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Whether long-term opioid use is an independent risk factor for cancer progression remains unclear. Therefore, we conducted a propensity score-matched population-based cohort study to compare cancer incidence between patients with chronic pain with and without opioid use.Data from January 2008 to December 2019 were obtained from the Taiwan National Health Insurance Research Database. Patients were categorised into two groups according to the presence or absence of opioid use, and matched at a 4:1 ratio. The incidence rate ratios for specific cancers were determined.Propensity score-matching yielded 63 610 patients: 50 888 with opioid use (the opioid group) and 12 722 without (the non-opioid group). In a multivariate Cox regression analysis, the adjusted hazard ratio (95% confidence interval) for cancers in the opioid group compared with the non-opioid group was 2.66 (1.44-2.94; P0.001). The incidence rate ratios (95% confidence interval) for lung, hepatocellular, colorectal, breast, prostate, head and neck, pancreatic, gastric, oesophageal, and ovarian cancers for the opioid group were 1.87 (1.41-2.43), 1.97 (1.56-2.50), 2.39 (1.87-3.03), 2.43 (1.75-3.33), 2.00 (1.35-3.03), 1.79 (1.14-2.86), 1.87 (1.13-2.12), 2.43 (1.52-3.85), 1.82 (0.92-3.70), and 2.33 (1.01-5.55), respectively.There was an association between long-term opioid use and development of cancer in patients with chronic pain, which should be confirmed in future studies.

Purpose No large-scale, prospective, randomized study has evaluated the effect of thoracic surgery on patients with unresectable stage IIIB–IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma who received and responded to EGFR tyrosine kinase inhibitor (TKI) treatment. Therefore, we designed a propensity-score-matched, nationwide, population-based, cohort study to investigate the effects of thoracic surgery on patients with EGFR-mutant lung adenocarcinoma. Patients and Methods We included patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma and categorized them into two groups according to their treatment modalities and compared their outcomes: the case group consisted of patients who underwent thoracic surgery for lung tumors after receiving and responding to EGFR-TKI treatment and the comparison group consisted of patients who received EGFR-TKI treatment alone until tumor progression. Patients in both groups were matched at a ratio of 1:4. Results The matching process yielded a final cohort of 1395 patients (279 and 1,116 in the case and comparison groups, respectively) who were eligible for further analysis. According to multivariable Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) for thoracic surgery for lung tumors after EGFR-TKI use and tumor response (group 2) compared with EGFR-TKI treatment alone (group 1) was 0.445 (0.351–0.564). Conclusions Thoracic surgery prolonged overall survival in patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinoma who received and responded to EGFR-TKI treatment.

Abdominal sacrocolpopexy is considered as the gold standard treatment for pelvic organ prolapse. Sacrocolpopexy can be performed using open (OSC), laparoscopic (LSC), and robotic-assisted (RSC) approaches. The aim of this study is to compare the outcomes between these three approaches for managing pelvic organ prolapse by conducting a systematic review and network meta-analysis. A systematic search was performed in different databases from their earliest records to April 2021 with no restriction on languages. Only randomized controlled trials that compared the outcomes between OSC, LSC, and RSC were included in this study. A total of 6 studies with 486 participants were included in this study. Operative time was significantly shorter in OSC than in RSC and LSC. The probability rank showed less estimated blood loss in RSC and lowest overall postoperative complications in LSC. Probability scores also showed best anatomical outcomes for postoperative points C and Bp in RSC and for point Ba in LSC. Despite significantly longer operative time, RSC and LSC may provide better anatomical outcomes, less estimated blood loss, and less overall postoperative complications than OSC. However, this study did not find significant differences between RSC and LSC in efficacy and safety.

OmpA, the most abundant porin in Stenotrophomonas maltophilia KJ, exists as a two-domain structure with an N-terminal domain of β-barrel structure embedded in the outer membrane and a C-terminal domain collocated in the periplasm. KJΔOmpA

Abdominal sacrocolpopexy is regarded as the gold standard for management of pelvic organ prolapse (POP). Nowadays, minimally invasive surgeries are preferred, and sacrocolpopexy can be performed using either a laparoscopic or robotic-assisted approach. The aim of the current study was to compare the efficacy and safety of robotic-assisted sacrocolpopexy (RASC) and laparoscopic sacrocolpopexy (LSC) through an updated systematic review and meta-analysis. We performed a systematic literature review of different databases and related references from their inception until July 2020 without language restrictions. All randomized control trials and comparative studies that compared RASC and LSC for the management of POP were included. A total of 13 studies including 2115 participants were included for the pooled analysis. The pooled results revealed that RASC was associated with a significantly longer operative time (weighted mean difference, 29.53 min; 95% confidence interval [CI], 12.88 to 46.18 min, P = 0.0005), significantly less estimated blood loss (weighted mean difference, −86.52 ml; 95% CI −130.26 to −42.79 ml, P = 0.0001), significantly fewer overall intraoperative complications (odds ratio [OR] 0.6; 95% CI 0.40 to 0.91; P = 0.01) and significantly lower conversion rate (OR 0.39; 95% CI 0.19 to 0.82; P = 0.01) compared with LSC. There were no significant differences between the length of hospital stays, overall postoperative complications, postoperative stress incontinence, mesh erosion and effectiveness between the two groups. The current study showed comparable efficacy between RASC and LSC. Though RASC was associated with less blood loss and a lower conversion rate, the differences were not clinically significant. The choice of surgical procedure with either RASC or LSC is according to surgeon discretion and patient preferences.

Cisplatin is a prevalent chemotherapeutic agent used for non-small cell lung cancer (NSCLC) that is difficult to treat by targeted therapy, but the emergence of resistance severely limits its efficacy. Thus, an effective strategy to combat cisplatin resistance is required. This study demonstrated that, at clinically achievable concentrations, the combination of selenium yeast (Se-Y) and fish oil (FO) could synergistically induce the apoptosis of cancer stem cell (CSC)-like A549 NSCLC sphere cells, accompanied by a reversal of their resistance to cisplatin. Compared to parental A549 cells, sphere cells have higher cisplatin resistance and possess elevated CSC markers (CD133 and ABCG2), epithelial–mesenchymal transition markers (anexelekto (AXL), vimentin, and N-cadherin), and cytoprotective endoplasmic reticulum (ER) stress marker (glucose-regulated protein 78) and increased oncogenic drivers, such as yes-associated protein, transcriptional coactivator with PDZ-binding motif, β-catenin, and cyclooxygenase-2. In contrast, the proapoptotic ER stress marker CCAAT/enhancer-binding protein homologous protein and AMP-activated protein kinase (AMPK) activity were reduced in sphere cells. The Se-Y and FO combination synergistically counteracted the above molecular features of A549 sphere cells and diminished their elevated CSC-like side population. AMPK inhibition by compound C restored the side population proportion diminished by this nutrient combination. The results suggest that the Se-Y and FO combination can potentially improve the outcome of cisplatin-treated NSCLC with phenotypes such as A549 cells.

Early life body mass index (BMI) trajectories influence the risk of asthma at 18 years of age. However, it is unclear if these are also associated with other allergic diseases.We investigated the associations between BMI trajectories and subsequent allergic rhinitis, eczema and food sensitisation/allergies.Parent-reported anthropometric data were collected 18 times in the first two years of life from a cohort of 620 participants in a high-risk cohort. Group-based trajectory modelling was applied to develop BMI trajectories. Associations between trajectories and allergic rhinitis, eczema and food sensitisation at 6, 12 and 18 years of age were assessed using logistic regression models. Potential effect modifications by parental allergic disease, sex and allocated infant formula were assessed.We identified five BMI trajectories: average, below average, persistently low, early low and catch up, and persistently high. None showed an association with allergic rhinitis. In participants with maternal allergic rhinitis, 'early-low and catch-up' (OR = 2.83;95%CI 1.34-5.96, PInfants with early-low and catch-up, or below average BMI growth, were at increased risk of allergic rhinitis at 18 years if they had a mother with allergic rhinitis. These results require replication, but suggest that interactions between poor intrauterine growth, failure to thrive and maternal allergies may influence the risk of allergic rhinitis.

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 25% of all NHL cases. Primary appendiceal lymphomas (PAL) presenting as acute appendicitis are very rare, occurring in only 0.015% of all cases of gastrointestinal lymphoma.A 57-year-old man who was initially presented as acute appendicitis and subsequently underwent interval laparoscopic appendectomy. Pathological examination revealed diffuse large B cell lymphoma with cut end involvement. Whole-body positron emission tomography (PET) scan revealed enlarged right palatine tonsil and raised a suspicion of lymphoma involvement in two right cervical lymph nodes (level II and III); biopsy, however, showed that the lymph nodes were benign, with non-specific cellular changes. Bone marrow biopsy of the iliac crest also did not show lymphoma involvement. Subsequently, a diagnosis of primary appendiceal diffuse large B cell lymphoma (Ann Arbor Stage II) was established. After six courses of definite chemotherapy with cyclophosphamide, doxorubicin HCl, vincristine, and rituximab (R-CHOP), PET/CT showed complete remission of the prior FDG-avid malignancy of appendiceal DLBCL. The patient continued to be stable with no recurrence for fifteen months of regular outpatient department follow-ups.PAL is rare, and it clinically manifests the signs and symptoms of acute appendicitis. Specific characteristics of lymphoma in CT scans may lead to a more confirmative diagnosis. PET/CT is important for staging the lymphoma. Patients with PAL should be managed with surgical resection followed by R-CHOP-21 for 6 cycles regardless of whether they have localized disease or disseminated disease.

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

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

The impact of opioid analgesic use before cancer diagnosis on survival in patients with chronic pain is unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare overall and cancer-related survival of patients with chronic pain who received long-term opioid analgesic treatment with that of those who did not receive such treatment.We included patients with chronic pain and categorised them into the following two groups according to their analgesic use: patients with cancer and chronic pain who were prescribed ≥180 defined daily doses of opioid analgesics per year3 months before cancer diagnosis comprised the case group, and those who were prescribed28 defined daily doses of opioid analgesics per year before cancer diagnosis comprised the control group. Patients in both groups were matched at a ratio of 1:5. The primary outcome was overall long-term survival.The matching process yielded a final cohort of 1716 patients (286 and 1430 in the case and control groups, respectively) who were eligible for further analysis. The adjusted hazard ratio for overall survival in patients receiving long-term opioids was 3.53 (95% confidence interval: 3.03-4.11; P0.001).Long-term opioid analgesic use before cancer diagnosis might be associated with poor overall survival in patients with chronic pain compared with such patients who did not receive long-term opioid analgesics.

Objective: We conducted this propensity score (PS)-matched, nationwide, population-based cohort study to estimate the effects of adjuvant oral or intravenous (IV) fluoropyrimidine in patients with high-risk stage II or III colon adenocarcinoma. Design: Using PS matching, we minimized the confounding effects on adjuvant oral or IV fluoropyrimidine outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. Setting: We selected patients from the Taiwan Cancer Registry database receiving adjuvant fluoropyrimidine monotherapy and divided them into those receiving IV fluoropyrimidine (IV group) and those receiving oral fluoropyrimidine (oral group). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratio (aHR) derived for the oral group was 1.34 (95% CI: 1.19-1.51) compared with the IV group. Moreover, in both univariate and multivariate analyses, aHR derived for significant independent prognostic risk factors for poor overall survival were male sex, age ≥ 60 years old, pathologic stage III, right-sided colon cancer, low income, and high Charlson comorbidity index. However, intergroup differences were not significant among female patients or patients < 60 years old on multivariate analysis, including no difference in overall survival. Conclusions: Adjuvant IV fluoropyrimidine is more suitable than adjuvant oral fluoropyrimidine for patients with stage II colon adenocarcinoma who have high-risk pathologic features or stage III colon adenocarcinoma.

Astragalus membranaceus is the most popular traditional Chinese medicine for managing vital energy deficiency. Its injectable polysaccharide PG2 has been used for relieving cancer-related fatigue, and PG2 has immune-modulatory and anti-inflammatory effects. In this study, we explored the effects of PG2 in lung adenocarcinoma A549 and CL1-2 cells and investigated its anticancer activity, and the results were validated in severe combined immunodeficiency (SCID) mice. Although PG2 did not inhibit the growth of these cells, it dose-dependently suppressed their migration and invasion, accompanied by reduced vimentin and AXL and induced epithelial cadherin (E-cadherin) expression. Regarding the underlying molecular mechanism, PG2 treatment reduced the macrophage migration inhibitory factor (MIF), an inflammatory cytokine that promotes the epithelial–mesenchymal transition and aggressiveness of cancer cells. Consistent with the previous finding that MIF regulates matrix metalloproteinase-13 (MMP-13) and AMP-activated protein kinase (AMPK), treatment with PG2 reduced MMP-13 and activated AMPK in A549 and CL1-2 cells in this study. In SCID mice injected with A549 cells through the tail vein, intraperitoneal injection with PG2 reduced lung and abdominal metastases in parallel with decreased immunohistochemical staining of AXL, vimentin, MMP-13, and MIF in the tumor. Collectively, data revealed a potential application of PG2 in integrative cancer treatment through the suppression of MIF in cancer cells and their aggressiveness.

Most patients with testicular germ cell tumor present with a painless scrotal mass. We report a 19-year-old patient who presented with neurological complains. Rapid clinical progression to coma was noted during the staging work up. A diagnosis of testicular mixed germ cell tumor with multiorgan metastasis (lymph node, lung, liver and brain) was made. Patients with brain metastasis should receive chemotherapy alone or combined with surgery or radiotherapy. Because the clinical symptoms deteriorated quickly, surgery was used upfront followed by chemotherapy and radiotherapy for the brain tumor. After the first stage of treatment, the clinical symptoms, tumor markers and imaging findings were improved. The residual brain tumor was eliminated by chemotherapy, and only sparse degenerated tumor cells were noted in the brain tissue. Longer follow up is required to assess the impact of our treatment strategy.

The staff music notation was originated from Gregorian chants of medieval Europe. It became the universal standard notation although there were music notations found in other ancient cultures. During 19th century, a new and simplified notation system in which Arabic numbers were used to represent musical notes began to circulate among amateurish music learners all over the world. While this notation system, named numbered music notation (NMN) in this article, started to wane in other countries in the early 20th century, Chinese adopted it earnestly and continued to use it as a major practice in music printings and education. In the field of traditional Chinese music, some readily assume it is a Chinese invention. This article puts forward a discussion on the emergence of the NMN and its application in China, compares it with the staff music notation, and exams how notations affect music training.

BACKGROUNDTo date, no data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT).PATIENTS AND METHODSCurrent-smoking patients with clinical stage IIIA-IIIB, lung SCC who had received standard definitive CCRT and categorized them into two groups based on their COPD status to compare overall survival outcomes. We also examined the effects of COPD severity (0, 1, or ≥2 hospitalizations for COPDA within 1 year before CCRT). The aHRs (95% CIs) of lung cancer death for 1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT were 1.21 (1.09, 1.39) and 1.63 (1.34, 1.97), respectively, compared with no hospitalization for COPDAE.RESULTSIn the inverse probability of treatment weighting (IPTW)-adjusted model, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) of all-cause death for COPD was 1.06 (1.07, 1.71) compared with the non-COPD group. Moreover, in the IPTW-adjusted model, the aHRs (95% CIs) of 1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT were 1.29 (1.16, 1.43) and 1.77 (1.41, 2.13), respectively, compared with no hospitalization for COPDAE.CONCLUSIONCOPD and its severity are significant independent risk factors for all-cause death in patients with stage IIIA-IIIB lung SCC receiving definitive CCRT. Hospitalization for COPDAE within 1 year before CCRT is the significant independent risk factors for lung cancer death in the patients with stages IIIA-IIIB lung SCC receiving definitive CCRT.

To estimate oncologic outcomes (overall survival [OS], locoregional recurrence [LRR], and distant metastasis [DM]) in patients with breast intraductal carcinoma (IDC) receiving breast conserving surgery (BCS) under propofol-based total intravenous anesthesia (TIVA) or volatile inhalational (INHA) general anesthesia (GA) without propofol. Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized by anesthesia techniques into propofol-based TIVA-GA and non-propofol-based INHA-GA groups, respectively. Cox regression analysis was performed to calculate hazard ratios and 95% confidence intervals (CIs). In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of all-cause mortality for TIVA-GA with propofol compared with INHA-GA without propofol was 0.94 (0.83-1.31). The aHR (95% CI) of LRR for TIVA-GA with propofol group compared with INHA-GA without propofol was 0.77 (0.58-0.87). The aHR (95% CI) of DM for TIVA-GA with propofol compared with INHA-GA without propofol was 0.91 (0.82-1.24). Propofol-based TIVA-GA might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with non-propofol-based INHA-GA.

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

Music education has been established in China for a long time. However, many people believe that the best way of teaching and learning a musical instrument is through one-on-one lessons with a teacher. This essay re-examines the fundamental keyboard courses offered in a four-year comprehensive university, and how the program fits in the curriculum of the music department and how to implement it more economically while maintaining the effectiveness.

e14560 Background: Serplulimab, a novel humanized IgG4 monoclonal antibody against PD-1 receptor, increased functional activities of human T cells and showed anti-tumor activity in several xenograft models. This phase 1 study was designed to assess the safety and tolerability of serplulimab in patients with metastatic or recurrent solid tumors. Methods: This prospective, open-label, two-cohort (dose-finding cohort [up to 30 patients]; dose expansion cohort [up to 27 patients]) phase 1 study was conducted in patients with metastatic or recurrent solid tumors who had failed standard therapy. In the dose-finding cohort, Bayesian optimal interval (BOIN) design was adopted to explore the MTD of serplulimab. Patients were administered serplulimab (Q2W) at doses of 0.3, 1, 3, or 10 mg/kg via intravenous infusion until disease progression, the maximum of 1 year, withdrawal from the study, or death, whichever occurred first. In the dose expansion cohort, nine eligible patients were enrolled in each dose group to receive fixed doses of serplulimab at 200 (Q2W), 300 (Q3W) or 400 mg (Q4W). The primary objective of this study was to identify the safety profile and the MTD of serplulimab. The PK profile and the preliminary efficacy were also examined as secondary objectives. Results: Here we only report the results from the dose-finding cohort. As of July 27, 2020, 29 patients were enrolled and treated with at least one dose of serplulimab (0.3 mg/kg group, n = 3; 1 mg/kg group, n = 4; 3 mg/kg group, n = 6; 10 mg/kg group, n = 16). At baseline, the mean age of enrolled patients was 60.0 years, with a mean BMI of 24.7 kg/m2, a mean BSA of 1.7 m2, and a mean LVEF of 67.1%. All patients presented with stage IV tumors at baseline, among whom 79.3% were diagnosed with metastatic disease. Only one patient in the 3 mg/kg dose group experienced DLTs, which was reported during the first cycle. The MTD was not determined yet. Overall, 28 (96.6%) patients experienced at least one TEAE during the study, mostly of grade 1 or 2. No notable differences were observed among the dose groups with regard to the incidence of TEAEs. The most frequently reported TEAEs was decreased appetite (41.4%), fatigue (31.0%), nausea (27.6%), pyrexia (27.6%), and pleural effusion (27.6%). Minimal accumulation of serplulimab was observed following multiple dose administrations. The preliminary anti-tumor efficacy of serplulimab was demonstrated by a DCR of 60.0%, an ORR of 8.0%, and a median PFS of 107.0 days. Conclusions: In summary, serplulimab up to 10 mg/kg was well tolerated and showed promising anti-tumor activity in patients with metastatic or recurrent solid tumors. Serplulimab is currently being investigated in phase 3 studies among patients with NSCLC, SCLC, esophageal cancer, mCRC, etc. Clinical trial information: NCT03468751.

Simple Summary This study highlights the epidemiological, cytogenetic and clinical difference between patients with multiple hit diffuse large B-cell lymphoma in Taiwan and those from western countries. Unlike in the West, the majority of patients with multiple hit lymphoma in Taiwan harbor a BCL6 rearrangement. Almost three in every five BCL6-rearranged double hit lymphoma cases in Taiwan are non-GCB phenotype, indicating, at least in part, that the preferential screening for double hit with BCL6 rearrangement may be a clinically-informative modality for patients with non-GCB phenotype DLBCL in Taiwan. This also suggests the need for a different treatment approach than is obtained in the West where BCL6 double hit lymphomas are seemingly GCB. Consistent with our present findings, mandatory screening for BCL6-rearrangement in suspected DLBCL cases in Taiwan may aid early diagnosis, therapy decision, and clinical outcome forecast. Abstract This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover, ~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.

The columnar mesophase, in which the molecular or supramolecular building blocks with rod-like geometry pack into two-dimensional (2D) lattices, is an important class of mesomorphic structure having been found in various liquid crystalline materials for practical applications. The cylindrical micelles assembled by amphiphilic surfactants may also form columnar mesophases with the micelle packing symmetry being tunable by the molecular characteristics of the surfactants. In this study, we demonstrate that a positively charged tree-like polymer, poly(amidoamine) (PAMAM) G4 dendrimer, acted as an effective structure-directing agent for the columnar mesophase of a common anionic surfactant, sodium dodecyl sulfate (SDS), via their electrostatic interaction. By adjusting the dendrimer charge density and the nominal binding ratio (Xn) of SDS to dendrimer, the electrostatic complexes self-assembled to form a body-centered cubic (BCC) sphere phase, wherein the dendrimers were staggered between the interspaces of the SDS spherical micelles packed in the BCC lattice. Four types of 2D columnar mesophase composed of SDS cylindrical micelles and dendrimers were accommodated within the interstitial tunnels, including the hexagonal columnar phase (Colhex), simple rectangular columnar phase (Colsr), oblique columnar phase (Colob) and centered rectangular columnar phase (Colcr). A detailed analysis of the geometry of the dendrimer in the columnar mesophases revealed that the structural transition was governed by the interplay among the lateral and axial deformations of the dendrimer, and the deformation of the SDS micelle cross section for achieving effective charge matching and accommodation of the dendrimer. The present study demonstrated the power of the dendrimer in directing the long-range ordered packing of oppositely charged cylinders to yield a rich structural polymorphism of the columnar mesophase that may be exploited for the development of functional materials.

Non-small cell lung cancer (NSCLC)-carrying specific epidermal growth factor receptor (EGFR) mutations can be effectively treated by a tyrosine kinase inhibitor such as gefitinib. However, the inevitable development of acquired resistance leads to the eventual failure of therapy. In this study, we show the combination effect of omega-3 fatty acid-enriched fish oil (FO) and selenium (Se) on reversing the acquired gefitinib-resistance of HCC827 NSCLC cells. The gefitinib-resistant subline HCC827GR possesses lowered proapoptotic CHOP (CCAAT/enhancer-binding protein homologous protein) and elevated cytoprotective GRP78 (glucose regulated protein of a 78 kDa molecular weight) endoplasmic reticulum (ER) stress response elements, and it has elevated &beta, catenin and cyclooxygenase-2 (COX-2) levels. Combining FO and Se counteracts the above features of HCC827GR cells, accompanied by the suppression of their raised epithelial-to-mesenchymal transition (EMT) and cancer stem markers, such as vimentin, AXL, N-cadherin, CD133, CD44, and ABCG2. Accordingly, an FO and Se combination augments the gefitinib-mediated growth inhibition and apoptosis of HCC827GR cells, along with the enhanced activation of caspase -3, -9, and ER stress-related caspase-4. Intriguingly, gefitinib further increases the elevated ABCG2 and cancer stem-like side population in HCC827GR cells, which can also be diminished by the FO and Se combination. The results suggest the potential of combining FO and Se in relieving the acquired resistance of NSCLC patients to targeted therapy.

Radiation recall, which was first described in 1959, remains a rare and erratic inflammatory phenomenon that manifests in previously irradiated areas after the subsequent administration of chemothe...

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.

Purpose Large-scale, prospective, randomized studies of the efficacy of thoracic radiotherapy (RT) in patients with unresectable stage IIIB–IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinomas who received and responded to EGFR tyrosine kinase inhibitor (TKI) treatment are not currently available. Therefore, we designed a propensity score-matched, nationwide, population-based, cohort study for estimating the effects of thoracic RT on patients with EGFR-mutant lung adenocarcinomas. Patients and methods We analyzed patients with unresectable stage IIIB–IV EGFR mutant lung adenocarcinomas and categorized them into two groups according to treatment modality and compared their outcomes; groups 1 and 2 consisted of patients who received EGFR TKI treatment alone until tumor progression and those who received and responded to EGFR TKI treatment and subsequently received thoracic RT for lung tumors, respectively. The patients in groups 2 and 1 were matched at a ratio of 1:4. Results The matching process yielded a final cohort of 1475 patients (1180 and 295 patients in groups 1 and 2, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) derived for thoracic RT for lung tumor after EGFR TKI use and tumor response (group 2) compared with EGFR TKI treatment alone (group 1) was 0.72 (0.60–0.85). Conclusions Thoracic RT might be associated with overall survival in patients with unresectable stage IIIB–IV EGFR-mutant lung adenocarcinomas who received and responded to EGFR TKI treatment.

Background No large-scale, head-to-head, phase III, randomized, controlled trial with an adequate sample size has investigated the effect of concurrent low-dose (LD) or high-dose (HD) cisplatin with radiotherapy on nasopharyngeal cancer (NPC). Thus, we conducted a propensity-score-matched, nationwide, population-based cohort study in Taiwan to investigate the outcomes of LD-concurrent chemoradiotherapy (CCRT) or HD-CCRT with intensity-modulated radiotherapy (IMRT) in patients with advanced NPC. Methods In this study, patients were categorized into 2 groups according to their chemotherapy regimen: HD-CCRT and LD-CCRT groups. Results We enrolled 1968 patients (328 and 1640 in the LD-CCRT and HD-CCRT groups, respectively) who had received CCRT with IMRT. According to both univariate and multivariate Cox regression analyses, a hazard ratio (95% confidence interval) of 0.75 (0.54–1.06, P = .103) was derived for the HD-CCRT group. Conclusion LD-CCRT or HD-CCRT with IMRT can be a standard treatment that can prolong the survival of patients with advanced NPC.

In the era of intensity modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of adjuvant therapies such as adjuvant concurrent chemoradiotherapy (CCRT), adjuvant sequential chemotherapy and radiotherapy (CT‐RT), and adjuvant CT alone in resectable pancreatic adenocarcinoma (PA). Through propensity score matching, we designed a nationwide, population‐based, head‐to‐head cohort study to determine the effects of dissimilar adjuvant treatments on resectable PA. We minimized the confounding of various adjuvant treatment outcomes among the following resectable PA groups of patients from the Taiwan Cancer Registry database: group 1, adjuvant CCRT; group 2, adjuvant sequential CT‐RT; and group 3, adjuvant CT alone. All the studied techniques are IMRTs. The matching process yielded a final cohort of 588 patients (196, 196, and 196 patients in groups 1, 2, and 3, respectively). In both univariate and multivariate Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of death derived for the adjuvant CCRT and adjuvant sequential CT‐RT cohorts compared with the adjuvant CT alone cohort were 0.398 (0.314–0.504) and 0.307 (0.235–0.402), respectively. A combination of adjuvant IMRT and CT for resectable PA treatment improves survival to a greater extent than does adjuvant CT alone.

Simple Summary The conventional methods that seek to predict clinical treatment response are based on the number of circulating tumor cells (CTCs) present in liquid biopsies or genetic profiling of extracted CTCs. This paper presents a novel process by which CTCs can be extracted from blood samples taken from head and neck cancer patients and then expanded ex vivo to form organoids that can be tested with a panel of anti-cancer treatments. The resulting drug sensitivity profiles derived from cisplatin treatment of organoids were subsequently found to correlate with clinical treatment response to cisplatin in patients. CTCs extracted from liquid biopsies for ex vivo expansion negates the need for complicated and potentially risky biopsies of tumor material, thereby supporting the application of this procedure for checkups and treatment monitoring. Abstract The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.

Purpose Marketers may proactively give customers personalized notices regarding their progress toward certain rewards as a means to stimulate ongoing behaviors. This paper aims to investigate the effect on customer repatronage intention by framed messages concerning either goal-distance or consequences of an action and it also seeks to identify important variables moderating those responses. Design/methodology/approach Five between-subjects experiments examined how participants’ repatronage intentions, in response to the framing of goal-distance (Study 1a) and consequences of an action (Study 2a), varied as a function of their level of progress toward goal completion and also tested if the framing effects might be attenuated when relationship benefit was high rather than low (Studies 1b and 2b). They further adopted perceived reciprocity as an underlying mechanism for examining the interplay between these two kinds of framing in stimulating ongoing behavior (Study 3). Findings Although messages which emphasized what individuals need to spend more to attain a reward (versus how short they are from earning a reward) or loss following inaction (versus gain following action) were likely to erode intention, such effects were confined to individuals with a moderate level of progress. This intention-eroding effect was further attenuated by attractive reward. The persuasive advantages of short-from-the-end framing of goal-distance over more-to-the-end counterparts were found to be diminished when paired with a loss-framed message concerning consequences of an action. Furthermore, the observed effects on intention were mediated by perceived reciprocity. Originality/value The studies add to the current understanding of how the way in which information is presented might enhance loyalty or fail to do so.

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