The electronic self report assessment and intervention for cancer: promoting patient verbal reporting of symptom and quality of life issues in a randomized controlled trial

Background: The electronic self report assessment - cancer (ESRA-C), has been shown to reduce symptom distress during cancer therapy The purpose of this analysis was to evaluate aspects of how the ESRA-C intervention may have resulted in lower symptom distress (SD). Methods: Patients at two cancer centers were randomized to ESRA-C assessment only (control) or the Web-based ESRA-C intervention delivered to patients’ homes or to a tablet in clinic. The intervention allowed patients to self-monitor symptom and quality of life (SxQOL) between visits, receive self-care education and coaching to report SxQOL to clinicians. Summaries of assessments were delivered to clinicians in both groups. Audio-recordings of clinic visits made 6 weeks after treatment initiation were coded for discussions of 26 SxQOL issues, focusing on patients’/caregivers’ coached verbal reports of SxQOL severity, pattern, alleviating/aggravating factors and requests for help. Among issues identified as problematic, two measures were defined for each patient: the percent SxQOL reported that included a coached statement, and an index of verbalized coached statements per SxQOL. The Wilcoxon rank test was used to compare measures between groups. Clinician responses to problematic SxQOL were compared. A mediation analysis was conducted, exploring the effect of verbal reports on SD outcomes. Results: 517 (256 intervention) clinic visits were audio-recorded. General discussion of problematic SxQOL was similar in both groups. Control group patients reported a median 75% of problematic SxQOL using any specific coached statement compared to a median 85% in the intervention group (p = .0009). The median report index of coached statements was 0.25 for the control group and 0.31 for the intervention group (p = 0.008). Fatigue, pain and physical function issues were reported significantly more often in the intervention group (all p < .05). Clinicians' verbalized responses did not differ between groups. Patients' verbal reports did not mediate final SD outcomes (p = .41). Conclusions: Adding electronically-delivered, self-care instructions and communication coaching to ESRA-C promoted specific patient descriptions of problematic SxQOL issues compared with ESRA-C assessment alone. However, clinician verbal responses were no different and subsequent symptom distress group differences were not mediated by the patients' reports. Trial registration NCT00852852; 26 Feb 200

QuPath Digital Immunohistochemical Analysis of Placental Tissue

Background: QuPath is an open‑source digital image analyzer notable for its user‑friendly design, cross‑platform compatibility, and customizable functionality. Since it was first released in 2016, at least 624 publications have reported its use, and it has been applied in a wide spectrum of settings. However, there are currently limited reports of its use in placental tissue. Here, we present the use of QuPath to quantify staining of G‑protein coupled receptor 18 (GPR18), the receptor for the pro‑resolving lipid mediator Resolvin D2, in placental tissue. Methods: Whole slide images of vascular smooth muscle (VSM) and extravillous trophoblast (EVT) cells stained for GPR18 were annotated for areas of interest. Visual scoring was performed on these images by trained and in‑training pathologists, while QuPath scoring was performed with the methodology described herein. Results: Bland–Altman analyses showed that, for the VSM category, the two methods were comparable across all staining levels. For EVT cells, the high‑intensity staining level was comparable across methods, but the medium and low staining levels were not comparable. Conclusions: Digital image analysis programs offer great potential to revolutionize pathology practice and research by increasing accuracy and decreasing the time and cost of analysis. Careful study is needed to optimize this methodology further

QuPath Digital Immunohistochemical Analysis of Placental Tissue

Background: QuPath is an open-source digital image analyzer notable for its user-friendly design, cross-platform compatibility, and customizable functionality. Since it was first released in 2016, at least 624 publications have reported its use, and it has been applied in a wide spectrum of settings. However, there are currently limited reports of its use in placental tissue. Here, we present the use of QuPath to quantify staining of G-protein coupled receptor 18 (GPR18), the receptor for the pro-resolving lipid mediator Resolvin D2, in placental tissue. Methods: Whole slide images of vascular smooth muscle (VSM) and extravillous trophoblast (EVT) cells stained for GPR18 were annotated for areas of interest. Visual scoring was performed on these images by trained and in-training pathologists, while QuPath scoring was performed with the methodology described herein. Results: Bland-Altman analyses showed that, for the VSM category, the two methods were comparable across all staining levels. For EVT cells, the high-intensity staining level was comparable across methods, but the medium and low staining levels were not comparable. Conclusions: Digital image analysis programs offer great potential to revolutionize pathology practice and research by increasing accuracy and decreasing the time and cost of analysis. Careful study is needed to optimize this methodology further

ICOS-Expressing Lymphocytes Promote Resolution of CD8-Mediated Lung Injury in a Mouse Model of Lung Rejection

Acute rejection, a common complication of lung transplantation, may promote obliterative bronchiolitis leading to graft failure in lung transplant recipients. During acute rejection episodes, CD8+ T cells can contribute to lung epithelial injury but the mechanisms promoting and controlling CD8-mediated injury in the lung are not well understood. To study the mechanisms regulating CD8+ T cell–mediated lung rejection, we used a transgenic model in which adoptively transferred ovalbumin (OVA)-specific cytotoxic T lymphocytes (CTL) induce lung injury in mice expressing an ovalbumin transgene in the small airway epithelium of the lungs (CC10-OVA mice). The lung pathology is similar to findings in humans with acute lung transplant. In the presence of an intact immune response the inflammation resolves by day 30. Using CC10-OVA.RAG-/- mice, we found that CD4+ T cells and ICOS+/+ T cells were required for protection against lethal lung injury, while neutrophil depletion was not protective. In addition, CD4+Foxp3 + ICOS+ T cells were enriched in the lungs of animals surviving lung injury and ICOS+/+ Tregs promoted survival in animals that received ICOS-/- T cells. Direct comparison of ICOS-/- Tregs to ICOS+/+ Tregs found defects in vitro but no differences in the ability of ICOS-/- Tregs to protect from lethal lung injury. These data suggest that ICOS affects Treg development but is not necessarily required for Treg effector function

25th Annual Midwest/Midsouth Estate Planning Institute

Materials from UK/CLE\u27s 25th Annual Midwest/Midsouth Estate Planning Institute held in July 1998

VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice

Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel series of steroidal analogues (VBP compounds) that have been previously shown to maintain anti-inflammatory properties such as NFκB-inhibition without inducing glucocorticoid receptor-mediated gene transcription. This study was undertaken to determine the effectiveness of the lead compound, VBP15, in a mouse model of allergic lung inflammation. We show that VBP15 is as effective as the traditional glucocorticoid, prednisolone, at reducing three major hallmarks of lung inflammation--NFκB activity, leukocyte degranulation, and pro-inflammatory cytokine release from human bronchial epithelial cells obtained from patients with asthma. Moreover, we found that VBP15 is capable of reducing inflammation of the lung in vivo to an extent similar to that of prednisone. We found that prednisolone--but not VBP15 shortens the tibia in mice upon a 5 week treatment regimen suggesting effective dissociation of side effects from efficacy. These findings suggest that VBP15 may represent a potent and safer alternative to traditional glucocorticoids in the treatment of asthma and other inflammatory diseases.Supported in part by grants from the NIH (1R41HL104939-01B; 1K26RR032082; 1P50AR060836-01; 1U54HD071601; 2R24HD050846-06, R01 HL033152- 25), DOD grants (W81XWH-11-1-0330; W81XWH-11-1-0782; W81XWH-10-1-0659; W81XWH-11-1-0809; W81XWH-09-1-0599) a translational research grant from MDA, pilot grant from Parent Project Muscular Dystrophy (PPMD), and a contribution from the Clark Family Foundation

Selenocysteine Insertion Sequence Binding Protein 2L Is Implicated as a Novel Post-Transcriptional Regulator of Selenoprotein Expression

The amino acid selenocysteine (Sec) is encoded by UGA codons. Recoding of UGA from stop to Sec requires a Sec insertion sequence (SECIS) element in the 3′ UTR of selenoprotein mRNAs. SECIS binding protein 2 (SBP2) binds the SECIS element and is essential for Sec incorporation into the nascent peptide. SBP2-like (SBP2L) is a paralogue of SBP2 in vertebrates and is the only SECIS binding protein in some invertebrates where it likely directs Sec incorporation. However, vertebrate SBP2L does not promote Sec incorporation in in vitro assays. Here we present a comparative analysis of SBP2 and SBP2L SECIS binding properties and demonstrate that its inability to promote Sec incorporation is not due to lower SECIS affinity but likely due to lack of a SECIS dependent domain association that is found in SBP2. Interestingly, however, we find that an invertebrate version of SBP2L is fully competent for Sec incorporation in vitro. Additionally, we present the first evidence that SBP2L interacts with selenoprotein mRNAs in mammalian cells, thereby implying a role in selenoprotein expression

Retinoblastoma seeds: Impact on American Joint Committee on Cancer clinical staging

Aim To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. Methods Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. Results Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). Conclusion This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.Fil: Tomar, Ankit Singh. New York Eye Cancer Center; Estados UnidosFil: Finger, Paul T.. New York Eye Cancer Center; Estados UnidosFil: Gallie, Brenda. University Of Toronto. Hospital For Sick Children; CanadáFil: Kivelä, Tero. University of Helsinki; Finlandia. Helsinki University Hospital; FinlandiaFil: Mallipatna, Ashwin. University Of Toronto. Hospital For Sick Children; Canadá. Narayana Nethralaya; IndiaFil: Zhang, Chengyue. Beijing Children's Hospital; ChinaFil: Zhao, Junyang. Beijing Children's Hospital; ChinaFil: Wilson, Matthew. University of Tennessee; Estados UnidosFil: Brennan, Rachel. St Jude Children's Research Hospital; Estados UnidosFil: Burges, Michala. University of Tennessee; Estados UnidosFil: Kim, Jonathan. Keck Medical School of the University of Southern California; Estados UnidosFil: Berry, Jesse L.. Children's Hospital Los Angeles; Estados UnidosFil: Jubran, Rima. Childrens Hospital Society of Los Angeles; Estados UnidosFil: Khetan, Vikas. Vitreo Retinal Services; IndiaFil: Ganeshan, Suganeswari. Vitreo Retinal Services; IndiaFil: Yarovoy, Andrey. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yarovaya, Vera. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Kotova, Elena. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Volodin, Denis. Fyodorov Eye Microsurgery Federal State Institution; RusiaFil: Yousef, Yacoub. King Hussein Cancer Center; JordaniaFil: Nummi, Kalle. University of Helsinki; Finlandia. Helsinki University Hospital; FinlandiaFil: Ushakova, Tatiana L.. N.N. Blokhin Russian Cancer Research Center; Rusia. Russian Academy of Postgraduate Medical Education; RusiaFil: Yugay, Olga V.. N.N. Blokhin Russian Cancer Research Center; RusiaFil: Polyakov, Vladimir G. N.N. Blokhin Russian Cancer Research Center; Rusia. Russian Academy of Sciences; RusiaFil: Ramirez Ortiz, Marco Antonio. Hospital Infantil de Mexico Federico Gomez; MéxicoFil: Esparza Aguiar, Elizabeth. Hospital Infantil de Mexico Federico Gomez; MéxicoFil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Yam, Jason C.. The Chinese University of Hong Kong Faculty of Medicine; Hong Kon