A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management. METHODS: A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included. RESULTS: Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group. CONCLUSIONS: IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.

Efficacy and safety of lasers versus topical medications for acanthosis nigricans and pseudo-acanthosis nigricans treatment: a systematic review.

Acanthosis nigricans (AN) is a cutaneous disorder identified by well-defined pigmented plaques mostly detected on skin folds. Timely diagnosis and treatment of AN is essential as it could be an early manifestation of an underlying condition. The treatment of choice for AN has not been determined yet. Our study aimed to compare the efficacy and safety of various lasers with topical medications, including cream and peel. PubMed, Scopus, and Web of Science databases, as well as the Google Scholar search engine, were thoroughly searched until May 1st, 2023. Study selection was restricted to clinical trials published in English language comparing lasers with topical treatments. This study followed the PRISMA guidelines for systematic reviews and meta-analyses. Out of 1748 studies, Six clinical trials met our inclusion criteria, with 133 patients. We examined laser therapies, including fractional CO2 laser, 1550-nm erbium fiber laser, and long-pulsed alexandrite laser, while the topical treatments comprised glycolic acid (GA) peel, retinoic acid peel, trichloroacetic acid (TCA) peel, and tretinoin cream. In two studies, GA peel demonstrated favorable results compared to fractional CO2 laser. Besides, fractional CO2 laser exhibited efficacy, surpassing TCA peel in AN management. Additionally, a fractional 1550-nm erbium fiber laser displayed superiority over tretinoin cream in reducing average roughness. Similarly, a long-pulsed alexandrite laser demonstrated its effectiveness in axillary AN treatment compared to the combination of tretinoin and ammonium lactate. Overall, the findings revealed that laser therapy was associated with superior results. Moreover, topical treatments are safe and efficacious in AN management.

Evaluation of ASGE Criteria for Prediction of Choledocholithiasis: Can Early Endoscopic Ultrasound Utilization Make the Prediction More Accurate?

Background: ASGE predictive model for the detection of choledocholithiasis is a reasonable approach for the management of patients with cholelithiasis. Surgeons do not pursue cholecystectomy without evaluation of the biliary system when laboratory tests and diagnostic imaging evidence show biliary duct involvement. Literature revisions reveal that the prediction of choledocholithiasis based on ASGE criteria suffers from poor accuracy which results in unnecessary ERCPs. We decided to estimate the sensitivity and specificity of the ASGE predictive model for the detection of choledocholithiasis with the hope that early EUS would obviate the need for unnecessary ERCPs among highly probable patients for choledocholithiasis based on ASGE criteria. Methods: This is a prospective intervention and control study on the accuracy of ASGE criteria for the prediction of choledocholithiasis. To evaluate the sensitivity and specificity of ASGE criteria, patients were followed in two groups of controls who were treated based on ASGE guidelines and cases who underwent primary EUS. The clinical relevance of the ASGE criteria was estimated by sensitivity and specificity using SPSS Statistics 28 software. Then, absolute risk reduction utilizing primary EUS was also calculated. Results: The sensitivity and specificity of the ASGE predictive guideline for choledocholithiasis were estimated to be 62.31% and 51.85%, respectively. Evaluation of the ASGE guideline also revealed that patients in the intermediate probability group who finally required ERCP based on EUS results (false-negatives) were estimated to be 49.1% and patients who were predicted to require ERCP but finally did not need ERCP (false positives) were estimated to be 37.68%. The comparison of the two groups revealed the need for ERCP in about 55.56% of the primary EUS group and 77.42% in the ASGE group. Utilization of primary EUS reduced the need for ERCP by an absolute risk reduction of 0.299. (Primary Endpoint). Conclusion: ASGE guideline is associated with the overestimation of ERCP in cholelithiasis. The usage of primary EUS will reduce the need for ERCP.

In vitro Development of Controlled-Release Nanoniosomes for Improved Delivery and Anticancer Activity of Letrozole for Breast Cancer Treatment.

Introduction: Breast cancer is among the most prevalent mortal cancers in women worldwide. In the present study, an optimum formulation of letrozole, letrozole-loaded niosome, and empty niosome was developed, and the anticancer effect was assessed in in vitro MCF-7, MCF10A and MDA-MB-231 breast cancer cell lines. Materials and Methods: Various niosomal formulations of letrozole were fabricated through thin-film hydration method and characterized in terms of size, polydispersity index (PDI), morphology, entrapment efficiency (EE%), release kinetics, and stability. Optimized niosomal formulation of letrozole was achieved by response surface methodology (RSM). Antiproliferative activity and the mechanism were assessed by MTT assay, quantitative real-time PCR, and flow cytometry. Furthermore, cellular uptake of optimum formulation was evaluated by confocal electron microscopy. Results: The formulated letrozole had a spherical shape and showed a slow-release profile of the drug after 72 h. The size, PDI, and eEE% of nanoparticles showed higher stability at 4°C compared with 25°C. The drug release from niosomes was in accordance with Korsmeyer-Peppa's kinetic model. Confocal microscopy revealed the localization of drug-loaded niosomes in the cancer cells. MTT assay revealed that all samples exhibited dose-dependent cytotoxicity against breast cancer cells. The IC50 of mixed formulation of letrozole with letrozole-loaded niosome (L + L3) is the lowest value among all prepared formulations. L+L3 influenced the gene expression in the tested breast cancer cell lines by down-regulating the expression of Bcl 2 gene while up-regulating the expression of p53 and Bax genes. The flow cytometry results revealed that L + L3 enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cell lines compared with the letrozole (L), letrozole-loaded niosome (L3), and control sample. Conclusion: Results indicated that niosomes could be a promising drug carrier for the delivery of letrozole to breast cancer cells.