Effect of “Speak Up” educational tools to engage patients in advance care planning in outpatient healthcare settings: A prospective before-after study

BackgroundTools for advance care planning (ACP) are advocated to help ensure patient values guide healthcare decisions. Evaluation of the effect of tools introduced to patients in clinical settings is needed.ObjectiveTo evaluate the effect of the Canadian Speak Up Campaign tools on engagement in advance care planning (ACP), with patients attending outpatient clinics.Patient involvement: Patients were not involved in the problem definition or solution selection in this study but members of the public were involved in development of tools. The measurement of impacts involved patients.MethodsThis was a prospective pre-post study in 15 primary care and two outpatient cancer clinics. The outcome was scores on an Advance Care Planning Engagement Survey measuring Behavior Change Process on 5-point scales and Actions (0?21-point scale) administered before and six weeks after using a tool, with reminders at two or four weeks.Results177 of 220 patients (81%) completed the study (mean 68 years of age, 16% had cancer). Mean Behavior Change Process scores were 2.9 at baseline and 3.5 at follow-up (mean change 0.6, 95% confidence interval 0.5 to 0.7; large effect size of 0.8). Mean Action Measure score was 3.7 at baseline and 4.8 at follow-up (mean change 1.1, 95% confidence interval 0.6–1.5; small effect size of 0.2).Practical valuePublicly available ACP tools may have utility in clinical settings to initiate ACP among patients. More time and motivation may be required to stimulate changes in patient behaviors related to ACP.     

Antitumor Activity of Small Activating RNAs Induced PAWR Gene Activation in Human Bladder Cancer Cells

Small double-stranded RNAs (dsRNAs) have been proved to effectively up-regulate the expression of particular genes by targeting their promoters. These small dsRNAs were also termed small activating RNAs (saRNAs). We previously reported that several small double-stranded RNAs (dsRNAs) targeting the PRKC apoptosis WT1 regulator (PAWR) promoter can up-regulate PAWR gene expression effectively in human cancer cells. The present study was conducted to evaluate the antitumor potential of PAWR gene induction by these saRNAs in bladder cancer. Promisingly, we found that up-regulation of PAWR by saRNA inhibited the growth of bladder cancer cells by inducing cell apoptosis and cell cycle arrest which was related to inhibition of anti‑apoptotic protein Bcl-2 and inactivation of the NF-κB and Akt pathways. The activation of the caspase cascade and the regulation of cell cycle related proteins also supported the efficacy of the treatment. Moreover, our study also showed that these saRNAs cooperated with cisplatin in the inhibition of bladder cancer cells. Overall, these data suggest that activation of PAWR by saRNA may have a therapeutic benefit for bladder cancer.     

MicroRNA-33/33* inhibit the activation of MAVS through AMPK in antiviral innate immunity

Innate immunity plays a prominent role in the host defense against pathogens and must be precisely regulated. As vital orchestrators in cholesterol homeostasis, microRNA-33/33* have been widely investigated in cellular metabolism. However, their role in antiviral innate immunity is largely unknown. Here, we report that VSV stimulation decreased the expression of miR-33/33* through an IFNAR-dependent manner in macrophages. Overexpression of miR-33/33* resulted in impaired RIG-I signaling, enhancing viral load and lethality whereas attenuating type I interferon production both in vitro and in vivo. In addition, miR-33/33* specifically prevented the mitochondrial adaptor mitochondrial antiviral-signaling protein (MAVS) from forming activated aggregates by targeting adenosine monophosphate activated protein kinase (AMPK), subsequently impeding the mitophagy-mediated elimination of damaged mitochondria and disturbing mitochondrial homeostasis which is indispensable for efficient MAVS activation. Our findings establish miR-33/33* as negative modulators of the RNA virus-triggered innate immune response and identify a previously unknown regulatory mechanism linking mitochondrial homeostasis with antiviral signaling pathways.     

Chemoradiation-induced changes in systemic inflammatory markers and their prognostic significance in oesophageal squamous cell carcinoma

Objective:Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma.Methods:A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection.Results:Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS.Conclusion:Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC.Advances in knowledge:We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.     

A review of staging chest CT in trunk and extremity soft tissue sarcoma

Objectives:To determine the incidence of pulmonary metastases on chest CT in trunk and extremity soft tissue sarcoma based on two size criteria, and to identify factors associated with metastases.Methods:Retrospective review of chest CT studies in patients with trunk and extremity soft tissue sarcoma over an 18-month period. Data collected included patient age/sex, tumour location, size and relationship to fascia. All chest CTs were reviewed for the presence of metastases which were diagnosed according to two size criteria: multiple nodules > 5 mm in size or multiple nodules > 10 mm in size. Follow-up CT studies were reviewed in cases initially considered indeterminate.Results:127 males and 73 females were included (mean age 57.1 years; range 10–90 years). 147 (73.5%) tumours were deep to the fascia and 53 (26.5%) superficial. Tumour size classified according to the 12 AJCC 2019 criteria was: T1 = 52, T2 = 76, T3 = 39, T4 = 33. Based on nodule size >5 mm, 73 (36.5%) patients had no metastases, 42 (21%) had metastases, while 85 (42.5%) studies were indeterminate. Based on nodule size >10 mm, 73 (36.5%) patients had no metastases, 28 (14%) had metastases, while 99 (49.5%) studies were indeterminate. Larger maximum dimension of the primary tumour was a risk factor for pulmonary metastases using both size criteria.Conclusion:The incidence of pulmonary metastases at presentation in trunk and extremity soft tissue sarcoma is 14–21%. 42.5–49.5% of chest CTs were indeterminate.Advances in knowledge:The incidence of pulmonary metastases at presentation in trunk and extremity soft tissue sarcoma is 14–21%. Indeterminate pulmonary nodules are also very common.     

Postobturation Pain Associated with Tricalcium Silicate and Resin-based Sealer Techniques: A Randomized Clinical Trial

IntroductionThe incidence of immediate postobturation pain associated with 2 sealer techniques was compared and potential prognostic factors identified.MethodsPatients referred for endodontic treatment were recruited with informed consent. Root canals were debrided and teeth rendered asymptomatic before random allocation to receive TotalFill BC (FKG Dentaire SA, La Chaux-de-Fonds, Switzerland) or AH Plus sealer (Dentsply Maillefer, Ballaigues, Switzerland). Patients blinded to the sealer reported their postobturation pain experience 1, 3, and 7 days after treatment. Blinded and calibrated assessors independently reviewed treatment quality, sealer extrusion, and radiographic data under standardized conditions.ResultsOne hundred sixty eligible patients (163 teeth, 95.3%) returned their pain diary. No postobturation pain difference was found between the 2 sealers (P > .05), although the AH Plus sealer technique was significantly associated with extrusion beyond the apex (P < .05; odds ratio [OR] = 3.02; 95% confidence interval [CI], 1.39–6.57). Thirty-three (20.6%) patients reported pain on day 1 (median 1 = very mild pain), 16 (10.0%) on day 3 (median 1 = very mild pain), and 9 (5.6%) on day 7 (median 2 = mild pain). The prognostic factors were as follows:(1) moderate/severe preoperative pain (OR = 4.41; 95% CI, 1.42–13.76 on day 3 and OR = 5.16; 95% CI, 1.17–22.78 on day 7),(2) provoked preoperative pain (OR = 4.24; 95% CI, 1.40–12.78 on day 3 and OR = 5.35; 95% CI, 1.27–22.51 on day 7),(3) pulpless tooth (OR = 0.11; 95% CI, 0.02–0.57 on day 3), and(4) sonic activation during treatment (OR = 3.02; 95% CI, 1.39–6.57 on day 1 and OR = 3.01; 95% CI, 1.05–8.59 on day 3).ConclusionsThere was no significant difference in pain experience between teeth filled using AH Plus or TotalFill BC Sealer 1, 3, and 7 days after obturation. Patient- and treatment-related factors could influence postobturation pain.     

Clinical effects of scaling and root planing with an adjunctive periodontal endoscope for residual pockets: a randomized controlled clinical study

目的 比较牙周内窥镜辅助龈下刮治和根面平整（SRP）与传统SRP对慢性牙周炎患者基础治疗后残留牙周袋的临床疗效。方法 将牙周基础治疗后口内每个区至少有1个位点探诊深度（PD）≥5 mm的患者纳入研究,随机分为内窥镜组和SRP组,分别对残留牙周袋位点进行内窥镜辅助SRP治疗和传统SRP治疗。在治疗前（基线）、治疗后3、6个月检查PD、探诊出血（BOP）和附着丧失（AL）,采用SPSS 20.0统计学软件对数据进行统计分析。结果 与基线相比,治疗后3、6个月内窥镜组及SRP组PD≥5 mm位点百分比、PD、AL、BOP阳性位点百分比均降低（P<0.05）。治疗后6个月与3个月相比,内窥镜组PD≥5 mm位点百分比、PD、AL、BOP阳性位点百分比均降低（P<0.05）,而SRP组差异无统计学意义（P>0.05）。与SRP组相比,内窥镜组治疗后3及6个月PD≥5 mm位点百分比、PD均降低,治疗后6个月AL、BOP阳性位点百分比降低（P<0.05）。结论 牙周内窥镜辅助SRP对于基础治疗后的残留牙周袋（PD≥5 mm）的临床疗效优于传统SRP,尤其具有更好的远期预后。