Clinical features of patients with systemic sclerosis positive for anti-SS-A antibody: a cohort study of 156 patients.

BACKGROUND: Anti-SS-A/Ro antibody (anti-SSA), the diagnostic marker of Sjögren's syndrome (SS), is often detected in systemic sclerosis (SSc). Some patients are diagnosed with SSc/SS overlap syndromes, while there are anti-SSA-positive SSc cases without SS. In this study, we investigated the clinical characteristics of SSc with anti-SSA and clarified the clinical impact of this antibody in SSc. METHODS: A retrospective chart review was conducted of 156 patients with SSc at Yokohama City University Hospital from 2018 to 2021. Clinical data, laboratory data, imaging, and autoantibody positivity status were collected and analysed to assess the association between these variables and anti-SSA using multivariable logistic regression analysis. RESULTS: This cohort included 18 men and 138 women with SSc (median age, 69.0 years). Thirty-nine patients had diffuse cutaneous SSc (dcSSc) (25%), and 117 patients had limited cutaneous SSc (75%). Forty-four patients were anti-SSA-positive. Among them, 24 fulfilled the SS criteria. Multivariable logistic regression revealed that anti-SSA was statistically associated with interstitial lung disease (ILD; odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.14-6.3; P = 0.024). Meanwhile, anti-SSA positivity tended to increase the development of digital ulcer (OR = 2.18; 95% CI, 0.99-4.82, P = 0.054). In the comparative analysis of the autoantibody single-positive and anti-SSA/SSc-specific autoantibody double-positive groups, the anti-SSA single-positive group showed a significantly increased risk of ILD (OR = 12.1; 95% CI, 2.13-140.57; P = 0.003). Furthermore, patients with SSc and anti-SSA indicated that anti-SSA-positive SSc without SS was strongly associated with dcSSc when compared to that in patients with SS (OR = 6.45; 95% CI, 1.23-32.60; P = 0.024). CONCLUSIONS: Anti-SSA positivity increases the risk of organ involvement, such as ILD, in patients with SSc. Additionally, the anti-SSA-positive SSc without SS population may have more severe skin fibrosis than others. Anti-SSA may be a potential marker of ILD and skin severity in SSc.

Retrospective study of the clinical significance of the neutrophil-to-lymphocyte ratio in 79 patients with palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic relapsing inflammatory skin disease characterized by multiple vesicles, pustules, and erythematous plaques on the palms and soles. The exacerbation of PPP is strongly associated with focal infections, such as tonsillitis, dental infections, and sinusitis, in Japan. Recently, the neutrophil-to-lymphocyte ratio (NLR) has been widely used as a convenient and useful marker for clinical conditions and various diseases; however, an association between PPP and NLR has not yet been established. We retrospectively analyzed 79 patients with PPP from our hospital to evaluate the clinical significance of the NLR. The average NLR value in patients with PPP was significantly higher than that in healthy controls (2.30 ± 1.02 vs 1.69 ± 0.45, P < 0.001). A comparative analysis of patients with PPP with and without infectious complications showed that there was a statistical difference in the NLR between patients with PPP with and without focal infections, whereas no significant difference was found for metal allergy, smoking, and pustulotic arthro-osteitis. Multivariate analysis indicated that the NLR was significantly associated with focal infections (odds ratio = 18.38, 95% confidence interval 3.86-87.35, P < 0.001). The NLR was also significantly correlated with C-reactive protein levels (P = 0.013, r = 0.2857). Interestingly, after symptom improvement, the NLR significantly decreased from the baseline levels. Furthermore, statistical analysis using the Youden's index revealed that an NLR of 2.28 or higher was associated with the risk of any focal infections in patients with PPP. These results suggest that the NLR has potential applications as a biomarker of the presence of focal infections in patients with PPP.

Head impact differences in blind football between Rio 2016 and Tokyo 2020 Paralympic Games: video-based observational study.

OBJECTIVE: In Tokyo 2020 Paralympic Games, there were the rule and goal size changes at the blind football competition. This study aimed to compare the scoring and head impact characteristics during blind football competition between the Rio 2016 and Tokyo 2020 Paralympic Games using the official videos. DESIGN: Video-based observational study. PARTICIPANTS: In total, 36 blind football (men's football 5-a-side) game videos were obtained from the official International Paralympic Committee. PRIMARY AND SECONDARY OUTCOME MEASURES: Head impact was defined as the sudden contact of any object with the head. Videos were analysed to assess the number of scores and head impacts along with their corresponding details (ie, round, playing phase, scoring situation, impact situation, occurrence area, impact object, head impact site, fall and foul). RESULTS: The total number of goals scored at the Tokyo 2020 Paralympic Games was nearly double that at the Rio 2016 Paralympic Games. Regarding head impacts, a total of 2036 cases (Rio 2016, n=1105; Tokyo 2020, n=931) were evaluated. Significant differences were observed in head impact characteristics between the Rio 2016 and Tokyo 2020 Paralympic Games among seven outcomes (round, scoring situation, impact situation, occurrence area, impact object, site of head impact and fall). CONCLUSIONS: Compared with the Rio 2016 Paralympic Games, the Tokyo 2020 Paralympic Games showed an increase in the number of points scored and different head impact characteristics.

Effectiveness of Metaverse Space-Based Exercise Video Distribution in Young Adults: Randomized Controlled Trial.

BACKGROUND: In response to the serious lack of physical activity among young adults, recent attempts have been made to encourage young people to exercise through exercise video distribution. However, merely distributing videos does not lead to improved physical activity levels. Metaverse space, which enables web-based interaction through avatars, allows users to watch exercise videos in the same space as other avatars. OBJECTIVE: This study explored whether exercise video distribution using metaverse space is effective in improving physical activity levels, along with mental health and locomotive function, among young people. METHODS: In this parallel-group randomized controlled trial participants were recruited using printed poster displays. A total of 48 young adults aged between 18 and 30 years were assigned to 3 groups of 16 each: the metaverse, YouTube, and control group. To encourage exercise, the metaverse group was given an exercise video each week with a load of around 4-8 metabolic equivalents of tasks (METs) for 8 videos delivered in the metaverse space. The YouTube group was sent a URL on YouTube every week to view exercise videos with the same content as the metaverse group. The control group was given no special instructions. The intervention period was 8 weeks. Pre- and postintervention physical activity, well-being, locomotive syndrome risk tests, and social capital were measured. Although this study was not blinded to the participants, the measurers did not know to which group the participants belonged. Mixed model repeated-measures analyses and a post hoc Wilcoxon signed rank sum test were performed to detect the effects of the intervention in all groups. RESULTS: The results of the mixed model repeated-measures analyses showed a significant interaction between groups and before and after the intervention for total physical activity (metaverse group: pre 737.1, SD 609.5 METs/week, post 1575.4, SD 1071.8 METs/week; YouTube group: pre 661.7, SD 710.7 METs/week, post 911.9, SD 1103.3 METs/week; and control group: pre 930.6, SD 665.1 METs/week, post 844.7, SD 701.8 METs/week; P=.04) but none for the indicators of well-being (P=.40), locomotive function scale (P=.17), and social capital (P=.23). A post hoc test showed a significant increase in physical activity in the metaverse group before and after the intervention (P=.006). CONCLUSIONS: This study is the first to show that delivering exercise videos through metaverse space can increase physical activity in young adults by providing a gathering space for individuals similarly motivated for exercise practice. This way, the sense of isolation during exercise is reduced compared with merely distributing videos on YouTube. The use of metaverse space in health promotion is likely to spread, and this study provides a useful reference for its exploration. TRIAL REGISTRATION: ClinicalTrials.gov NCT06019156; https://ichgcp.net/clinical-trials-registry/NCT06019156.

Periostin-An inducer of pro-fibrotic phenotype in monocytes and monocyte-derived macrophages in systemic sclerosis.

Enhanced circulating blood periostin levels positively correlate with disease severity in　patients with systemic sclerosis (SSc). Monocytes/macrophages are predominantly associated with the pathogenesis of SSc, but the effect of periostin on immune cells, particularly monocytes and macrophages, still remains to be elucidated. We examined the effect of periostin on monocytes and monocyte-derived macrophages (MDM) in the pathogenesis of SSc. The modified Rodnan total skin thickness score in patients with dcSSc was positively correlated with the proportion of CD80-CD206+ M2 cells. The proportion of M2 macrophages was significantly reduced in rPn-stimulated MDMs of HCs compared to that of SSc patients. The mRNA expression of pro-fibrotic cytokines, chemokines, and ECM proteins was significantly upregulated in rPn-stimulated monocytes and MDMs as compared to that of control monocytes and MDMs. A similar trend was observed for protein expression in the respective MDMs. In addition, the ratio of migrated cells was significantly higher in rPn-stimulated as compared to control monocytes. These results suggest that periostin promotes inflammation and fibrosis in the pathogenesis of SSc by possible modulation of monocytes/macrophages.

Post-orgasmic illness syndrome with positive intradermal test for autologous semen.

Post-orgasmic illness syndrome (POIS) is a rare disease characterized by flu-like symptoms persisting for 2-7 days after ejaculation. POIS has been chiefly attributed to allergic reactions to autologous seminal plasma. However, the exact pathophysiology remains unclear, and there is no effective treatment. We present the case of a 38-year-old man with a 10-year history of recurrent episodes of flu-like symptoms of 1-week duration after ejaculation. The patient was diagnosed with irritating bowel syndrome because of fatigue, myalgia, and lateral abdominal pain. After starting infertility treatment and increasing the frequency of intercourse with his wife, the patient noticed these symptoms after ejaculation. Based on these episodes and symptoms, POIS was suspected. To diagnose POIS, a skin prick test and an intradermal test were performed using his seminal fluid, with the latter yielding a positive result. The patient was diagnosed with POIS, and treatment with antihistamines was continued. Due to its rarity, POIS is often underdiagnosed and underreported; however, the skin test can be a valid diagnostic tool. In this case, the intradermal test result was positive according to the broadly accepted criteria for POIS. Although quality of life is often severely affected in patients with POIS, a lack of a clear understanding of the pathogenesis of POIS prevents early diagnosis. To make diagnoses earlier, it is undoubtedly important to take a detailed medical history and perform skin allergy tests, although the latter requires further validation.

Cutaneous manifestations associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block key mediators of tumor-mediated immune evasion. The frequency of its use has increased rapidly and has extended to numerous cancers. ICIs target immune checkpoint molecules, such as programmed cell death protein 1 (PD-1), PD ligand 1 (PD-L1), and T cell activation, including cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). However, ICI-driven alterations in the immune system can induce various immune-related adverse events (irAEs) that affect multiple organs. Among these, cutaneous irAEs are the most common and often the first to develop. Skin manifestations are characterized by a wide range of phenotypes, including maculopapular rash, psoriasiform eruption, lichen planus-like eruption, pruritus, vitiligo-like depigmentation, bullous diseases, alopecia, and Stevens-Johnson syndrome/toxic epidermal necrolysis. In terms of pathogenesis, the mechanism of cutaneous irAEs remains unclear. Still, several hypotheses have been proposed, including activation of T cells against common antigens in normal tissues and tumor cells, increased release of proinflammatory cytokines associated with immune-related effects in specific tissues/organs, association with specific human leukocyte antigen variants and organ-specific irAEs, and acceleration of concurrent medication-induced drug eruptions. Based on recent literature, this review provides an overview of each ICI-induced skin manifestation and epidemiology and focuses on the mechanisms underlying cutaneous irAEs.

CXCL9 Links Skin Inflammation and Fibrosis through CXCR3-Dependent Upregulation of Col1a1 in Fibroblasts.

Morphea is characterized by initial inflammation followed by fibrosis of the skin and soft tissue. Despite its substantial morbidity, the pathogenesis of morphea is poorly studied. Previous work showed that CXCR3 ligands CXCL9 and CXCL10 are highly upregulated in the sera and lesional skin of patients with morphea. We found that an early inflammatory subcutaneous bleomycin mouse model of dermal fibrosis mirrors the clinical, histological, and immune dysregulation observed in human morphea. We used this model to examine the role of the CXCR3 chemokine axis in the pathogenesis of cutaneous fibrosis. Using the REX3 (Reporting the Expression of CXCR3 ligands) mice, we characterized which cells produce CXCR3 ligands over time. We found that fibroblasts contribute the bulk of CXCL9-RFP and CXCL10-BFP by percentage, whereas macrophages produce high amounts on a per-cell basis. To determine whether these chemokines are mechanistically involved in pathogenesis, we treated Cxcl9-, Cxcl10-, or Cxcr3-deficient mice with bleomycin and found that fibrosis is dependent on CXCL9 and CXCR3. Addition of recombinant CXCL9 but not CXCL10 to cultured mouse fibroblasts induced Col1a1 mRNA expression, indicating that the chemokine itself contributes to fibrosis. Taken together, our studies provide evidence that CXCL9 and its receptor CXCR3 are functionally required for inflammatory fibrosis.

Risks of malignancies among patients with psoriasis: A cohort study of 360 patients.

Psoriasis is a systemic, chronic, immunologically-mediated disease affecting approximately 2%-4% of the worldwide population. It is well known that psoriasis is associated with several comorbidities such as metabolic syndrome, cardiovascular disease, and malignancy. Although meta-analyses and large prospective cohort studies have shown an increased risk of malignancies in patients with psoriasis worldwide, an association between psoriasis and malignancy onset has not yet been established in Japan. We retrospectively analyzed 360 patients with psoriasis at our hospital to evaluate the incidence and types of malignancies in these patients. The incidence rate of malignancy was 14.4% (52/360). Colorectal cancer was the most commonly associated malignancy (20.9%), followed by skin cancer (16.4%), gastric cancer (10.4%), and lung cancer (10.4%). The calculated age- and sex-standardized incidence ratio of malignancies was 1.235 (95% CI 0.952-1.601) which indicated that the malignancy rate was higher in patients with psoriasis than in the general population, although the difference was not statistically significant. Furthermore, the multivariate analysis revealed increased risk of malignancy in males (HR = 3.15; 95% CI 1.381-7.187; p < 0.001), psoriasis onset at older age (HR = 1.08; 95% CI 1.058-1.111; p < 0.01), and psoriatic erythroderma (HR = 4.44; 95% CI 1.354-14.581; p < 0.05). We also observed that treatment with biological agents tends to reduce the risk of developing malignancy; however, no statistical significance was found. These results suggest that periodic screening for malignancy should be recommended in patients with psoriasis having these risk factors and in those with poorly controlled psoriatic inflammation.

Serum levels of C-C motif chemokine ligand 2 and interleukin-8 as possible biomarkers in patients with toxic epidermal necrolysis accompanied by acute respiratory distress syndrome.

Toxic epidermal necrolysis (TEN) is a fatal cutaneous adverse reaction that occasionally affects multiple organs. Acute respiratory distress syndrome (ARDS) is a rare complication that can cause rapid and potentially fatal pulmonary dysfunction. However, the mechanisms underlying TEN-induced ARDS remain unknown. This retrospective single-center study aimed to identify potential biomarkers for predicting ARDS onset in TEN patients. Pre-treatment serum samples were collected from 16 TEN patients and 16 healthy controls (HCs). The serum levels of cytokines/chemokines were determined using the Luminex Assay Human Premixed Multi-analyte kit. The expression levels of cytokines and chemokines in the skin were examined via immunohistochemistry. The serum levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-6, and IL-8 were significantly higher in TEN patients with ARDS than in those without ARDS and in HCs, whereas those of CCL2 and IL-8 were not significantly different between TEN patients without ARDS and HCs. There was no significant difference in CCL2 and IL-8 expression in the skin between TEN patients with and without ARDS. Interestingly, there were no significant differences in the cytokine/chemokine levels between TEN and other organ damage, other than ARDS and TEN without any organ damage. We further analyzed the changes in cytokine/chemokine levels before and after treatment in two TEN patients with ARDS. CCL2, IL-6, and IL-8 levels decreased after systemic treatment compared to their baseline levels before treatment at an early stage. These results suggest that IL-8 and CCL2 may be involved in the pathogenesis of TEN-induced ARDS and have potential application as predictive markers for ARDS onset.

Deep Learning Enables Instant and Versatile Estimation of Rice Yield Using Ground-Based RGB Images.

Rice (Oryza sativa L.) is one of the most important cereals, which provides 20% of the world's food energy. However, its productivity is poorly assessed especially in the global South. Here, we provide a first study to perform a deep-learning-based approach for instantaneously estimating rice yield using red-green-blue images. During ripening stage and at harvest, over 22,000 digital images were captured vertically downward over the rice canopy from a distance of 0.8 to 0.9 m at 4,820 harvesting plots having the yield of 0.1 to 16.1 t·ha-1 across 6 countries in Africa and Japan. A convolutional neural network applied to these data at harvest predicted 68% variation in yield with a relative root mean square error of 0.22. The developed model successfully detected genotypic difference and impact of agronomic interventions on yield in the independent dataset. The model also demonstrated robustness against the images acquired at different shooting angles up to 30° from right angle, diverse light environments, and shooting date during late ripening stage. Even when the resolution of images was reduced (from 0.2 to 3.2 cm·pixel-1 of ground sampling distance), the model could predict 57% variation in yield, implying that this approach can be scaled by the use of unmanned aerial vehicles. Our work offers low-cost, hands-on, and rapid approach for high-throughput phenotyping and can lead to impact assessment of productivity-enhancing interventions, detection of fields where these are needed to sustainably increase crop production, and yield forecast at several weeks before harvesting.

Ameliorating Fibrosis in Murine and Human Tissues with END55, an Endostatin-Derived Fusion Protein Made in Plants.

Organ fibrosis, particularly of the lungs, causes significant morbidity and mortality. Effective treatments are needed to reduce the health burden. A fragment of the carboxyl-terminal end of collagen XVIII/endostatin reduces skin and lung fibrosis. This fragment was modified to facilitate its production in plants, which resulted in the recombinant fusion protein, END55. We found that expression of END55 had significant anti-fibrotic effects on the treatment and prevention of skin and lung fibrosis in a bleomycin mouse model. We validated these effects in a second mouse model of pulmonary fibrosis involving inducible, lung-targeted expression of transforming growth factor ß1. END55 also exerted anti-fibrotic effects in human lung and skin tissues maintained in organ culture in which fibrosis was experimentally induced. The anti-fibrotic effect of END55 was mediated by a decrease in the expression of extracellular matrix genes and an increase in the levels of matrix-degrading enzymes. Finally, END55 reduced fibrosis in the lungs of patients with systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) who underwent lung transplantation due to the severity of their lung disease, displaying efficacy in human tissues directly relevant to human disease. These findings demonstrate that END55 is an effective anti-fibrotic therapy in different organs.

Adsorption Kinetics of Polystyrene and Poly(9-anthracenyl methyl methacrylate) onto SiO2 Surface Measured by Chip Nano-Calorimetry.

The alternating current (AC) chip nano-calorimetry is a powerful tool to investigate the physical properties of polymer thin films. In this paper, we report on the adsorption kinetics of polymers in which an AC chip nano-calorimetry was used for the first time. This technique allows for the real-time measurement of the adsorption kinetics of polymer chains onto the SiO2 surface. We used polystyrene (PS) and poly(9-anthracenyl methyl methacrylate) (PAMMA), which have different chemical natures and side group sizes. It was confirmed that the observed adsorption kinetics for PS were consistent with previously reported results obtained by dielectric spectroscopy. For PAMMA, we found characteristic adsorption kinetics, which shows a clear kink at the crossover between the early and later stages, while PS exhibits a lesser tendency of showing the kink as demonstrated by previously reported results.

E4 engages uPAR and enolase-1 and activates urokinase to exert antifibrotic effects.

Fibroproliferative disorders such as systemic sclerosis (SSc) have no effective therapies and result in significant morbidity and mortality. We recently demonstrated that the C-terminal domain of endostatin, known as E4, prevented and reversed both dermal and pulmonary fibrosis. Our goal was to identify the mechanism by which E4 abrogates fibrosis and its cell surface binding partner(s). Our findings show that E4 activated the urokinase pathway and increased the urokinase plasminogen activator (uPA) to type 1 plasminogen activator inhibitor (PAI-1) ratio. In addition, E4 substantially increased MMP-1 and MMP-3 expression and activity. In vivo, E4 reversed bleomycin induction of PAI-1 and increased uPA activity. In patients with SSc, the uPA/PAI-1 ratio was decreased in both lung tissues and pulmonary fibroblasts compared with normal donors. Proteins bound to biotinylated-E4 were identified as enolase-1 (ENO) and uPA receptor (uPAR). The antifibrotic effects of E4 required uPAR. Further, ENO mediated the fibrotic effects of TGF-ß1 and exerted TGF-ß1-independent fibrotic effects. Our findings suggest that the antifibrotic effect of E4 is mediated, in part, by regulation of the urokinase pathway and induction of MMP-1 and MMP-3 levels and activity in a uPAR-dependent manner, thus promoting extracellular matrix degradation. Further, our findings identify a moonlighting function for the glycolytic enzyme ENO in fibrosis.

Recent Dermatological Treatments for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Japan.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious conditions characterized by necrosis of the skin and mucus membranes, and are mainly caused by medication and infections. Although the exact pathomechanism of SJS/TEN remains unclear, keratinocyte death is thought to be triggered by immune reactions to these antigens. While there is no established therapy for SJS/TEN, corticosteroids and intravenous immunoglobulin (IVIG) have been utilized as immunomodulator. We previously conducted a study to evaluate the efficacy of IVIG therapy in Japanese patients with SJS/TEN. IVIG was administered at a dosage of 400 mg/kg/day for 5 consecutive days as an additional therapy with systemic steroids. Prompt amelioration was observed in seven of the eight patients. All patients survived without sequelae. Recently, we retrospectively analyzed 132 cases of SJS/TEN treated in our two hospitals. The mortality rates in the patients treated with methylprednisolone pulse were 0% (0/31) for SJS and 7.0% (3/43) for TEN, and 0% (0/10) in the TEN patients treated with methylprednisolone pulse in combination with IVIG. These results suggest that early treatment with high-dose steroids, including methylprednisolone pulse therapy, and IVIG together with corticosteroids are possible therapeutic options to improve the prognosis of SJS/TEN.

A pediatric case of Stevens-Johnson syndrome with acute liver failure, resulting in liver transplantation.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are fatal adverse skin reactions characterized by high fever, epidermal detachment, and mucositis. It is well known that SJS/TEN occasionally affects various organs, leading to permanent damage and death in some patients. Although acute liver dysfunction is a relatively common complication of SJS/TEN, severe acute liver dysfunction requiring liver transplantation is rare. We present the case of a 14-year-old girl with SJS complicated by severe and rapidly progressive liver dysfunction, specifically, acute liver failure (ALF) requiring liver transplantation. A lymphocyte transformation test showed positive results for acetaminophen and cefdinir. Furthermore, human leukocyte antigen (HLA) genotyping revealed the presence of the HLA-A*02:06 genotype, which is reported to be strongly associated with acetaminophen-related SJS/TEN with severe ocular complications. These results suggested that our patient may have presented with acetaminophen-induced SJS complicated by ALF, but no ocular complications. This is the first report of a pediatric patient with SJS who required liver transplantation. In rare instances, severe liver dysfunction requiring liver transplantation should be considered as a possible complication of SJS/TEN.

Downregulated IRF8 in Monocytes and Macrophages of Patients with Systemic Sclerosis May Aggravate the Fibrotic Phenotype.

Monocytes and macrophages may be involved in the pathogenesis of systemic sclerosis (SSc); however, the etiology and regulation of monocyte and macrophage function in SSc remain unknown. IRF8 is a transcriptional regulator that is essential for the differentiation and function of monocytes and macrophages and thus may be involved in the regulation of macrophage phenotypes in SSc fibrosis. In this study, we measured IRF8 levels in circulating monocytes of 26 patients with SSc (diffuse cutaneous SSc, n = 11; limited cutaneous SSc, n = 15) and 14 healthy controls. IRF8 levels were significantly suppressed in monocytes of patients with diffuse cutaneous SSc and correlated negatively with the modified Rodnan total skin thickness score. Next, we assessed expression levels of cell surface markers, cytokine profiles, and components of extracellular matrix in IRF8-silenced monocyte-derived macrophages. IRF8-silenced monocyte-derived macrophages displayed an M2 phenotype and significantly upregulated mRNA and protein levels of profibrotic factors and extracellular matrix components. Finally, we assessed skin fibrosis in myeloid cell-specific IRF8 conditional knockout (Irf8flox/flox; Lyz2Cre/+) mice and found upregulated mRNA levels of extracellular matrix components and increased bleomycin-induced skin fibrosis. In conclusion, altered IRF8 regulation in monocytes and macrophages may be involved in SSc pathogenesis.

Mortality and risk factors on admission in toxic epidermal necrolysis: A cohort study of 59 patients.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening disorders characterized by widespread epidermal necrosis of the skin and mucosa. The severity-of-illness scoring system for TEN (SCORTEN) was widely used since 2000 as a standard prognostic tool consisting of seven clinical values. METHODS: To evaluate the prognosis using current treatments and risk factors for mortality, we retrospectively analyzed 59 cases of TEN, including SJS/TEN overlap treated in two university hospitals from January 2000 to March 2020. RESULTS: The mortality rate of TEN was 13.6% (8/59). All patients treated with high-dose steroid administration in combination with plasma exchange and/or immunoglobulin therapy recovered. Logistic regression analysis showed nine clinical composite scores, namely: heart rate (≧120 bpm), malignancy present, percentage of body surface area with epidermal detachment (>10%), blood urea nitrogen (>28 mg/dL), serum bicarbonate level (<20 mEq/L), serum glucose level (>252 mg/dL), age (≧71 years), the interval between disease onset and treatment initiation at the specialty hospital (≧8 days), and respiratory disorder within 48 h after admission. The receiver operating characteristic curves confirmed a high potential for predicting the prognosis of TEN. CONCLUSIONS: Recent developments in treatment strategies have contributed to the improved prognosis of TEN patients. A modified severity scoring model composed of nine scores may be helpful in the prediction of TEN prognosis in recent patients. Further large-scale studies are needed to confirm mortality findings to improve prognostication in patients with TEN.