Key Terms and Definitions in Acute Porphyrias: Results of an International Delphi Consensus Led by the European Porphyria Network

Background: Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Many terms used frequently in the literature and in clinical practice are ambiguous, which can lead to confusion in the way patients are managed, studied, and reported in clinical studies. Agreed definitions are a necessary first step in developing management guidelines and will facilitate communication of results of future clinical research. Methods: The Delphi method was used to generate consensus on key terms and definitions in acute porphyria. The process started with a brainstorming phase offered to all members of the European Porphyria Network followed by 2 Delphi rounds among international experts in the field of porphyria (the Acute Porphyria Expert Panel). A consensus of 75% or more was defined as the agreement threshold. Results: 63 respondents from 26 countries participated in the brainstorming phase, leading to the choice of 9 terms and definitions. 34 experts were invited to take part in the Delphi rounds. 7 of the initial 9 terms and definitions which entered the first Delphi round achieved the threshold for agreement. Following a second Delphi round, all 9 definitions achieved agreement. Conclusion: Agreement on the definitions for 9 important terms describing acute porphyrias represents a significant step forward for the porphyria community. It will facilitate more accurate comparison of outcomes among porphyria centres and in clinical trials and provide a strong framework for developing evidence based clinical guidelines

Key Terms and Definitions in Acute Porphyrias: Results of an International Delphi Consensus Led by the European Porphyria Network

Background: Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Many terms used frequently in the literature and in clinical practice are ambiguous, which can lead to confusion in the way patients are managed, studied, and reported in clinical studies. Agreed definitions are a necessary first step in developing management guidelines and will facilitate communication of results of future clinical research. Methods: The Delphi method was used to generate consensus on key terms and definitions in acute porphyria. The process started with a brainstorming phase offered to all members of the European Porphyria Network followed by 2 Delphi rounds among international experts in the field of porphyria (the Acute Porphyria Expert Panel). A consensus of 75% or more was defined as the agreement threshold. Results: 63 respondents from 26 countries participated in the brainstorming phase, leading to the choice of 9 terms and definitions. 34 experts were invited to take part in the Delphi rounds. 7 of the initial 9 terms and definitions which entered the first Delphi round achieved the threshold for agreement. Following a second Delphi round, all 9 definitions achieved agreement. Conclusion: Agreement on the definitions for 9 important terms describing acute porphyrias represents a significant step forward for the porphyria community. It will facilitate more accurate comparison of outcomes among porphyria centres and in clinical trials and provide a strong framework for developing evidence based clinical guidelines.Background: Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Many terms used frequently in the literature and in clinical practice are ambiguous, which can lead to confusion in the way patients are managed, studied, and reported in clinical studies. Agreed definitions are a necessary first step in developing management guidelines and will facilitate communication of results of future clinical research. Methods: The Delphi method was used to generate consensus on key terms and definitions in acute porphyria. The process started with a brainstorming phase offered to all members of the European Porphyria Network followed by 2 Delphi rounds among international experts in the field of porphyria (the Acute Porphyria Expert Panel). A consensus of 75% or more was defined as the agreement threshold. Results: 63 respondents from 26 countries participated in the brainstorming phase, leading to the choice of 9 terms and definitions. 34 experts were invited to take part in the Delphi rounds. 7 of the initial 9 terms and definitions which entered the first Delphi round achieved the threshold for agreement. Following a second Delphi round, all 9 definitions achieved agreement. Conclusion: Agreement on the definitions for 9 important terms describing acute porphyrias represents a significant step forward for the porphyria community. It will facilitate more accurate comparison of outcomes among porphyria centres and in clinical trials and provide a strong framework for developing evidence based clinical guidelines

The Prognostic Value and Clinical Utility of the 40-Gene Expression Profile (40-GEP) Test in Cutaneous Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

Background: The current tumor staging systems for cutaneous squamous cell carcinoma (cSCC) are considered inadequate and insufficient for evaluating the risk of metastasis and for identifying patients at high risk of cSCC. This meta-analysis aimed to assess the prognostic significance of a 40-gene expression profile (40-GEP) both independently and integrated with clinicopathologic risk factors and established staging systems (American Joint Committee on Cancer, eighth edition (AJCC8) and Brigham and Women’s Hospital (BWH)). Methods: Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar, were systematically searched to identify cohort studies and randomized controlled trials on evaluations of the prediction value of 40-GEP in cSCC patients up to January 2023. The metastatic risk analysis of a given 40-GEP class combined with tumor stage and/or other clinicopathologic risk factors was based upon log hazard ratios (HRs) and their standard error (SE). Heterogeneity and subgroup analyses were performed, and data quality was assessed. Results: A total of 1019 patients from three cohort studies were included in this meta-analysis. The overall three-year metastatic-free survival rates were 92.4%, 78.9%, and 45.4% for class 1 (low risk), class 2A (Intermediate risk), and class 2B (high risk) 40-GEP, respectively, indicating a significant variation in survival rates between the risk classification groups. The pooled positive predictive value was significantly higher in class 2B when compared to AJCC8 or BWH. The subgroup analyses demonstrated significant superiority of integrating 40-GEP with clinicopathologic risk factors or AJCC8/BWH, especially for class 2B patients. Conclusions: The integration of 40-GEP with staging systems can improve the identification of cSCC patients at high risk of metastasis, potentially leading to improved care and outcomes, especially in the high-risk class 2B group

Additional file 1 of Modifiable risk factors for cancer in the middle East and North Africa: a scoping review

Supplementary Material 1: Supplementary File A. Detailed search strateg

Spectrophotometric Analysis of Dental Enamel Staining to Antiseptic and Dietary Agents: In Vitro Study

Background/Objectives. Use of antiseptics as an adjunct to a traditional mechanical tooth brushing method has limited their application for long duration because of their side effects such as staining and calculus formation. The objective of this in vitro study is to analyse the staining effects of antiseptic mouthwashes on dental enamel and compare it with those containing nanoparticles, dietary agents, and distilled water (control). Material and Methods. 105 intact premolars extracted for orthodontic reasons and without any caries or anatomical defects were selected for analysis. The samples were randomly divided into 7 different groups of fifteen teeth each for different solutions. A spectrophotometer was used to assess the colorimeter analysis of buccal dental enamel surface at R1 (baseline examination), R2 (24 hours after immersion in different solutions), and R3 (after brushing). Statistical analysis was done using the Kolmogorov–Smirnov test and Levene’s test (p<0.05), respectively. One-way ANOVA was used to compare the difference in color (∆E) between the readings, R1, R2, and R3. Results. The mouthwash containing titanium dioxide (TiO2) nanoparticles produced the greater enamel discoloration compared to that of chlorhexidine. Brushing had little effect on removal of stains induced by all mouthwashes except for dietary solutions (lemon with sodium bicarbonate and olive with laurel) and distilled water (control). Conclusion. The results from this study show that mouthwashes containing TiO2 nanoparticles and other antiseptic mouthwashes cause change in color of the teeth and lead to poor esthetic appearance when compared to dietary and control solutions. Thus, future in vivo studies have to be conducted to confirm these findings as in vitro studies may not provide a reliable simulation of the clinical situations

Nonsteroidal Anti-inflammatory Drugs for Chemoprevention in Patients With Familial Adenomatous Polyposis: A Systematic Review and Meta-Analysis

Background and Aims: Published literature shows mixed reports of the benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) on reducing colorectal polyps in patients with familial adenomatous polyposis (FAP). We conducted a systematic review and performed a meta-analysis to assess the impact of NSAIDs on colorectal polyp burden in patients with FAP. Methods: We searched PubMed, EMBASE, and Cochrane for randomized controlled trials (RCTs) comparing the effect of NSAIDs vs placebo on the percent change in polyp number and polyp size in patients with FAP. Mean differences between the 2 study arms were pooled using RevMan. The risk of bias (RoB) was assessed using the Cochrane Risk of Bias tool for RCTs, and certainty in the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Results: The search strategy identified 1021 studies, out of which we included 8 RCTs with a total of 279 patients. Treatment for 6.4 ± 2.2 months with NSAIDs reduced polyp numbers by −17.4% (95% confidence interval −26.41%, −8.29%) (low certainty [I2 89%] due to imprecision and issues with RoB) and polyp size by −15.9% (95% confidence interval −24.98%, −6.73%) (very low certainty (I2 84%) due to imprecision, inconsistency, and issues with RoB). The most common gastrointestinal adverse events reported were stomatitis, diarrhea, and abdominal pain. Side effects leading to drug discontinuation were gastroenteritis and drug allergy. Conclusion: Short-term use of NSAIDs reduced polyp number and polyp size but with low to very low certainty of evidence. Further large multicenter studies are needed to further explore NSAIDs as a chemopreventive measure in patients with FAP

The clinical value of peripheral immune cell counts in pancreatic cancer.

BackgroundElevated neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in pancreatic cancer. We aim to investigate the association of the various hematologic markers, in particular NLR among others, with distant metastases, a common feature in pancreatic cancer.MethodsClinical data from 355 pancreatic cancer patients managed at King Hussein Cancer Center (Amman-Jordan) have been reviewed. We examined the relationship between absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophilic count (AEC), absolute monocytic count (AMC), NLR, monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) with the presence of baseline distant metastases and OS. Receiver Operating Characteristic (ROC) curve analysis was plotted to identify the NLR optimum cutoff value indicative of its association with distant metastases.ResultsOn univariate and multivariate analyses patients whom on presentation had high NLR (≥3.3) showed more baseline distant metastases compared to patients with low NLR (ConclusionThis study presents additional evidence of the association of some of the hematologic markers; in particular ANC, NLR, AMC, and MLR, with baseline distant metastases and poor outcome in pancreatic cancer. Whether these immune phenomena can help in identifying patients at higher risk for the subsequent development of distant metastases is unknown

The Clinical Potential of Circulating Immune Cell Counts in Primary Gastric Lymphoma

Background: High neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in gastrointestinal tract cancers. This study explores the clinical value of NLR, in addition to absolute lymphocyte count (ALC) and other hematologic parameters in association with distant metastases and OS in primary gastric lymphoma (PGL) patients. Methods: Clinical data of 139 PGL patients who received treatment at King Hussein Cancer Center (KHCC), Amman-Jordan were retrospectively evaluated. Using data from complete blood count (CBC) tests, the following hematologic parameters: absolute neutrophil count (ANC), ALC, absolute eosinophil count (AEC), absolute monocyte count (AMC), NLR, platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) were assessed in association with the following clinical outcomes: presence or absence of baseline distant metastases and OS. We conducted univariate and multivariate analyses assessing the various hematologic parameters in association with distant metastases. Results: Univariate and multivariate analyses indicated that patients with an elevated NLR (\u3e3.14) displayed more baseline distant metastases compared to patients with a low NLR (≤3.14), (P value: 0.02 and 0.018, respectively). High baseline ALC (\u3e1,819/µL) was associated with lower baseline distant metastases (P value: 0.04). In the OS analysis, high baseline ANC (\u3e5,100/µL), NLR (\u3e2.75), and PLR (\u3e0.16) were associated with poor OS, (P value: 0.027, 0.016, and 0.011 respectively). Conclusions: High NLR and ALC were associated with baseline distant metastases. High baseline ANC, NLR, and PLR were associated with poor OS. Hematologic parameters might be potentially helpful in assessing and correlating NLR with the response success to treatment in PGL

Guidelines for the secondary prevention of rheumatic heart disease

Rheumatic fever is a rare yet serious condition develop as a consequence of throat infection caused by Streptococcus pyogenes. It is the leading cause for rheumatic heart disease. Rheumatic heart disease is a worldwide public health concern. It is a chronic condition that results in carditis, irreversible valve damage and heart failure in children and young adults living in low-income countries. The age of onset peaks between 5 and 15 years. Approximately, 3% of patients with untreated acute streptococcal sore throats develop rheumatic fever. Rheumatic fever and rheumatic heart disease can be prevented with appropriate antibiotics administration to prevent the progression of valve damage. The current use of primary and secondary prevention antibiotics in Saudi Arabia is not known. Therefore, this clinical practice guideline is developed, based on the best available evidence, to promote appropriate antibiotics secondary prophylaxis use for prevention of rheumatic heart disease

Sulfadiazine Exerts Potential Anticancer Effect in HepG2 and MCF7 Cells by Inhibiting TNFα, IL1b, COX-1, COX-2, 5-LOX Gene Expression: Evidence from In Vitro and Computational Studies

Drug repurposing is a promising approach that has the potential to revolutionize the drug discovery and development process. By leveraging existing drugs, we can bring new treatments to patients more quickly and affordably. Anti-inflammatory drugs have been shown to target multiple pathways involved in cancer development and progression. This suggests that they may be more effective in treating cancer than drugs that target a single pathway. Cell viability was measured using the MTT assay. The expression of genes related to inflammation (TNFa, IL1b, COX-1, COX-2, and 5-LOX) was measured in HepG2, MCF7, and THLE-2 cells using qPCR. The levels of TNFα, IL1b, COX-1, COX-2, and 5-LOX were also measured in these cells using an ELISA kit. An enzyme binding assay revealed that sulfadiazine expressed weaker inhibitory activity against COX-2 (IC50 = 5.27 μM) in comparison with the COX-2 selective reference inhibitor celecoxib (COX-2 IC50 = 1.94 μM). However, a more balanced inhibitory effect was revealed for sulfadiazine against the COX/LOX pathway with greater affinity towards 5-LOX (IC50 = 19.1 μM) versus COX-1 (IC50 = 18.4 μM) as compared to celecoxib (5-LOX IC50 = 16.7 μM, and COX-1 IC50 = 5.9 μM). MTT assays revealed the IC50 values of 245.69 ± 4.1 µM and 215.68 ± 3.8 µM on HepG2 and MCF7 cell lines, respectively, compared to the standard drug cisplatin (66.92 ± 1.8 µM and 46.83 ± 1.3 µM, respectively). The anti-inflammatory effect of sulfadiazine was also depicted through its effect on the levels of inflammatory markers and inflammation-related genes (TNFα, IL1b, COX-1, COX-2, 5-LOX). Molecular simulation studies revealed key binding interactions that explain the difference in the activity profiles of sulfadiazine compared to celecoxib. The results suggest that sulfadiazine exhibited balanced inhibitory activity against the 5-LOX/COX-1 enzymes compared to the selective COX-2 inhibitor, celecoxib. These findings highlight the potential of sulfadiazine as a potential anticancer agent through balanced inhibitory activity against the COX/LOX pathway and reduction in the expression of inflammatory genes