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Background: Laboratory-based biomarkers accurately presenting systemic lupus erythematosus (SLE) disease activity may have a practical value in clinical routine. As shown in many other conditions, complete blood count (CBC)-derived biomarkers may also play a role in SLE. Objectives: We aimed to study for the first time the pan-immune-inflammation value (PIV, monocytes x platelets x neutrophils/lymphocytes) and the more established systemic immune-inflammation index (SII, neutrophils x platelets /lymphocytes) in SLE patients and correlate it with serological and clinical findings including disease outcomes. Methods: In this retrospective multicentric investigation, we reviewed the clinical records of 148 SLE who had an available CBC at baseline. The latter served for the determination of the neutrophil-to-lymphocyte ratio (NLR), SII, and the PIV. Control groups were studied as well. Univariable as well as multivariable statistics were employed. Results: The values for baseline systemic immune-inflammation biomarkers (SIIB) studied were significantly (p < 0.0001) higher than those observed in healthy controls but comparable to those obtained from patients with other inflammatory conditions. Multivariable analysis revealed that ANA titer > 1:640 remained the only significant (p < 0.0001) baseline predictor of SLE flare (odds ratio: 7.6, 95% CI 3.1 to 18.8). Improvement of SLE following treatment was associated with the absence of lymphopenia as well as ANA > 1:640 (p = 0.041). The SLEDAI-2K significantly correlated with NLR, SII, CRP, lymphocytes, and monocytes only on univariable testing. Conclusions: Compared to healthy controls the CBC-based SIIB investigated are significantly increased in SLE patients. However, SIIB do not appear to be useful in managing SLE clinically. Nevertheless, we confirm that higher ANA titers can predict flares of SLE. [ABSTRACT FROM AUTHOR]

Purpose: Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased risk of malignancy. The aim of this systematic review was to investigate the prevalence of different malignancies in HS. Methods: This review meets the PRISMA criteria. A data-driven approach was used to conduct the research, which involved a detailed keyword search. The study considered meta-analyses, experimental studies, case-control studies, cross-sectional studies, cohort studies, and recently published cases, published in English or German. Excluded were reviews, summaries, and letters to the editor, as well as studies, which are not based on the human population. Results: Out of the initial 443 publications found, 25 met the inclusion criteria for this systematic review. Patients with HS have a significantly increased risk of cancer, up to 50%. Additionally, the risk of oropharyngeal, central nervous system, colorectal, prostate, vulvar and non-melanocytic skin cancers increase with the severity of HS. The likelihood of comorbid lymphoma in patients with HS is significantly higher compared to healthy controls. In severe cases of HS, malignant degeneration of lesions in the groin, perianal, perineal, and gluteal region can occur in up to 4.6% of cases. This leads to the development of cSCC, which often have a complicated course, are more refractory to treatment and associated with a poorer outcome. The pathogenic mechanisms responsible for the malignant transformation of HS are currently unknown. Conclusions: Patients with HS have a higher risk of cancer compared to the general population. Untreated, long-standing HS lesions can lead to complicated malignant degeneration resulting in cutaneous squamous cell carcinoma. The mechanisms underlying this malignant degeneration are not fully understood. HS patients also have an increased risk of developing other cancers, including prostate, oral, pharyngeal and colorectal cancers of the central nervous system and lymphomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous melanoma (CM) is an aggressive skin cancer that develops from melanocytic cells. The most important prognostic factor is still the vertical tumour thickness according to Breslow. Liver function is associated with better overall patient outcomes and is currently under increasing investigation in cancer patients. Current findings show that liver function is an important factor in different tumour entities and represents a potential biomarker. Therefore, we aimed to evaluate liver metabolism by using liver scores in CM. High tumour thickness (≥1.66 mm) and aspartate transaminase-to-platelet ratio index (APRI ≥ 0.2241) at the initial diagnosis were associated with a worse prognosis in stage I and II melanoma. Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan–Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37–126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5–126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14–5.75; HR 2.94, 95% CI 1.42–6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms. [ABSTRACT FROM AUTHOR]

Immune responses of the epithelia of the upper respiratory tract are likely crucial in early inhibition of the viral replication and finally clearance of SARS-CoV-2. We aimed to compare the expression profiles of antimicrobial peptides/proteins (AMPs) and related cytokines observed in the nasopharynx of SARS-CoV-2-infected patients and non-infected controls and to assess the associations between these parameters and COVID-19 patients' outcomes. We included 45 subjects who had tested positive for SARS-CoV-2 and 22 control subjects who had tested negative for SARS-CoV-2. Biomaterial for SARS-CoV-2 detection, as well as gene and protein expression studies, was obtained from all subjects using nasopharyngeal swabs which were performed a maximum of 7 days before inclusion in the study. Univariable and multivariable statistics were performed. When compared to the controls, the mRNA expression levels of human β-defensin 1 (hBD-1), LL-37, and trappin-2 were significantly higher in specimens of nasopharyngeal swabs from COVID-19 patients. Protein expression of hBD-1 was also increased in the COVID-19 group. mRNA expression levels of interferon-ɣ (IFN-ɣ), tumor necrosis factor- ɑ (TNF-ɑ), and interleukin-6 (IL-6) measured in SARS-CoV-2-infected patients were significantly higher than those observed in the controls, which could also be confirmed in the protein levels of IFN-ɣ and IL-6. A significant correlation between mRNA and protein levels could be observed only for IL-6. Univariable analysis revealed that low IFN-ɣ mRNA levels were associated with severe/fatal outcomes. The occurrence of COVID-19 pneumonia was significantly associated with lower expression levels of IL-6 mRNA, IFN-ɣ mRNA, and TNF-ɑ mRNA. Concerning the severe/fatal outcomes, the multivariable logistic regression model revealed that none of the aforementioned parameters remained significant in the model. However, the logistic regression model revealed that higher TNF-ɑ mRNA expression was a significant independent predictor of absence of pneumonia [odds ratio: 0.35 (95% CI 0.14 to 0.88, p = 0.024)]. In conclusion, nasopharyngeal expression of AMPs (hBD-1, LL-37, and trappin-2) and cytokines (IL-6, IFN-ɣ, and TNF-ɑ) is upregulated in response to early SARS-CoV-2 infection, indicating that these AMPs and cytokines play a role in the local host defense against the virus. Upregulated nasopharyngeal TNF-ɑ mRNA expression during the early phase of SARS-CoV-2 infection was a significant independent predictor of the absence of COVID-19 pneumonia. Hence, high TNF-ɑ mRNA expression in the nasopharynx appears to be a protective factor for lung complications in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL). Comprehensive analysis of MF cells in situ and ex vivo is complicated by the fact that is challenging to distinguish malignant from reactive T cells with certainty. Methods: To overcome this limitation, we performed combined single-cell RNA (scRNAseq) and T-cell receptor TCR sequencing (scTCRseq) of skin lesions of cutaneous MF lesions from 12 patients. A sufficient quantity of living T cells was obtained from 9 patients, but 2 had to be excluded due to unclear diagnoses (coexisting CLL or revision to a fixed toxic drug eruption). Results: From the remaining patients we established single-cell mRNA expression profiles and the corresponding TCR repertoire of 18,630 T cells. TCR clonality unequivocally identified 13,592 malignant T cells. Reactive T cells of all patients clustered together, while malignant cells of each patient formed a unique cluster expressing genes typical of naive/memory, such as CD27, CCR7 and IL7R, or cytotoxic T cells, e.g., GZMA, NKG7 and GNLY. Genes encoding classic CTCL markers were not detected in all clusters, consistent with the fact that mRNA expression does not correlate linearly with protein expression. Nevertheless, we successfully pinpointed distinctive gene signatures differentiating reactive malignant from malignant T cells: keratins (KRT81, KRT86), galectins (LGALS1, LGALS3) and S100 genes (S100A4, S100A6) being overexpressed in malignant cells. Conclusions: Combined scRNAseq and scTCRseq not only allows unambiguous identification of MF cells, but also revealed marked heterogeneity between and within patients with unexpected functional phenotypes. While the correlation between mRNA and protein abundance was limited with respect to established MF markers, we were able to identify a single-cell gene expression signature that distinguishes malignant from reactive T cells. [ABSTRACT FROM AUTHOR]

Background Immune complex vasculitides may be subdivided into adult IgA small vessel vasculitis (aIgA-SVV; i.e. adult Henoch–Schönlein purpura) and non-IgA-SVV (hypersensitivity vasculitis, etc.). Objectives To evaluate the clinical and laboratory parameters of inpatients fulfilling the diagnostic criteria for aIgA-SVV and non-IgA-SVV. Methods Twenty-nine adults aged ≥ 20 years with aIgA-SVV [according to the European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) criteria] and 53 adults 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 by uni- and multivariable analyses. Results Compared with patients with aIgA-SVV, the platelet-to-lymphocyte ratio was significantly higher in patients with non-IgA-SVV. Serum C3 levels and mean corpuscular haemoglobin concentration in patients with non-IgA-SVV were significantly lower compared with patients with aIgA-SVV. Proteinuria and haematuria were significantly more common in patients with aIgA SVV, and were significantly correlated with systemic immune-inflammation biomarkers only in patients with aIgA-SVV. In patients with aIgA-SVV, higher lactate dehydrogenase and C-reactive protein 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. Distinct predictors for renal involvement were not observed in either group, indicating that aIgA-SVV and non-IgA-SVV are similar conditions but do not appear to represent the same entity. [ABSTRACT FROM AUTHOR]

Introduction: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a poor prognosis, which only improved with the introduction of immunotherapies. An MCC prediction model with high diagnostic accuracy is lacking. The aim was to develop an MCC prognostic score (MCC-PS) based on combinations of previously proposed risk factors. Methods: A multicentric, retrospective study was conducted to develop MCCPS, which included age, neuron-specific enolase (NSE), C-reactive protein (CRP), creatinine, bilirubin, and international normalized ratio (INR). Creatinine, bilirubin, and INR were used to calculate the model of end-stage liver disease (MELD) score. A total of 98 patients were included in the study, including 36.7% with stage I according to American Joint Committee on Cancer 2018 (n = 36), 30.6% with stage II (n = 30), 25.5% with stage III (n = 25), and 7.1% with stage IV (n = 7). Survival data of MCC patients were correlated with selected laboratory parameters and risk factors. Primary endpoint was MCC-specific survival (MSS) and the secondary endpoint was progression-free survival. Several statistical methods were used to develop the prognostic score, including correlation analysis, Kaplan-Meier curves, Cox regression, and time-dependent receiver operating characteristic analysis. Results: The MCC-PS is based on the sum of the following baseline variables: elevated CRP (≥5.5 mg/l), elevated NSE (≥22.8 μg/l), MELD score ≥ 11, and age ≥ 75 years. An MELD score ≥ 11 was scored as 4 points, elevated NSE level as 3 points, elevated CRP level as 2 points, and age ≥ 75 years as 1 point. A high-risk group according to the MCC-PS was characterized by a score of 4 or more points. The high-risk group was associated with a worse prognosis than the lowrisk group (1-year MSS 62%, 2-year 43.1%, 5-year 17.6% as compared to 1-year MSS 79.5%, 3-year 75%, 5-year 72%). Notably, the developed MCC-PS predicts MCC outcome measures with high accuracy (3-year MSS: area under the curve (AUC) 0.934, sensitivity 87.5% and specificity 82.2%; 5-year MSS: AUC 0.93, sensitivity 89% and specificity 82%). Conclusion: MCC-PS is the first prognostic score predicting MCC outcome with a high accuracy based on five easily available laboratory parameters and patient's age. An MCC-PS of 4 or more indicates a high-risk patient associated with a poor prognosis. Conclusion: MCC-PS is the first prognostic score predicting MCC outcome with a high accuracy based on five easily available laboratory parameters and patient's age. An MCC-PS of 4 or more indicates a high-risk patient associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

The article explores the expression of programmed cell death proteins in patients with atypical fibroxanthoma and pleomorphic dermal sarcoma, indicating their potential for anti-PD-1/PD-L1 therapy. The study analyzed tissue samples from patients and found higher PD-L1 expression in pleomorphic dermal sarcoma compared to atypical fibroxanthoma. The research suggests that immunotherapeutic interventions may be more relevant for pleomorphic dermal sarcoma due to its higher rate of metastases. The findings also highlight the association of tumor thickness with disease relapse and survival in these types of skin cancers. [Extracted from the article]

The article discusses a rare occurrence of bullous pemphigoid (BP) and lichen planus pemphigoides (LPP) in identical twins with a long history of psoriasis. The twins developed these blistering skin conditions in their third decade of life, with one twin having BP and the other LPP. The study highlights the genetic background of autoimmune blistering skin diseases and the close relationship between BP and LPP, suggesting a common underlying genetic basis for these conditions. [Extracted from the article]