The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework offers a structured approach to assess the certainty of evidence (CoE) in systematic reviews (SRs). The CoE for each outcome falls into one of the four categories: very low, low, moderate, or high. The judgment of CoE is based on five downgrading factors (including the risk of bias, indirectness, inconsistency, imprecision, and publication bias) and three upgrading factors (including large effect size, dose-response relationship, and opposing plausible residual bias and confounding). To improve the transparency of SRs, authors should indicate how they grade the CoE for each outcome and provide a rationale for downgrading or upgrading the CoE.

Background: Hyperpigmentation occurs when excess melanin accumulates in the skin and causes the skin to become darker in color. Pursuing attractive appearance and colorism have promoted the development of the skin whitening market globally. The proteins targeted in this research are tyrosinase-related protein 1, cyclic adenosine monophosphate response element-binding protein, receptor tyrosine kinase, and endothelin receptor type B. Objectives: This study aims to identify the potential of coumarin derivatives as novel effective, safe, and natural antimelanogenesis agents for whitening purposes or therapeutical intention to treat hyperpigmentation disorders. Methods: Four three-dimensional structures of the targeted proteins and 94 ligands were obtained from Protein Data Bank and PubChem, respectively. The ligands were docked against modified targeted proteins to examine the binding affinity and protein-ligand interactions using PyRx and BIOVIA Discovery Studio. The top 13 derivatives were selected for further analysis on the pharmacokinetic properties through SwissADME and pkCSM web servers. A total of eight compounds were further chosen to conduct multiple ligand simultaneous docking (MLSD). Results: Difenacoum is the most potential antimelanogenesis agent due to its strong inhibitory binding affinity in targeted protein models (5M8M, 4TQN, 5X93), but it does not exhibit favorable behavior pharmacokinetic properties. From the in silico pharmacokinetics screening, novobiocin sodium is the most potent derivative due to its relatively appropriate and safer properties. However, none of the ligand pairs investigated in MLSD possesses a synergistic effect on the binding affinity. Conclusion: Our findings identified colladin, farnesiferol C and novobiocin sodium may be promising natural resources for developing antimelanogenesis agents.

Background: Information on the cause of death is critical in guiding decisions on health infrastructure. However, there is a relative paucity of mortality data in patients with dermatologic diseases. Objectives: We aim to assess the overall mortality from dermatological disorders in a third-level university hospital which serves as a dermatology referral center. Methods: A retrospective medical note review of patients with dermatologic diseases who died during an 11-year period (from March 2008 to February 2020) was undertaken. Results: There were 63 death cases out of 2810 admissions for patients with dermatologic diseases (crude mortality 2.24%). The average age was 61.8 years and the male-to-female ratio was 2.3. Cutaneous malignancies (53.96%) were the primary causes of death, followed by drug reactions (23.8%). Among skin cancers, squamous cell carcinoma (SCC; 47.05%) and melanoma (35.29%) were the leading causes of death. Toxic epidermal necrolysis (53.33%) was the leading cause of death among drug reactions. Sepsis (30.74%) was the most common immediate cause of mortality in this series. A large fraction of patients (73%) had significant underlying comorbidities. Conclusion: The principal cause of mortality was cutaneous malignancies (mainly SCC and melanoma) followed by drug reactions. Sepsis was the most common immediate cause of death.

Background: Indoleamine 2,3-dioxygenase (IDO), an enzyme in the first step of tryptophan catabolism, plays a role in the pathogenesis of various malignancies and inflammatory diseases. Although its pathogenesis is unclear, vascular dysregulation and chronic inflammation are the most common culprits for rosacea. Objectives: The aim of this study is to evaluate the relationship between IDO and rosacea and whether there is a correlation with disease severity. Methods: Fifty-two patients with rosacea and 29 healthy volunteers were recruited. The patients were grouped according to severity stage, period, and subtype of the disease. Serum IDO levels were measured with enzyme-linked immunosorbent assay. Results: Serum IDO levels were significantly higher in the patients with rosacea compared to the healthy controls (P < 0.001) and were significantly higher in the patients in remission period and with papulopustular type rosacea compared to the controls (P = 0.002 and P = 0.001, respectively). The serum IDO levels of the female rosacea patients were higher than those of the healthy female controls (P < 0.001). When the diagnostic value of the parameter was investigated, it was observed that the serum IDO level has high sensitivity (83.3%) and specificity (76.1%), with a cutoff value of 47.1 ng/mL for female rosacea patients. Conclusion: IDO was found to increase in rosacea patients. With the high specificity and sensitivity observed, especially in female patients, IDO may be a supporting parameter in the diagnosis of rosacea.

Dermatomyositis (DM) is a systemic autoimmune disease characterized by unique cutaneous manifestations and inflammatory myopathies. With the discovery of myositis-specific antibodies (MSAs), patients with DM, especially those with a higher risk of life-threatening complications, can be classified according to the MSA type. This retrospective study aimed to investigate the clinical significance of MSAs in patients with DM in Taiwan. A total of 33 patients with DM who underwent the MSA test, including 26 with classic DM and 7 with amyopathic DM, were included. There were 13 men and 20 women, with a mean age at diagnosis of 49.6 years. MSA was detected in 26 (78.8%) of 33 patients with DM. The most frequently detected MSA was anti-melanoma differentiation-associated protein 5 (MDA5) (10/33, 30.3%) followed by anti-transcription intermediary factor-1γ (TIF-1γ) (8/33, 24.2%). Dysphagia was present in 6 (18.2%) of the 33 patients and more frequently developed in patients with anti-TIF-1γ (+) (5/8, 62.5%) than those with anti-TIF-1γ (−) (1/25, 4.0%). Interstitial lung disease was noted in 15 patients (45.5%) and developed more frequently in patients with anti-MDA5 (+) (7/10, 70.0%) than those with anti-MDA5 (−) (8/23, 34.8%). Malignancies were detected in 4 (12.1%) patients, with one each of anti-Mi-2 (+), anti-TIF-1γ (+), anti-ARS (+), and MSA (−). Mortality occurred in 6 (18.2%) patients, of whom 4 were anti-MDA5 (+). Anti-MDA5 and anti-TIF-1γ were the two most commonly detected MSAs. The presence of specific MSAs is associated with a certain phenotype, and integrating MSAs while evaluating DM aids in accurate patient management.