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Porous materials are highly explored platforms for fertilizer delivery. Among porous materials, metal-organic frameworks (MOFs) are an important class of coordination polymers in which metal ions and organic electron donors as linkers are assembled to form crystalline structures with stable nanoporosity. Selected amino acids were inherently found to have the capacity to hold the leaf cuticle. Hence, MOF synthesis was attempted in the presence of amino acids, which can act as surface terminators and can assist as hands to hold to the leaf for a controlled nutrient supply. By serendipity, the amino acids were found to act as modulators, resulting in well-stabilized porous MOF structures with iron metal nodes, which are often noted to be unstable. Thus, the composite, i.e., (MOF@aa) MOF modulated with amino acids, has efficient nutrient-feeding ability through the foliar route when compared to the control., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients with <5 years of disease duration enrolled at scleroderma centres in the USA. The objective of this study was to investigate the relationship between gastrointestinal tract symptoms and self-reported resource utilization in CONQUER participants., Methods: CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0-0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 months., Results: Among the 211 CONQUER participants who met the inclusion criteria, most (64%) had mild GIT symptoms, 26% had moderate symptoms, and 10% severe GIT symptoms at 12 months. The categorization of GIT total severity score by RUQ showed that more upper endoscopy procedures and inpatient hospitalization occurred in the CONQUER participants with severe GIT symptoms. These patients with severe GIT symptoms also reported the use of more adaptive equipment., Conclusion: This report from the CONQUER cohort suggests that severe GIT symptoms result in more resource utilization. It is especially important to understand resource utilization in early disease cohorts when disease activity, rather than damage, primarily contributes to health-related costs of SSc., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Systemic Sclerosis (SSc) is frequently associated with gastrointestinal tract (GIT) involvement. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative study collecting longitudinal follow up data on SSc patients with less than 5-years disease duration enrolled at Scleroderma centres of excellence. This manuscript presents the GIT natural history and outcomes in relation to other scleroderma manifestations and medication exposures., Methods: CONQUER participants that had completed a minimum of two serial Scleroderma Clinical Trials Consortium GIT Questionnaires (GIT 2.0) were included in this analysis. Patients were categorised by total GIT 2.0 severity at baseline, and by category change: none-to-mild (0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00) at the subsequent visit. Based on this data, four groups were identified: none-to-mild with no change, moderate-to-severe with no change, improvement, or worsening. Clinical features and medications, categorised as gastrointestinal tract targeted therapy, anti-fibrotic, immunosuppression, or immunomodulatory drugs, were recorded. Analysis included a proportional odds modelaccounting for linear and mixed effects of described variables., Results: 415 enrolled CONQUER participants met project inclusion criteria. Most participants had stable mild GIT symptoms at baseline and were on immunomodulatory and anti-reflux therapy. In most patients, anti-reflux medication and immunosuppression initiation preceded the baseline visit, whereas anti-fibrotic initiation occurred at or after the baseline visit. In the proportional odds model, worsening GIT score at the follow-up visit was associated with current tobacco use (odds ratio: 3.48 (1.22, 9.98, p 0.020)., Conclusions: This report from the CONQUER cohort, suggests that most patients with early SSc have stable and mild GIT disease. Closer follow-up was associated with milder, stable GIT symptoms. There was no clear association between immunosuppression or anti-fibrotic use and severity of GIT symptoms. However, active tobacco use was associated with worse GIT symptoms, highlighting the importance of smoking cessation counselling in this population.

Nanoparticles (NPs) have gained recognition for diagnosis, drug delivery, and therapy in fatal diseases. This review focuses on the benefits of green synthesis of bioinspired NPs using various plant extract (containing various biomolecules such as sugars, proteins, and other phytochemical compounds) and their therapeutic application in cardiovascular diseases (CVDs). Multiple factors including inflammation, mitochondrial and cardiomyocyte mutations, endothelial cell apoptosis, and administration of non-cardiac drugs, can trigger the cause of cardiac disorders. Furthermore, the interruption of reactive oxygen species (ROS) synchronization from mitochondria causes oxidative stress in the cardiac system, leading to chronic diseases such as atherosclerosis and myocardial infarction. NPs can decrease the interaction with biomolecules and prevent the incitement of ROS. Understanding this mechanism can pave the way for using green synthesized elemental NPs to reduce the risk of CVD. This review delivers information on the different methods, classifications, mechanisms and benefits of using NPs, as well as the formation and progression of CVDs and their effects on the body., Competing Interests: Declaration of competing interest The authors declare that they do not have any conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Despite many efforts over the last few decades, cardiac-based drug delivery systems are experiencing major problems, such as the effective delivery of the precise amount of a drug. In the current study, an effort has been made to prepare a nano-herbformulation (NHF) to overcome the major problem of conventional intervention. Copper oxide-based NHF was prepared using plant extract of Alternanthera sessilis and characterized using physicochemical techniques such as Transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Dynamic light scattering (DLS), UV-Vis spectroscopy, and Fourier-transform infrared spectroscopy (FTIR). TEM analysis revealed that spherical NHF obtained of size 20-50 nm. In addition, XRD and FTIR confirmed the presence of phytochemicals with biological properties over the surface of copper oxide-based NHF. It was demonstrated that dose-dependent antiapoptotic activity was shown against DOX-induced cardiomyocytes, where ROS levels were significantly reduced to 0.29% from 37.99%. The results of the flow cytometry analysis using PI and Annexin staining further confirmed the antiapoptotic activity of NHF against DOX-induced cardiomyocytes by ROS scavenging. Thus, NHF might be used for cardiovascular disease treatment.

In the present study, beneficial microbes-mediated zirconia nanoparticles were prepared using endophytic bacteria isolated from the seed of Terminalia chebula which were evaluated on inhibition of bacterial adherence and promotion to exhibit antibiofilm properties. The structure and distribution of the zirconia nanoparticles were examined through SEM (Scanning Electron Microscopy), EDS (Energy-Dispersive X-Ray spectroscopy), and XRD (X-ray diffraction analysis), which reveal the distribution of the particles. The morphology of biogenic zirconia nanoparticles was monoclinic and cubic. The formation of zirconia particle was confirmed using UV spectrum and the functional groups were intensified in FTIR (Fourier-transform infrared spectroscopy). The antibiofilm activity of the synthesized nanoparticles was tested in oral pathogens that cause biofilm by membrane integrity and leads to periodontal associated disease. The results showed that the particles had a significant effect on biofilm removal caused by oral pathogens. For determined concentration, the cytotoxicity of the endophytic bacterial facilitated zirconia nanoparticle (Zr NPs) was examined in HGF (Human gingival fibroblast cell line)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The potentiality of nanomedicine in the cancer treatment being widely recognized in the recent years. In the present investigation, the synergistic effects of chitosan-modified selenium nanoparticles loaded with paclitaxel (PTX-chit-SeNPs) were studied. These selenium nanoparticles were tested for drug release analysis at a pH of 7.4 and 5.5, and further characterized using FTIR, DLS, zeta potential, and TEM to confirm their morphology, and the encapsulation of the drug was carried out using UPLC analysis. Quantitative evaluation of anti-cancer properties was performed via MTT analysis, apoptosis, gene expression analysis, cell cycle arrest, and over-production of ROS. The unique combination of phytochemicals from the seed extract, chitosan, paclitaxel, and selenium nanoparticles can be effectively utilized to combat cancerous cells. The production of the nanosystem has been demonstrated to be cost-effective and have unique characteristics, and can be utilized for improving future diagnostic approaches.

Objective: Although a high-resolution computed tomography (HRCT) scan of the chest is the gold standard test for the detection of interstitial lung disease (ILD), there is no consensus among rheumatologists regarding the use of HRCT to screen for ILD in their patients with systemic sclerosis (SSc). The aims of this study were to describe the HRCT ordering practices at SSc centers in the United States and to determine which patient characteristics are associated with HRCT performance., Methods: We performed a prospective cohort study of patients with SSc enrolled in the US-based Collaborative National Quality and Efficacy Registry (CONQUER). We performed univariate logistic regression followed by multivariable logistic regression to determine which patient characteristics were associated with HRCT performance., Results: Of the 356 patients with SSc enrolled in CONQUER, 286 (80.3%) underwent HRCT at some point during their disease course. On multivariable analyses, missing total lung capacity percent predicted (odds ratio [OR] 3.26, 95% confidence interval [CI]: 1.53-7.41, P = 0.007) was positively associated with ever having undergone HRCT, whereas a positive anti-centromere antibody (OR 0.27, 95% CI: 0.12-0.61, P = 0.008) and missing forced vital capacity percent predicted (OR 0.29, 95% CI: 0.10-0.80, P = 0.005) were negatively associated with ever having undergone HRCT. There was a trend toward a positive association between crackles on pulmonary exam and ever having undergone HRCT (OR 2.28, 95% CI: 0.97-6.05, P = 0.058), although this relationship did not reach statistical significance., Conclusion: The majority of patients with SSc enrolled in CONQUER underwent HRCT. A positive anti-centromere antibody was the key clinical variable inversely associated with performance of HRCT., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Aim: Interstitial lung disease (ILD) is the leading cause of disease-related death in systemic sclerosis (SSc). Here, we assess baseline characteristics of SSc subjects with and without restrictive lung disease (RLD) in a multi-center, US-based registry., Methods: SSc patients within 5 years of disease onset were enrolled in the Collaborative National Quality and Efficacy Registry (CONQUER), a multi-center US-based registry of SSc study participants (age ≥ 18 years) enrolled at 13 expert centers. All subjects met 2013 American College of Rheumatology / European League Against Rheumatism criteria. Subjects with a pulmonary function test (PFT) at baseline before April 1, 2020 were included. High-resolution computed tomography scan of the chest was not available to characterize ILD for all subjects. RLD was defined as forced vital capacity (FVC) <80% or total lung capacity (TLC) <80% predicted., Results: There were 160 (45%) SSc subjects characterized as having RLD. There was no significant difference in age, gender or disease duration. RLD subjects had a mean disease duration from date of first non-Raynaud's symptom of 2.6 years and a mean FVC% predicted of 67% at baseline. In multivariable analysis, non-White race, higher physician global health assessment and modified Medical Research Council (mMRC) dyspnea scores, were independently associated with RLD. In the subgroup of RLD subjects with ILD, ILD had a negative correlation with RNA polymerase III antibody., Conclusion: CONQUER is the largest, multi-center, prospective cohort of early SSc patients in the US. Non-White race was independently associated with RLD. In addition, 45% of CONQUER subjects already had RLD, highlighting the importance of screening for SSc-ILD at initial diagnosis., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to report that are related to the reported content of this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Early diffuse cutaneous systemic sclerosis (dcSSc) has the highest case fatality among rheumatic diseases. We report baseline characteristics, current immunosuppressive therapies, progression of skin and internal organ involvement, and mortality in a multicenter prospective cohort from the United States (US) of America., Methods: We performed a longitudinal analysis of participants from 12 US centers, from April 2012 to July 2020. All participants had early dcSSc or were at-risk for dcSSc, with ≤2 years since the first non-Raynaud's phenomenon (RP) symptom., Results: Three hundred one patients were included with a baseline median disease duration of 1.2 years since RP and a mean modified skin score of 21.1 units. At baseline, 263 (87.3%) had definite dcSSc and 38 (12.7%) were classified as at-risk; 112 (49.6%) patients were positive for anti-RNA polymerase III antibodies. The median follow-up duration was 24.5 months (IQR = 10.3-40.7 months). One hundred ninety (63.1%) participants were treated with an immunosuppressive therapy, of which mycophenolate mofetil was most used at baseline and follow-up. Of 38 who were classified as at-risk at baseline, 27 (71%) went on to develop dcSSc; these patients were characterized by higher baseline mean HAQ-DI (0.8 versus 0.4, p = 0.05) and higher baseline mRSS (8.8 versus 4.4, p < 0.01) in comparison with those who remained as limited cutaneous SSc. In the overall cohort, 48 participants (21.1%) had clinically significant worsening of skin fibrosis, mainly occurring in the first year of follow-up; 41 (23.3%) had an absolute forced vital capacity decline of ≥10%. Twenty participants (6.6%) died, of which 18 died in the first 3 years of follow-up. Cardiac involvement (33.3%), gastrointestinal dysmotility (22.2%), and progressive interstitial lung disease (ILD) (16.7%) were the main causes of death., Conclusion: This US cohort highlights the management of early SSc in the current era, demonstrating progression of skin and lung involvement despite immunosuppressive therapy and high mortality due to cardiac involvement.

Objective: Response to immunosuppression is highly variable in systemic sclerosis (SSc)-related interstitial lung disease (ILD). This study was undertaken to determine whether a composite serum interferon (IFN)-inducible protein score exhibits predictive significance for the response to immunosuppression in SSc-ILD., Methods: Serum samples collected in the Scleroderma Lung Study II, a randomized controlled trial of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC), were examined. Results were validated in an independent observational cohort receiving active treatment. A composite score of 6 IFN-inducible proteins IFNγ-inducible 10-kd protein, monokine induced by IFNγ, monocyte chemotactic protein 2, β 2 -microglobulin, tumor necrosis factor receptor type II, and macrophage inflammatory protein 3β) was calculated, and its predictive significance for longitudinal forced vital capacity percent predicted measurements was evaluated., Results: Higher baseline IFN-inducible protein score predicted better response over 3 to 12 months in the MMF arm (point estimate = 0.41, P = 0.001) and CYC arm (point estimate = 0.91, P = 0.009). In contrast, higher baseline C-reactive protein (CRP) levels were predictive of a worse ILD course in both treatment arms. The predictive significance of the IFN-inducible protein score and CRP levels remained after adjustment for baseline demographic and clinical predictors. During the second year of treatment, in which patients in the CYC arm were switched to placebo, a higher IFN-inducible protein score at 12 months showed a trend toward predicting a worse ILD course (point estimate = -0.61, P = 0.068), while it remained predictive of better response to active immunosuppression in the MMF arm (point estimate = 0.28, P = 0.029). The predictive significance of baseline IFN-inducible protein score was replicated in the independent cohort (r s = 0.43, P = 0.028)., Conclusion: A higher IFN-inducible protein score in SSc-ILD is predictive of better response to immunosuppression and could potentially be used to identify patients who may derive the most benefit from MMF or CYC., (© 2020, American College of Rheumatology.)

During the COVID-19 pandemic, rheumatology educational programs around the world, face the daunting challenge of maintaining education for their trainees. Reduced in-person clinic exposures and social distancing requirements have significantly affected trainee education. Similar to programs around the USA, in early March 2020, our program was faced with an urgent need to pivot both our clinical and educational programs to virtual platforms. Within these limitations, we harnessed innovative educational models and restructured our curriculum to ensure adequate clinical and didactic exposure. We divided trainee's clinical rotations into four blocks, which include Inpatient consult service, Outpatient in-person and procedure clinics, Telehealth Clinics and Research/Elective week. By assigning specific rotations, we were able to ensure fellows were seeing adequate numbers of patients both through telemedicine and inperson while ensuring we complied with social distancing requirements. We further were able to ensure that trainee hands-on procedure training was not compromised. Acknowledging challenges presented by the COVID-19 pandemic and learner engagement in virtual environment, we designed an innovative educational portfolio. Utilizing synchronous and asynchronous learning methods, we have developed multiple complementary educational initiatives including: Rocket Rheumatology, Board Games, At the Elbow, Radiology Reading Rheum, Ultrasound Buddies, The History Rheum, and Rapid-Fire Journal Club. Virtual learning methods will become a cornerstone of medical education moving forwards. The GW Division of Rheumatology has rapidly incorporated innovative educational tools into our curriculum. Our approach will help Rheumatology training programs across the globe enhance rheumatology training.

The objective of this analysis is to examine whether the severity of systemic sclerosis (SSc)-hand involvement influences patient-reported outcome measure (PROM) completion rate in a US cohort of early disease. Participants included SSc patients with less than 5 years disease duration consented and enrolled in the Collaborative, National, Quality, and Efficacy Registry (CONQUER) between June 2018 and December 2019. Participants' socio-demographics, hand clinical features (severe modified Rodnan skin score, presence of small joint contractures, acro-osteolysis, calcinosis, and digital ulcers), and completion rates of seven PROMs including a Resource Use Questionnaire were analyzed. Cohort characteristics and baseline PROM completion were evaluated. Multivariable logistic regression assessed the relationship between hand limitations and PROM incompletion at several time points using generalized estimating equations. At the time of data lock, 339 CONQUER subjects had a total of 600 visits available for analysis. Calcinosis (odds ratio [OR] 6.35, confidence interval [CI] 2.41-16.73 and acro-osteolysis OR 3.88 (1.57-9.55) were significantly associated with incomplete PROM. The Resource Use Questionnaire was the PROM most commonly not completed. Increasing age was correlated with resource use questionnaire incompletion rate. Acro-osteolysis and calcinosis were associated with lower PROM completion rates in a US SSc cohort, independent of the length of the questionnaires or the modality of administration (electronic or paper). Resource Use Questionnaires are important for understanding the economic impact and burden of chronic disease; however, in this study, it had lower completion rates than PROMs devoted to clinical variables. Key points •Multiple strategies are needed to ensure optimal completion of PROM in longitudinal cohort studies. Even if patients request electronic surveys, we have found it is important to follow up incomplete surveys with paper forms provided at the time of a clinical visit. •The Resource Utilization Questionnaire was lengthy and prone to non-completion in the younger population. •Acro-osteolysis and calcinosis were associated with reduced PROM completion rates.

Background: Scientists are working on creating novel materials that can help in the treatment of diverse cancer-related diseases having trademark highlights like the target siting, specificity, improved therapeutic index of radiotherapy and chemotherapeutic treatments. The utilization of novel nanomaterials which are surface adorned with drugs or natural compounds can be used in diverse medical applications and helps in setting up a new platform for its improvement in the chemotherapeutic potentiality. One such nanomaterial is the trace element selenium in its nanoparticulate form that has been proved to be a potential chemotherapeutic agent recently., Methods: The English language papers were gathered from electronic databases like Sciencedirect, Pub Med, Google Scholar and Scopus, the papers are published from 2001 to 2019., Results: In the initial phase, approximately 200 papers were searched upon, out of which 118 articles were included after screening and critical reviewing. The information included was also tabulated for better knowledge and easy read. These articles contain information on the nanotechnology, inflammation, cancer and selenium as nanoparticles., Conclusion: The overview of the paper explains the enhancement of potentiality of anticancer drugs or phytochemicals which restricts its utilization in chemotherapeutic applications by the encapsulation or adsorption of them on selenium nanoparticles proven to accelerate the anticancerous properties with better results when compared with individual components. SeNPs (selenium nanoparticles) have demonstrated chemotherapeutic activity due to pro-oxidant property, where the anti-oxidant enzymes are stimulated to produce reactive active species, which induces oxidative stress, followed by activation of the apoptotic signalling pathway, cell cycle arrest, mitochondrial dysfunction and other pathways that ultimately lead to cell death. Selenium in nanoparticulate form can be used as a micronutrient to human health, thereby having low toxicity, can easily be degraded and also has good biocompatibility., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Objective: Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc). Although pulmonary function tests (PFTs) are commonly used to screen for ILD in patients with SSc, studies have shown that they lack sensitivity for the detection of ILD in general SSc cohorts. This study was undertaken to assess the performance characteristics of PFTs for the detection of ILD in patients with early diffuse cutaneous SSc (dcSSc), a population at high risk for the development of ILD., Methods: We performed a retrospective cohort study of patients enrolled in the Prospective Registry of Early Systemic Sclerosis at 11 sites in the US between April 2012 and January 2019. Patients were included if they underwent spirometry and high-resolution computed tomography (HRCT) of the chest. We calculated the performance characteristics of PFTs for the detection of ILD on HRCT., Results: The study included 212 patients, 54% of whom had radiographic ILD. For the detection of ILD on HRCT imaging, a forced vital capacity (FVC) <80% predicted had a sensitivity of 63%. The combination of FVC <80% predicted or diffusing capacity for carbon monoxide (DLco) <80% predicted improved the sensitivity to 85%. An FVC <80% predicted had a negative predictive value (NPV) of 61%, while the combination of FVC <80% predicted or DLco <80% predicted had an NPV of 70%., Conclusion: PFTs alone are an inadequate screening tool for the diagnosis of ILD in patients with early dcSSc. HRCT should be part of the ILD screening algorithm in patients with dcSSc., (© 2020, American College of Rheumatology.)

Mass spectrometry imaging (MSI) is used increasingly to simultaneously detect a broad range of biomolecules while mapping their spatial distributions within biological tissue sections. Matrix-assisted laser desorption ionization (MALDI) is recognized as the method-of-choice for MSI applications due in part to its broad molecular coverage. In spite of the remarkable advantages offered by MALDI, imaging of neutral lipids, such as triglycerides (TGs), from tissue has remained a significant challenge due to ion suppression of TGs by phospholipids, e.g. phosphatidylcholines (PCs). To help overcome this limitation, silicon nanopost array (NAPA) substrates were introduced to selectively ionize TGs from biological tissue sections. This matrix-free laser desorption ionization (LDI) platform was previously shown to provide enhanced ionization of certain lipid classes, such as hexosylceramides (HexCers) and phosphatidylethanolamines (PEs) from mouse brain tissue. In this work, we present NAPA as an MSI platform offering enhanced ionization efficiency for TGs from biological tissues relative to MALDI, allowing it to serve as a complement to MALDI-MSI. Analysis of a standard lipid mixture containing PC(18:1/18:1) and TG(16:0/16:0/16:0) by LDI from NAPA provided an ~49 and ~227-fold higher signal for TG(16:0/16:0/16:0) relative to MALDI, when analyzed without and with the addition of a sodium acetate, respectively. In contrast, MALDI provided an ~757 and ~295-fold higher signal for PC(18:1/18:1) compared with NAPA, without and with additional Na + . Averaged signal intensities for TGs from MSI of mouse lung and human skin tissues exhibited an ~105 and ~49-fold increase, respectively, with LDI from NAPA compared with MALDI. With respect to PCs, MALDI provided an ~2 and ~19-fold increase in signal intensity for mouse lung and human skin tissues, respectively, when compared with NAPA. The complementary coverage obtained by the two platforms demonstrates the utility of using both techniques to maximize the information obtained from lipid MS or MSI experiments., (© 2019 John Wiley & Sons, Ltd.)

Objectives: Determine global skin transcriptome patterns of early diffuse systemic sclerosis (SSc) and how they differ from later disease., Methods: Skin biopsy RNA from 48 patients in the Prospective Registry for Early Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and 33 matched healthy controls was examined by next-generation RNA sequencing. Data were analysed for cell type-specific signatures and compared with similarly obtained data from 55 previously biopsied patients in Genetics versus Environment in Scleroderma Outcomes Study cohort with longer disease duration (mean 7.4 years) and their matched controls. Correlations with histological features and clinical course were also evaluated., Results: SSc patients in PRESS had a high prevalence of M2 (96%) and M1 (94%) macrophage and CD8 T cell (65%), CD4 T cell (60%) and B cell (69%) signatures. Immunohistochemical staining of immune cell markers correlated with the gene expression-based immune cell signatures. The prevalence of immune cell signatures in early diffuse SSc patients was higher than in patients with longer disease duration. In the multivariable model, adaptive immune cell signatures were significantly associated with shorter disease duration, while fibroblast and macrophage cell type signatures were associated with higher modified Rodnan Skin Score (mRSS). Immune cell signatures also correlated with skin thickness progression rate prior to biopsy, but did not predict subsequent mRSS progression., Conclusions: Skin in early diffuse SSc has prominent innate and adaptive immune cell signatures. As a prominently affected end organ, these signatures reflect the preceding rate of disease progression. These findings could have implications in understanding SSc pathogenesis and clinical trial design., Competing Interests: Competing interests: DK reports consultancy fees from Acceleron, Actelion, Bayer, Blade Therapeutics, BMS, Galapagos, Genentech/Roche, GSK, Mitsubishi Tanabi, Sanofi-A ventis/Genzyme, and UCB Pharma, and reports grants from Bayer, BMS, and Genentech/Roche outside the submitted work, and reports ownership interest in Eicos Sciences, Inc. WRS reports consulting fees from UT Health Science Center at Houston. JKG reports grants from Corbus Pharmaceuticals, Cumberland Pharmaceuticals and Eicos Pharmaceuticals outside the submitted work. AAS reports support from Sanofi outside the submitted work. MLW reports grants and personal fees from Celdara Medical, LLC and personal fees from Abbvie, Acceleron, BMS, Corbus Pharmaceuticals and Boehringer Ingelheim outside the submitted work. JLB reports grants from Hoffman La Roche and the Scleroderma Foundation outside the submitted work. SB and PB are employees of Boehringer Ingelheim. FVC reports personal fees from Boehringer Ingelheim outside the submitted work. EJB reports a grant from Pfizer and support from Bohringer Ingelheim, Corbus Pharmaceuticals and Eicos outside the submitted work. MDM reports personal fees from Medtelligence, Actelion Pharma, Astellas, Mitsubishi-Tanabe, and Boehringer Ingelheim and grants from Bayer, Reata, Sanofi, Corbus, Eicos and Boehringer Ingelheim outside the submitted work. SA reports personal fees from Boehringer Ingelheim and grants from Boehringer Ingelheim, Bayer and Momenta outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1 * 08:04 and HLA-DRB1 * 11:02 alleles were associated with overall SSc risk, and the HLA-DRB1 * 08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1 * 13:01 and HLA-DRB1 * 07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1 * 13:01 allele with the ATA + subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1 * 13:01 allele frequency in multiple populations was observed ( r = 0.98, P = 3 × 10 -6 ). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA α/β allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc., Competing Interests: Competing interest statement: M.D.M. received consulting fees from Mitsubishi Tanabe, Astellas, Boehringer Ingelheim, Gerson Lehrman Group, Smart Analyst, and Guidepoint Global. R.T.D. received consulting fees from Eicos Sciences. D.K. received consulting fees from Actelion, Bristol-Myers Squibb, CSL Behring, Inventiva, EMD Merck-Serono, Sanofi-Aventis, GlaxoSmithKline, Corbus, Cytori, UCB, Bayer, Boehringer Ingelheim, and Genentech-Roche, and research support from Bayer, Bristol-Myers Squibb, and Pfizer, and owns stock or stock options in Eicos Sciences, Inc. (CiViBioPharma, Inc.). L.A.S. received consulting fees from Axon Pharma. H.G. received consulting fees from Pfizer, AbbVie, Actelion, and Horizon Pharmaceuticals. C.T.D. received research support from Gilead, Actelion, and Cytori. V.K.S. received research support from AbbVie. E.J.B. received consulting fees from Genentech. L.C. received consulting fees or served on the board of Reata, Bristol-Myers Squibb, Boehringer-Ingelheim, Eicos, and Mitsubishi Tanabe. S.L.B. and M.J.D. are coauthors on a 2015 research article., (Copyright © 2020 the Author(s). Published by PNAS.)

The Collaborative National Quality and Efficacy Registry (CONQUER) for Scleroderma is a multicenter US-based longitudinal study of patients with systemic sclerosis (SSc) within 5 years of first non-Raynaud's symptom. The data collection methodology incorporates successful models from other SSc registries. The cohort is designed to provide linked bio-specimen and clinical outcomes data on a longitudinal cohort of SSc patients for validation of hypothesis-driven research and to provide a platform for studying patient-reported outcomes in scleroderma. The CONQUER registry was developed using the guidelines of the International Society for Biological Repositories, and was an iterative process between physicians with an expertise in SSc, patient stakeholders, and information technology experts. Enrollment commenced in June 2018. During the first 6 months of the CONQUER Scleroderma study, 151 SSc patients with less than 5 years of disease duration (from first non-Raynaud's symptom) have been recruited. The mean age is 51 ± 14 years, 83% are female, and 60% of patients have diffuse disease. Survey completion rates are above 88% for all patient-reported outcome surveys. Bio-specimen collection rates are over 97%, and disease severity score completion rates are over 98%. Pulmonary function test data is available on 91% of patients, and echocardiography is available 80%. The CONQUER scleroderma study provides a unique and growing resource for studying scleroderma in a longitudinal, US-based population. KEY POINTS : • The Collaborative National Quality and Efficacy Registry (CONQUER) for Scleroderma is a multicenter US-based longitudinal study of patients with systemic sclerosis (SSc) within 5 years of first non-Raynaud's symptom. • The CONQUER scleroderma study provides a unique and growing resource for studying scleroderma in a longitudinal, US-based population. • CONQUER is innovative in its design in that it is focused on prospective collection of paired clinical and patient outcome data with bio-specimens.

Background: Hidradenitis suppurativa (HS) is a recurrent inflammatory disease of the apocrine sweat glands. Immune dysregulation probably contributes to the pathogenesis of HS., Aim: To harness mRNA expression arrays to investigate the transcriptome profile in HS compared with control skin., Methods: Illumina ® HumanHT-12 v4 Expression BeadChips were used to measure mRNA expression in skin samples from HS (n = 10) and abdominoplasty (n = 11) skin specimens. Differentially expressed genes were detected by fitting genewise linear models to the normalized expression data and then modelling using the web-based software Ingenuity ® Pathway Analysis., Results: The antimicrobial peptide Dermcidin and the cytokine regulator interleukin (IL)-37 were both significantly downregulated in the HS specimens (Dermcidin expression log ratio -3.93, expression P = 0.04; IL-37 expression log ratio -3.29, expression P < 0.001). Pathway analysis revealed the interferon-signalling pathway, leucocyte extravasation pathway, T helper 1 and 2 pathways and nuclear factor of activated T cells as the top-five upregulated pathways in the HS samples., Conclusion: Evaluation of transcriptome patterns in HS compared with normal skin demonstrated downregulation of the antimicrobial peptide Dermcidin and the innate immune regulator IL-37, as well as upregulation of interferon pathways and pathways of leucocyte activation., (© 2019 British Association of Dermatologists.)

Neutral lipids have been implicated in a host of potentially debilitating human diseases, such as heart disease, type-2 diabetes, and metabolic syndrome. Matrix-assisted laser desorption ionization (MALDI), the method-of-choice for mass spectrometry imaging (MSI), has led to remarkable success in imaging several lipid classes from biological tissue sections. However, due to ion suppression by phospholipids, MALDI has limited ability to efficiently ionize and image neutral lipids, such as triglycerides (TGs). To help overcome this obstacle, we have utilized silicon nanopost arrays (NAPA), a matrix-free laser desorption ionization (LDI) platform. Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease of the apocrine sweat glands. The ability of NAPA to efficiently ionize lipids is exploited in the analysis of human skin samples from sufferers of HS. Ionization by LDI from NAPA allows for the detection and imaging of a number of neutral lipid species, including TGs comprised of shorter, odd-chain fatty acids, which strongly suggests an increased bacterial load within the host tissue, as well as hexosylceramides (HexCers) and galabiosyl-/lactosylceramides that appear to be correlated with the presence of HS. Our results demonstrate that NAPA-LDI-MSI is capable of imaging and potentially differentiating healthy and diseased human skin tissues based on changes in detected neutral lipid composition.

Biocalcification or microbially induced carbonate precipitation (MICP) is gaining attention from the research fraternity, primarily ascribed to their eco-friendly applications. Bacterial strains have been isolated from various sources and their ability to precipitate carbonate has been studied extensively. In spite of the fact that the deep-sea environment is a potential source for bioprospecting, meager reports exist on the isolation of biocalcifying bacterial strains from deep-sea. In this study, a deep-sea sediment sample obtained from off-Barren Island coast in the Andaman Sea was investigated for biocalcifying strains. Based on the urease activity and the ability to produce calcite crystals, the strain NIOTVJ5 was chosen for further investigations. The strain showed a similarity to Bacillus thuringiensis through 16S rRNA sequencing and was shown to possess positive urease, protease, amylase, catalase, and oxidase activities. The isolate was found to be piezotolerant as it was able to survive at 100 bar pressure with significant changes in the spore morphology. The strain was able to produce strong monoxenic biofilms as well. Maximum urease activity was 554.03 U/mL and it precipitated 1.80 g/L of carbonate crystals. Scanning electron microscopy coupled with energy dispersive X-ray spectroscopy confirmed the presence of calcium carbonate. The carbonate polymorph was identified as calcite using X-ray powder diffraction. The impact of biocalcification by NIOTVJ5 on concrete specimens indicated an increase of 30.91% in their compressive strength. This is the first report of a biocalcifying strain from a deep-sea sediment around the Indian subcontinent region. This study indicates the potential of the strain NIOTVJ5, which can be employed for various biotechnological applications.

Chronic wounds are wounds that have failed to heal after 3 months of appropriate wound care. Previous reports have identified a diverse collection of bacteria in chronic wounds, and it has been postulated that bacterial profile may contribute to delayed healing. The purpose of this study was to perform a microbiome assessment of the Wound Healing and Etiology (WE-HEAL) Study cohort, including underlying comorbidities less commonly studied in the context of chronic wounds, such as autoimmune diseases, and investigate possible relationships of the wound microbiota with clinical healing trends. We examined chronic wound specimens from 60 patients collected through the WE-HEAL Study using 16S ribosomal RNA gene sequencing. A group of co-occurring obligate anaerobes was identified from taxonomic analysis guided by Dirichlet multinomial mixtures (DMM) modeling. The group includes members of the Gram-positive anaerobic cocci (GPAC) of the Clostridia class (i.e., Anaerococcus, Finegoldia, and Peptoniphilus) and additional strict anaerobes (i.e., Porphyromonas and Prevotella). We showed that the co-occurring group of obligate anaerobes not only co-exists with commonly identified wound species (such as Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas, Corynebacterium, and Streptococcus), but importantly, they could also predominate the wound microbiota. Furthermore, examination of clinical comorbidities of the WE-HEAL specimens showed that specific obligate and facultative anaerobes were significantly reduced in wounds presented with autoimmune disease. With respect to future healing trends, no association with the wound microbiome community or the abundance of individual wound species could be established. In conclusion, we identified a co-occurring obligate anaerobic community type that predominated some human chronic wounds and underrepresentation of anaerobes in wounds associated with autoimmune diseases. Possible elucidation of host environments or key factors that influence anaerobe colonization warrants further investigation in a larger cohort.

Objectives: This observational study was designed to evaluate the impact of a student-led Rheumatology Interest Group on medical student interest in rheumatology., Methods: The mean numbers of student-rheumatology interactions per six months were assessed for elective enrollment, abstract submissions, and manuscripts, in the pre- and postinterest group period., Results: Enrollment in the rheumatology elective increased from 2.0 ± 0.36 per six months in the preintervention period to 6.2 ± 1.24 per six months in the postintervention period (p=0.0064). Abstract submissions increased from 0.5 ± 0.34 to 5.86 ± 1.49 (p=0.0077), and manuscript submissions from 0.16 ± 0.16 to 1.57 ± 0.37 (p=0.074)., Conclusion: The Rheumatology Interest Group significantly increased medical student engagement in rheumatology.

Multiple types of inflammations caused by foreign pathogens or chemicals and mutations that upregulate inflammation enhancers kindle the need of developing new vectors for the treatment of inflammation. Nanoparticles have been used in various fields ranging from the food industry, cosmetic industry and agricultural industry to devices like sensors, solar cells, and batteries. Nanoparticles have been used in the medical and research fields due to their high penetration power even inside cells and have the excellent ligand-binding properties due to their high surface area to volume ratio. Mechanistic study of anti-inflammatory activities of various metal and metal oxide nanoparticles like silver, gold, zinc oxide, titanium dioxide, and selenium have been discussed in the following literature review. The present study focuses on the differential uptake of nanoparticles into cells and the anti-inflammatory mechanism adopted by the nanoparticles synthesized by green routes. It also gives a concise literature review of the various green sources used for the synthesis of nanoparticles and the mechanism of action of each nanoparticle., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Whole-exome sequencing (WES) studies in systemic sclerosis (SSc) patients of European American (EA) ancestry have identified variants in the ATP8B4 gene and enrichment of variants in genes in the extracellular matrix (ECM)-related pathway that increase SSc susceptibility. This study was undertaken to evaluate the association of the ATP8B4 gene and the ECM-related pathway with SSc in a cohort of African American (AA) patients., Methods: SSc patients of AA ancestry were enrolled from 23 academic centers across the US under the Genome Research in African American Scleroderma Patients consortium. Unrelated AA individuals without serologic evidence of autoimmunity who were enrolled in the Howard University Family Study were used as unaffected controls. Functional variants in genes reported in the 2 WES studies in EA patients with SSc were selected for gene association testing using the optimized sequence kernel association test (SKAT-O) and pathway analysis by Ingenuity Pathway Analysis in 379 patients and 411 controls., Results: Principal components analysis demonstrated that the patients and controls had similar ancestral backgrounds, with roughly equal proportions of mean European admixture. Using SKAT-O, we examined the association of individual genes that were previously reported in EA patients and none remained significant, including ATP8B4 (P = 0.98). However, we confirmed the previously reported association of the ECM-related pathway with enrichment of variants within the COL13A1, COL18A1, COL22A1, COL4A3, COL4A4, COL5A2, PROK1, and SERPINE1 genes (corrected P = 1.95 × 10 -4 )., Conclusion: In the largest genetic study in AA patients with SSc to date, our findings corroborate the role of functional variants that aggregate in a fibrotic pathway and increase SSc susceptibility., (© 2018, American College of Rheumatology.)

Aim: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of the apocrine sweat glands. Tumor necrosis factor-alpha (TNF-α) inhibitors are commonly used to treat HS. However, prior to initiating therapy patients must be screened for mycobacterium tuberculosis (mTB) exposure. Several mTB screening tests based on interferon gamma release assays are commercially available, but the performance of these assays in the HS population is unknown. The purpose of this study was to investigate the performance of the QuantiFERON gold in-tube assay (QFT-GIT) in a cohort of patients with HS., Methods: This prospective study was conducted through the Wound Etiology and Healing (WE-HEAL) study. QFTGIT testing was performed using a commercial laboratory. Patients with positive test results underwent follow-up testing to evaluate for latent tuberculosis infection (LTBI). Data were collected on demographics and disease activity scores including Hurley stage, HS Sartorius score (HSS) and active nodule (AN) count., Results: Of the 69 patients with a confirmed diagnosis of HS, seven (10.1%) tested QFT-GIT positive and 5.8% were diagnosed with LTBI., Conclusions: QFT-GIT results did not correlate with demographic characteristics or HS disease activity.

Aim: The purpose of this study was to investigate the prevalence of antinuclear antibody (ANA) positivity in a cohort of patients with hidradenitis suppurativa (HS), and to assess the frequency of seroconversion during treatment with tumor necrosis factor (TNF)-α inhibitor therapy., Methods: This prospective study was conducted through the Wound Etiology and Healing (WE-HEAL) Study. Immunofluorescence ANA testing was performed at baseline, and repeated when clinically indicated. ANA titers of ≥1 : 160 were considered positive. Data were collected on demographics and disease activity scores including the Hurley stage, the HS Sartorius score (HSS) and the active nodule (AN) count., Results: At the time of data lock, 73 patients with a confirmed diagnosis of HS were enrolled, and four (5.4%) had baseline positive ANA. None of the patients had clinical evidence of systemic lupus erythematosus or other autoimmune diseases. There were no significant differences in demographics, baseline HSS (43.25 ± 47.55 compared to 59.48 ± 56.67, P = 0.58) or AN count (3.25 ± 3.20 compared to 3.45 ± 2.36, P = 0.87) in the ANA positive group. Of the 69 patients who were ANA negative at enrollment, 31 (45%) received TNF-α inhibitor therapy. During follow up, one patient developed drug-induced lupus secondary to TNF-α inhibitor use. Additionally, one patient seroconverted to ANA positive without sequelae and one patient developed drug-induced hepatitis secondary to TNF-α inhibitor use., Conclusion: The prevalence of baseline ANA positivity in this HS population was similar to that seen in the general population (5.4%). The rate of seroconversion and drug-induced complications in this population were low., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Digital ulcers (DU) are a common clinical problem in systemic sclerosis (SSc); however, there is no standardization of local wound care protocols for management of these lesions. There is a well-recognized need to develop and standardize non-pharmacological management of DU in patients with SSc, and to adopt these protocols in future clinical trials that focus on DU healing. The purpose of this review is to outline the types of DU that occur in SSc, and provide an update on the principles of wound management for these lesions based on the current literature and expert opinion., Competing Interests: Conflict of interest: None of the authors has financial interest related to this study to disclose.

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1-4% of the population. Defective keratinocyte function has been postulated to play a role in HS pathogenesis. Using an in vitro scratch assay, differences between normal, HS, and chronic wound (CW) keratinocytes were evaluated. Normal keratinocytes exhibited faster scratch closure than HS or CW, with normal samples showing 93.8% closure at 96 hours compared to 80.8% in HS (p = 0.016) and 71.5% in CW (p = 0.0012). The keratinocyte viability was similar in normal and HS (91.12 ± 6.03% and 86.55 ± 3.28%, respectively, p = 0.1583), but reduced in CW (72.34 ± 13.12%, p = 0.0138). Furthermore, apoptosis measured by annexin V/propidium iodide, was higher in CW keratinocytes (32.10 ± 7.29% double negative cells compared to 68.67 ± 10.37% in normal and 55.10 ± 9.46% in HS, p = 0.0075). Normal keratinocytes exhibited a significantly higher level of IL-1α (352.83 ± 42.79 pg/ml) compared to HS (169.96 ± 61.62 pg/ml) and CW (128.23 ± 96.61 pg/ml, p = 0.004). HS keratinocytes exhibited significantly lower amounts of IL-22 (8.01 pg/ml) compared to normal (30.24 ± 10.09 pg/ml) and CW (22.20 ± 4.33 pg/ml, p = 0.0008), suggesting that defects in IL-22 signaling may play a role in HS pathogenesis. These findings support intrinsic differences in keratinocyte function in HS which cannot be attributed to reduced keratinocyte viability or increased apoptosis.

Background: Hidradenitis supppurativa (HS) is a chronic inflammatory disease of the apocrine sweat glands affecting 1-4% of the population. While surgical excision is a mainstay of therapy, lesions often recur. Biologic therapies, including tumor necrosis factor-α and IL-12/23 inhibitors, are effective for mild to moderate HS. However, longitudinal studies investigating biologic therapy in conjunction with surgery are limited. The purpose of this analysis was to investigate impact of surgery and biologic therapy on HS disease activity., Methods: Data from 68 HS patients were analyzed. Outcome measures included hidradenitis suppurativa Sartorius Score (HSS), active nodule (AN) count, Hurley stage, and probability of achieving 75% reduction in active nodule count (AN75)., Results: Mean age was 40 ± 14 years; 66% were female and 72% were African American. Mean disease duration was 10 years, and Hurley stage III disease was seen in 63% of patients. Patients who received biologics had a larger drop in HSS and AN count than those who never received biologics (P = 0.002). Biologic treatment was associated with average reduction in 22 (15-29) HSS points (P < 0.0001). The effect of biologics was greater in patients who also underwent surgery (P = 0.013). Timing of biologics relative to surgery did not impact efficacy. Patients who received HS surgery with biologic therapy were most likely to achieve the AN75 (P = 0.017)., Conclusions: In this diverse cohort of patients with severe HS, biologic therapy was associated with a more rapid decline in disease activity, with the greatest effect in patients who also underwent HS surgery., (© 2017 The International Society of Dermatology.)

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987-2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ± 13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ≤50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort.Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other causes, including vasculitis, pyoderma gangrenosum, and other autoimmune diseases. The purpose of this article was to review the literature across medical and surgical specialties with regard to refractory chronic wounds associated with vasculitis and autoimmune diseases and to delineate clinical outcomes of these wounds in response to vascular and other interventions., Methods: An electronic search encompassing MEDLINE, PubMed, Cochrane Library, and Scopus was completed using the following search terms: rheumatoid arthritis; systemic sclerosis; systemic lupus erythematosus; antineutrophil cytoplasmic antibody-associated vasculitis; mixed connective tissue disease; antiphospholipid syndrome; pyoderma gangrenosum; thromboangiitis obliterans; cryoglobulinemia; hydroxyurea; sickle cell; atrophie blanche; livedoid vasculitis; cholesterol emboli; calciphylaxis; antiphospholipid antibodies; prothrombotic; combined with the terms: chronic wound and leg ulcer. Full-text articles published in English up to March 1, 2016, that investigated the clinical outcomes of chronic wounds associated with autoimmune diseases were included. Review articles and evaluations of management of chronic wounds were also reviewed. Primary outcomes included in the review were amputation, ulcer healing, reduction in wound size, overall survival, and freedom from reintervention. Owing to the heterogeneity of data reporting among articles, qualitative analysis is also reported., Results: Vasculitis and autoimmune diseases play a role in 20% to 23% of patients with chronic lower extremity ulcers. Furthermore, patients with autoimmune disease have a significantly high rate of split thickness skin graft failure (50% compared to 97% in patients without autoimmune disease; P = .0002). The management of leg ulcers associated with autoimmune diseases is discussed., Conclusions: Autoimmune and vasculitic causes should be considered in patients with chronic wounds who do not respond to appropriate vascular intervention and standard local wound care. A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory disease of apocrine glands which affects 1-4% of young adults. The purpose of this study was to investigate inflammatory cytokines in effluent from HS lesions and to identify potential local drivers of inflammation in HS. Wound fluid specimens from HS patients (n = 8) and age-matched chronic wound patients (n = 8) were selected for analysis. The hidradenitis suppurativa score (HSS) was used to determine the extent of HS activity. Cytokine analysis was conducted using Meso Scale Discovery cytokine and proinflammatory panels. Interferon-gamma (IFN-γ) was significantly elevated in the HS effluent compared to chronic wounds (1418 ± 1501 pg/ml compared to 102.5 ± 138 pg/ml, p = 0.027). HS effluent also had significantly higher levels of tumor necrosis factor-β (TNF-β) (9.24 ± 7.22 pg/ml compared to 1.65 ± 2.14 pg/ml, p = 0.03). There was no significant difference in any other cytokines. There was no significant difference in demographics in the HS compared to chronic wound cohorts. Mean HSS in the HS cohort was 68.88 (SD ± 41.45). In this proof-of-concept pilot study, IFN-γ was significantly elevated in HS effluent. TNF-β/LT-α levels were also elevated in HS, although the levels were more modest. Further studies should focus on molecular drivers of tissue injury in HS and the relationship between HS effluent cytokine profile and disease activity.

Opioids are routinely used analgesics in patients with chronic wounds; however the impact of opioid exposure on wound healing is poorly understood. The purpose of this study was to investigate the association between opioid exposure and wound outcome in the Wound Etiology and Healing study. This longitudinal observational study was conducted on 450 subjects enrolled in the Wound Etiology and Healing biorepository. Data were collected prospectively including baseline characteristics, pain score, longitudinal opioid exposure, and total wound surface area (tWSA). Data were analyzed using static multivariate models, fixed-effects mixed models, and time to event analysis. Using fixed-effects models, opioid dose was significantly associated with tWSA after accounting for the effects of pain score and baseline co-variates (p < 0.0001). For each 1-unit increase in ln(opioid dose + 1) the ln(tWSA + 1) increased by 0.16 units (95% confidence interval 0.13-0.19, p < 0.0001). Visits where opioids were present had ln(tWSA + 1) 0.48 units larger (95% confidence interval 0.38-0.58, p < 0.0001) than visits with no opioid exposure. Using time-to-event analysis, patients who never received opioids healed faster than those who received opioids (log-rank chi-square 11.00, p  = 0.0009). Using Cox regression analysis, patients with mean opioid dose ≥10 mg were significantly less likely to heal than those with no opioid (HR 0.67 [0.49-0.91], p = 0.011) after adjusting for wound size. Patients with opioid dose >0 to <10 mg had a similar hazard of not healing as those with no opioid exposure (HR 0.88 [0.65-1.19], p = 0.40). In conclusion, opioid analgesics are commonly prescribed to patients with chronic wounds; however, the data presented suggest that opioid exposure is associated with reduced likelihood of healing in patients with chronic wounds. Whether this is a causal relationship will require further study., (© 2016 by the Wound Healing Society.)

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1-4% of the population. The disease is more common in women and patients of African American descent and approximately one-third of patients report a family history. Obesity and smoking are known risk factors, but associations with other immune disorders, especially inflammatory bowel disease, are also recognized. The pathogenesis of HS is poorly understood and host innate or adaptive immune response, defective keratinocyte function, and the microbial environment in the hair follicle and apocrine gland have all been postulated to play a role in disease activity. While surgical interventions can be helpful to reduce disease burden, there is a high recurrence rate. Increasingly, data supports targeted immune therapy for HS, and longitudinal studies suggest benefit from these agents, both when used alone and as an adjunct to surgical treatments. The purpose of this review is to outline the current data supporting use of targeted immune therapy in HS management.

Purpose: Autoimmune diseases are a common cause of delayed wound healing and should be considered in patients with chronic wounds who do not respond to local wound care or who fail skin grafting in the absence of infection., Recent Findings: Epidemiologic studies have shown that, of patients with chronic wounds evaluated in specialized wound healing clinics, 20-23% have autoimmune etiologies for their wounds including vasculitis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, pyoderma gangrenosum and other autoimmune diseases., Summary: In this article autoimmune diseases known to be associated with chronic wounds and delayed wound healing are reviewed and the importance of a multidisciplinary approach for patients with chronic wounds, with involvement of rheumatology and dermatology is highlighted. This approach allows for investigation of underlying systemic disease and improves clinical outcomes for many of these challenging patients.

Background: Trials demonstrating the efficacy of biologic therapy for moderate to severe hidradenitis suppurativa (HS) have inspired new multidisciplinary treatment strategies. We present our experience with combined biologic and surgical therapy for recalcitrant HS., Methods: Between 2011 and 2014, 21 patients (57 cases) with Hurley Stage III HS underwent radical resection with delayed primary closure alone, or in combination with adjuvant biologic therapy. Demographic data, treatment regimen, outcomes, and complications were retrospectively reviewed for all cases., Results: Eleven patients underwent combined surgical and biologic therapy, whereas radical resection alone was performed in 10 patients. The average soft tissue deficit, before closure, for the combined and surgery-only patients was 56 cm and 48.5 cm, respectively (P = 0.66). Biologic agents including infliximab (n = 8) and ustekinumab (n = 3) were initiated 2 to 3 weeks after closure and were continued for an average of 10.5 months. Recurrence was noted in 19% (4/29) and 38.5% (10/26) of previously treated sites for combined and surgery-only patients (P < 0.01). For the combined cohort, the disease-free interval was approximately 1 year longer on average (P < 0.001); however, this difference was reduced to 4.5 months when considering time to recurrence after cessation of biologic therapy (P = 0.09). New disease developed in 18% (2/11) and 50% (5/10) of combined and surgery-only patients, respectively (P < 001). No adverse events were noted among patients who received biologic therapy., Conclusions: Lower rates of recurrence and disease progression, as well as a longer disease-free interval may be achieved with the use of adjuvant biologic therapy after radical resection for recalcitrant HS.

In clinical practice, point-of-care diagnostic testing has progressed rapidly in the last decade. For the field of wound care, there is a compelling need to develop rapid alternatives for bacterial identification in the clinical setting, where it generally takes over 24 hours to receive a positive identification. Even new molecular and biochemical identification methods require an initial incubation period of several hours to obtain a sufficient number of cells prior to performing the analysis. Here we report the use of an inexpensive, disposable electrochemical sensor to detect pyocyanin, a unique, redox-active quorum sensing molecule released by Pseudomonas aeruginosa, in wound fluid from patients with chronic wounds enrolled in the WE-HEAL Study. By measuring the metabolite excreted by the cells, this electrochemical detection strategy eliminates sample preparation, takes less than a minute to complete, and requires only 7.5 μL of sample to complete the analysis. The electrochemical results were compared against 16S rRNA profiling using 454 pyrosequencing. Blind identification yielded 9 correct matches, 2 false negatives, and 3 false positives giving a sensitivity of 71% and specificity of 57% for detection of Pseudomonas. Ongoing enhancement and development of this approach with a view to develop a rapid point-of-care diagnostic tool is planned., (© 2016 by the Wound Healing Society.)

To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human-mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2-mm punch biopsy. Wounds were harvested on sequential days to allow tissue-based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase-2 (COX-2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human-mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX-2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human-mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing., (© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

We present the case of a 53-year-old Caucasian male smoker with remote history of left lower extremity deep venous thrombosis (DVT) and a strong family history of thrombosis, who presented to the Center for Wound Healing at MedStar Georgetown University Hospital with spontaneous left leg ulceration. Prothrombotic evaluation showed homozygosity for the factor V Leiden (FVL) mutation. Therapeutic anticoagulation was commenced with warfarin (Coumadin®) and the patient underwent successful debridement and Apligraf® followed by split-thickness skin graft (STSG) of two wounds. He had an uneventful postoperative course and on the 27th postoperative day the grafts were 95% intact. However, by postoperative day 41 there was 10% graft loss, and over the subsequent 2 weeks both grafts necrosed. On further questioning, it transpired that the patient had discontinued his warfarin on postoperative day 37 because he thought that it was no longer necessary. The patient is enrolled in the Wound Etiology and Healing (WE-HEAL) study, and at the time of the original graft, residual skin fragments from the STSG were transplanted onto a nude mouse for development of an animal model of wound healing. The mouse graft was successful and was harvested at postoperative day 87 for pathological examination. We review the mechanisms by which prothrombotic states, particularly FVL mutation, can contribute to skin graft failure and delayed wound healing. This case highlights the importance of considering prothrombotic conditions in patients with spontaneous leg ulcerations and the impact of therapeutic anticoagulation on healing. It further allows us to demonstrate the efficacy of the animal model in which residual fragments of STSG tissue are utilised for transplant onto nude mice for manipulation in the laboratory., (© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)