SIR 1.21, 95% CI 1.01-1.43).This study indicated that the overall cancer risk was not elevated among OCD patients. An increased SIR observed among OCD patients within the first year of OCD diagnosis may be caused by a surveillance bias, and because paraneoplastic manifestations presented with obsessive-compulsive behaviors. Prospective study is necessary to confirm these findings.