Explore the vast range of titles available.

The contribution of the immune system to idiopathic pulmonary fibrosis (IPF) remains poorly understood. While most sources agree that IPF does not result from a primary immunopathogenic mechanism, evidence gleaned from animal modeling and human studies suggests that innate and adaptive immune processes can orchestrate existing fibrotic responses. This review will synthesize the available data regarding the complex role of professional immune cells in IPF. The role of innate immune populations such as monocytes, macrophages, myeloid suppressor cells, and innate lymphoid cells will be discussed, as will the activation of these cells pathogen-associated molecular patterns derived from invading or commensural microbes, and danger-associated molecular patterns derived from injured cells and tissues. The contribution of adaptive immune responses driven by T-helper cells and B cells will be reviewed as well. Each form of immune activation will be discussed in the context of its relationship to environmental and genetic factors, disease outcomes, and potential therapies. We conclude with discussion of unanswered questions and opportunities for future study in this area.

In spite of the psychosocial burden and medical risks associated with skin picking disorder, the health care system does not provide sufficient treatment for affected individuals to date. Therefore, an internet-based self-help program for skin picking was developed to offer easily accessible support for this population. This pilot study evaluated the internet-based self-help program SaveMySkin. The 12-week program is based on cognitive-behavioral therapy and contains comprehensive information and exercises, a daily supportive monitoring system, and dermatological and psychological counseling via internet chat. Primary objectives were the investigation of attitudes and expectations toward the program, intervention effects on skin picking severity, user satisfaction, adherence, and willingness to participate. Secondary outcomes included the feasibility of study procedures, adequacy of assessment instruments, effects on skin picking-related impairment, dimensions of skin picking, and general psychological impairment. A two-arm randomized controlled trial was conducted in a sample of 133 participants (female: 124/133, 93.2%; mean age 26.67 [SD 6.42]) recruited via the internet. Inclusion required a minimum age of 17 years and at least mild skin picking severity. Participants were randomly allocated to the intervention (64/133, 48.1%) or waitlist control group (69/133, 51.9%). All assessments were conducted online and based on self-report. The willingness to participate was very high in the study, so the initially planned sample size of 100 was exceeded after only 18 days. Participant expectations indicate that they believed the program to be beneficial for them (131/133, 98.5%) and provide a feeling of support (119/133, 89.5%). Reasons for study participation were insufficient outpatient health care (83/133, 62.4%) and flexibility regarding time (106/133, 79.7%) and location (109/133, 82.0%). The post-assessment was completed by 65.4% (87/133) of the sample. The majority of the intervention group who completed the entire post-assessment were satisfied with SaveMySkin (28/38, 74%) and agreed that the program is an appropriate support service (35/38, 92%). On average, participants viewed 29.31 (SD 42.02) pages in the program, and 47% (30/64) of the intervention group used the monitoring at least once a week. In comparison with the control group, the intervention group displayed substantial improvements in the skin picking severity total score (Cohen d=0.67) and especially on the subscale Symptom Severity (Cohen d=0.79). No effects on secondary outcomes were found. This study confirms the need for easily accessible interventions for skin picking disorder and the high interest in internet-based self-help within the target population. It provides important insights into the attitudes toward online support and actual user experiences. Participant feedback will be used to further enhance the intervention. Our results point to the preliminary efficacy of SaveMySkin and may lay the foundation for future research into the efficacy and cost-effectiveness of the program in a multicenter clinical trial. German Clinical Trial Register DRKS00015236; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00015236. RR2-10.1016/j.conctc.2018.100315.

Abstract Rationale Idiopathic pulmonary fibrosis (IPF) involves the accumulation of α-smooth muscle actin–expressing myofibroblasts arising from interactions with soluble mediators such as transforming growth factor-β1 (TGF-β1) and mechanical influences such as local tissue stiffness. Whereas IPF fibroblasts are enriched for aerobic glycolysis and innate immune receptor activation, innate immune ligands related to mitochondrial injury, such as extracellular mitochondrial DNA (mtDNA), have not been identified in IPF. Objectives We aimed to define an association between mtDNA and fibroblast responses in IPF. Methods We evaluated the response of normal human lung fibroblasts (NHLFs) to stimulation with mtDNA and determined whether the glycolytic reprogramming that occurs in response to TGF-β1 stimulation and direct contact with stiff substrates, and spontaneously in IPF fibroblasts, is associated with excessive levels of mtDNA. We measured mtDNA concentrations in bronchoalveolar lavage (BAL) from subjects with and without IPF, as well as in plasma samples from two longitudinal IPF cohorts and demographically matched control subjects. Measurements and Main Results Exposure to mtDNA augments α-smooth muscle actin expression in NHLFs. The metabolic changes in NHLFs that are induced by interactions with TGF-β1 or stiff hydrogels are accompanied by the accumulation of extracellular mtDNA. These findings replicate the spontaneous phenotype of IPF fibroblasts. mtDNA concentrations are increased in IPF BAL and plasma, and in the latter compartment, they display robust associations with disease progression and reduced event-free survival. Conclusions These findings demonstrate a previously unrecognized and highly novel connection between metabolic reprogramming, mtDNA, fibroblast activation, and clinical outcomes that provides new insight into IPF.

Dear Editor, Scleromyxedema is known as a rare, severe mucinosis with characteristic waxy skin papules along with sclerodermiform induration of the skin and rare systemic manifestations. Monoclonal gammopathy of undetermined significance (MGUS; mostly monoclonal immunoglobulin G [IgG] type lambda) can be detected in up to 90% of patients. [...]

Chronic graft-versus-host disease (cGVHD) remains the most significant long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), despite increasing insights into its pathogenesis. The development of reliable prognostic biomarkers is essential for identifying patients at high risk of developing cGVHD which may benefit from pre-emptive intervention. However, valid biomarkers remain elusive, and cGVHD is typically treated after clinical onset only, when irreversible manifestations such as ocular involvement may already be present. In this exploratory study, we identified ten cytokines and chemokines with potential prognostic value for predicting subsequent cGVHD. Using bead-based multiplex analysis, we assessed serum samples from 60 adult allo-HSCT recipients at day +90 and day +180 post-transplant to identify proteins distinguishing patients who later developed cGVHD from those who remained tolerant. Significant differences were found in the serum levels of BAFF, CCL4, CXCL9, and sRAGE between patients with de novo cGVHD and those without GVHD. In contrast, elevated IL-6, IL-17A, PAI-1, IL-10, CX3CL1, CXCL1, and CCL4 levels were prognostic for quiescent cGVHD compared with patients with resolved acute GVHD only. These findings underscore the biological heterogeneity of cGVHD and the limited value of single-biomarker approaches, emphasizing the need to consider distinct clinical subgroups and prior disease courses in future predictive models.

Pemphigus vulgaris is a severe and often therapy-resistant bullous autoimmune disease. Standard therapy with steroids often administered together with another immunosuppressant does not respond in all patients or may not be a good therapeutic option in patients with severe underlying diseases. Intravenous immunoglobulins (IVIgs) represent a treatment alternative, often showing a rapid response which allows one to reduce concomitant immunosuppression. Here, we report on two patients with a complex disease history suffering from severe pemphigus vulgaris who received treatment with a new IVIg preparation (Yimmugo ® , 2 g per kg body weight every 4 weeks). IVIg preparations differ regarding manufacturing process and show a varying side effect profile. Both of our patients did not experience any side effects from IVIgs and showed a significant improvement of skin and mucosal erosions. More reports on IVIgs are desirable to help in selecting the optimal preparation and dosing regarding tolerability and effectiveness for individual patients.

Generative AI is increasingly used to create texts, including fictional stories. Do stories generated by AI differ from stories created by humans regarding linguistic properties and recipients’ experiences? To answer these questions, we first asked ChatGPT and 100 non-professional human authors (i.e., students) to create stories based on similar prompts (Study 1). Linguistic analyses showed that ChatGPT stories included fewer personal pronouns and fewer descriptions of relativity than human stories, but more positive emotions. In Study 2 ( N  = 380), naïve participants were randomly assigned to read an AI-generated or a human story from the pool of 200 stories from Study 1. No differences in novelty or entertainment experiences were found, but the readers of AI stories were less transported into the story world. Mediation analyses show that this difference can be attributed to ChatGPT’s use of fewer personal pronouns. Differences in the use of literary techniques between AI and humans are discussed.

Treatment of metastatic melanoma remains challenging, despite a variety of new and promising immunotherapeutic and targeted approaches to therapy. New treatment options are still needed to improve long-term tumour control. We present a case series of seven patients with metastatic melanoma who were treated individually with the anti-CD20 antibody rituximab between July 2014 and July 2015. Two of the patients were treated in an adjuvant setting. All patients had already received a variety of treatments. During an induction phase, the administration of four cycles of weekly rituximab 375 mg/m2 body surface area was planned. After imaging, patients with stable disease continued therapy with rituximab 375 mg/m2 body surface area every 4 weeks up to a maximum of 24 weeks. Two patients experienced grade 2 infusion reactions during the first infusion. Otherwise, treatment was well tolerated and there were no grade 3 or 4 side effects. Staging after the induction phase showed stable disease in five patients, and two patients had progressive disease. Median progression-free survival was 6.3 months (95% CI 4.97–7.53), median overall survival was 14.7 months (95% CI 4.52–24.94), and one patient was still alive in December 2016. In conclusion, rituximab might be a therapeutic option for metastatic melanoma. However, further studies on rituximab among larger patient cohorts are warranted. Evaluation of therapy in an adjuvant setting or in combination with other systemic treatment might, therefore, be of particular interest.

Abstract Introduction: We provide a case report on a patient with scleromyxedema treated with high-dose intravenous immunoglobulins (IVIgs) who reported less fatigue and fewer headaches after transitioning to Yimmugo, a novel IVIg preparation. Scleromyxedema is a rare and chronic cutaneous mucinosis, frequently associated with monoclonal gammopathy and systemic complications, which may be life-threatening. The disease is characterized by papular eruptions and sclerosis of the skin. Treatment of scleromyxedema is challenging because of its unclear pathogenesis. High-dose IVIgs are a promising treatment option to improve cutaneous manifestations. Case Presentation: We present the case of a 57-year-old patient with scleromyxedema and monoclonal gammopathy with end-stage renal failure on hemodialysis (3 times a week). Stabilization of skin symptoms was finally achieved by high-dose IVIg therapy administered at 2 g per kg bodyweight distributed over 2 days every 3 weeks. However, disease stabilization came at the expense of flu-like side effects that significantly affected daily life. After transitioning to Yimmugo®, the patient reported an improved quality of life. Conclusion: Further follow-up is essential to conclusively evaluate effectiveness and tolerability of this novel IVIg preparation.

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis (AIBD) characterized by painful blistering of the skin and mucosa caused by autoantibodies that lead to loss of adhesion in the epidermis. Standard therapy for PV is corticosteroids, either alone or in combination with steroid-sparing immunosuppressants or infusions with rituximab. According to the published European guideline, high-dose intravenous immunoglobulin (IVIg) therapy with a dosage of 2 g per kg body weight distributed over 2–5 days every 4 weeks is a promising treatment option, especially for severe or refractory disease. This report describes a 73-year-old female patient with severe and recurrent disease who achieved stabilization with IVIg treatment. However, the patient experienced side effects such as headaches, nausea, and vomiting, which affected daily life. Hence, she was transitioned to a new IVIg preparation with a new manufacturing process, resulting in fewer side effects and an improved quality of life. Further follow-up is necessary to fully evaluate the effectiveness and tolerability of this new IVIg product.