Comparison of clinical and laboratory data of adult patients with cutaneous IgA-vasculitis and non-IgA vasculitis.

BACKGROUND: Immune complex vasculitides may be subdivided into adult IgA small vessel vasculitis (aIgA-SVV, adult Henoch-Schönlein purpura) and non-IgA-SVV (hypersensitivity vasculitis, etc.). OBJECTIVES: We aimed to evaluate clinical and laboratory parameters of inpatients fulfilling the diagnostic criteria for aIgA-SVV and non-IgA-SVV. METHODS: 29 adult patients (≥ 20years) with aIgA-SVV according to the EULAR/PRINTO/PRES criteria and 53 adult patients with non-IgA-SVV according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides were compared with respect to a variety of clinical and laboratory parameters using uni- and multivariable statistics. RESULTS: Compared to aIgA-SVV patients, the platelet-to-lymphocyte ratio was significantly higher in non-IgA-SVV patients. Serum C3 levels and mean corpuscular haemoglobin concentration observed in non-IgA-SVV patients were significantly lower compared to aIgA-SVV patients. Laboratory-based evidence for proteinuria and haematuria was significantly more common in patients with aIgA SVV. Only in patients with aIgA-SVV, proteinuria and haematuria significantly correlated with systemic immune-inflammation biomarkers. In patients with aIgA-SVV, higher LDH and CRP were strong independent predictors for the presence of proteinuria and proteinuria. In patients with non-IgA-SVV, female sex was a protective factor for proteinuria, while skin lesions on the upper extremities proved to be a significant independent predictor of haematuria. CONCLUSIONS: We detected several clinical and laboratory differences between patients with aIgA-SVV and non-IgA-SVV. In both groups, distinct predictors for renal involvement could be observed indicating that aIgA-SVV and non-IgA-SVV are very similar conditions but do not appear to present the same entity.

Primary Thyroid Dysfunction Is Prevalent in Hidradenitis Suppurativa and Marked by a Signature of Hypothyroid Graves' Disease: A Case-Control Study.

Hidradenitis suppurativa (HS) is a chronic skin disease that can have an association with endocrine disorders. There is conflicting information in the literature regarding the role of the thyroid gland in HS. This study aimed to close this knowledge gap and investigate how thyroid disease is involved in patients with HS. We carried out a case-control study with a total of 160 patients, of whom 108 were patients with HS and 52 were controls matched for age and sex. Parametric and non-parametric methods were used to analyze the results. We calculated structural parameters of thyroid homeostasis to detect subclinical thyroid disease, non-thyroid disease syndrome and other forms. The severity of HS was not associated with thyroid hormone levels and antibodies (p > 0.05). HS patients with or without hypothyroidism had decreased FT4 levels and a decreased thyroid secretory capacity (SPINA-GT). Titers of TSH receptor autoantibodies (TRAb) were significantly higher in smoking HS patients compared to non-smokers (median: 1.18 vs. 1.08; p = 0.042). The rate of subclinical hypothyroidism was significantly higher in HS patients; thus, subclinical hypothyroidism is an important comorbidity of HS (p < 0.05). Further studies are needed to investigate whether the chronic inflammation of HS is a cause of increased rates of (subclinical) hypothyroidism.

Cold Plasma Therapy in Chronic Wounds-A Multicenter, Randomized Controlled Clinical Trial (Plasma on Chronic Wounds for Epidermal Regeneration Study): Preliminary Results.

Chronic wounds (CWs) pose a significant health challenge in clinical practice. Standard wound therapy (SWT) is currently considered the gold standard. However, recent evidence suggests that cold plasma therapy (CPT) holds promise for improving CWs. In light of this, the POWER study was conducted as a multicenter, randomized clinical trial to investigate the effect of large-area plasma application compared with SWT in patients with chronic, non-healing arterial or venous wounds on the lower leg. To analyze the interim results, we employed a comprehensive range of statistical tests, including both parametric and non-parametric methods, as well as GLS model regression and an ordinal mixed model. Our findings clearly demonstrate that CPT therapy significantly accelerates wound closure compared with SWT. In fact, complete wound closure was exclusively observed in the CPT group during the intervention period. Additionally, the CPT group required significantly less antibiotic therapy (4%) compared with the SWT group (23%). Furthermore, CPT led to a significant reduction in wound pain and improved quality of life compared with SWT. In conclusion, the study highlights that the combination of CPT and SWT surpasses monotherapy with SWT alone.

The effect of GP-2250 on cultured virus-negative Merkel cell carcinoma cells: preliminary results.

BACKGROUND: Even in the novel immunotherapy era, Merkel cell carcinoma (MCC) remains challenging in its treatment. Apart from Merkel cell polyomavirus (MCPyV) associated MCC, this cancer is linked in about 20% of cases to ultraviolet-induced mutational burden frequently causing aberrations in Notch and PI3K/AKT/mTOR signalling pathways. The recently developed agent GP-2250 is capable to inhibit growth of cells of different cancers, including pancreatic neuroendocrine tumors. The objective of the present study was to investigate the effects of GP-2250 on MCPyV-negative MCC cells. METHODS: Methods We employed three cell lines (MCC13, MCC14.2, MCC26) which were exposed to different GP-2250doses. GP-2250's effects on cell viability, proliferation, and migration were evaluated by means of MTT, BrdU, and scratch assays, respectively. Flow cytometry was performed for the evaluation of apoptosis and necrosis. Western blotting was implemented for the determination of AKT, mTOR, STAT3, and Notch1 protein expression. RESULTS: Cell viability, proliferation, and migration decreased with increasing GP-2250 doses. Flow cytometry revealed a dose response to GP-2250 in all three MCC cell lines. While the viable fraction decreased, the share of necrotic and in a smaller amount the apoptotic cells increased. Regarding Notch1, AKT, mTOR, and STAT3 expression a comparatively time- and dose-dependent decrease of protein expression in the MCC13 and MCC26 cell lines was observed. By contrast, Notch1, AKT, mTOR, and STAT3 expression in MCC14.2 was scarcely altered or even increased by the three dosages of GP-2250 applied. CONCLUSIONS: The present study indicates GP-2250 having anti-neoplastic effects in MCPyV-negative tumor cells in regard to viability, proliferation, and migration. Moreover, the substance is capable of downregulating protein expression of aberrant tumorigenic pathways in MCPyV-negative MCC cells.

Model for End-Stage Liver Disease Correlates with Disease Relapse and Death of Patients with Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a highly malignant skin tumor that occurs mainly in elderly and/or immunosuppressed patients. MCC prognosis has been significantly improved by the introduction of immune checkpoint inhibitor treatment. Recently, blood-based biomarkers have been investigated that can potentially predict the outcome of MCC patients. In this context, parameters of liver scores have not yet been investigated. We retrospectively recruited 47 MCC patients with available relevant laboratory data at primary diagnosis. At this time, we investigated blood-based scores as follows: model for end-stage liver disease (MELD), aspartate aminotransferase/platelet count ratio index (APRI), and the alanine transaminase/aspartate aminotransferase ratio (De Ritis ratio). MCC relapse was negatively correlated with the De Ritis score (r = -0.3, p = 0.024) and positively correlated with the MELD score (r = 0.3, p = 0.035). Moreover, MCC-specific death positively correlated with CCI score (r = 0.4, p = 0.01) and MELD score (r = 0.4, p = 0.003). In multivariable analysis, the MELD score remained in the regression model as significant independent predictor for MCC relapse (hazard ratio: 1.16 (95% CI 1.04 to 1.29; p = 0.008) and MCC-specific death (hazard ratio: 1.2 (95% CI 1.04 to 1.3; p = 0.009). We observed for the first time that the MELD score appears to independently predict both MCC relapse and MCC-specific death. These results should be further investigated in larger prospective studies.

Screening for Diabetes Mellitus in Patients with Hidradenitis Suppurativa-A Monocentric Study in Germany.

Hidradenitis suppurativa (HS) is a chronic skin disease that is often associated with metabolic disorders. Diabetes mellitus (DM) is a frequent comorbidity in HS. There is currently no established screening for DM in HS patients. The aim of our study was to identify high-risk groups of HS patients that develop DM and to assess the frequency of different types of DM present in HS patients. To do so, we conducted a monocentric study in 99 patients with HS. All patients underwent detailed clinical and laboratory assessments, including the determination of glycated hemoglobin. Among the 20.2% of patients that presented with DM, type 2 was by far the most prevalent (19 out of 20 patients). Moreover, male gender, age, BMI, Hurley stage, modified Hidradenitis Suppurativa Score (mHSS), DLQI and hypertension all correlated with the glycated hemoglobin levels in the HS patients. In the multivariable analysis, Hurley stage III, older age, and higher BMI were significantly associated with DM. Specifically, patients at Hurley stage III were at a 5.3-fold increased risk of having DM type II compared to patients at earlier Hurley stages. Since many of the HS patients had not been diagnosed, our study reveals shortcomings in the screening for DM and suggest that this should be routinely performed in HS patients at high risk to avoid secondary complications.

Current Medical and Surgical Treatment of Hidradenitis Suppurativa-A Comprehensive Review.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease presenting with recurrent inflammatory lesions in intertriginous body regions. HS has a pronounced impact on patients' quality of life and is associated with a variety of comorbidities. Treatment of HS is often complex, requiring an individual approach with medical and surgical treatments available. However, especially in moderate-to-severe HS, there is an urgent need for new treatment approaches. In recent years, increased research has led to the identification of new potential therapeutic targets. This review aims to give a comprehensive and practical overview of current treatment options for HS. Furthermore, the clinically most advanced novel treatment approaches will be discussed.

The Role of Hormones in Hidradenitis Suppurativa: A Systematic Review.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented to better understand the pathomechanisms of HS. The review is based on the PRISMA criteria. Systematic research was carried out using keywords. Subsequently, the data were analyzed based on the clinical response and other relevant information. The main focus of our systematic review was on HS manifestation, exacerbation, sex hormones, antiandrogen therapy, thyroid function, polycystic ovary syndrome, insulin resistance, and adipokines. In HS, there appears to be a dysregulated adipokine release that is shifted towards pro-inflammatory adipokines. Insulin resistance is significantly more common in HS than in healthy patients regardless of BMI, age, and gender. Insulin resistance in HS patients leads to further cardiovascular disease. The mechanism of insulin resistance and role of adipokines should be investigated in future studies to better provide the pathomechanisms of HS. The role of androgens seems to be important in a certain subgroup of female patients. Anti-androgenic therapy can be useful and helpful in some patients. However, further studies are needed to better understand the hormonal relationship in HS.

Prognostic Potential of the Baseline Pan-Immune-Inflammation Value and Neutrophil/Lymphocyte Ratio in Stage I to III Melanoma Patients.

Prognostic biomarkers derived from complete blood count (CBC) have received marked interest as an indirect measure of the inflammatory pressure in cancers such as metastatic melanoma. Here, we evaluated the novel pan-immune-inflammation value (PIV) and the frequently assessed neutrophil/lymphocyte ratio (NLR) in a large cohort of patients with cutaneous melanoma (CM) without distant metastases (stages I to III). PIV and NLR were calculated at CM diagnosis. Healthy controls were also included. We used the Kaplan-Meier method to estimate crude survival probabilities and used Cox proportional hazards regression for multiple adjustment of hazard ratios. We observed that higher PIV (HR: 1.72, 95% CI 1.14 to 2.58 and HR: 1.696, 95% CI 1.029 to 2.795, respectively) and NLR (HR: 1.70, 95% CI 1.10 to 2.62) values were associated with CM relapse and CM-specific death in the crude analysis. However, when adjusting for potential confounders, in particular age and tumor thickness, the total effect of PIV and NLR on CM-relapse-free (HR: 1.28, 95% CI 0.83 to 1.98 and HR: 1.26, 95% CI 0.80 to 1.98, respectively) and CM-specific survival (HR: 1.36, 95% CI 0.80 to 2.30 and HR: 1.37, 95% CI 0.80 to 2.33, respectively) was substantially reduced. However, both PIV and NLR were positively correlated with age and tumor thickness, which are important independent predictors for CM relapse and CM-specific death. In conclusion, in stage I to III CM patients PIV as well as NLR appear to be confounded by age and tumor thickness and probably have no potential to further improve the prediction of survival of stage I to III CM patients beyond standard prognostic factors.

Sarcoidal immune reaction following SARS-CoV-2 vaccination.

Vaccination against the SARS-CoV-2 virus is a milestone in combating the current pandemic. Nevertheless, there is increasing evidence that COVID-19 vaccination also may trigger immune- or autoimmune-mediated skin diseases. We here report the association of COVID-19 vaccination with sarcoidal immune reaction.

Mismatch Repair Protein Expression and Microsatellite Instability in Cutaneous Squamous Cell Carcinoma.

There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell carcinoma (cSCC, 102 patients in total) by immunohistochemistry, and search for MSI-H in patients with low-level MMR or dMMR using multiplex-PCR. Low-level MMR protein expression was observed in five patients: One patient with primary cSCC < 2 mm thickness and low-level MLH1, three patients with primary cSCC > 6 mm (including one with low-level MSH2, as well as MSH6 expression, and two with low-level PMS2), and one patient with a cSCC metastasis showing low-level MSH2 as well as MSH6. Intergroup protein expression analysis revealed that MLH1 and MSH2 expression in actinic keratosis was significantly decreased when compared to Bowen's disease, cSCC < 2 mm, cSCC > 6 mm, and cSCC metastasis. In cases with low-level MMR, we performed MSI-H tests revealing three cases with MSI-H and one with low-level MSI-L. We found low-level MMR expression in a small subset of patients with invasive or metastatic cSCC. Hence, loss of MMR expression may be associated with tumour progression in a small subgroup of patients with non-melanoma skin cancer.

Expression of Mismatch Repair Proteins in Merkel Cell Carcinoma.

We aimed to assess for the first time the mismatch repair (MMR) protein expression in Merkel cell carcinoma (MCC). Immunohistochemistry was performed for MLH1, MSH2, MSH6, and PMS2 on patients' tumor tissue (n = 56), including neighbored healthy control tissue. In cases with low-level MMR expression (<10th percentile), we performed multiplex PCR in combination with high-resolution capillary electrophoresis in order to confirm microsatellite instability (MSI). Microscopic evaluation revealed a high median expression for all MMR proteins studied (91.6-96.3%). However, six patients (56/10.7%) had low-level MLH1 expression, six (55/10.9%) had low-level MSH2 expression, five (56/8.9%) had low-level MSH6 expression, and six (54/11.1%) had low-level PMS2 expression. Together, we observed nine (56/16.1%) patients who had low-level MMR expression of at least one protein. Of the patients with low-level MMR expression, MSI evaluation was possible in five cases, revealing one case with high-level MSI. In all MMR proteins assessed, low-level expression was significantly (p = 0.0004 to p < 0.0001) associated with a negative Merkel cell polyomavirus (MCPyV) status. However, the expression profiles of the MMR proteins did not correlate with clinical outcome measures such as disease relapse or death (p > 0.05). MCC appears to be a malignancy characterized by low-level MMR rather than completely deficient MMR in a subset of cases, predominantly affecting MCPyV-negative tumors. Future studies will establish whether this subset of MCC patients respond better to immune checkpoint inhibitor therapy.