In recent decades, the volume of health publications has increased. A well-conducted systematic review (SR), with or without a meta-analysis, is considered the best reference for health care professionals to catch up with the best evidence. With the rapid increase in the number of published SRs, their study quality varies despite well established reporting guidelines and references. Understanding the process of producing SRs is critical to the execution and is not trivial due to the obstacles researchers may encounter. The aim of this article was to provide a step-by-step approach to help researchers (mostly novices) keep their SR up to standard. The steps presented here are a quick tutorial with reference to known and accepted international guidances and our expertise.

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Background: Diphenylcyclopropenone (DPCP) is a topical contact allergen used for contact immunotherapy in alopecia areata (AA). Objectives: We aimed to evaluate the treatment effectiveness and prognostic factors in Taiwanese patients with AA treated with topical DPCP. Methods: We performed a retrospective study of all consecutive patients with AA affecting more than 10% of scalp area treated with topical DPCP for more than 90 days. Results: Eighty-six patients were assessed in the study. The greatest hair regrowth percentages of 0%, 1%–25%, 26%–50%, 51%–75%, and 76%–100% were 26.7% (23/86), 7.0% (6/86), 2.3% (2/86), 10.5% (9/86), and 53.5% (46/86) of patients, respectively. 32.6% (28/86) of patients achieved near-complete remission (with or without maintenance DPCP therapy), defined as more than 90% sustainable hair regrowth. Positive prognostic factors include older age of onset, shorter duration of AA before DPCP treatment, less severity of hair loss, and no nonscalp hair loss. Multivariate logistic regression analysis showed that more than a 2-year duration of AA before DPCP treatment (P = 0.015) and more than 90% of hair loss (P = 0.032) had a poorer treatment outcome. Factors including eczematous sensitization reaction, history of atopy, adverse reactions, or concentrations of DPCP do not predict treatment effectiveness. Pigmentary change may cause cosmetic concerns in Chinese ethnicity. Conclusion: Topical DPCP is effective for AA. Various factors were associated with the clinical outcomes. Monitoring the possible adverse events is warranted.

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As predisposing factors and pathogenic mechanisms of inflammatory keratinization disorders of the skin have become increasingly elucidated in recent years, a number of inflammatory keratinization disorders are now known to have the excessive activation of innate immunity as their pathogenesis. Autoinflammation-associated pathogeneses have been clarified in patients with generalized pustular psoriasis (GPP), pityriasis rubra pilaris (PRP) type V, and familial keratosis lichenoides chronica (KLC). Thus, based on these findings, in 2017, we proposed the clinical entity “autoinflammatory keratinization disease (AiKD),” which comprehensively includes inflammatory keratinization disorders with pathogenic mechanisms related to autoinflammation (the excessive activation of innate immunity). In 2017, GPP and associated diseases, PRP type V, and familial KLC came to be considered as AiKDs. In addition to these diseases, hidradenitis suppurative, porokeratosis, keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome, and AiKDs with hepatitis and autism have been newly recognized as AiKDs. The concept of AiKD may contribute to the selection of novel treatment methods. For example, recognizing hidradenitis suppurativa precisely as an AiKD has resulted in the application of adalimumab, an anti-tumor necrosis factor alpha antibody, as a treatment. The concept of AiKD is thought to be useful toward our accurate understanding of the pathogeneses of inflammatory keratinization disorders and our choice of appropriate treatment methods. As the pathogenic mechanisms of inflammatory keratinization disorders are further elucidated, it is presumed that the number of keratinization diseases whose pathogeneses are associated with autoinflammation will increase and that the number of diseases recognized as AiKDs will grow more and more.

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Mycobacterium leprae causes leprosy and can impair peripheral nerves. If nerve function is damaged and is not treated immediately and effectively, it can cause disability. Hence, early detection of peripheral neuropathy is critical. Toronto Clinical Scoring System (TCSS) is a simple neuropathy assessment instrument for diabetic neuropathy, chemotherapy-induced peripheral neuropathy, and human immunodeficiency virus neuropathy. Therefore, TCSS is expected to be an alternative tool for diagnosing leprosy neuropathy. This study aims to determine the diagnostic value of TCSS in leprosy neuropathy. This is a cross-sectional observational study with 40 participants. The TCSS and Semmes–Weinstein Monofilament tests were used to assess neuropathy. The diagnostic analysis showed that the sensitivity was 85.7%, specificity was 84.2%, positive predictive value was 85.7%, negative predictive value was 84.2%, positive likelihood ratio (LR+) was 5.42, negative (LR-) was 0.17, accuracy was by 85%, and area under curve value of 93.2%. The optimal cut-off point score of TCSS is ≥6. It can be concluded that TCSS is an alternative diagnostic tool with a high accuracy value and can be used as a routine examination for the early detection of leprosy neuropathy.

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Background: Psoriasis is a common skin inflammatory disease. Dysregulated growth and differentiation of keratinocytes are the main characteristics of psoriasis. Diosmetin is a naturally occurring flavonoid with antioxidant, anti-inflammatory, and antibacterial properties. However, the anti-psoriatic role and mechanism of diosmetin remain unclear. Objectives: To investigate anti-psoriatic role and mechanism of diosmetin. Methods: Human immortalized epidermal cells (HaCaT) were treated with tumor necrosis factor-alpha (TNF-α) to establish the cell model of psoriasis. Mice were treated with imiquimod (IMQ) to establish the animal model of psoriasis. Cell viability and apoptosis were detected by methyl thiazolyl tetrazolium and flow cytometry, respectively. Reverse transcription-quantitative polymerase chain reaction and ELISA assays were performed to detect the expression of interleukin (IL)-6 and IL-8. Hematoxylin and eosin staining was used to detect the skin lesion. Results: Diosmetin reduced cell viability and promoted the apoptosis of TNF-α-induced HaCaT. Protein expression of Bax in TNF-α-induced HaCaT was up-regulated, while Bcl-2 was down-regulated by diosmetin. Diosmetin attenuated TNF-α-induced increase in IL-6 and IL-8 in HaCaT. The enhanced protein expression of toll-like receptor 4 (TLR 4) (toll-like receptor 4), p65 and IκBα phosphorylation, as well as reduced IκBα in TNF-α-induced HaCaT were restored by diosmetin. Diosmetin improved IMQ-induced skin lesion and attenuated inflammatory response in psoriasis-like mouse model. Conclusion: Diosmetin exerted anti-inflammatory and pro-apoptotic effects on TNF-α-induced HaCaT and IMQ-induced mice through inactivation of TLR4/nuclear factor kappa B pathway.

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Background: Perianal Paget disease (PPD), an uncommon extramammary Paget disease, is characterized by intraepidermal pagetoid spread of atypical Paget cells in the perianal skin. PPDs can be primary or secondary. Secondary PPDs have poorer prognosis due to progression of the underlying anorectal carcinoma. Objectives: We analyzed the clinicopathological features of PPDs to determine the primary versus secondary PPD. Methods: We reviewed the clinicopathological features, including evidence of underlying anorectal carcinomas, tumor immunoprofiles, treatments, and outcomes of 8 cases of PPD diagnosed in our department during 1992–2019. Results: Colonoscopy was performed in 6 cases; rectal adenocarcinoma and anal canal adenocarcinoma were detected in 2 cases each. Three patients had local recurrence(s). Based on the detection of underlying anorectal cancers and immunoprofiles, 2 cases were classified as primary (one with perianal squamous cell carcinoma), 4 secondary, and 2 inconclusive for primary or secondary PPD. The immunoprofiles were CK7(+)/CK20(−)/GCDFP-15(−)/CDX2(−) in the primary PPDs; CK7(+/−)/CK20(+)/GCDFP-15(−)/CDX2(+) in the secondary and inconclusive PPDs. Eventually, all patients with secondary PPD died of the disease; one primary PPD and one inclusive PPD cases died of unrelated causes. Conclusion: We report the clinicopathological features of 8 cases of PPD in Taiwanese and first describe differential CK7 expression in the epidermal and dermal tumor cells in 2 cases of secondary PPDs, which may provide a clue to the diagnosis of secondary PPD. Since an underlying anorectal carcinoma in PPDs may be undetectable by colonoscopy, it is essential to consider anoscopy and/or anal canal mucosal biopsy to search for an occult anorectal carcinoma.

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