Protocol for a feasibility trial (EXPRESS-C-GVHD) for an expressive helping intervention within a support group for cutaneous graft-versus-host-disease.

BACKGROUND: Cutaneous graft-versus-host disease (cuGVHD) is a complication of allogeneic hematopoietic stem cell transplantation that presents with varying severity and can significantly affect one's quality of life (QOL). No trials have yet tested nonpharmacologic interventions to improve the QOL of patients with cuGVHD. The primary objective of the Expressive Helping in Support Groups for Cutaneous GVHD (EXPRESS-C-GVHD) Trial is to evaluate the effect of a support group that employs expressive writing on cutaneous and systemic GVHD symptoms, general distress, and QOL immediately after the intervention. Secondary objectives include evaluating the impact of the intervention on QOL at 1 month post intervention, as well as willingness to participate, compliance, feasibility, and satisfaction. METHODS: The EXPRESS-C-GVHD Trial will include patients with chronic cuGVHD who are at least 18 years old and able to use a writing utensil, have access to Zoom, an online video conference platform, and attend all four live support group sessions. Subjects will be recruited from the Department of Dermatology, Northwestern University, Chicago, IL and will participate in a 4 week program via Zoom. Program activities will be 1 h long and consist of 40 min of participant-led verbal reflection and discussion in a group setting in response to prompts, and 20 min of expressive writing. Participants will fill out a baseline willingness survey, follow-up surveys after every session, and post-intervention surveys at 2 weeks and 1 month after intervention. DISCUSSION: The EXPRESS-C-GVHD Trial is a pilot trial and will assess whether a Zoom-based expressive writing intervention within the framework of a support group is feasible and can improve QOL outcomes among individuals with cuGVHD. TRIAL REGISTRATION: The trial is registered under number NCT05694832.

Concomitance of Hidradenitis Suppurativa and Porokeratoses.

Objective: No known studies have attempted to describe the pathophysiological relationship between patients who develop both porokeratosis and hidradenitis suppurativa (HS). The purpose of this report is to present possible immunological mechanisms that predispose patients to developing both porokeratosis and HS. Methods: In this case series, patients were identified during routine clinical encounters and data was extracted from the electronic medical record from October 2010 until April 2021. This study is a single center case series including patients from the department of dermatology at the UNC School of Medicine in Chapel Hill, North Carolina. Patients were selected via digital chart review if they had simultaneous diagnoses of disseminated porokeratosis and HS. Two eligible patients were identified as actively receiving care. One patient is a Black female and the other a White male. No primary study outcomes were planned. This investigation utilized chart review to identify disease time course, which was subsequently used to elucidate study outcomes. Results: Patient A is a 54-year-old Black female and Patient B is a 65-year-old White male. Both patients developed porokeratosis after multiple years of living with HS. Immunosuppression with adalimumab, corticosteroids, or other medications did not clearly precede porokeratosis development in either patient. Limitations: Limitations include that this study was conducted at a single center and prevalence of patients with concomitance of both conditions is low. Conclusion: In patients who demonstrate simultaneous HS and porokeratosis, activation of the innate immune system and associated IL-1 production may lead to autoinflammation and a phenotype of hyperkeratinization. Mutations in genes such as mevalonate kinase may predispose subjects to the development of porokeratoses and HS.

Readability of Online Patient Education Materials for Graft-Versus-Host Disease.

Graft-versus-host disease (GVHD) is a complex systemic diagnosis which is associated with significant symptom distress in patients. Patient education has shown to mitigate uncertainty and distress, but to our knowledge, no studies have evaluated patient education materials on GVHD. We characterized the readability and understandability of patient education materials on GVHD available online. We conducted a Google search of the top 100 non-sponsored search results, selecting for full-text patient education that is not peer-reviewed or a news article. We evaluated the text of the eligible search results against the Flesch-Kincaid Reading Ease, Flesch Kincaid Grade Level, Gunning Fog, Automated Readability, Linsear Write Formula, Coleman-Liau Index, Smog Index, and Patient Education Materials Assessment Tool (PEMAT) for understandability. Among 52 included Web results, 17 (32.7%) were provider-authored and 15 (28.8%) were hosted on university Web sites. The total average scores on validated readability tools were Flesch-Kincaid Reading Ease (46.4), Flesch Kincaid Grade Level (11.6), Gunning Fog (13.6), Automated Readability (12.3), Linsear Write Formula (12.6), Coleman-Liau Index (12.3), Smog Index (10.0), and PEMAT Understandability (65.5). Provider-authored links scored poorer than non-provider-authored links on all metrics, with significant differences for the Gunning Fog index (p < 0.05). University-hosted links scored better than non-university-hosted links on all metrics. Evaluation of online patient education materials for GVHD demonstrates the need for more readable and understandable resources to mitigate the distress and uncertainty that patients may feel upon being diagnosed with GVHD.

Characterization of online support group resources for patients with dermatologic conditions.

Dermatologic conditions can have significant quality of life effects on patients. The internet is a first-line accessible resource for patients to seek support and community in managing dermatologic diagnoses. The accessibility and content of online support resources for patients with dermatologic conditions is unclear so we sought to characterize these resources. We conducted online searches utilizing incognito Google, Yahoo, and Bing search engines and identified a total of 36 support group resources. 9 links were for single dermatology support groups and 27 links were for databases of support groups for different dermatologic conditions. We tallied number totals and percentages of online support resources and found wide variability of material in terms of the readability of the group websites, as well as content, medium, and hosts of the groups. Furthermore, we observed an imbalance in representation of resources for certain dermatologic conditions as opposed to others, further highlighting the strong need for the creation of easy-to-access support groups for patients across the spectrum of dermatological disease.

Content analysis and dermatologic gaps in online patient education materials for graft-versus-host disease.

Graft-versus-host disease (GVHD) is a complex systemic disease which is associated with significant physical and psychological distress in patients. Given the complexity of this disorder and its multifactorial effects, it is important for patients to have access to education and learning about their disease. Patient education has been shown to reduce the uncertainty and stress that follows complex diseases such as GVHD. To our knowledge no studies have evaluated the content of patient education materials on GVHD, especially from a dermatologic perspective. Despite the complexity of GVHD, cutaneous manifestations are common and often require management by dermatology. In this cross-sectional study, a Google search engine was utilized to assess websites for information on GVHD etiology, pathophysiology, symptoms, treatment, coverage of Acute GVHD, Chronic GVHD, cutaneous presentations, dermatologic management, and quality of life. It was evident that there was inconsistent inclusion of cutaneous manifestations of acute and chronic GVHD and dermatologic management of GVHD. Results of this study emphasize the need for more robust integration of skin-specific information guided by expert dermatologist opinion in publicly available patient education materials online.

Mesothelin Enhances Tumor Vascularity in Newly Forming Pancreatic Peritoneal Metastases.

Over 90% of pancreatic ductal adenocarcinomas (PDAC) express mesothelin (MSLN). Overexpression or knockdown of MSLN has been implicated in PDAC aggressiveness. This activity has been ascribed to MSLN-induced activation of MAPK or NF-κB signaling pathways and to interaction of MSLN with its only known binding partner, MUC16. Here, we used CRISPR/Cas9 gene editing to delete MSLN from PDAC, then restored expression of wild-type (WT) or Y318A mutant MSLN by viral transduction. We found that MSLN KO cells grew in culture and as subcutaneous tumors in mouse xenografts at the same rate as WT cells but formed intraperitoneal metastases poorly. Complementation with WT MSLN restored intraperitoneal growth, whereas complementation with Y318A mutant MSLN, which does not bind MUC16, was ineffective at enhancing growth in both MUC16(+) and MUC16(-) models. Restoration of WT MSLN did enhance growth but did not affect cell-to-cell binding, cell viability in suspension or signaling pathways previously identified as contributing to the protumorigenic effect of MSLN. RNA deep sequencing of tumor cells identified no changes in transcriptional profile that could explain the observed phenotype. Furthermore, no histologic changes in tumor cell proliferation or morphology were observed in mature tumors. Examination of nascent MSLN KO tumors revealed decreased microvascular density as intraperitoneal tumors were forming, followed by decreased proliferation, which resolved by 2 weeks postimplantation. These data support a model whereby MSLN expression by tumor cells contributes to metastatic colonization. IMPLICATIONS: MSLN confers a growth advantage to tumor cells during colonization of peritoneal metastasis. Therapeutic blockade of MSLN might limit peritoneal spread.

Protein Synthesis Inhibition Activity of Mesothelin Targeting Immunotoxin LMB-100 Decreases Concentrations of Oncogenic Signaling Molecules and Secreted Growth Factors.

LMB-100 is a mesothelin-targeted recombinant immunotoxin (iTox) that carries a modified Pseuodomonas exotoxin A (PE) payload. PE kills cells by inhibiting synthesis of new proteins. We found that treatment of pancreatic cancer cells with LMB-100 for 24⁻48 h did not change total protein level despite inducing protein synthesis inhibition (PSI). Further, increased levels of ubiquitinated proteins were detected, indicating that cells may have limited ability to compensate for PSI by reducing protein degradation. Together, these data suggest that PE depletes concentrations of a minority of cellular proteins. We used reverse phase protein array and Luminex assay to characterize this subset. LMB-100 decreased the abundance of 24 of 32 cancer-related proteins (including Bcl-x, Her2, Her3 and MUC16) without compensatory increases in other analytes. Further, cancer cells failed to maintain extracellular concentrations of cancer cell secreted growth factors (CCSGFs), including Vascular Endothelial Growth Factor (VEGF) following treatment with cytostatic LMB-100 doses both in culture and in mouse tumors. Decreased VEGF concentration did not change tumor vasculature density, however, LMB-100 caused tissue-specific changes in concentrations of secreted factors made by non-cancer cells. In summary, our data indicate that PSI caused by cytostatic LMB-100 doses preferentially depletes short-lived proteins such as oncogenic signaling molecules and CCSGFs.