Curcumin is effective in managing oral inflammation: An in vitro study.

BACKGROUND: Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions. METHODS: This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. RESULTS: LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. CONCLUSION: This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.

Epigenetics in the diagnosis and prognosis of head and neck cancer: A systematic review.

BACKGROUND: Aberrant epigenetic modifications significantly develop and progress human malignancies including head and neck squamous cell carcinoma (HNSCC). Taking into account issues of late diagnosis and poor prognosis associated with HNSCC, this systematic review is designed to provide an up-to-date insight of epigenetic changes in the management of HNSCC. METHODS: All studies that assessed the diagnostic and prognostic utilities of epigenetic changes (DNA methylation and histone modifications) among patients diagnosed with HNSCC or oral potentially malignant disorders (OPMDs) were considered for inclusion till June 2023. Pre-defined Medical Subject Headings terms were used to search Web of Science, Pubmed, Scopus and Embase Ovid databases. RESULTS: Twenty-five studies were deemed eligible for inclusion with a total number of 3790 samples (2123 HNSCCs, 334 OPMDs and 1333 as controls). DNA methylation was investigated in 18 studies while the role of histone modifications was assessed in seven studies. The most investigated biomarkers among the studies were H3, DAPK and TIMP3. The diagnostic accuracy of the epigenetic biomarkers in detecting HNSCC was assessed in eight studies where the following biomarkers showed the highest area under the curve values: TIPM3, DCC, DAPK, SEPT9, SHOX9, HOXA9 and TRH. None of the studies assessed the predictability of the epigenetic biomarkers in HNSCC and OPMDs. CONCLUSION: Although initial promising results were seen using the epigenetic biomarkers in the early detection of HNSCC, the limited number of patients and the absence of well-designed longitudinal studies limit the clinical applicability of the outcomes.

Saliva-based cell-free DNA and cell-free mitochondrial DNA in head and neck cancers have promising screening and early detection role.

BACKGROUND: Cell-free DNA (cfDNA) and cell-free mitochondrial DNA (cf-mtDNA) have been postulated as potential diagnostic and prognostic biomarkers for different human malignancies. Early detection of head and neck malignancies is fundamental for optimal patient management. This study, therefore, aimed to assess the utility of saliva-based liquid biopsy as a noninvasive source of cfDNA and cf-mtDNA for detecting head and neck cancer (HNSCC). METHODS: One hundred thirty-three patients diagnosed with either oral leukoplakia (OLK) or HNSCC were compared with 137 healthy volunteers. An unstimulated whole saliva sample was collected from each participant. The absolute copy numbers of salivary cf-mtDNA and cfDNA were quantified using Multiplex Quantitative PCR. Two diagnostic indices based on the investigated molecules were assessed for their ability to differentiate between different diagnostic categories. RESULTS: The median scores of cfDNA and cf-mtDNA were statistically significantly higher among HNSCC patients (p < 0.05), revealing area under the curve values of 0.758 and 0.826, respectively. The associated accuracy for this test in discriminating HNSCC from other diagnostic categories was 77.37% for the cfDNA-based index and 80.5% for the cf-mtDNA-based index. The median score of cfDNA was statistically significantly higher for patients with severe epithelial dysplasia (OED) compared to those with epithelial keratosis with no OED and mild OED. However, there was no significant difference between controls and OLK individuals. CONCLUSION: cfDNA and cf-mtDNA showed potential for use as precision medicine tools to detect HNSCC. Further multi-centre prospective studies are warranted to assess the prognostic utility of these molecules.

Automated immunohistochemical quantification of hypoxia biomarkers shows correlation with dysplastic epithelial changes.

BACKGROUND: Dysregulation of the hypoxia-aerobic system has been postulated in various malignancies. Nonetheless, the contribution of hypoxia to oral carcinogenesis is yet to be elucidated. Understanding this mechanism is important for improving diagnostic tools and targeted therapies. This study aimed to assess the dysregulation of hypoxia-related factors during different stages of oral squamous cell carcinoma (OSCC) development. METHODS: Ninety-two patients diagnosed clinically with oral leukoplakia or OSCC were included and classified according to their histopathological diagnoses. A panel of seven hypoxia-related antibodies were used for immunohistochemical staining of each case. Automated quantification of immunostaining was used for objective reporting. Microvessel density was also assessed. RESULTS: Significant associations were reported for non-dysplastic epithelial changes and malignancy for Glut1, HIF-1α, vascular endothelial growth factor, and signal transducer and activator of transcription 3(p < 0.005). Similarly, microvessel density significantly increased with the severity of epithelial disorders. A multiple regression model including the H-score of HIF-1α and microvessel density could statistically significantly predict the grade of epithelial disorder (p < 0.005). The associated diagnostic accuracy of this approach was 88%. CONCLUSIONS: Hypoxia-associated events are observed during early epithelial dysplastic changes and have a potential role in oral carcinogenesis. The level of hypoxia may assist in stratifying the severity of epithelial changes among patients with oral leukoplakia.

Clinical competency of dental health professionals and students in diagnosing oral mucosal lesions.

OBJECTIVE: Proper identification of oral potentially malignant disorders (OPMDs) provides an opportunity for oral cancer prevention. This study aims to assess the competency of dental health professionals in identifying OPMDs and, in turn, reducing the incidence of oral malignancy by early detection. METHODS: A 26-case online questionnaire of oral mucosal lesions was distributed to cohorts of 363 dental health professionals and dental students in Australia. The participants were asked to provide their provisional diagnosis for each case based on the available information. RESULTS: The overall accuracy in identifying oral mucosal lesions was 65.9%. There were no significant differences in the overall diagnostic accuracies between dental specialists, general dental practitioners and final-year dental students (p > 0.05). The lowest diagnostic accuracies were associated with normal mucosal variations and OPMDs. The predoctoral dental curriculum showed statistically significant values in terms of improving skills in diagnosing oral mucosal lesions. CONCLUSIONS: Lack of adequate knowledge in identifying OPMDs was evident among the participants, highlighting a non-promising figure in reducing the incidence of oral cancers in Australia. Comprehensive modifications of the current continuing professional development system are required to ensure adequate knowledge among dental health providers in Australia.

Immunoexpression of oral brush biopsy enhances the accuracy of diagnosis for oral lichen planus and lichenoid lesions.

BACKGROUND: This study assessed the efficacy of using oral liquid-based brush cytology (OLBC) coupled with immunostained cytology-derived cell-blocks, quantified using machine-learning, in the diagnosis of oral lichen planus (OLP). METHODS: Eighty-two patients diagnosed clinically with either OLP or oral lichenoid lesion (OLL) were included. OLBC samples were obtained from all patients before undergoing surgical biopsy. Liquid-based cytology slides and cell-blocks were prepared and assessed by cytomorphology and immunocytochemistry for four antibodies (Ki-67, BAX, NF-κB-p65, and AMACR). For comparison purposes, a sub-group of 31 matched surgical biopsy samples were selected randomly and assessed by immunohistochemistry. Patients were categorized according to their definitive diagnoses into OLP, OLL, and clinically lichenoid, but histopathologically dysplastic lesions (OEDL). Machine-learning was utilized to provide automated quantification of positively stained protein expression. RESULTS: Cytomorphological assessment was associated with an accuracy of 77.27% in the distinction between OLP/OLL and OEDL. A strong concordance of 92.5% (κ = 0.84) of immunostaining patterns was evident between cell-blocks and tissue sections using machine-learning. A diagnostic index using a Ki-67-based model was 100% accurate in detecting lichenoid cases with epithelial dysplasia. A BAX-based model demonstrated an accuracy of 92.16%. The accuracy of cytomorphological assessment was greatly improved when it was combined with BAX immunoreactivity (95%). CONCLUSIONS: Cell-blocks prepared from OLBC are reliable and minimally-invasive alternatives to surgical biopsies to diagnose OLLs with epithelial dysplasia when combined with Ki-67 immunostaining. Machine-learning has a promising role in the automated quantification of immunostained protein expression.

Oral lichen planus has a very low malignant transformation rate: A systematic review and meta-analysis using strict diagnostic and inclusion criteria.

BACKGROUND: The malignant transformation (MT) potential of oral lichen planus (OLP) has sparked heated debates for almost a century, despite the fact that global figures of OLP prevalence and oral cancer incidence do not support an association mathematically. In this study, we performed a systematic review and meta-analysis, using strict inclusion criteria, to more precisely assess the malignant potential rate of OLP and the influence of associated risk factors. METHODS: All reports that documented MT of OLP and published in the English language until January 2020 were included if they met the following strict criteria: (a) the presence of a properly verified OLP diagnosis, (b) a clear description of the cancerous lesion developing at the same site as the verified OLP lesion; and (c) a follow-up period of a minimum of 6 months prior to carcinoma development. RESULTS: Thirty-three studies were included in this analysis with a total of 12 838 OLP patients. Of these, 151 cases were initially considered to have progressed to carcinoma (1.2%). However, after applying strict criteria, only 56 cases were considered to have undergone MT from OLP (0.44%). The risk of MT was significantly higher among OLP patients who smoked (OR = 4.62), consumed alcohol (OR = 3.22), were seropositive for HCV (OR = 3.77) and/or displayed a red OLP subtype (OR = 0.37). CONCLUSIONS: Our results suggest that the reported OLP malignant transformation rates are exaggerated, and these do not reflect the actual clinical course of the disease according to strict clinical and histopathological criteria.

A machine-learning algorithm for the reliable identification of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a relatively common oral disorder which shares clinical and histopathological features with other lichenoid lesions, leading to considerable inter-observer disagreement. This negatively impacts understanding of the pathogenesis and malignant transformation potential of this condition. METHODS: Artificial intelligence was employed to create a machine-learning artificial neural network to identify and quantify mononuclear cells and granulocytes within the inflammatory infiltrates in digitized hematoxylin and eosin microscopic slides. Twenty-four regions of interest were extracted from OLP cases for learning purposes and validated on a retrospective cohort of 130 cases. All cases were related to patients with confirmed diagnoses of OLP, oral lichenoid lesions (OLLs), or oral epithelial dysplasia (OED) with lichenoid host response. RESULTS: The number of inflammatory cells was statistically significantly higher in OLP compared to OLLs or OED with lichenoid host response (p < 0.0005). The proposed machine-learning method was reliably capable of detecting OLP cases based on the number of inflammatory cells and the number of mononuclear cells with an area under the curve of 0.982 and 0.988, respectively. Identifying a cut-off point between OLP and other lichenoid conditions based on the number of mononuclear cells showed a sensitivity of 100% and an accuracy of 94.62%. CONCLUSION: Artificial intelligence has shown promising outcomes and provides a robust approach to enhance the accuracy of anatomical pathologists in accurately diagnosing OLP using features of disease pathogenesis.

Efficacy of oral brush cytology cell block immunocytochemistry in the diagnosis of oral leukoplakia and oral squamous cell carcinoma.

OBJECTIVES: This study assessed the efficacy of using oral liquid-based brush cytology and cell block immunocytochemistry in the diagnosis of oral leukoplakia as minimally invasive diagnostic adjuncts. METHODS: Seventy-two patients diagnosed clinically with either oral leukoplakia (OLK) or oral squamous cell carcinoma were included. Oral brush samples using Orcellex® brushes were obtained from all participants directly before undergoing surgical biopsy. Cell blocks were prepared for all samples and assessed for cytomorphology and immunocytochemistry of DNA mismatch repair proteins (MSH-6, MSH-2, MLH-1 and PMS-2). A combined index score of immunocytochemistry expression and cytology grading was compared against the gold standard (histopathological diagnosis). RESULTS: A significant association was observed between the cytological assessments of oral liquid-based brush cytology samples and the histopathological diagnosis (P < .005). In addition, there was a significant inverse correlation between the grade of oral epithelial dysplasia and the cumulative score of the studied DNA mismatch repair proteins (P < .005). Grading criteria for both oral liquid-based brush cytology and immunocytochemistry cumulative index scores are proposed based on the analysis of receiver operating characteristic curve coordinates. The diagnostic accuracy of this approach was outstanding in terms of discrimination between the presence or absence of oral epithelial dysplasia (0.961) and squamous cell carcinoma (0.977) separately. CONCLUSION: Oral liquid-based brush cytology cell block immunocytochemistry provides a reliable strategy to investigate oral mucosal epithelial disorders. This approach presents a minimally invasive, highly accurate and non-technically demanding method for the surveillance of oral potentially malignant disorders and squamous cell carcinoma.

Observer agreement in the diagnosis of oral lichen planus using the proposed criteria of the American Academy of Oral and Maxillofacial Pathology.

BACKGROUND: Oral lichen planus (OLP) is a common chronic inflammatory condition with an undefined malignant transformation potential. There have been many attempts at providing a specific definition of OLP without conclusive outcomes. A new set of diagnostic criteria was proposed in 2016 by the American Academy of Oral and Maxillofacial Pathology (AAOMP) in an endeavour to resolve this issue, and this has not yet been evaluated. This study aimed to assess the utility of AAOMP proposed criteria for the diagnosis of OLP. METHODS: Five pathologists blindly assessed a cohort of 215 digital whole slide images (WSI) obtained from haematoxylin and eosin-stained microscopic slides. Forty-six WSI were included twice to assess the intra-observer agreement. Included cases were diagnosed clinically as either OLP or oral lichenoid reaction. Each pathologist was asked to utilize the AAOMP histopathological criteria while assessing slides. The variations in diagnoses were assessed by unweighted kappa statistics. RESULTS: The level of intra-observer agreement was very good (0.801 to 0.899). The level of inter-observer agreement among the observers varied from good (0.658) to very good (0.842) when the responses were categorized as evident/compatible OLP versus no OLP and was good (0.62 to 0.725) when the responses were categorized as evident OLP, versus compatible OLP, versus no OLP. The clinico-pathological correlation was 87.6%. CONCLUSION: A reliable level of agreement can be achieved by pathologists for the diagnosis of OLP using the AAOMP criteria for differentiation between lichenoid and other conditions. There are still limitations in discriminating OLP from oral lichenoid lesions microscopically.

Patients' and physicians' attitudes and perception about asthma in the Gulf: A subset analysis from the Asthma Insights and Management Survey in the Gulf and Russia.

Background: Asthma is a prevalent disorder in the Gulf region. However, available data concerning asthma control and patients' perception with regard to their disease are still insufficient. Objective: To investigate patients' perception and behavior with regard to the asthma-related burden, the level of asthma control, and asthma management in three Gulf countries. Methods: This study presented a subset analysis of the Asthma Insights and Management survey about the asthma burden and management in the Gulf region and Russia. In this subset analysis, we retrieved the data of the patients from Saudi Arabia, United Arab Emirates, and Kuwait. Results: The current survey's population was composed of 452 patients. One hundred fifty-four patients (34.1%) rated themselves as having poorly controlled asthma, whereas 60.3% of the patients perceived their asthma as completely or well controlled. However, only two patients (0.4%) had controlled asthma according to the global asthma guidelines criteria for asthma control. Most of the patients (67.7%) reported that their asthma got worse when outdoors. Almost 70% of the patients on daily control plus a quick relief regimen reported that their asthma got worse when they were outdoors. Over the past 12 months, 95 patients (21%) reported asthma exacerbation. More than half of the included patients experienced an asthma attack that stopped their activities, whereas 54.2% of the patients were forced to leave work or school due to an asthma attack, and 53.1% had to cancel an appointment or had to go to bed due to the severity of the attack. With concern to asthma management, only 30.5% of the patients were given a lung function test for the assessment of their asthma. A written action plan for asthma treatment was developed by the physician or the practice nurse for only 21.7% of the patients. Conclusion: In the Gulf region, asthma exerts a substantial burden on patients who are affected. Such a burden significantly impacted patients' quality of life.

Association between Diabetes Mellitus and Periodontal Diseases: A Survey of the Opinions of Dental Professionals.

OBJECTIVE: This cross-sectional survey aimed to assess the knowledge of dentists and dental assistants practicing in Saudi Arabia regarding diabetes mellitus (DM) and periodontal diseases. SUBJECTS AND METHODS: We used a pretested, closed-ended, multiple-choice questionnaire covering 2 principal sections: the assessment of previous educational training and practice, and the knowledge and scientific background regarding DM and periodontal diseases. The responses were grouped using the Likert-type scale. RESULTS: The questionnaire showed a high reliability value of 0.805 as determined by a Cronbach's α. Out of 365 subjects who were initially interviewed, 239 subjects participated (response rate 65.5%): general dentists (45.6%) and dental hygienists and assistants (54.4%). Of the participating dentists, 70.4% were males; in contrast, 87.7% of dental assistants were female. Eighty-five percent of the participants strongly agreed that evidence supports the association between periodontal diseases and DM. Remarkably, dental assistants (78%) agreed more than dentists (68.5%) that diabetic patients with periodontal conditions would have worse glycemic control compared to diabetic patients with no periodontal diseases. Seventy-five percent of the respondents were confident about performing oral health screening for diabetic patients. Significantly more dental assistants showed their desire to expand their practice to include oral health screening (85%) and education compared to dentists (74%). CONCLUSIONS: Both dentists and dental assistants in Saudi Arabia revealed a satisfactory knowledge level regarding the periodontal disease-diabetes interactions with no significant difference between the two groups. Further studies are recommended to assess the attitude of dental care providers while dealing with diabetic patients.

Cross-sectional study on Asthma Insights and Management in the Gulf and Russia.

Background: Asthma is a chronic and complex lung disease that is not completely understood. It involves airway inflammation, reversible airflow obstruction, and bronchial hyperresponsiveness. The most common symptoms are recurrent wheezing, chest tightness, shortness of breath, and coughing. Objective: The Asthma Insights and Management study gathered information on the burden of asthma in the Gulf region (United Arab Emirates, Kuwait, Saudi Arabia) and Russia. Methods: This was a cross-sectional, multinational, noninterventional, two-phase study that collected data from patients ages ≥ 12 years, through interviews and a survey questionnaire. Phase 1 consisted of survey questions focused on estimating the asthma prevalence in the community. Phase 2 was designed to assess the level of asthma control, asthma-related perceptions and behaviors, and presentation patterns. Data were summarized by using descriptive analyses. Results: Analysis of data of 711 patients revealed that the prevalence of asthma among patients who lived in the community was 7.9% and that 66% subjectively perceived their asthma as being controlled. However, 97% of the patients' asthma were partially controlled or uncontrolled based on the Global initiative for Asthma control classification. Troubling symptoms were daytime coughing (33.3%) and shortness of breath (20.3%). With respect to medications for asthma, 76.2% of the patients reported the use of quick relief medication and 80.8% of maintenance medication during the past 4 weeks. Asthma exacerbation in the past year was reported by 40% of adults and adolescents in the study. Conclusion: The results showed that a significant proportion of the patients experienced bothersome symptoms and that many had a lack of knowledge about asthma control and treatment recommendations, which indicated that there is a need for improvements in patient education and asthma care in the Gulf and Russia regions.

Vocal cord dysfunction in bronchial asthma. A review article.

INTRODUCTION: Vocal cord dysfunction (VCD) is a condition in which the larynx exhibits paradoxical vocal cord adduction during inspiration, resulting in extra-thoracic variable airway obstruction. It has been described as a mimic of asthma, and hence, many patients with VCD are diagnosed as difficult-to-treat asthma and suffer significant morbidity as such. METHODS: In completing this review we searched the literature using the database from MEDLINE, PubMed, and the Cochrane library using the medical terms "vocal cord/vocal cord dysfunction and asthma". RESULTS: During the last few decades, many publications have described many conditions that may cause or coexist with VCD. In addition, the association between asthma and VCD was recognized. In this narrative review we provide an overview of the current knowledge about VCD and, in particular its relationship to asthma. We also provide a pragmatic diagnostic algorithm and treatment options based on our collaborative multi-disciplinary management of patients attending a difficult to control asthma clinic. CONCLUSION: Most VCD patients present with inadequately controlled asthma rather than the typical symptoms described in association with VCD. Careful diagnostic strategy as outlined in this review may be helpful in confirming the diagnosis.

Expert consensus on oral corticosteroids stewardship for the treatment of severe asthma in the Middle East and Africa.

In the Middle East and Africa (MEA) region, overuse of oral corticosteroids (OCS) for asthma management, both as burst and maintenance therapy, poses a significant challenge. Gaps in knowledge regarding the need to taper OCS in patients with severe asthma and the use of OCS in comorbid conditions have been noted. OCS stewardship can help attain optimal and effective OCS tapering along with reducing OCS overuse and over-reliance. In this paper, we discuss current practices regarding the use of OCS in asthma, globally and in the MEA region. Expert recommendations for achieving OCS stewardship in the MEA region have also been presented. Regional experts recommend increasing awareness among patients about the consequences of OCS overuse, engaging community pharmacists, and educating primary healthcare professionals about the benefits of prompt appropriate referral. Innovative local referral tools like ReferID can be utilized to refer patients with asthma to specialist care. The experts also endorse a multidisciplinary team approach and accelerating access to newer medicines like biologics to implement OCS stewardship and optimize asthma care in the MEA region.

Generic orphan drug substitution: a critical analysis of global practices and Saudi Arabia's perspective.

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction.

The Saudi initiative for asthma - 2024 update: Guidelines for the diagnosis and management of asthma in adults and children.

The Saudi Initiative for Asthma 2024 (SINA-2024) is the sixth version of asthma guidelines for the diagnosis and management of asthma for adults and children that was developed by the SINA group, a subsidiary of the Saudi Thoracic Society. The main objective of the SINA is to have guidelines that are up-to-date, simple to understand, and easy to use by healthcare workers dealing with asthma patients. To facilitate achieving the goals of asthma management, the SINA Panel approach is mainly based on the assessment of symptom control and risk for both adults and children. The approach to asthma management is aligned for age groups: adults, adolescents, children aged 5-12 years, and children aged <5 years. SINA guidelines have focused more on personalized approaches reflecting a better understanding of disease heterogeneity with the integration of recommendations related to biologic agents, evidence-based updates on treatment, and the role of immunotherapy in management. The medication appendix has also been updated with the addition of recent evidence, new indications for existing medication, and new medications. The guidelines are constructed based on the available evidence, local literature, and the current situation at national and regional levels. There is also an emphasis on patient-doctor partnership in the management that also includes a self-management plan.

Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study.

BACKGROUND: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. OBJECTIVE: This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. METHODS: A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3 years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. RESULTS: The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142 patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. CONCLUSIONS: These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. CLINICALTRIALS: gov: NCT02637050; registered December 2015.

Assessing oral cancer knowledge among Saudi medical undergraduates.

Oral cancer is the sixth most common malignancy worldwide with more than 263,000 patients diagnosed in 2008. Nonspecialists' negative attitudes and poor working knowledge of oral cancer significantly contribute to suboptimal detection of early-stage disease which leads to delays in diagnosis. We aimed to assess the working knowledge and views associated with oral cancer prevention among medical students in Saudi Arabia. A cross-sectional questionnaire-based survey of 4th, 5th, and 6th year undergraduate medical students was undertaken. Questions included knowledge of oral cancer, risk factors, and opinions on oral cancer prevention. The overall response rate was 82 % (137/167). Mean score of cancer knowledge was 57.8 % which was below the expected standard of 70 %. Only 53 % correctly answered all questions related to oral cancer. This result had no association with either the academic year (p = 0.23) or gender (p = 0.37). Interestingly, 72 % of the respondents did not feel confident in performing an oral examination. Sixty-three percent of the medical students believed it to be beyond their role to aid patients in smoking cessation measures or to take part in other disease preventative strategies. This study demonstrates a dearth of knowledge relating to the diagnosis and management of oral cancer among clinical students within an established Saudi medical school. An immediate refinement of current medical curricula to address these deficiencies is warranted.

A Curcumin-Based Oral Gel Has Potential Protective Efficacy against Oral Mucositis: In Vitro Study.

Oral mucositis is a common distressing complication of cancer therapy, characterised by painful sores within the oral cavity. Current management options offer limited symptomatic relief. Curcumin, a natural polyphenolic compound with recognised anti-inflammatory and antioxidant properties, has emerged as a potential protective agent against oral mucositis. This study explores the therapeutic potential of curcumin in mitigating the impact of oral mucositis by investigating a commercially available curcumin-based oral gel, PerioGold®. Liquid chromatography-tandem mass spectrometry was used to characterise the main constituents of PerioGold®. The cytotoxicity of curcumin constituent was investigated in four cell lines: primary oral keratinocytes (HOKs), immortalised oral keratinocytes (OKF6), dysplastic oral keratinocytes (DOKs), and oral squamous cell carcinoma cells (PE/CA-PJ15). Concentrations of hydrogen peroxide were optimised to develop in vitro models that mimic oral mucositis. The inhibitory effects of PerioGold® against the production of reactive oxygen species were assessed using a designated kit. OKF6 cells were the most sensitive to oxidative stress, while PE/CA-PJ15 cells showed the highest resistance. Pretreatment of the investigated cells for 24 h with PerioGold® demonstrated a significant antioxidative effect in all cells based on a dose-response pattern. PerioGold® exhibits clinical potential for protecting against oxidative stress, warranting further individualised clinical investigations.