Gene Expression Signatures in Inflammatory and Sclerotic Morphea Skin and Sera Distinguish Morphea from Systemic Sclerosis.

Morphea is an inflammatory fibrotic disorder of the skin that has been likened to systemic sclerosis (SSc). We sought to examine the molecular landscape of morphea by examining lesional skin gene expression and blood biomarkers and comparing the gene expression profiles with those from site-matched nonlesional and SSc lesional skin. We found the morphea transcriptome is dominated by IFN-γ-mediated T helper 1 immune dysregulation, with a relative paucity of fibrosis pathways. Specifically, expression profiles of morphea skin clustered with the SSc inflammatory subset and were distinct from the those of SSc fibroproliferative subset. Unaffected morphea skin also differed from unaffected SSc skin because it did not exhibit pathological gene expression signatures. Examination of downstream IFN-γ-mediated chemokines, CXCL9 and CXCL10, revealed increased transcription in the skin but not in circulation. In contrast to transcriptional activity, CXCL9 was elevated in serum and was associated with active, widespread cutaneous involvement. Taken together, these results indicate that morphea is a skin-directed process characterized by T helper 1 immune-mediated dysregulation, which contrasts with fibrotic signatures and systemic transcriptional changes associated with SSc. The similarity between morphea and the inflammatory subset of SSc on transcriptional profiling indicates that therapies under development for this subset of SSc are also promising for treatment of morphea.

Recovery homes coping with COVID-19.

Recovery homes are a widespread community resource that might be utilized by some individuals with substance use disorders (SUD) and COVID-19. A growing collection of empirical literature suggests that housing can act as a low-cost recovery support system which could be effective in helping those with SUD sustain their recovery. Such settings could be already housing many residents affected by COVID-19. Many of these residents are at high risk for COVID-19 given their histories of SUD, homelessness, criminal justice involvement, and psychiatric comorbidity. Stable housing after treatment may decrease the risk of relapse to active addiction, and these types of settings may have important implications for those with housing insecurity who are at risk for being infected with COVID-19. Given the extensive network of community-based recovery homes, there is a need to better understand individual- and organizational-level responses to the COVID-19 pandemic among people in recovery homes as well as those managing and making referrals to the houses. At the present time, it is unclear what the effects of COVID-19 are on recovery home membership retention or dropout rates. This article attempts to provide a better understanding of the possible impact of COVID-19 on the infected and on recovery resources in general.

Medication assisted therapy and recovery homes.

There is a need to better understand improved recovery supportive services for those on Medication Assisted Treatment (MAT) for opioid use disorder (OUD) and, at the same time, enhance the available treatment interventions and positive long-term outcomes for this vulnerable population. A growing empirical literature supports the assertion that improved access to housing and recovery support is a low-cost, high-potential opportunity that could help former substance users who are utilizing MAT to sustain their recovery. Recovery home support could serve the populations that need them most, namely servicing a significant number of the enrolled in MAT programs. The two largest networks of recovery homes are staff run Traditional Recovery Homes (TRH) and self-run Oxford House Recovery Homes (OH). There is a need to better understand how substance users on MAT respond to recovery homes, as well as how those in recovery homes feel toward those on MAT and how any barriers to those utilizing MAT may be reduced. Recovery may be an outcome of the transactional process between the recovering individual and his/her social environment. In particular, how recovery houses can help people on MAT attain long-term recovery.

The Emergence, Role, and Impact of Recovery Support Services.

Various community recovery support services help sustain positive behavior change for individuals with alcohol and drug use disorders. This article reviews the rationale, origins, emergence, prevalence, and empirical research on a variety of recovery support services in U.S. communities that may influence the likelihood of sustained recovery. The community recovery support services reviewed include recovery high schools, collegiate recovery programs, recovery homes, recovery coaches, and recovery community centers. Many individuals are not provided with the types of environmental supports needed to solidify and support their recovery, so there is a need for more research on who may be best suited for these services as well as when, why, and how they confer benefit.

Changes in Disease Activity and Damage Over Time in Patients With Morphea.

Importance: Prospective studies of the disease course in patients with morphea are lacking, particularly those comparing adults and children. Objective: To investigate the disease course in patients with morphea treated with standard-of-care therapy using validated clinical outcome measures. Design, Setting, and Participants: Prospective cohort study of 130 adults and children from the Morphea in Adults and Children cohort with at least 2 years of clinical follow-up and Localized Scleroderma Cutaneous Assessment Tool scores recorded at each study visit. Study patients were seen at a tertiary referral center (UT Southwestern Medical Center, Dallas, Texas) from November 1, 2008, through April 1, 2016. The dates of analysis were May 2016 through July 2019. Exposures: All patients received standard-of-care therapy. Main Outcomes and Measures: Patterns in disease activity and recurrence were examined. The time to recurrence of morphea disease activity from the first visit with inactive disease was assessed using survival analysis with the log-rank test to compare differences between morphea subtypes. Results: In total, 130 adults and children (663 study visits) were included in this study. The mean (SD) age of patients was 34.4 (23.8) years, and 101 of 130 (78%) were female. The mean (SD) follow-up was 4.3 (1.7) years. Fifty patients had at least 5 years of follow-up. Most patients were white individuals (96 of 130 [74%]) and had linear subtype (72 of 130 [55%]) or generalized subtype (40 of 130 [31%]). Overall, 13 of 30 (43%) with generalized subtype had recurrence of disease activity compared with 14 of 66 (21%) with linear subtype (hazard ratio, 3.28; 95% CI, 1.38-7.79). The median (interquartile range) time to first recurrence of disease activity after initial resolution of disease activity was 1.1 (0.8-1.9) years for generalized subtype and 2.3 (1.0-3.3) years for linear subtype. Of the 50 patients followed up for at least 5 years, 18 (36%) had recurrence of disease activity. Conclusions and Relevance: Disease activity appeared to improve in most patients with morphea over 6 to 12 months using previously published treatment plans, underscoring their effectiveness. Sclerosis improved more slowly (over 2-5 years), often after discontinuation of treatment, but atrophy increased slightly as sclerosis subsided. Standard-of-care therapy appears to improve disease activity, which allows sclerosis to improve, and provides relative stability of other features of disease damage. A substantial number of patients, particularly those with generalized subtype, have a relapsing-remitting course over many years. Patients with morphea should be monitored for recurrent disease activity over extended periods.

Linear morphea: Clinical characteristics, disease course, and treatment of the Morphea in Adults and Children cohort.

BACKGROUND: Prospective, longitudinal studies examining the features of linear morphea are limited. OBJECTIVE: To utilize the Morphea in Adults and Children cohort to determine clinical characteristics, impact on life quality, and disease course of linear morphea in a prospective, longitudinal manner. METHODS: Characteristics of linear morphea versus other subtypes were compared in a cross-sectional manner. Next, linear morphea participants were examined in depth over a 3-year period. RESULTS: Linear morphea was the most common morphea subtype (50.1%, 291/581) in the cohort. Deep involvement was more common in linear (64.3%, 187/291) than other morphea subtypes. Linear morphea participants with deep involvement were more likely to have a limitation in range of motion (28.6%, 55/192) than those without (11.1%, 11/99, P < .001). Adult-onset disease occurred in 32.6% (95/291) of those with linear morphea. Frequency of deep involvement was similar between pediatric (66.8%, 131/196) and adult-onset linear morphea (58.9%, 56/95, P = .19). Quality of life and disease activity scores improved over time, while damage stabilized with treatment. LIMITATIONS: Results of the study are associative, and the University of Texas Southwestern Medical Center is a tertiary referral center. CONCLUSION: A substantial number of linear morphea patients have adult-onset disease. In all age groups, linear morphea with deep involvement was associated with functional limitations.

Not Just Skin Deep: Systemic Disease Involvement in Patients With Cutaneous Lupus.

Cutaneous lupus erythematosus, specifically discoid lupus erythematosus, disproportionately affects those with skin of color and may result in greater dyspigmentation and scarring in darker skin types. In this article, we review investigations relevant to cutaneous lupus patients with skin of color at University of Texas Southwestern Medical Center, associations and risk of progression to systemic lupus, and recommendations for monitoring for systemic disease spread. Between 5% and 25% of patients with cutaneous lupus can develop systemic lupus. If they progress to systemic disease, patients often develop mild systemic disease with primarily mucocutaneous and musculoskeletal manifestations. Patients with cutaneous lupus should be followed up closely to monitor for systemic disease involvement. The University of Texas Southwestern Cutaneous Lupus Erythematosus Registry, of which almost two thirds of participants are those with skin of color, is a part of an ongoing effort to better understand the pathophysiologic mechanisms of CLE and to identify prognostic indicators of risk of progression to systemic lupus.

Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea.

IFN-related pathways have not been studied in morphea, and biomarkers are needed. We sought to characterize morphea serum cytokine imbalance and IFN-related gene expression in blood and skin to address this gap by performing a case-control study of 87 participants with morphea and 26 healthy control subjects. We used multiplexed immunoassays to determine serum cytokine concentrations, performed transcriptional profiling of whole blood and lesional morphea skin, and used double-staining immunohistochemistry to determine the cutaneous cellular source of CXCL9. We found that CXCL9 was present at increased concentrations in morphea serum (P < 0.0001), as were other T helper type 1 cytokines. CXCL9 serum concentration correlated with the modified Localized Scleroderma Skin Severity Index (r = 0.44, P = 0.0001), a validated measure of disease activity. CXCL9 gene expression was also increased in inflammatory lesional morphea skin (fold change = 30.6, P = 0.006), and preliminary transcriptional profiling showed little evidence for IFN signature in whole blood. Double-staining immunohistochemistry showed CXCL9 co-localized with CD68+ dermal macrophages. In summary, inflammatory morphea is characterized by T helper type 1 cytokine imbalance in serum, particularly CXCL9, which is associated with disease activity. CXCL9 expression in lesional macrophages implicates the skin as the source of circulating cytokines. CXCL9 is a promising biomarker of disease activity in morphea.

Quantitative assessment of synovitis in Legg-Calvé-Perthes disease using gadolinium-enhanced MRI.

A quantitative method to assess hip synovitis in Legg-Calvé-Perthes disease (LCPD) is not currently available. To develop this method, the areas of synovial enhancement on gadolinium-enhanced MRI (Gd-MRI) were measured by two independent observers. The volume of synovial enhancement was significantly increased in the initial and the fragmentation stages of LCPD (Waldenström stages I and II), with a persistence of synovitis into the reossification stage (stage III). The Gd-MRI method had high interobserver and intraobserver agreements and may serve as a useful method to monitor the effect of various treatments on hip synovitis in LCPD.

Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.

Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome.

The use of next-of-kin to estimate pain in cancer patients.

The clinical management of pain could be improved if more were known about the intensity and duration of the pain. The cancer patient, however, is often unable to communicate this information to caregivers. Relying on next-of-kin to provide information about the patient's pain could help, but little has been done to verify next-of-kin responses with respect to subjective experiences. For the present study 42 pairs of cancer patients and their next-of-kin were independently surveyed in 1982 in Washington state regarding their cancer pain and various aspects of medical treatment to determine whether proxies can give reliable responses. Close agreement between subject and next-of-kin was observed for the items which were salient and had a limited choice of responses, such as the presence of pain. Agreement in the aggregate was achieved for the items having several possible responses, such as the intensity and frequency of pain. Correspondence was virtually random for those items which had a variety of listed responses. The use of proxies in obtaining information, future research directions, and difficulties with measuring agreement are discussed.