Predictors of Patient Engagement in Telehealth-Delivered Tobacco Cessation Treatment during the COVID-19 Pandemic.

Smoking causes one in three cancer deaths and may worsen COVID-19 outcomes. Telehealth tobacco cessation treatment is offered as a covered benefit for patients at the Stanford Cancer Center. We examined predictors of engagement during the COVID-19 pandemic. Data were abstracted from the Electronic Health Record between 3/17/20 (start of pandemic shelter-in-place) and 9/20/22, including patient tobacco use, demographics, and engagement in cessation treatment. Importance of quitting tobacco was obtained for a subset (53%). During the first 2.5 years of the pandemic, 2595 patients were identified as recently using tobacco, and 1571 patients were contacted (61%). Of the 1313 patients still using tobacco (40% women, mean age 59, 66% White, 13% Hispanic), 448 (34%) enrolled in treatment. Patient engagement was greater in pandemic year 1 (42%) than in year 2 (28%) and year 3 (19%). Women (41%) engaged more than men (30%). Patients aged 36-45 (39%), 46-55 (43%), 56-65 (37%), and 66-75 (33%) engaged more than patients aged 18-35 (18%) and >75 (21%). Hispanic/Latinx patients (42%) engaged more than non-Hispanic/Latinx patients (33%). Engagement was not statistically significantly related to patient race. Perceived importance of quitting tobacco was significantly lower in pandemic year 1 than year 2 or 3. Nearly one in three cancer patients engaged in telehealth cessation treatment during the COVID-19 pandemic. Engagement was greater earlier in the pandemic, among women, Hispanic/Latinx individuals, and patients aged 36 to 75. Sheltering-in-place, rather than greater perceived risk, may have facilitated patient engagement in tobacco cessation treatment.

Perspectives on Cybersecurity and Plastic Surgery: A Survey of Plastic Surgeons and Scoping Review of the Literature.

BACKGROUND: Data breach costs in the United States are among the highest in the world, making robust cybersecurity an important bulwark of national defense. Healthcare is a popular target for cyber threats, and there is increasing emphasis on cybersecurity safeguards to protect sensitive patient data. OBJECTIVES: The objective of this national survey and scoping review is to (1) identify cybersecurity awareness, preparedness, and practices among plastic surgeons, and (2) to provide guidelines to mitigate the threat of cyberattacks. METHODS: A 16-question, anonymous online survey was developed and distributed to The Aesthetic Society registrants to ascertain plastic surgeons' cybersecurity practices. Utilizing PubMed, CINAHL, and Embase databases, eligible articles were identified as part of this scoping review. RESULTS: Of 89 individuals who began the survey, 69 completed it (77.5%). Sixty respondents agreed or strongly agreed that cybersecurity is an important issue in plastic surgery. The greatest perceived limitations for protection against cyberattacks were insufficient expertise (41.7%), followed by lack of funding and insufficient time to dedicate to this goal. Most respondents (78.7%) had cybersecurity policies incorporated into their practice. Those who agreed or strongly agreed they had technology to prevent data theft/breach were significantly more likely to be older than 54 years of age (P < .001). No articles identified in the literature specifically addressed cybersecurity in plastic surgery; however, 12 articles detailing cybersecurity in healthcare were identified and included. CONCLUSIONS: Despite possessing adequate technology and procedures in place to prevent cyberattacks, plastic surgeons perceive significant barriers to cybersecurity protection, including insufficient expertise and lack of dedicated funding. It is imperative that our field establishes standards and protocols to protect our patients.

Barriers to conducting deprescribing in the elderly population amid the COVID-19 pandemic.

Deprescribing aims to reduce polypharmacy, especially in the elderly population, in order to maintain or improve quality of life, reduce harm from medications, and limit healthcare expenditure. Coronavirus disease (COVID-19) is an infectious disease that has led to a pandemic and has changed the lives many throughout the world. The mode of transmission of this virus is from person to person through the transfer of respiratory droplets. Therefore, non-essential healthcare services involving direct patient interactions, including deprescribing, has been on hiatus to reduce spread. Barriers to deprescribing before the pandemic include patient and system related factors, such as resistance to change, patient's knowledge deficit about deprescribing, lack of alternatives for treatment of disease, uncoordinated delivery of health services, prescriber's attitudes and/or experience, limited availability of guidelines for deprescribing, and lack of evidence on preventative therapy. Some of these barriers can be mitigated by using the following interventions:patient education, prioritization of non-pharmacological therapy, incorporation of electronic health record (EHR), continuous prescriber education, and development of research studies on deprescribing. Currently, deprescribing cannot be delivered through in person interactions, so virtual care is a reasonable alternative format. The full incorporation of EHR throughout Canada can add to the success of this strategy. However, there are several challenges of conducting deprescribing virtually in the elderly population. These challenges include, but are not limited, to their inability to use technology, lack of literacy, lack of assistance from others, greater propensity for withdrawal effects, and increased risk of severe consequences, if hospitalized. Virtual care is the future of healthcare and in order to retain the benefits of deprescribing, additional initiatives should be in place to address the challenges that elderly patients may experience in accessing deprescribing virtually. These initiatives should involve teaching elderly patients how to use technology to access health services and with technical support in place to address any concerns.

Integration of Tobacco Treatment Services into Cancer Care at Stanford.

As part of a National Cancer Institute Moonshot P30 Supplement, the Stanford Cancer Center piloted and integrated tobacco treatment into cancer care. This quality improvement (QI) project reports on the process from initial pilot to adoption within 14 clinics. The Head and Neck Oncology Clinic was engaged first in January 2019 as a pilot site given staff receptivity, elevated smoking prevalence, and a high tobacco screening rate (95%) yet low levels of tobacco cessation treatment referrals (<10%) and patient engagement (<1% of smokers treated). To improve referrals and engagement, system changes included an automated "opt-out" referral process and provision of tobacco cessation treatment as a covered benefit with flexible delivery options that included phone and telemedicine. Screening rates increased to 99%, referrals to 100%, 74% of patients were reached by counselors, and 33% of those reached engaged in treatment. Patient-reported abstinence from all tobacco products at 6-month follow-up is 20%. In July 2019, two additional oncology clinics were added. In December 2019, less than one year from initiating the QI pilot, with demonstrated feasibility, acceptability, and efficacy, the tobacco treatment services were integrated into 14 clinics at Stanford Cancer Center.

Novel Treatment Setup for Urethral Cancer: Use of the Prone Technique for Radiotherapy of the Penis.

Urethral cancer (UC) is a rare malignancy with a poor prognosis. Since local recurrence is common and associated with morbidity, case series have reported on the use of adjuvant radiotherapy. Radiotherapy treatment setup for malignancies of the penis can be challenging because of variability in anatomic positioning. This variability can lead to lack of reproducibility. We propose a novel external beam radiotherapy technique for the treatment of UC: prone positioning. This technique has been used to treat breast cancers successfully and can be used to treat any variety of penile malignancies. We present 2 patients who were treated using this positioning.

The Pseudomonas aeruginosa type III translocon is required for biofilm formation at the epithelial barrier.

Clinical infections by Pseudomonas aeruginosa, a deadly Gram-negative, opportunistic pathogen of immunocompromised hosts, often involve the formation of antibiotic-resistant biofilms. Although biofilm formation has been extensively studied in vitro on glass or plastic surfaces, much less is known about biofilm formation at the epithelial barrier. We have previously shown that when added to the apical surface of polarized epithelial cells, P. aeruginosa rapidly forms cell-associated aggregates within 60 minutes of infection. By confocal microscopy we now show that cell-associated aggregates exhibit key characteristics of biofilms, including the presence of extracellular matrix and increased resistance to antibiotics compared to planktonic bacteria. Using isogenic mutants in the type III secretion system, we found that the translocon, but not the effectors themselves, were required for cell-associated aggregation on the surface of polarized epithelial cells and at early time points in a murine model of acute pneumonia. In contrast, the translocon was not required for aggregation on abiotic surfaces, suggesting a novel function for the type III secretion system during cell-associated aggregation. Supernatants from epithelial cells infected with wild-type bacteria or from cells treated with the pore-forming toxin streptolysin O could rescue aggregate formation in a type III secretion mutant, indicating that cell-associated aggregation requires one or more host cell factors. Our results suggest a previously unappreciated function for the type III translocon in the formation of P. aeruginosa biofilms at the epithelial barrier and demonstrate that biofilms may form at early time points of infection.

Assessment of folate receptor-α and epidermal growth factor receptor expression in pemetrexed-treated non-small-cell lung cancer patients.

INTRODUCTION: Folate receptor-α regulates cellular uptake of folates and antifolates (eg, pemetrexed) and is frequently expressed in pulmonary adenocarcinoma. EGFR is an established therapeutic target in NSCLC. Therapies targeting FRA or EGFR are available. The association between FRA and EGFR expression in advanced NSCLC has not been explored. Combining therapeutic FRA antibodies with an EGFR inhibitor might be beneficial, if both of the targets are significantly coexpressed. PATIENTS AND METHODS: Specimens from 160 advanced NSCLC patients receiving pemetrexed-based chemotherapy were assessed for membranous FRA and EGFR protein expression using immunohistochemistry and the Hybrid (H)-score. EGFR (exons 18-21) and Kirsten RNA-associated rat sarcoma 2 virus (exon 2) mutations were determined. Results were correlated to patients' clinicopathological data, progression-free survival (PFS), and overall survival (OS). RESULTS: Forty-seven patients (29%) had tumors with strong FRA and EGFR expression, but no statistically significant correlation was seen between protein levels of FRA and EGFR. High membranous FRA expression (H-score ≥ 20) was associated with prolonged PFS (5.5 vs. 3.4 months; hazard ratio [HR], 0.6060; P = .0254) and improved OS (12.1 vs. 6.4 months; HR, 0.5726; P = .0076). CONCLUSION: Survival times are improved in NSCLC patients whose tumors show strong membranous FRA expression. No statistical correlation between membranous FRA and EGFR expression was demonstrated in advanced NSCLC, but 47 patients (29%) had higher expression of both of the receptors and could be suitable for combined targeted therapies.

Assessing Pseudomonas virulence using host cells.

While human or animal models are often considered the gold standard experimental system for defining virulence factors, cell culture-based infection models have proven useful for identifying important virulence factors and for examining the interactions between pathogens and the epithelial barrier. The first step in infections for most mucosal pathogens involves binding (adhesion) to the epithelial cells that line the mucosa. Successful pathogens can then penetrate the barrier by (1) inducing their uptake (i.e., "entry" or "invasion") into epithelial cells, (2) crossing the barrier by inducing epithelial cell death, and/or (3) penetrating between cells. This chapter describes growth conditions to form polarized cultures, either two-dimensional monolayers or three-dimensional cysts, of various immortalized epithelial cell lines. It describes assays to measure key early interactions between P. aeruginosa and host cells, including binding, invasion, and cytotoxicity. Many virulence factors defined by these criteria have been shown to be important for pathogenesis of P. aeruginosa infections in animals or humans. These methods are also applicable to other pathogens.

Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection.

The mucosal epithelium consists of polarized cells with distinct apical and basolateral membranes that serve as functional and physical barriers to external pathogens. The apical surface of the epithelium constitutes the first point of contact between mucosal pathogens, such as Pseudomonas aeruginosa, and their host. We observed that binding of P. aeruginosa aggregates to the apical surface of polarized cells led to the striking formation of an actin-rich membrane protrusion with inverted polarity, containing basolateral lipids and membrane components. Such protrusions were associated with a spatially localized host immune response to P. aeruginosa aggregates that required bacterial flagella and a type III secretion system apparatus. Host protrusions formed de novo underneath bacterial aggregates and involved the apical recruitment of a Par3/Par6α/aPKC/Rac1 signaling module for a robust, spatially localized host NF-κB response. Our data reveal a role for spatiotemporal epithelial polarity changes in the activation of innate immune responses.

Significance of folate receptor alpha and thymidylate synthase protein expression in patients with non-small-cell lung cancer treated with pemetrexed.

INTRODUCTION: Folate receptor alpha (FRA) regulates cellular uptake of folates and antifolates. Information about FRA protein expression in metastatic non-small-cell lung cancer (NSCLC) is limited. We investigated FRA as a biomarker for pemetrexed-based chemotherapy and compared it with thymidylate synthase (TS), the main target of pemetrexed. METHODS: Pretreatment tumor specimens from 207 patients with advanced NSCLC were assessed for FRA and TS protein expression by immunohistochemistry using the H-score (range, 0-300) and correlated to patients' clinicopathological data, radiographic response, progression-free survival (PFS), and overall survival (OS). RESULTS: Low total (cytoplasmic and nuclear) TS protein expression (H-score < 210) was associated with improved PFS (median: 5.6 versus 3.5 months; hazard ratio [HR] = 0.6379, p = 0.0131) and prolonged OS (median: 22.5 versus 11.5 months; HR = 0.5680,p = 0.0107). An association between lower TS levels and response to pemetrexed-based therapy was found-mean H-score 187 ± 5, median 180 for responders versus mean H-score 201 ± 4, median 210, for non-responders, p = 0.0244. High intracellular FRA expression (H-score ≥110) was associated with prolonged OS (28.9 versus 11.7 months, HR = 0.5316, p = 0.0040) and a trend for association with PFS (5.6 versus 4.1 months, HR = 0.7395, p = 0.0801) was noted. Membranous FRA expression was seen in 83% of patients, moreover, high membranous expression (H-score ≥20) was associated with improved PFS (5.6 versus 3.7 months, HR = 0.6445, p = 0.0306) and OS (22.1 versus 11.5 months, HR = 0.5378, p = 0.0131). CONCLUSIONS: A large number of NSCLC patients have high expression of FRA and/or a low level of TS expression. Expression levels of FRA and TS were associated with clinical benefit from pemetrexed therapy.

Inhibition of constitutive aryl hydrocarbon receptor (AhR) signaling attenuates androgen independent signaling and growth in (C4-2) prostate cancer cells.

The aryl hydrocarbon receptor is a member of the basic-helix-loop-helix family of transcription factors. AhR mediates the biochemical and toxic effects of a number of polyaromatic hydrocarbons such as 2,3,7,8,-tetrachloro-dibenzo-p-dioxin (TCDD). AhR is widely known for regulating the transcription of drug metabolizing enzymes involved in the xenobiotic metabolism of carcinogens and therapeutic agents, such as cytochrome P450-1B1 (CYP1B1). Additionally, AhR has also been reported to interact with multiple signaling pathways during prostate development. Here we investigate the effect of sustained AhR signaling on androgen receptor function in prostate cancer cells. Immunoblot analysis shows that AhR expression is increased in androgen independent (C4-2) prostate cancer cells when compared to androgen sensitive (LNCaP) cells. RT-PCR studies revealed constitutive AhR signaling in C4-2 cells without the ligand induced activation required in LNCaP cells. A reduction of AhR activity by short RNA mediated silencing in C4-2 cells reduced expression of both AhR and androgen responsive genes. The decrease in androgen responsive genes correlates to a decrease in phosphorylated androgen receptor and androgen receptor expression in the nucleus. Furthermore, the forced decrease in AhR expression resulted in a 50% decline in the growth rate of C4-2 cells. These data indicates that AhR is required to maintain hormone independent signaling and growth by the androgen receptor in C4-2 cells. Collectively, these data provide evidence of a direct role for AhR in androgen independent signaling and provides insight into the molecular mechanisms responsible for sustained androgen receptor signaling in hormone refractory prostate cancer.

Folylpoly-glutamate synthetase expression is associated with tumor response and outcome from pemetrexed-based chemotherapy in malignant pleural mesothelioma.

BACKGROUND: Pemetrexed-based chemotherapy represents the standard of care in first-line treatment of advanced malignant pleural mesothelioma (MPM). However, there are no established predictors of clinical benefit. Pemetrexed inhibits multiple enzymes involved in pyrimidine and purine synthesis, but the main target is thymidylate synthase (TS). After cellular uptake pemetrexed is converted into more effective polyglutamated forms by folylpoly-γ-glutamate synthetase (FPGS). We hypothesized that FPGS and TS protein expressions are associated with clinical outcome after pemetrexed-based chemotherapy. METHODS: Pretreatment tumor samples from 84 patients with histologically confirmed MPM, who received pemetrexed combined with platinum (79 of 84) or single-agent pemetrexed (5 of 84) as first-line treatment, were retrospectively analyzed. FPGS and TS protein expressions were semiquantitatively assessed by using the Hybrid (H)-scoring system (range, 0-300). H-scores were correlated with radiological response according to modified Response Evaluation Criteria in Solid Tumors, progression-free survival (PFS) and overall survival (OS). RESULTS: Median H-score of the entire cohort was 230 for FPGS (range, 100-300), and 210 for TS (range, 100-300). High FPGS protein expression was significantly associated with longer PFS (pCOX = 0.0337), better objective tumor response (partial response versus stable disease + progressive disease; pKW = 0.003), and improved disease-control rate (partial response + stable disease versus progressive disease; pKW = 0.0208), but not with OS. In addition, high TS protein expression was associated with progressive disease under pemetrexed-based therapy (p = 0.0383), and shorter OS (pCOX = 0.0071), but no association with PFS was observed. CONCLUSION: FPGS and TS expressions were associated with clinical response and outcome to pemetrexed-based first-line chemotherapy in MPM. Prospective evaluation of FPGS and TS expressions and their prognostic/predictive power in MPM patients is warranted.

A Pilot Study Evaluating the Usability and Usefulness of a Multi-language Online Patient Education Tool for Patients Undergoing Radiation Treatment: Findings from a Student Project.

PURPOSE: Treatment-related information is the most important informational need of cancer patients and online media sources are gaining popularity as a cancer communication method. Our aim was to determine if new multilanguage patient online education modules in radiation therapy are usable and beneficial for the multicultural cancer patient population who may face language barriers. METHODS: Eight new patients from the radiation oncology clinic at the Odette Cancer Centre (OCC) were recruited to participate in the study over a 3-month period. Testing involved a combination of interviewing, observation, think-aloud methodology, and short survey. Results were analyzed using thematic analysis of responses to the interviews and open-ended survey questions, in addition to Likert scale ratings. RESULTS: Patients were satisfied with the survey (mean = 96/100) and indicated a high usability score citing the general ease of navigation and clear presentation of information. The usefulness mean score was relatively lower; participants wanted more specific information related to their treatment site and anticipated side effects. There was no consensus on the accessibility of the module. Although all participants appreciated the multilanguage capabilities of the modules, they indicated that the number of languages represented in the modules should be increased. CONCLUSION: Multilanguage online modules were a good communication tool for patients; however, improvements on the content and language availability were indicated by the study participants.

EGFR protein expression in non-small cell lung cancer predicts response to an EGFR tyrosine kinase inhibitor--a novel antibody for immunohistochemistry or AQUA technology.

INTRODUCTION: Epidermal growth factor receptor (EGFR) protein expression in non-small cell lung cancer (NSCLC) is not recommended for predicting response to EGFR tyrosine kinase inhibitors (TKI) due to conflicting results, all using antibodies detecting EGFR external domain (ED). We tested the predictive value of EGFR protein expression for response to an EGFR TKI with an antibody that detects the intracellular domain (ID) and compared fluorescence-based Automated QUantitative Analysis (AQUA) technology to immunohistochemistry (IHC). METHODS: Specimens from 98 gefitinib-treated NSCLC Japanese patients were evaluated by IHC (n = 98 of 98) and AQUA technology (n = 70 of 98). EGFR ID (5B7)- and ED-specific antibodies (3C6 and 31G7) were compared. RESULTS: EGFR expression evaluated with 5B7 was significantly higher in responders versus nonresponders to gefitinib both with IHC and with AQUA. ED-specific antibodies did not significantly predict response. Using AQUA and ID-specific antibody resulted in the best prediction performance with a positive and negative predictive value (PPV/NPV) for responders of 50% and 87%, respectively. EGFR expression with ID-specific antibody and AQUA also predicted responders in EGFR-mutated patients. Increased EGFR expression with the ID antibody is associated with increased median progression free survival (PFS; 11.7 months vs. 5.0, log rank, P = 0.034) and overall survival (OS; 38.6 vs. 14.9, P = 0.040) from gefitinib therapy. CONCLUSIONS: EGFR protein expression using an ID-specific antibody specifically predicts response to gefitinib in NSCLC patients, including in EGFR-mutated patients, and increased PFS/OS from gefitinib. These data suggest that the choice of diagnostic antibody and methodology matters to predict response and outcome to specific therapies. The potential clinical application needs further validation. Clin Cancer Res; 17(24); 7796-807. ©2011 AACR.

Alveolar macrophage suppression in sepsis is associated with high mobility group box 1 transmigration.

Macrophage dysfunction occurs late in sepsis and is implicated in increased mortality. Interferon gamma (IFN-gamma) stimulates transmigration of high mobility group box 1 (HMGB-1) from the nucleus into cytoplasm of macrophages and subsequent release. Because HMGB-1 release also occurs late, and because one of the actions of HMGB-1 in the nucleus is to enhance transcription factors, we investigated if HMGB-1 transmigration is involved in macrophage suppression in sepsis. Alveolar macrophages were isolated 12 and 24 h from sham controls, cecal ligation and puncture (CLP), and CLP rats given IFN-gamma antibody (1.2 mg/kg, i.v.). All injections were given immediately after surgery. At 12 h, 60% of cells from sham controls had HMGB-1 located primarily in the nucleus, whereas 35% of cells had diffuse staining in both cytoplasm and nucleus. In CLP rats, HMGB-1 was located predominantly in the cytoplasm of 37% of cells, and 48% had diffuse staining, whereas in IFN-gamma antibody (Ab)-treated rats, HMGB-1 was located predominantly in the nucleus of 56% of cells, whereas 32% had diffuse staining. At 24 h, most cells from CLP rats (82%) had HMGB-1 located in the cytoplasm, whereas in contrast, HMGB-1 was located in the nucleus of 80% and 82% of cells from sham control and IFN-gamma Ab-treated rats, respectively. Gene expression of TNF-alpha was not significantly changed 12 h after surgery, but at 24 h, alveolar macrophages from CLP rats had reduced gene expression of TNF-alpha. Interferon gamma Ab treatment prevented the reduction in TNF-alpha gene expression. TNF-alpha release was not altered at 12 h. At 24 h, LPS-stimulated release of TNF-alpha was decreased in macrophages from CLP rats compared with sham controls. Interferon gamma Ab treatment prevented the decrease in LPS-stimulated TNF-alpha release. The results suggest that alveolar macrophage suppression after CLP is associated with HMGB-1 transmigration out of the cell nucleus and provides evidence that intranuclear HMGB-1 may play an integral role in macrophage activation in sepsis.

Coping with prostate cancer: a meta-analytic review.

The present meta-analytic review assessed the relations between coping categories and indices of adjustment in men with prostate cancer. Relevant methodological and statistical information was extracted from 33 target studies (n = 3,133 men with prostate cancer). Men with prostate cancer who used approach, problem-focused, and emotion-focused coping were healthier both psychologically and physically, although the effect sizes for problem-focused coping and emotion-focused coping were more modest. For approach coping these effect sizes were particularly strong for measures of self-esteem, positive affect, depression, and anxiety. Conversely, men with prostate cancer who used avoidance coping experienced heightened negative psychological adjustment and physical health, and particularly for measures of positive mood and physical functioning. The findings of this study suggest that active approaches to coping with prostate cancer are beneficial psychologically, physically, and are positively associated with a return to pre-cancer activities.

The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate.

Quantal release of the principal excitatory neurotransmitter glutamate requires a mechanism for its transport into secretory vesicles. Within the brain, the complementary expression of vesicular glutamate transporters (VGLUTs) 1 and 2 accounts for the release of glutamate by all known excitatory neurons. We now report the identification of VGLUT3 and its expression by many cells generally considered to release a classical transmitter with properties very different from glutamate. Remarkably, subpopulations of inhibitory neurons as well as cholinergic interneurons, monoamine neurons, and glia express VGLUT3. The dendritic expression of VGLUT3 by particular neurons also indicates the potential for retrograde synaptic signaling. The distribution and subcellular location of VGLUT3 thus suggest novel modes of signaling by glutamate.