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Key Clinical Message: There is a need to pay more attention to cutaneous leishmaniasis in endemic regions which may mimic other dermatoses and treatment should be initiated with a strong clinical suspicion even without any histopathologic or PCR confirmation to avoid disfigurement or development of secondary malignancy. Leishmaniasis is a vector‐borne disease with a variety of Clinical manifestations. Cutaneous leishmaniasis (CL) is the most common form of disease and can mimic other dermatoses. We describe two unusual cases of chronic leishmaniasis that remained undiagnosed for many years and led to superimposition of squamous cell carcinoma (SCC) on lesions of one patient. These reports showed that the leishmaniasis should be borne in mind by clinicians when encountering any infiltrated lesion in patients from endemic regions and treatment should be initiated with a strong clinical suspicion even without any histopathologic or PCR confirmation to avoid disfigurement or development of secondary malignancy. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN). Methods In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels. Results The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74). Conclusion As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN.

Background: The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN).Methods: In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels.Results: The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74).Conclusion: As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN. [ABSTRACT FROM AUTHOR]

Aims: Cell matrix modulating protein SPARCL-1 is highly expressed by astrocytes during CNS development and following acute CNS damage. Applying NanoLC-MS/MS to CSF of RRMS and SPMS patients, we identified SPARCL-1 as differentially expressed between these two stages of MS, suggesting a potential as CSF biomarker to differentiate RRMS from SPMS and a role in MS pathogenesis. Methods: This study examines the potential of SPARCL-1 as CSF biomarker discriminating RRMS from SPMS in three independent cohorts (n = 249), analyses its expression pattern in MS lesions (n = 26), and studies its regulation in cultured human brain microvasculature endothelial cells (BEC) after exposure to MS-relevant inflammatory mediators. Results: SPARCL-1 expression in CSF was significantly higher in SPMS compared to RRMS in a Dutch cohort of 76 patients. This finding was not replicated in 2 additional cohorts of MS patients from Sweden (n = 81) and Switzerland (n = 92). In chronic MS lesions, but not active lesions or NAWM, a vessel expression pattern of SPARCL-1 was observed in addition to the expression by astrocytes. EC were found to express SPARCL-1 in chronic MS lesions, and SPARCL-1 expression was regulated by MS-relevant inflammatory mediators in cultured human BEC. Conclusions: Conflicting results of SPARCL-10s differential expression in CSF of three independent cohorts of RRMS and SPMS patients precludes its use as biomarker for disease progression. The expression of SPARCL-1 by BEC in chronic MS lesions together with its regulation by inflammatory mediators in vitro suggest a role for SPARCL-1 in MS neuropathology, possibly at the brain vascular level. [ABSTRACT FROM AUTHOR]

To investigate the role of mast cells (MCs) renal infiltration in the progression of human anti-GBM nephritis, 38 patients diagnosed with anti-GBM nephritis were enrolled. Renal biopsies were performed. Immunohistochemistry was conducted to detect MCs in renal tissues. Patients were divided into group 1 (MCs <50 mm−2,n = 18) and group 2 (MCs ≥50 mm−2,n = 20) according to the infiltrating renal MC count. The clinical–pathological indices were compared. And, correlation between MCs and the clinical–pathological indices was analyzed. Patients of group 2 had more severe renal dysfunctions, expressed as higher levels of serum creatinine (SCr 8.95 ± 3.66 vs. 4.75 ± 2.73 mg/dL,p < 0.001), urine retinol-binding protein (RBP 29.8 ± 13.9 vs. 15.7 ± 11.5 mg/dL,p = 0.005), and lower urinary osmotic pressure. Pathologically, patients of group 2 had a higher percentage of fibrous/fibrocellular crescents (66.7 ± 21.9 vs. 47.0 ± 33.6%,p = 0.037) but a lower percentage of cellular crescents. More CD8 (268 mm−2vs. 180 mm−2,p = 0.045) and CD68 (268 mm−2vs. 180 mm−2,p = 0.045) positive cells infiltrating the interstitium were observed in group 2. Furthermore, renal MCs correlated significantly with the total number of crescents and the tubular interstitial CD8 and CD68 positive cells. And, the number of MCs was associated with the histological types. The renal function was significantly different between the two groups at presentation. However, at 3 and 6 month follow-up, the patient outcome was associated with the histological types. Our study showed that MC infiltrations were associated with chronic lesions in anti-GBM nephritis and may be involved in the loss of renal function with pathological changes. [ABSTRACT FROM PUBLISHER]

Background A subset of T-cells expresses the B-cell marker CD20 and in rheumatoid arthritis secretes Interleukin (IL)-17. IL-17 secreting T-cells (Th17) have also been implicated in the inflammatory response in the central nervous system in multiple sclerosis (MS) and may be a potential target for elimination by biologic therapeutics. ScFvRit:sFasL comprises of a rituximab-derived antibody fragment scFvRit genetically fused to human soluble FasL that specifically eliminated T-cells. Objective To determine the presence and phenotype of CD20+T-cells in blood and brain of MS patients. Second, to determine whether scFvRit:sFasL can selectively eliminate CD20+T-cells. After CD20-selective binding, scFvRit:sFasL is designed to trigger FasL-mediated activation-induced cell death of T-cells, but not B-cells. Methods Flow cytometry and immunohistochemistry were used to screen for CD20+inflammatory T-cells in MS blood and brain tissue. ScFvRit:sFasL pro-apoptotic activity was evaluated by Annexin-V/PI staining followed by flow cytometry assessment. Results Peripheral blood (n=11) and chronic but not active lesions of MS patient brains (n=5) contained CD20+inflammatory T-cells. Activated CD20+T-cells were predominantly CD4+and secreted both IL-17 and INF-γ. ScFvRit:sFasL triggered CD20-restricted FasL-mediated activation-induced cell death in peripheral blood CD20+T-cells, but not CD20+B-cells. Conclusion CD20+inflammatory T-cells are present in blood and chronic brain lesions of MS patients. ScFvRit:sFasL selectively eliminated CD20+T-cells and may eliminate pathogenic T-cells without B-cell depletion. [ABSTRACT FROM AUTHOR]

Abstract: Background: Clinicians widely regard placental abruption as an acute event, though accumulating data point towards abruption being the end-result of chronic processes early in pregnancy, and perhaps even extending to conception. The Collaborative Perinatal Project was a prospective cohort study performed from 1959 to 1966 in the United States. Since enrolled pregnancies were managed without the biases created by modern perinatal surveillance and interventions, the natural history of disease in these data is ideal to study obstetrical complications such as placental abruption. Objective: We assessed the associations versus contributions of the clinical feature of early gestational vaginal bleeding and histologic lesions (chronic and acute) with placental abruption. Study design: Women enrolled in the Collaborative Perinatal Project (1959–1966) were used, restricting the analysis to those that delivered singleton births (n =46,364). Risks of placental abruption were compared between women with and without vaginal bleeding at <20 weeks gestation. We also examined the relationships between placental abruption and chronic and acute histologic lesions, including infarcts, decidual necrosis, presence of macrophages in the decidua, amnion or chorion, and neutrophil infiltration in the amnion, chorion, placental surface, and umbilical vein. Results: Any episode of vaginal bleeding at <20 weeks in pregnancy conferred an increased risk of placental abruption (adjusted relative risk (RR) 1.6, 95% confidence interval (CI) 1.3, 1.8). The greatest risk occurred with bleeding in both the first two trimesters (RR 3.1, 95% CI 2.3, 4.1). The presence of histologic lesions in the placenta, cord and membranes similarly carried an increased risk of placental abruption, even in the absence of vaginal bleeding. The risk of abruption was, however, highest in the presence of both histologic lesions and vaginal bleeding early in pregnancy. Conclusion: Vaginal bleeding early in pregnancy and histologic lesions of the placenta, umbilical cord, and membranes are associated with increased risk of placental abruption in later pregnancy. However, the increased risk associated with placental lesions, especially chronic inflammatory lesions, even in the absence of early vaginal bleeding, suggests that prolonged inflammation may be implicated in placental abruption. [Copyright &y& Elsevier]

Chronic oral mucosal lesions can be associated with several mucocutaneous diseases. This article reviews the autoimmune and immune-mediated, reactive, genetic, and infectious diseases that may present with chronic oral and/or cutaneous manifestations and provides a rational approach to diagnosis and management., Competing Interests: Disclosure This article represents an original writing that is not being considered for publication elsewhere. All authors have read and approved the article. The authors report no conflicts of interest related to the content of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)