Deep cardiac phenotyping by cardiovascular magnetic resonance reveals subclinical focal and diffuse myocardial injury in patients with psoriasis (PSOR-COR study).

BACKGROUND: Psoriasis vulgaris (PV) is a chronic inflammatory disorder frequently associated with cardiovascular disease (CVD). This study aims to provide a prospective tissue characterization in patients with PV without major CVD using cardiovascular magnetic resonance (CMR). METHODS: Patients with PV underwent laboratory assessment, a 12-lead and 24-h ECG, and a CMR exam at a 1.5-T scanner. Scan protocol included assessment of left (LV) and right (RV) ventricular function and strain analysis, native and post-contrast T1 mapping, T2 mapping and late gadolinium enhancement (LGE). RESULTS: In total, 60 PV patients (median(IQR) age in years: 50.0 (36.0-60.8); 34 men (56.7%)) were recruited and compared to 40 healthy volunteers (age in years: 49.5 (37.3-57.8); 21 men (53.0%)). No differences were found regarding LV and RV function (p = 0.78 and p = 0.75). Global radial and circumferential strains were lower in patients (p < 0.001 and p < 0.001, respectively). PV had higher global T1 times (1001 (982-1026) ms vs. 991 (968-1005) ms; p = 0.01) and lower global T2 times (48 (47-49) ms vs. 50 (48-51) ms; p < 0.001); however, all values were within local reference ranges. Focal non-ischemic fibrosis was observed in 17 (28.3%) PV patients. CONCLUSION: Deep cardiac phenotyping by CMR revealed subclinical myocardial injury in patients with PV without major CVD, despite preserved LV and RV function. Diffuse and focal fibrosis might be the first detectable signs of adverse tissue remodeling leading to reduced circumferential and radial myocardial deformation. In the background of local and systemic immunomodulatory therapy, no signs of myocardial inflammation were detected. The exact impact of immunomodulatory therapies on the myocardium needs to be addressed in future studies. STUDY REGISTRATION: ISRCTN71534700.

Patient-reported assessment of medical care for chronic inflammatory skin diseases: an enterprise-based survey.

Background: Chronic inflammatory skin diseases (CISDs) are among the most common diseases in the Western world. Current estimates of medical care for CISDs are primarily based on surveys among patients in medical care facilities and on health insurance data. Aim: Survey-based examination to what extent CISD patients in health-aware environment consider their skin disease to be controlled. Methods: The survey of CISD patients was carried out in 2022 among the employees of a pharmaceutical company located in Germany and Switzerland. Software-based, anonymous, self-reported questionnaires were used. Results: The number of employees, who answered the questionnaire, was 905. Of these, 222 participants (24.5%) reported having at least one CISD. 28.7% of participants with CISD described their disease as being hardly or not controlled. Regarding the nature of disease, more than one third of participants suffering from hidradenitis suppurativa (HS) or psoriasis fell into the hardly/not controlled category. In contrast, the largest proportion of participants with chronic spontaneous urticaria (43%) or atopic dermatitis (42%) considered their CISD to be completely or well controlled. Only 35.5% of CISD sufferers stated that they were currently under medical care for their skin condition. Being under medical care, however, had no influence on the extent CISD sufferers considered their skin disease to be controlled. The number of active CISD episodes but not the total number of symptomatic days per year was negatively associated with poor disease control (p = 0.042 and p = 0.856, respectively). Poor disease control had a negative effect on the personal and professional lives of those affected, as deduced from its positive association with the extent of daily activity impairment and presenteeism (p = 0.005 and p = 0.005, respectively). Moreover, 41.4 and 20.7% of participants with hardly/not controlled disease stated that their CISD had a moderate and severe or very severe impact on their overall lives (p < 0.001), respectively. A severe or very severe impact of their CISD on their overall life was most commonly reported by participants with HS. Conclusion: Medical care for CISDs, even in an environment with high socio-economic standard and high health-awareness, still appears to be limited and has a negative impact on individuals and society.

Single-cell sequencing reveals Hippo signaling as a driver of fibrosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.

Molecular and functional changes in neutrophilic granulocytes induced by nicotine: a systematic review and critical evaluation.

Background: Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory diseases. Although neutrophilic granulocytes (neutrophils) play a role in the pathogenesis of many of these diseases, the impact of nicotine on neutrophils has not been systematically reviewed so far. Objectives: The aim of this systematic review was to evaluate the direct influence of nicotine on human neutrophil functions, specifically on cell death/damage, apoptosis, chemotaxis, general motility, adhesion molecule expression, eicosanoid synthesis, cytokine/chemokine expression, formation of neutrophil extracellular traps (NETs), phagocytosis, generation of reactive oxygen species (ROS), net antimicrobial activity, and enzyme release. Material and methods: This review was conducted according to the PRISMA guidelines. A literature search was performed in the databases NCBI Pubmed® and Web of Science™ in February 2023. Inclusion criteria comprised English written research articles, showing in vitro studies on the direct impact of nicotine on specified human neutrophil functions. Results: Of the 532 originally identified articles, data from 34 articles were finally compiled after several evaluation steps. The considered studies highly varied in methodological aspects. While at high concentrations (>3 mmol/l) nicotine started to be cytotoxic to neutrophils, concentrations typically achieved in blood of smokers (in the nmol/l range) applied for long exposure times (24-72h) supported the survival of neutrophils. Smoking-relevant nicotine concentrations also increased the chemotaxis of neutrophils towards several chemoattractants, elevated their production of elastase, lipocalin-2, CXCL8, leukotriene B4 and prostaglandin E2, and reduced their integrin expression. Moreover, while nicotine impaired the neutrophil phagocytotic and anti-microbial activity, a range of studies demonstrated increased NET formation. However, conflicting effects were found on ROS generation, selectin expression and release of ß-glucuronidase and myeloperoxidase. Conclusion: Nicotine seems to support the presence in the tissue and the inflammatory and selected tissue-damaging activity of neutrophils and reduces their antimicrobial functions, suggesting a direct contribution of nicotine to the pathogenesis of chronic-inflammatory diseases via influencing the neutrophil biology.

Biology of Interleukin-17 and Novel Therapies for Hidradenitis Suppurativa.

Skin disorders affect ∼40% of the human population. One of the most debilitating cutaneous disorders is Hidradenitis suppurativa (HS), a noncommunicable chronic inflammatory disease with an estimated global prevalence of 0.4% to 2.5%. In January 2011, high levels of IL-17 were discovered in skin lesions of HS patients. In the following years, translational and clinical research led to a better understanding of the pathogenesis of HS. In June 2023, more than 12 years after the initial note, secukinumab, an anti-IL-17A monoclonal antibody, was approved for the treatment of moderate to severe HS. This is the next milestone in improving the treatment of these patients after the approval of the anti-TNF-α monoclonal antibody adalimumab in 2015. In this review article, we present the IL-17 pathway in HS and discuss the use of secukinumab as a therapeutic option for this disease. Our review starts with a description of the epidemiology, clinical features, etiology, and pathogenesis of HS. An overview of the IL-17/IL-17 receptor system in general and a detailed description of the known facts about the expression and action of IL-17 in HS follow. Afterward, we consider the results of clinical trials evaluating the safety and efficacy of IL-17 inhibitors in HS. Finally, a comparison is made between secukinumab and adalimumab and the characteristics of the patients that may be particularly suitable for each of these biologics are described.

Targeting Metabolic Syndrome in Hidradenitis Suppurativa by Phytochemicals as a Potential Complementary Therapeutic Strategy.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the appearance of painful inflamed nodules, abscesses, and pus-draining sinus tracts in the intertriginous skin of the groins, buttocks, and perianal and axillary regions. Despite its high prevalence of ~0.4-1%, therapeutic options for HS are still limited. Over the past 10 years, it has become clear that HS is a systemic disease, associated with various comorbidities, including metabolic syndrome (MetS) and its sequelae. Accordingly, the life expectancy of HS patients is significantly reduced. MetS, in particular, obesity, can support sustained inflammation and thereby exacerbate skin manifestations and the chronification of HS. However, MetS actually lacks necessary attention in HS therapy, underlining the high medical need for novel therapeutic options. This review directs attention towards the relevance of MetS in HS and evaluates the potential of phytomedical drug candidates to alleviate its components. It starts by describing key facts about HS, the specifics of metabolic alterations in HS patients, and mechanisms by which obesity may exacerbate HS skin alterations. Then, the results from the preclinical studies with phytochemicals on MetS parameters are evaluated and the outcomes of respective randomized controlled clinical trials in healthy people and patients without HS are presented.

Blood T Helper Memory Cells: A Tool for Studying Skin Inflammation in HS?

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful lesions on intertriginous body areas such as the axillary, inguinal, and perianal sites. Given the limited treatment options for HS, expanding our knowledge of its pathogenetic mechanisms is a prerequisite for novel therapeutic developments. T cells are assumed to play a crucial role in HS pathogenesis. However, it is currently unknown whether blood T cells show specific molecular alterations in HS. To address this, we studied the molecular profile of CD4+ memory T (Thmem) cells purified from the blood of patients with HS and matched healthy participants. About 2.0% and 1.9% of protein-coding transcripts were found to be up- and down-regulated in blood HS Thmem cells, respectively. These differentially expressed transcripts (DETs) are known to be involved in nucleoside triphosphate/nucleotide metabolic processes, mitochondrion organization, and oxidative phosphorylation. The detected down-regulation of transcripts involved in oxidative phosphorylation suggest a metabolic shift of HS Thmem cells towards glycolysis. The inclusion of transcriptome data from skin from HS patients and healthy participants in the analyses revealed that in HS skin lesions, the expression pattern of transcripts identified as DETs in blood HS Thmem cells was very similar to the expression pattern of the totality of protein-coding transcripts. Furthermore, there was no significant association between the extent of the expressional changes in the DETs of blood HS Thmem cells and the extent of the expressional changes in these transcripts in HS skin lesions compared to healthy donor skin. Additionally, a gene ontology enrichment analysis did not demonstrate any association of the DETs of blood HS Thmem cells with skin disorders. Instead, there were associations with different neurological diseases, non-alcoholic fatty liver disease, and thermogenesis. The levels of most DETs linked to neurological diseases showed a positive correlation to each other, suggesting common regulatory mechanisms. In summary, the transcriptomic changes in blood Thmem cells observed in patients with manifest cutaneous HS lesions do not appear to be characteristic of the molecular changes in the skin. Instead, they could be useful for studying comorbidities and identifying corresponding blood biomarkers in these patients.

Management of Infections in Psoriatic Patients Treated with Systemic Therapies: A Lesson from the Immunopathogenesis of Psoriasis.

Modern treatments continue to be developed based on identifying targets within the innate and adaptive immune pathways associated with psoriasis. Whilst there is a sound biologic rationale for increased risk of infection following treatment with immunomodulators, the clinical evidence is confounded by these agents being used in patients affected with several comorbidities. In an era characterized by an ever greater and growing risk of infections, it is necessary to always be updated on this risk. In this mini-review, we will discuss recent updates in psoriasis immunopathogenesis as a rationale for systemic therapy, outline the risk of infections linked to the disease itself and systemic therapy as well, and provide an overview of the prevention and management of infections.

The impact of surgical interventions on the psychosocial well-being of patients with hidradenitis suppurativa.

BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa is a chronic inflammatory skin disease. Depending on disease severity, a combination of conservative and surgical treatments is necessary. This analysis aimed to determine the impact of surgical interventions on patient psychosocial well-being. PATIENTS AND METHODS: This is a prospective, noninterventional, multicenter study. The medical history, medical examination, and patient-reported outcomes, including the Hospital Anxiety and Depression Scale, Dermatology Life Quality Index, and the Short Form-12 Health Survey, were collected from 481 patients with hidradenitis suppurativa. RESULTS: Among all patients with hidradenitis suppurativa included in this study, 74.2% reported surgery before study inclusion, of whom 92.4% could identify surgery type and location. Although adjusted for confounding factors, such as disease severity and activity, the aforementioned patient reported outcomes, did not vary significantly between groups of patients with different techniques and number of prior surgical intervention. However, patients without any prior surgical intervention yielded significantly better scores. CONCLUSIONS: In patients with hidradenitis suppurativa, previous surgery was associated with worse outcomes in anxiety, depression, and quality of life, showing the apparent need of psychological support. It remains unclear whether the morbidity of surgical procedures or a possible higher severity score in patients undergoing surgery is responsible.

The impact of hidradenitis suppurativa on professional life.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin. OBJECTIVES: To determine the extent of work ability and productivity impairment as a result of HS in Germany. METHODS: A prospective, multicentre, epidemiological, noninterventional study of patients with HS was conducted. Medical history, medical examination performed by dermatologists and patient-reported outcomes [Work Ability Index (WAI) and Work Productivity and Activity Impairment (WPAI)] were collected. RESULTS: Of the 481 patients with HS included in the study, 99% were below the current statutory retirement age. In total, 53·3% of patients were working full time, 16·8% part time and 7·3% had retired. The unemployment rate was 12·6%, two times higher than in the general German population. Medical leave because of HS, within the last 6 months, was reported in 41·4% [95% confidence interval (CI) 36·9-46·0], with a duration of 39·3 days on average (95% CI 32·4-46·1). The mean HS-related WPAI absenteeism was 13.3% (95% CI 9·7-16·8), and the loss in productivity because of HS during working hours (WPAI presenteeism) was 25.2% (95% CI 21·8-28·6). Presenteeism was associated with HS disease severity. Overall work impairment because of HS was 33·4% (95% CI 29·3-37·6). The WAI score for patients was 32·2, ∼20% lower than for the average German employee. Only 62·8% of patients were relatively certain that they would be able to perform their work in the coming 2 years. Being more depressed and having more severe pain were associated with lower work ability and overall work impairment. The estimated annual loss of gross value added because of HS for Germany was ∼€12.6 billion (€3.3 billion related to a lower employment rate, €3.5 billion related to absenteeism and €5.8 billion related to presenteeism). CONCLUSIONS: HS leads to a substantial decrease in work ability and productivity and considerable loss of gross value added. Impairment during working hours correlates with disease severity, underlining the socioeconomic importance of early and adequate treatment. Furthermore, decreased work ability and productivity is linked to depressed mood and severe pain, aspects that need more attention in patient care.

Interleukin-19 Levels Are Increased in Palmoplantar Pustulosis and Reduced following Apremilast Treatment.

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterised by neutrophilic granulocyte (neutrophil)-filled pustules on the palms and soles. The pathogenesis of PPP is poorly understood. This study conducted an identification of the immune mediators associated with PPP and an exploration of apremilast treatment effects on them. We screened for immune mediators elevated in blood taken from 68 patients with PPP versus control participants and included the most promising parameters in the protocol of phase the 2, multicentre study of apremilast (PDE4 inhibitor) in 21 patients with moderate-to-severe PPP (APLANTUS; EudraCT 2016-005122-11) for respective analysis of blood and skin samples of study patients. We investigated stimulated neutrophils and three-dimensional reconstituted epidermis cultures. Interleukin (IL)-19 was found to be the most upregulated immune mediator in the blood of PPP patients. IL-19 serum levels were independent of patients' age, gender, and BMI but were associated with strongly upregulated cutaneous IL-19 expression and correlated with the number of palmoplantar pustules. In patients participating in the APLANTUS study, apremilast reduced pustules more effectively than erythema and scaling. Moreover, this treatment significantly reduced IL-19 blood and skin levels. The reduction in IL-19 blood levels at week 4 correlated with the reduction in pustule counts at week 20 (end of treatment). IL-19 was expressed by neutrophils activated in vitro and induced CXCL6, a neutrophil-attracting chemokine, in epidermis models. This work demonstrates elevated IL-19 levels in the blood and skin of PPP patients and suggests a relevant role of this cytokine in the appearance of pustules in this disorder. It also suggests the suitability of IL-19 blood levels as a predictive biomarker for the treatment response of PPP patients, which should be validated in further studies.

Neutrophilic granulocyte-derived B-cell activating factor supports B cells in skin lesions in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by painful inflamed nodules, abscesses, and pus-draining tunnels appearing in axillary, inguinal, and perianal skin areas. HS lesions contain various types of immigrated immune cells. OBJECTIVE: This study aimed to characterize mediators that support lesional B/plasma cell persistence in HS. METHODS: Skin samples from several cohorts of HS patients and control cohorts were assessed by mRNA sequencing, quantitative PCR on reverse-transcribed RNA, flow cytometry, and immunohistofluorescence. Blood plasma and cultured skin biopsy samples, keratinocytes, dermal fibroblasts, neutrophilic granulocytes (neutrophils), monocytes, and B cells were analyzed. Complex systems biology approaches were used to evaluate bulk and single-cell RNA sequencing data. RESULTS: Proportions of B/plasma cells, neutrophils, CD8+ T cells, and M0 and M1 macrophages were elevated in HS lesions compared to skin of healthy and perilesional intertriginous areas. There was an association between B/plasma cells, neutrophils, and B-cell activating factor (BAFF, aka TNFSF13B). BAFF was abundant in HS lesions, particularly in nodules and abscesses. Among the cell types present in HS lesions, myeloid cells were the main BAFF producers. Mechanistically, granulocyte colony-stimulating factor in the presence of bacterial products was the major stimulus for neutrophils' BAFF secretion. Lesional upregulation of BAFF receptors was attributed to B cells (TNFRSF13C/BAFFR and TNFRSF13B/TACI) and plasma cells (TNFRSF17/BCMA). Characterization of the lesional BAFF pathway revealed molecules involved in migration/adhesion (eg, CXCR4, CD37, CD53, SELL), proliferation/survival (eg, BST2), activation (eg, KLF2, PRKCB), and reactive oxygen species production (eg, NCF1, CYBC1) of B/plasma cells. CONCLUSION: Neutrophil-derived BAFF supports B/plasma cell persistence and function in HS lesions.

Sex-disaggregated population analysis in patients with hidradenitis suppurativa.

Background: Hidradenitis suppurativa (HS) is a common chronic inflammatory skin disease, which affects both sexes. Objectives: Identification of sex-specific risk factors, comorbidity, clinical manifestations, and treatments in HS patients. Methods: A non-interventional, cross-sectional, mono-centric study with 500 HS patients. All patients were examined by dermatologists. Prospectively collected demographic, anamnestic, clinical data, and blood parameters were evaluated. Results: There were no significant differences in age at HS onset and in disease duration between female and male patients. Furthermore, no differences regarding the family history for HS were found between sexes. Regarding further risk factors for HS, central obesity was more frequent in women while extensive cigarette smoking and acne vulgaris were more commonly found among male patients. Regarding comorbidity, lower HDL-levels were significantly more frequent in men. Female patients were found to suffer significantly more often from back pain, especially in the neck/shoulder region and lower back. Analyzing the clinical manifestation of HS, the groin was more frequently involved in women and the axillae in men. Women showed a higher number of skin sites with inflammatory nodules, whereas fistulas were observed more frequently in men. Nevertheless, there was no difference in HS treatment applied to female vs. male patients. Limitations: Data were obtained from a mono-centric study. Conclusion: Significant differences in HS risk factors, comorbidity, and clinical manifestation exist between female and male patients. Thus, sex-specific differences should be taken into account in the prevention as well as medical and surgical treatment of HS patients.

Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep-seated, inflamed nodules and pus-discharging abscesses and fistulas. Affecting about 1% of the population, this common disease has gained appropriate clinical attention in the last years. Associated with numerous comorbidities including metabolic syndrome, HS is considered a systemic disease that severely impairs the quality of life and shortens life expectancy. Therapeutic options for HS are limited, comprising long-term antibiotic treatment, the surgical removal of affected skin areas, and neutralization of TNF-α, the only approved systemic treatment. Novel treatment options are needed to close the therapeutic gap. HS pathogenesis is increasingly better understood. In fact, neutrophilic granulocytes (neutrophils) seem to be decisive for the development of the purulent destructive skin inflammation in HS. Recent findings suggest a key role of the immune mediators IL-1ß, IL-17A and G-CSF in the migration into and activation of neutrophils in the skin. Although phytomedical drugs display potent immunoregulatory properties and have been suggested as complementary therapy in several chronic disorders, their application in HS has not been considered so far. In this review, we describe the IL-1/IL-17/G-CSF axis and evaluate it as potential target for an integrated phytomedical treatment of HS.

Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases.

An estimated 20-25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.

Early prediction of renal graft function: Analysis of a multi-center, multi-level data set.

PURPOSE OF THE STUDY: Long-term graft survival rates after renal transplantation are still poor. We aimed to build an early predictor of an established long-term outcomes marker, the estimated glomerular filtration rate (eGFR) one year post-transplant (eGFR-1y). MATERIALS AND METHODS: A large cohort of 376 patients was characterized for a multi-level bio-marker panel including gene expression, cytokines, metabolomics and antibody reactivity profiles. Almost one thousand samples from the pre-transplant and early post-transplant period were analysed and employed for machine learning-assisted prediction. RESULTS: Pre-transplant data led to a prediction achieving a Pearson's correlation coefficient of r=0.38 between measured and predicted eGFR-1y. Two weeks post-transplant, the correlation was improved to r=0.63, and at the third month, to r=0.76. eGFR values were stable throughout the first post-transplant year. Several characteristics were predictive for eGFR, including age of donor and recipient, body mass index, HLA mismatch, cytomegalovirus mismatch and valganciclovir prophylaxis. Additionally, a subset of 19 nuclear magnetic resonance bins of the urine metabolome data was shown to have potential applications in non-invasive eGFR monitoring. Importantly, we identified the expression of the genes TMEM176B and HMMR as potential prognostic markers for changes in the eGFR after the second post-transplantation week. CONCLUSIONS: Our multi-center, multi-level data set represents a milestone in the efforts to predict transplant outcome. While an acceptable predictive capacity was achieved, we are still far from predicting changes in the eGFR precisely. Additional studies employing further marker panels are needed to establish predictors of eGFR-1y for clinical application; herein, gene expression markers seem to hold the most promise.

The Effect of TNF-α Inhibitors on Nail Psoriasis and Psoriatic Arthritis-Real-World Data from Dermatology Practice.

Patients with psoriatic arthritis (PsA) often develop joint symptoms years after their initial diagnosis of psoriasis disease; therefore, dermatologists should test for and detect PsA early. In this study, we focused on patients with psoriasis with both nail and joint disease being treated with tumor necrosis factor-α inhibitors by dermatologists. We performed a noninterventional, prospective, multicenter, and open-label study to evaluate the effectiveness of adalimumab, etanercept, or infliximab over 24 months of continuous therapy in patients with moderate to severe plaque-type psoriasis (Pso) and PsA. Disease assessments with the Psoriasis Area and Severity Index, Nail Psoriasis Severity Index (NAPSI), joint assessment, Dermatology Life Quality Index (DLQI), and Health Assessment Questionnaire (HAQ) instruments were performed every 3 months for the first year and twice annually thereafter. The cohort included 100 patients with Pso, nail psoriasis, and PsA. A significant reduction of NAPSI was observed 3 months after therapy initiation compared with the baseline (mean ± SD, 22.9 ± 17.8 vs. 33.8 ± 21.4; p < 0.001). Similarly, the mean ± SD number of both tender and swollen joints decreased significantly within the first 3 months of treatment, from 10.8 ± 11.5 to 6.4 ± 10.3 (p < 0.001) and from 6.4 ± 9.5 to 3.1 ± 7.2 (p < 0.001), respectively. Additionally, the distal interphalangeal joint involvement improved throughout the observation time, and DLQI and HAQ scores decreased. Improvements in control of skin, nail, and joint symptoms were seen, as well as in patients' quality of life and functionality. Dermatologists have an important role not only in PsA diagnosis but also in PsA long-term care.

Risk factors for Epstein-Barr virus reactivation after renal transplantation: Results of a large, multi-centre study.

Epstein-Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions.