Heterogeneity of outcome measures in the clinical trials of treatment for oral submucous fibrosis-Systematic review.

OBJECTIVE: This systematic review was performed to evaluate the range of outcome measures used in interventional trials for oral submucous fibrosis (OSF). MATERIALS AND METHODS: PubMed, Scopus, and Cochrane databases were searched to identify randomized controlled trials (RCTs) published from 2004 to 2018 about OSF treatment. All the outcome measures and measurement methods mentioned in the trials were extracted and analyzed. RESULTS: Out of 120 published papers, 12 RCTs that met the inclusion criteria were included. A total of 38 single outcome measures and 29 composite outcome measures were considered under four different outcome domains, of which clinical symptoms and clinical response were the most commonly used. The linear measurement of mouth opening (11 trials; 91.66%) and Visual Analogue Scale (10 trials, 83.33%) were the predominant measurement methods. CONCLUSIONS: This systematic review highlights the high heterogeneity in outcome measures in therapeutic RCTs of OSF. This lack of widely agreed standard outcome measures in OSF is a great concern as it prevents the comparison of studies and meta-analyses to gather evidence. There is a dire need of establishing a core outcome set for reporting in the future clinical trials that may help facilitate treatment choice for OSF to improve life quality of patients.

Malignant transformation in oral submucous fibrosis: Tertiary level evidence: An umbrella review.

OBJECTIVES: An umbrella review is a systematic review of systematic reviews, which provides a tertiary level of evidence. This umbrella review of systematic reviews and meta-analysis (SR-MA) aimed to determine the proportion of oral cancer (OC) development in oral submucous fibrosis (OSF) patients. MATERIALS AND METHODS: We searched electronic databases including PubMed, Scopus, Web of Science, Cochrane and grey literature. Two reviewers independently screened abstracts and assessed for eligible papers. The methodological quality of SR-MA was evaluated using AMSTAR2, and we also checked the quality of evidence of the included papers. RESULTS: Out of 454 papers identified in the primary search, 105 underwent eligibility screening. Inclusion criteria were met by four SR-MA. OC ratios ranged between 4.2% and 6% for OSF. Substantial heterogeneity was observed for this outcome in all four MA (I2 = 71.31% to 86.37%). None of the SRs assessed the quality of evidence, and half of them were judged to be of critically low methodological quality. CONCLUSION: There is lack of quality of evidences and critically low methodological quality among SRs and MA leading to substantial heterogeneity. However, due to potentially malignant nature, OSF patients should be monitored carefully for early detection of OC.

Environmental tobacco smoke and children's health: a bibliometric and altmetric analysis of 100 most cited articles.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is arguably the most ubiquitous and hazardous, even at very low levels, starting in early life. The objective of this study was to describe the state of research and future trends on ETS exposure and Children's Health (CH) topics with bibliometrics and altmetrics. METHODS: An electronic search was performed in Scopus database on January 31, 2023. Consensus was arrived on 100 most-cited articles by two reviewers. These papers were then cross matched with citations harvested from Web of Science (WoS) and Google Scholar. Altmetric Attention Score (AAS) and Dimension counts were also collected. Analysis and network visualization of authors, countries, and keywords were generated using VOSviewer software. RESULTS: Among a total of 1107 articles published on ETS and CH, the 100 top-cited articles appeared in 54 journals, with Pediatrics (n = 12) contributing a maximum number of articles. The time period between 2000 and 2009 accounted for 44% of all publications. With respect to the research design employed across these studies, cross-sectional design took precedence over others accounting for approximately 40%. Predominantly, articles focused on childhood asthma; however, current research trends have shifted towards emerging fields such as children's oral health and DNA methylation. Twitter, policy documents, and news outlets were the main platforms where outputs were discussed. The AAS was not associated with journal impact factor or access type. Weak correlations were observed between AAS and citation count in Scopus, WoS, and Google Scholar (r = 0.17 to 0.27) while a positive association existed between dimension count and the number of citations across all three databases (r = 0.84 to 0.98). CONCLUSION: This study demonstrates the evolution, digital dissemination and research hotspots in the field of ETS and CH, predicting the possible future research directions. High-quality studies with more specific exposure classification are warranted to better understand the relationship between ETS and CH.

Hemangiomatous Proliferation in Oral Squamous Cell Carcinoma and Its Mimicry in the Regional Lymph Nodes.

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity with pathognomonic histopathologic features of invading nests, islands, or chords of malignant epithelial cells. Although the histological features are quite uniform across a majority of the cases, they can drastically change in different variants of OSCC, such as clear cell, spindle cell/sarcomatoid, adenoid/acantholytic/pseudoglandular, basaloid, papillary and adenosquamous, etc.

A novel method to detect intracellular metabolite alterations in MCF-7 cells by doxorubicin induced cell death.

BACKGROUND: Metabolic reprogramming within cancer cells has been recognized as a potential barrier to chemotherapy. Additionally, metabolic tumor heterogeneity is the one of factors behind discernible hallmarks such as drug resistance, relapse of the tumor and the formation of secondary tumors. METHODS: In this paper, cell-based assays including PI/annexin V staining and immunoblot assay were performed to show the apoptotic cell death in MCF-7 cells treated with DOX. Further, MCF-7 cells were lysed in a hypotonic buffer and the whole cell lysate was purified by a novel and specifically designed metabolite (~ 100 to 1000 Da) fractionation system called vertical tube gel electrophoresis (VTGE). Further, purified intracellular metabolites were subjected to identification by LC-HRMS technique. RESULTS: Cleaved PARP 1 in MCF-7 cells treated with DOX was observed in the present study. Concomitantly, data showed the absence of active caspase 3 in MCF-7 cells. Novel findings are to identify key intracellular metabolites assisted by VTGE system that include lipid (CDP-DG, phytosphingosine, dodecanamide), non-lipid (N-acetyl-D-glucosamine, N1-acetylspermidine and gamma-L-glutamyl-L-cysteine) and tripeptide metabolites in MCF-7 cells treated by DOX. Interestingly, we reported the first evidence of doxorubicinone, an aglycone form of DOX in MCF-7 cells that are potentially linked to the mechanism of cell death in MCF-7 cells. CONCLUSION: This paper reported novel methods and processes that involve VTGE system based purification of hypotonically lysed novel intracellular metabolites of MCF-7 cells treated by DOX. Here, these identified intracellular metabolites corroborate to caspase 3 independent and mitochondria induced apoptotic cell death in MCF-7 cells. Finally, these findings validate a proof of concept on the applications of novel VTGE assisted purification and analysis of intracellular metabolites from various cell culture models.

Dietary Choices Modulate Colorectal Cancer Stem Cells: A Role of FXR Nuclear Receptor.

Intra- and inter-tumor heterogeneity (TMH) among colorectal cancer patients is considered as major hurdles to develop precise, potent, and personalized cancer therapeutics. The discernible factors that contribute to the existence of TMH and associated problems are suggested as genetic, molecular, epigenetic, and environmental pressures including shifts in trend from high-fiber diet to high-fat/processed sugar diet. In essence, components of high fat/processed sugar diet potentiate metabolic re-programing of inherent cellular heterogeneity of cancer stem cells (CSCs) by genetic and epigenetic pathways intersected by the farnesoid X receptor (FXR) nuclear receptor. Therefore, choices of dietary components shape up protumor or antitumor microenvironment by the modulation of FXR regulated transcriptional and epigenetic events in CSCs. In this article, we highlight the major understanding emanated from preclinical and clinical studies that indicate the potential contribution of high fiber/saturated sugar diet toward carcinogenesis of colorectal cancer.

CD8+ T cell dysfunction by TOX intoxication: a protumorigenic event in the tumor microenvironment.

Accumulating evidence suggests the role of cellular components in achieving antitumor to protumor microenvironments. Among the various types of cells within the tumor niche, the state of CD8+ T cells apparently changes from cytotoxic T effector cells and memory T cells to exhausted CD8+ T cells. These changes in the phenotype of CD8+ T cells promote the protumor microenvironment. Recently, comprehensive experimental data delineated the role of thymocyte selection-associated high-mobility group-box protein (TOX), which regulates the transcriptional process and epigenetic remodeling, with implications in tumor and chronic viral infections. This perspective summarizes the molecular mechanisms that link CD8+ T cells, TOX, and transcriptional and epigenetic reprogramming as well as future directions for determining new avenues of cancer therapeutics.

Lay abstract Cellular components within the tumor are related to the success and failure of anticancer drugs for patients. The reasons behind the changes from antitumor to protumor microenvironments are being explored to understand the immune cells. Among several types of cells, the state of CD8⁺ cells in the immune system apparently changes from cytotoxic immune effector cells and memory effector cells to depleted CD8⁺ immune cells. These changes in the phenotype of CD8⁺ T cells promote a favorable tumor microenvironment. This minireview summarizes the importance of CD8⁺ immune cells and their regulation in the development of anticancer drugs.

Oral health-related quality of life in oral cancer patients: systematic review and meta-analysis.

Aim: The purpose of this meta-analysis was to evaluate the impact of oral health on quality of life in oral cancer patients (OCPs). Methods: PubMed, Scopus and Web of Science databases were searched for publications on oral health-related quality of life (OHRQoL) in OCP and the information was extracted according to the PRISMA guidelines. A random effect model was used to obtain the pooled standard mean differences of Oral Health Impact Profile (OHIP)-14 questionnaire responses in meta-analysis. Results: total of 12 research papers were analyzed and revealed poor OHRQoL in OCPs (standard mean difference: 2.53; 95% CI: 1.55-3.50; p < 0.00001) compared with healthy individuals due to the effects of oncotherapy. Moreover, OHRQoL deteriorated with combinations of different treatment modalities. Conclusion: Oral health and oncotherapy can affect the quality of life in OCPs.

Revisiting Sports Dentistry with a Critical Appraisal.

Dental traumas caused due to sports and other athletic activities are the connecting bridge between sports and dentistry. Studies show that 13-39% of all dental injuries are accounted for sports, out of which 11-18% are maxillofacial injuries. This editorial broadly discusses the interconnection between sports and dentistry. It highlights the importance of Parents', children's, sportspersons', and even dental practitioners' education on this topic of sports dentistry. The significant need for "team dentist" in schools and professional sports teams is also brought into the spotlight. Keywords: Dentistry, Injury, Sport, Trauma.

Facial Masking and SAMPPs: Potential "Variolation" in COVID-19.

Variolation is an important phenomenon in the field of immunology and has a rich historical background that has changed the perception of immunity reinforcement in human beings.1 This methodology was first used to immunize humans against smallpox infection by inoculating the infective material taken from infected patients.2 The intention was to induce a mild form of infection that would germane antibody response for tackling the future smallpox infection. To be more precise the procedure involves the application of powered smallpox scabs or fluid obtained from the pustules of the infected patients. This application is on the superficial scratches made on the skin surface of normal healthy individuals.3 Thus, the variolation is the process in which the virus is inoculated in the patient to produce an antibody response. This process produces signs and symptoms similar to the intended viral infection but usually of the milder form, possibly due to mild quantum exposure of virus particles. In the case of smallpox, this methodology was first used in China, India, and the Middle East before it was introduced into England and North America in the 1720s.4 Due to advancements done in the field of vaccination, this crude method is no longer used today. However, this process was a milestone in science that has led to the development of many vaccines available nowadays.

Why do Only Certain Cases of Oral Submucous Fibrosis Undergo Malignant Transformation?

Oral submucous fibrosis (OSMF) causes desmoplasia and rigidity of submucosa of the oral cavity, resulting in reduced mouth opening, and in advanced stage causes difficulty in swallowing. OSMF has poor morbidity in terms of oral function as well as general health due to loss of oral function, such as eating. In severe conditions, it can cause dysphagia and hearing loss. Various clinicians have tried the different treatment modalities to reverse the disease process, but with limited success and that too in alleviating the associated symptoms.

Oral Cancer in Young vs Old Individuals: A Systematic Review.

AIM: To compare various parameters associated with oral cancer in young and old patients and systematically compile the data on prognosis or outcome of oral cancer in young and old patients that include case series, matched-pair analyses, institutional series, and database reviews. BACKGROUND: Though oral cancer is considered a disease of old age, a recent clinical scenario witnesses its increasing incidence among young persons. When compared to old patients, young patients with oral cancer are exposed to the carcinogens for a very petite period of time suggesting underlying pathogenesis to be distinct from that in older individuals. Literature reports several studies about the occurrence of oral cancer in young patients; however, no unanimous opinion exists about its prognosis and treatment outcomes when compared to older patients. Keeping this in mind, we have extensively studied all the possible aspects (location, local and regional recurrence, nodal and distant metastasis, overall survival, etc.) from the English literature and systematically compiled the available data on prognosis or outcomes of oral cancer. REVIEW RESULTS: The overall outcome of the case series shows poorer prognosis in young patients, matched-pair analyses, and institutional series suggesting no significant differences whereas the databases favored a better prognosis in young patients. The mean overall survival rate was found to be better for young patients in the database and institutional review whereas worse in the matched-pair analyses. The mean 5-year survival rate was found to be more in young individuals in matched-pair analyses, database reviews, and institutional series as compared to older oral cancer patients. CONCLUSION: Though data extracted from various study designs are heterogeneous, the present review gives a scoping view of the papers published on oral cancer in young vs old patients. More prospective studies are suggested with a larger sample size in the future. CLINICAL SIGNIFICANCE: The present review will help to better understand the nature, course, and biologic behavior of oral cancer in young patients leading to the development of specific treatment strategies to manage the patients based on their age-groups.

Are electronic nicotine delivery systems (ENDs) helping cigarette smokers quit?-Current evidence.

BACKGROUND: Electronic cigarettes (e-cigarettes) and other electronic vaping devices are commonly used as a method to help tobacco smoking cessation. However, the data on their safety and efficacy are currently scarce. The aim of this review was to explore the role of e-cigarettes in tobacco cessation among tobacco users. TYPES OF STUDIES REVIEWED: PubMed, EMBASE, Scopus, Web of Science, and grey literature from January 1990 were searched up to and including September 2018. Two independent reviewers performed the study selection according to eligibility criteria. RESULTS: A total of 13 studies that met the eligibility criteria were included. The majority of studies were done in the USA, and all studies were longitudinal cohort studies. The odds of increased smoking cessation in association with e-cigarette use ranged from onefold to sixfolds. No significant increase in smoking cessation was found among e-cigarette users compared with non-e-cigarette users. Pattern of e-cigarette had positive influence on smoking cessation among users. CONCLUSIONS AND PRACTICAL IMPLICATIONS: E-cigarette use was not significantly associated with increased smoking cessation among cigarette smokers. We also found that pattern of e-cigarette may have significant effect on smoking cessation capability of e-cigarettes. Well-designed randomized controlled clinical trials are needed to assess the clinical efficacy of e-cigarettes in comparison with approved smoking cessation therapies.

Natural history of trigeminal neuralgia-A hospital-based retrospective study.

OBJECTIVE: The objective of this study was to assess the natural history of trigeminal neuralgia (TN) and pretrigeminal neuralgia (PTN) in a hospital-based sample using a retrospective and descriptive study design. METHODS: This study followed a retrospective study design, which yielded a sample size of 216 patients who were reclassified as per the new classification and diagnostic grading for practice and research proposed by the American Academy of Neurology. Based on an in-depth analysis of patient history and the treatments administered, a possible state of PTN prior to TN development was determined. RESULTS: TN shows a female predilection with predominantly unilateral involvement. A total of 45.83% of patients had left-side involvement with V3 primarily affected. Additionally, 11.11% of patients did not have any clinically apparent trigger zone, while 68.05% had a single trigger zone. Twenty-one patients were found to have suspected PTN prior to TN. The time interval between PTN onset and TN development ranged from 6 months to 6 years. The PTN pain varied, and the clinical overlap between the site of PTN and the site of future TN was 100%. CONCLUSION: An in-depth patient history can serve as a reliable modality for TN diagnosis. PTN should be considered as a differential diagnosis for pain of orofacial origin because of its overlapping features with other painful conditions.

A bibliometric analysis of the 100 most cited articles on early childhood caries.

BACKGROUND: Bibliometric analysis aids to quantify the research prolificacy. The citation count acquired by a scientific article is one of the measures of its influence within a field. AIM: To employ bibliometrics to offer a quantitative-qualitative analysis of publications on early childhood caries (ECC) published between 1950 and 2019. DESIGN: Two researchers independently read all the titles and abstracts of articles retrieved from Scopus database on 16 October 2019. The articles were categorized according to citation and study characteristics. Collaboration network amongst authors, countries, and keywords were generated using VOSviewer software. RESULTS: Amongst a total of 10 578 articles published on ECC, 100 most cited articles were sorted. The top-cited articles appeared in 34 journals, with Community Dentistry and Oral Epidemiology journal (n = 18) contributing maximum number of articles. The papers originated from 25 countries, with the United States (n = 54) accounting for largest number. Amid the papers with high levels of evidence, 11 were systematic reviews and 8 were randomized clinical trials. The topic most commonly addressed was aetiology/associated factors (63%). Amongst a total of 990 keywords, 'dental caries' appeared 89 times. CONCLUSION: The findings of this paper will help researchers, academicians, and students for appropriate article referrals for evidence-based clinical decision-making.

Perspective on Forensic Odontology and COVID-19.

Novel coronavirus infection (COVID-19) is the most deadly pandemic disease of the century and is now known for its high infectivity, morbidity, and mortality. It is conceivable to expect the ramifications of this pandemic in the form of depression and frustration. An increase in crime rate and violence is expected in the near future. Forensic experts along with forensic odontologists will be receiving many cases shortly and they should be ready to face the challenges. In the present paper, a critical perspective is presented on COVID-19 and its socioeconomic impact. Recommendations are provided for effectively carrying out the investigative procedures related to forensic odontology. Clinical relevance: Novel coronavirus infection (COVID-19) is the most deadly pandemic disease of the century and is now known for its high infectivity, morbidity, and mortality. Hence, it is recommended to treat every forensic sample as potential COVID-19 infected. In this regard, the present paper gives some important recommendations for handling the samples that are related to forensic odontology. These will prevent the infection spread in the forensic experts, which are considered as the backbone of this critical COVID-19 situation. Keywords: Coronavirus, COVID-19, Forensic medicine, Forensic odontology.

Novel Viewpoints on Tobacco Smoking and COVID-19.

We read with great interest an article by Karanasos et al. titled "Impact of smoking status on disease severity and mortality of hospitalized patients with COVID-19 infection: a systematic review and meta-analysis".1 It is inferred that there is an adverse impact of smoking on disease severity and mortality of hospitalized COVID-19 patients, which is more pronounced in younger patients without diabetes. Literature is flooded with papers on possible interaction and outcome of COVID-19 association with smoking. However, there are still conflicting views on the effect of smoking in patient outcomes. These conclusions are data-driven and lack valid pathogenetic background for interpretation.

Angiotensin-converting Enzyme 2 Specific Cell Subset Identification in Oral Tissues: A Need of the Hour in COVID-19 Research.

It is well known that angiotensin-converting enzyme 2 (ACE2) is an important host factor responsible for the attachment of severe acute respiratory syndrome coronavirus clad 2 (SARS-CoV-2). ACE2 has been predominantly reported to be present in lungs and nasal mucosa, which is the most common site for the initiation of COVID-19.1 Apart from lungs, ACE2 is also expressed in heart, blood vessels, kidneys, brain, intestines, etc.2 Recently various locations of the oral cavity have been found to be associated with differential expression of ACE2 protein, with the tongue being the most common site.3 Moreover, the salivary glands have also been regarded as a potential source of SARS-CoV-2 infection due to the presence of the ACE2 receptor.4 However, till date there is no strong scientific evidence that has proved the existence and interaction of ACE2 protein and spike receptor of SARS-CoV-2 on oral mucosal and salivary gland epithelial cells.

GLUT-1 Expression: An Aid in Complementing the WHO Oral Epithelial Dysplasia Grading System.

AIM AND OBJECTIVES: The clinicopathologic parameters alone are not sufficient to precisely predict if oral potentially malignant disorders (OPMDs) remain unchanged, i.e., without any malignant changes, regress, or advance to oral squamous cell carcinomas (OSCC). Few of the OPMDs, with or without epithelial dysplasia, may transform to frank OSCC. Discovering various molecular markers that can predict OSCC transformation is essential to develop effective therapeutic strategies. GLUT-1 is one of the hypoxia as well as metabolic indicator markers that have been used to study the metabolic activity of the cells. Hence, given by the World Health Organization (WHO), GLUT-1 expression was studied in various grades of dysplasia to see whether it complements the WHO grading system (mild, moderate, and severe). MATERIALS AND METHODS: The study was carried out on paraffin-embedded tissues of 10 normal oral mucosa and 30 OPMD cases. OPMD cases were classified into hyperkeratosis, mild dysplasia, moderate dysplasia, and severe dysplasia groups. Immunohistochemistry was carried out to evaluate the expression of GLUT-1 antigen. RESULTS: According to the WHO grading system of dysplasia, 11 (36.66%) cases were classified as hyperkeratosis, 9 (30%) cases were classified as mild dysplasia, 6 (20%) cases as moderate dysplasia, and 4 (13.33%) cases as severe dysplasia. There was a significant increase in GLUT-1 expression from normal to mild, moderate, and severe dysplasia (p value = 0.00). CONCLUSION: The expression of GLUT-1 marker complements the WHO grading system of oral epithelial dysplasia. CLINICAL SIGNIFICANCE: GLUT-1 expression can be used to complement the WHO grading system to grade epithelial dysplasia.