The enteric nervous system relays psychological stress to intestinal inflammation.

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-ß2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.

Multiscale 3D genome organization underlies ILC2 ontogenesis and allergic airway inflammation.

Innate lymphoid cells (ILCs) are well-characterized immune cells that play key roles in host defense and tissue homeostasis. Yet, how the three-dimensional (3D) genome organization underlies the development and functions of ILCs is unknown. Herein, we carried out an integrative analysis of the 3D genome structure, chromatin accessibility and gene expression in mature ILCs. Our results revealed that the local 3D configuration of the genome is rewired specifically at loci associated with ILC biology to promote their development and functional differentiation. Importantly, we demonstrated that the ontogenesis of ILC2s and the progression of allergic airway inflammation are determined by a unique local 3D configuration of the region containing the ILC-lineage-defining factor Id2, which is characterized by multiple interactions between the Id2 promoter and distal regulatory elements bound by the transcription factors GATA-3 and RORα, unveiling the mechanism whereby the Id2 expression is specifically controlled in group 2 ILCs.

A new perspective on mesenchymal-immune interactions in adipose tissue.

The mammalian immune system has crucial homeostatic functions in different adipose depots. However, white adipose tissue (WAT) inflammation is a hallmark of obesity and can contribute to type 2 diabetes mellitus (T2DM). Recently, mesenchymal cells were identified as highly heterogenous populations displaying specialized immune functions in immune cell migration, activation, survival, and overall lymphoid tissue organization in several tissues. How they regulate the inflammatory milieu within different adipose depots remains unknown. Using recently published single-cell RNA-sequencing (scRNAseq) data sets, we analyze cytokine and chemokine expression of mouse WAT mesenchymal cell subpopulations to highlight potential immunological heterogeneity and specialization, hypothesizing on their immunological functions. This new perspective on immune-mesenchymal cell interactions in adipose tissue may promote studies that heighten our understanding of immune cell processes within WAT during health and obesity. We hope that these studies redefine our knowledge of the roles of mesenchymal cells in regulating adipose tissue inflammation and physiology.

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing methylation-controlled J protein (MCJ) in three preclinical models of IRI and liver regeneration, focusing on metabolically compromised animal models. APPROACH AND RESULTS: Wild-type (WT), MCJ knockout (KO), and Mcj silenced WT mice were subjected to 70% partial hepatectomy (Phx), prolonged IRI, and 70% Phx with IRI. Old and young mice with metabolic syndrome were also subjected to these procedures. Expression of MCJ, an endogenous negative regulator of mitochondrial respiration, increases in preclinical models of Phx with or without vascular occlusion and in donor livers. Mice lacking MCJ initiate liver regeneration 12 h faster than WT and show reduced ischemic injury and increased survival. MCJ knockdown enables a mitochondrial adaptation that restores the bioenergetic supply for enhanced regeneration and prevents cell death after IRI. Mechanistically, increased ATP secretion facilitates the early activation of Kupffer cells and production of TNF, IL-6, and heparin-binding EGF, accelerating the priming phase and the progression through G1 /S transition during liver regeneration. Therapeutic silencing of MCJ in 15-month-old mice and in mice fed a high-fat/high-fructose diet for 12 weeks improves mitochondrial respiration, reduces steatosis, and overcomes regenerative limitations. CONCLUSIONS: Boosting mitochondrial activity by silencing MCJ could pave the way for a protective approach after major liver resection or IRI, especially in metabolically compromised, IRI-susceptible organs.

New insights into the taxonomy of autoimmune diseases based on polyautoimmunity.

OBJECTIVE: The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed "overt polyautoimmunity" (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as "latent PolyA". We aimed to explore a new taxonomy of ADs based on PolyA. METHODS: In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs. RESULTS: Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes. CONCLUSIONS: This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials.

Body Contouring Using a Combination of Pulsed Ultrasound and Unipolar Radio Frequency: A Prospective Pilot Study.

OBJECTIVE: To assess the efficacy and safety of a new non-invasive body contouring device in patients with localized fat in abdomen or in abdomen and hips. Additionally, we also evaluated the patient satisfaction with the procedure. METHODS: Prospective and non-randomized open label study. The patients underwent four sessions, separated by 1 week each, with the Alma PrimeX, a non-invasive body contouring device that combines pulsed non-focus ultrasound and a Unipolar radiofrequency. The primary end point was the mean change in fat tissue thickness, assessed by diagnostic ultrasound, from baseline to 3-months after the last treatment-session. RESULTS: Fifteen subjects were evaluated. As compared to pre-treatment thickness, Hodges-Lehmann median difference (95% CI) was - 85.3 (- 107.5 to - 62.0) mm, p = 0.0001; - 70.3 (- 95.0 to - 48.5) mm, p = 0.0001; - 100.0 (- 140.5 to - 49.5) mm, p = 0.0039; and - 71.8 (- 132.5 to - 23.0) mm, p = 0.0078 in infraumbilical, supraumbilical, right hip, and left hip, respectively. Pretreatment fat volume was significantly reduced from 32.9% to 31.2%, p = 0.0006. The median (interquartile range) degree of patient satisfaction was 4.0 (1.0-5.0), with 13 (86.7%) patients being "Highly satisfied" or "Satisfied" with the treatment results. The most common adverse event was discomfort, followed by erythema. All the adverse events were mild and were successfully resolved without treatment. CONCLUSIONS: Combine therapy of a Pulsed non-focus ultrasound and Unipolar radiofrequency using the non-invasive device Alma PrimeX was an effective and safe treatment for reducing fat tissue thickness in abdomen and hips in patients with localized fat. Patients' satisfaction with the procedure was high. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

An intronic enhancer of Bmp6 underlies evolved tooth gain in sticklebacks.

Threespine stickleback fish offer a powerful system to dissect the genetic basis of morphological evolution in nature. Marine sticklebacks have repeatedly invaded and adapted to numerous freshwater environments throughout the Northern hemisphere. In response to new diets in freshwater habitats, changes in craniofacial morphology, including heritable increases in tooth number, have evolved in derived freshwater populations. Using a combination of quantitative genetics and genome resequencing, here we fine-mapped a quantitative trait locus (QTL) regulating evolved tooth gain to a cluster of ten QTL-associated single nucleotide variants, all within intron four of Bone Morphogenetic Protein 6 (Bmp6). Transgenic reporter assays revealed this intronic region contains a tooth enhancer. We induced mutations in Bmp6, revealing required roles for survival, growth, and tooth patterning. Transcriptional profiling of Bmp6 mutant dental tissues identified significant downregulation of a set of genes whose orthologs were previously shown to be expressed in quiescent mouse hair stem cells. Collectively these data support a model where mutations within a Bmp6 intronic tooth enhancer contribute to evolved tooth gain, and suggest that ancient shared genetic circuitry regulates the regeneration of diverse vertebrate epithelial appendages including mammalian hair and fish teeth.

Face and neck rejuvenation using an improved non-ablative fractional high power 1064-nm Q-switched Nd:YAG Laser: clinical results in 16 women.

OBJECTIVE: To evaluate the safety and efficacy of a specific treatment protocol using a new and improved non-ablative fractional high-power 1064-nm Q-switched Nd:YAG laser for face and neck rejuvenation. METHODS: Sixteen women, aged 30 to 60 years old, were selected to undergo three consecutive treatment sessions with this new laser at maximum energy (2,400 mJ/pulse, Clear Lift laser®-Harmony XL-Pro, Alma Lasers Ltd.). Face and neck were treated in eight patients, respectively. Each treatment used the same protocol. The efficacy was evaluated by the therapist (TS), the patient (PS), and two separate independent experts who were blind to the study (E1 and E2). RESULTS: According to E1 and E2, the mean reduction in signs of skin aging on a Global Esthetic Improvement Scale was 30-40%. Using a 0-10 points scale, TS and PS mean (range) satisfaction rates were 9.0 (8-10); 9.2 (6-10) for the face and 8.7 (8-10); 8.0 (3-10), for the neck, respectively. The procedure was practically painless, no significant adverse effects were observed, and the patients returned to their daily and work activities without downtime. CONCLUSION: This laser was safe and effective for face and neck minimally invasive rejuvenation, with excellent results using our usual routine use conditions.

Correction to: Concomitant Use of Hyaluronic Acid and Laser in Facial Rejuvenation.

The article Concomitant Use of Hyaluronic Acid and Laser in Facial Rejuvenation written by Urdiales-Gálvez et al. was originally published electronically on the publisher's internet portal (currently SpringerLink) on May 9, 2019, without open access.

The Unintended Impact of Colombia's Covid-19 Lockdown on Forest Fires.

The covid-19 pandemic led to rapid and large-scale government intervention in economies and societies. A common policy response to covid-19 outbreaks has been the lockdown or quarantine. Designed to slow the spread of the disease, lockdowns have unintended consequences for the environment. This article examines the impact of Colombia's lockdown on forest fires, motivated by satellite data showing a particularly large upsurge of fires at around the time of lockdown implementation. We find that Colombia's lockdown is associated with an increase in forest fires compared to three different counterfactuals, constructed to simulate the expected number of fires in the absence of the lockdown. To varying degrees across Colombia's regions, the presence of armed groups is correlated with this fire upsurge. Mechanisms through which the lockdown might influence fire rates are discussed, including the mobilisation of armed groups and the reduction in the monitoring capacity of state and conservation organisations during the covid-19 outbreak. Given the fast-developing situation in Colombia, we conclude with some ideas for further research.

Cluster analysis of autoimmune rheumatic diseases based on autoantibodies. New insights for polyautoimmunity.

Autoimmune diseases (ADs) are a chronic and clinically heterogeneous group of diseases characterized by share common immunopathogenic mechanisms and risk factors (i.e., the autoimmune tautology), which explain the fact that one AD may coexist with others (i.e., polyautoimmunity - PolyA). In the present exploratory study, a mixed-cluster analysis of the most common autoimmune rheumatic diseases (ARDs) was done. A total of 187 consecutive women with established systemic lupus erythematosus (n = 70), rheumatoid arthritis (n = 51), systemic sclerosis (n = 35) and Sjögren's syndrome (n = 31) were included. A comprehensive clinical, autoantibody and cytokine assessment was simultaneously done. Total PolyA was registered in 142 (75.9%) patients. Six clusters were obtained, built mainly on autoantibodies: PolyA-I to -VI. The PolyA-III cluster showed the highest frequency of overt PolyA (p = 0.01), and the PolyA-I, -III, and -IV clusters exhibited the highest positivity for IL-12/23p40 (p = 0.015). These results provide new insights into the pathophysiology of PolyA and warrant prospective validation to enable development of a more accurate taxonomy of ARDs.

Cytokine imbalance in patients with systemic sclerosis and resilience: the key role of interleukin-6.

OBJECTIVES: Resilience, the ability to respond positively to adverse events, may be influenced by long-term stressors and autoimmune/inflammatory conditions such as systemic sclerosis (SSc). Since the immune system plays a role in the development of resilience, we aimed to evaluate the relationship between a panel of cytokines and resilience in patients with SSc. METHODS: Thirty-five consecutive women with established SSc were involved in this exploratory study. Clinical characteristics, including severity of symptoms and resilience, a panel of 15 serum cytokines and 17 autoantibodies were assessed simultaneously. Multivariate methods were used to analyse the data. RESULTS: Interleukin-6 (IL-6) levels were associated with severity of symptoms (ß=1.8395, p=0.04), and low resilience scores (ß= -0.581120, p=0.02). Furthermore, resilience was not associated with clinical manifestations nor polyautoimmunity. Cytokine levels did not significantly differ between groups based on regular physical activity. CONCLUSIONS: The results highlight the importance of IL-6 as a key mediator in the altered cytokine network of SSc.

Watershed integrity and associations with gastrointestinal illness in the United States.

Gastrointestinal (GI) illnesses are associated with various environmental factors, such as water quality, stormwater runoff, agricultural runoff, sewer overflows, and wastewater treatment plant effluents. However, rather than assessing an individual factor alone, two indices incorporating a combination of ecological and environmental stressors were created to represent (1) overall watershed integrity, Index of Watershed Integrity (IWI) and (2) catchment integrity, Index of Catchment Integrity (ICI). These indices could provide a more comprehensive understanding of how watershed/catchment integrity potentially impact the rates of GI illness, compared to assessing an individual stressor alone. We utilized the IWI and ICI, as well as agricultural and urban land uses, to assess associations at the county level with the rates of GI illness in a population of adults over 65 years of age. Our findings demonstrated that both watershed and catchment integrity are associated with reduced hospitalizations for any GI outcomes, though association varied by urbanicity. We believe that improved versions of the IWI and ICI may potentially be useful indicators for public health analyses in other circumstances, particularly when considering rural areas or to capture the complex stressors impacting the ecological health of a watershed.

Histopathological Changes After Experimental Skin Resurfacing Using an Improved Fractional High-Power 1064-nm Q-Switched Nd:YAG Laser

BACKGROUND: Several studies confirm microscopic changes in the cutaneous architecture following various rejuvenation techniques using non-ablative lasers. OBJECTIVE: To investigate the histological changes that occur after the application of an improved high-power 1064-nm fractional Q-switched Nd: YAG laser, using different focusing tips. MATERIAL AND METHODS: Experimental skin resurfacing of the retroauricular area in 15 female volunteers, in three treatment sessions of one pass each, using the Clear Lift® laser (Alma Lasers, Israel) and five different focusing tips. Biopsies were taken before and immediately after the first treatment session, one month after the first session, and one month after the third session. A total of 60 microscopic images were evaluated at a micrometric scale. RESULTS: The five tips used caused characteristic and similar histological changes in both the dermis and the epidermis. The signs of thermal damage and the formation of new collagen were observed at different depths, in accordance with the focal length of each tip. Neo-formation of collagen with the increase, reorganization and compaction of fibers began one month after the first treatment session, and was blindly confirmed, with all the tips used, one month after the third treatment session. CONCLUSION: The skin takes on a new conformation, with histological signs of skin rejuvenation, concordant with previous clinical observations. J Drugs Dermatol. 2019;18(12):1261-1266.

Concomitant Use of Hyaluronic Acid and Laser in Facial Rejuvenation.

BACKGROUND: Facial aging is a process that involves many different changes. Therefore, in many patients, it may be necessary to perform a combined treatment. Botulinum toxin A and dermal fillers are the two most popular nonsurgical cosmetic procedures performed globally to treat age-associated changes. However, there are not many studies reporting the concomitant use of dermal fillers and laser technology for facial rejuvenation. This review aims to assess the concomitant use of dermal hyaluronic acid (HA) fillers and laser technology for facial rejuvenation. METHODS: The present updated consensus recommendations are based on the experience and opinions of the authors and on a literature search. RESULTS: If a combined procedure (HA and light treatments) is to be performed, on the same day, the panel recommends starting always with the light treatments, avoiding skin manipulations after having injected HA. To customize the therapeutic management, it is crucial to establish a precise diagnosis of the photodamage and loss of volumes suffered by the patients. CONCLUSIONS: The currently available scientific evidence about the combined use of HA fillers and laser-radiofrequency-intense pulsed light (laser/RF/IPL) is limited and encompasses mainly small and nonrandomized studies. Nevertheless, most of these studies found that, on average, the concomitant use (same day) of laser and HA fillers for facial rejuvenation represents an effective and safe strategy which improves clinical results and patient's satisfaction. Future well-designed clinical studies are needed regarding the effectiveness and safety of combination filler/laser treatments. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cytokine and autoantibody clusters interaction in systemic lupus erythematosus.

BACKGROUND: Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed. METHODS: This was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables. RESULTS: First, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity. CONCLUSION: These results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.

A comprehensive analysis and immunobiology of autoimmune neurological syndromes during the Zika virus outbreak in Cúcuta, Colombia.

We have focused on the epidemiology and immunobiology of Zika virus (ZIKV) infection and factors associated with the development of Guillain-Barré syndrome (GBS) and other neurological syndromes in Cúcuta, the capital of North Santander department, Colombia. Data of patients with ZIKV disease reported to the national population-based surveillance system were used to calculate the basic reproduction number (R0) and the attack rates (ARs) as well as to develop epidemiological maps. Patients with neurological syndromes were contacted and their diagnoses were confirmed. A case-control study in which 29 patients with GBS associated with ZIKV compared with 74-matched control patients with ZIKV infection alone was undertaken. Antibodies against arboviruses and other infections that may trigger GBS were evaluated. The estimated value of R0 ranged between 2.68 (95% CI 2.54-2.67) to 4.57 (95% CI 4.18-5.01). The sex-specific ARs were 1306 per 100,000 females, and 552 per 100,000 males. A non-linear interaction between age and gender on the ARs was observed. The incidence of GBS in Cúcuta increased 4.41 times secondary to ZIKV infection. The lag time between ZIKV infection and neurological symptoms was 7 days (interquartile range 2-14.5). Patients with GBS appeared to represent a lower socioeconomic status and were living near to environmentally contaminated areas. All GBS patients were positive for IgG antibodies against both ZIKV and Dengue virus, and 69% were positive for Chikungunya virus. Noteworthy, GBS was associated with a previous infection with M. pneumoniae (OR: 3.95; 95% CI 1.44-13.01; p = 0.006). No differences in antibody levels against C. jejuni, Epstein-Barr virus and cytomegalovirus were observed. High rates of cranial nerves involvement and dysautonomia were present in 82% and 75.9%, respectively. Intensive care unit (ICU) admission was necessary in 69% of the GBS patients. Most of the patients disclosed a high disability condition (Hughes grade 4). Dysautonomia was the main risk factor of poor GBS prognosis (i.e., ICU admission and disability). Thirteen patients were diagnosed with other neurological syndromes different to GBS (6 with transverse myelitis, 3 with encephalitis, 3 with peripheral facial palsy and one with thoraco-lumbosacral myelopathy). Our data confirm an increased transmission of ZIKV in Cúcuta, and provide support to the view that severe neurological syndromes are related to ZIKV disease. The complex ways by which previous infections and socioeconomic status interact to increase the risk of GBS in people infected by ZIKV should be further investigated.

Evolved tooth gain in sticklebacks is associated with a cis-regulatory allele of Bmp6.

Developmental genetic studies of evolved differences in morphology have led to the hypothesis that cis-regulatory changes often underlie morphological evolution. However, because most of these studies focus on evolved loss of traits, the genetic architecture and possible association with cis-regulatory changes of gain traits are less understood. Here we show that a derived benthic freshwater stickleback population has evolved an approximate twofold gain in ventral pharyngeal tooth number compared with their ancestral marine counterparts. Comparing laboratory-reared developmental time courses of a low-toothed marine population and this high-toothed benthic population reveals that increases in tooth number and tooth plate area and decreases in tooth spacing arise at late juvenile stages. Genome-wide linkage mapping identifies largely separate sets of quantitative trait loci affecting different aspects of dental patterning. One large-effect quantitative trait locus controlling tooth number fine-maps to a genomic region containing an excellent candidate gene, Bone morphogenetic protein 6 (Bmp6). Stickleback Bmp6 is expressed in developing teeth, and no coding changes are found between the high- and low-toothed populations. However, quantitative allele-specific expression assays of Bmp6 in developing teeth in F1 hybrids show that cis-regulatory changes have elevated the relative expression level of the freshwater benthic Bmp6 allele at late, but not early, stages of stickleback development. Collectively, our data support a model where a late-acting cis-regulatory up-regulation of Bmp6 expression underlies a significant increase in tooth number in derived benthic sticklebacks.

Autoimmune thyroid disease in Colombian patients with systemic lupus erythematosus.

OBJECTIVES: To determine the prevalence and the predictive factors of autoimmune hypothyroidism (AH) within a systemic lupus erythematosus (SLE) cohort and to analyse the current information concerning the prevalence and impact of autoimmune thyroid disease (AITD) and thyroid autoimmunity in patients with SLE. METHODS: A total of 376 patients with SLE were assessed for the presence of the following: (i) confirmed AH, (ii) positive thy-roperoxidase/thyroglobulin antibodies [TPOAb/TgAb] without hypothyroidism, (iii) nonautoimmune hypothyroidism and (iv) SLE patients with neither. Multivariate analysis and a classification and regression tree model were used to analyse data. The current information was discussed through a systematic literature review (SLR). RESULTS: In our cohort, the prevalence of confirmed AH was 12%. However, in euthyroid patients with SLE, TPOAb and TgAb were observed in 21% and 10%, respectively. Patients with confirmed AH were significantly older and had later age at onset of the disease. Smoking (adjusted odds ratio (AOR) 6·93, 95% CI 1·98-28·54, P = 0·004), Sjögren's Syndrome (SS) (AOR 23·2, 95% CI 1·89-359·53, P = 0·015) and positivity for anticyclic citrullinated peptide (anti-CCP) (AOR 10·35, 95% CI 1·04-121·26, P = 0·047) were associated with AH-SLE, regardless of gender and duration of the disease. Smoking and SS were confirmed as predictors of AH-SLE. In the SLR, the prevalence of AITD ranged from 1% to 60%. The factors associated with this polyautoimmunity were female gender, older age, smoking, certain autoantibodies, SS, and cutaneous and articular involvement. CONCLUSIONS: AITD is frequent in SLE and does not affect the severity of SLE. Identified risk factors will assist clinicians in the search for AITD. Our results encourage smoke-free policies in patients with SLE.

Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation.

This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum ferritin in patients who did not discontinue deferasirox therapy was significantly greater than that found in those who prematurely discontinued the treatment (from 1541 to 581 ng/mL vs. from 1416 to 1486 ng/mL; P=0.008). Drug-related adverse events, reported in 17 patients (56.7%), were mostly mild to moderate in severity. There were no drug-related serious adverse events. Twelve patients (40.0%) showed an increase of over 33% in serum creatinine compared to baseline and greater than the upper limit of normal on two consecutive visits. Two patients (6.7%) with active graft-versus-host disease showed an increase in alanine aminotransferase exceeding 10 times upper limit of normal; both resolved. In this prospective study, deferasirox provided a significant reduction in serum ferritin and liver iron concentration over one year of treatment in allogeneic hematopoietic stem cell transplant recipients with iron overload. In addition, the majority of adverse events related to deferasirox were mild or moderate in severity. (clinicaltrials.gov identifier:01335035).