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.

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.

Significance of HIF-1α and CD105 in establishing oral squamous cell carcinoma associated with oral submucous fibrosis a distinct clinicopathological entity.

Context: Oral squamous cell carcinoma associated with oral submucous fibrosis (OSCC with OSMF) is clinicopathologically a distinct entity. However, scientific proof in view of assessment of biomarkers of hypoxia and neoangiogenesis to differentiate them are lacking. The expression of hypoxia-inducible factor 1-α (HIF-1α) and CD105 in OSCC with and without OSMF possibly will be explicated along these lines. Aim: This study aims to evaluate the molecular basis of hypoxia and neoangiogenesis in terms of immunohistochemical expression of HIF-1α and CD105 in OSCC with and without OSMF cases. Settings and Design: A retrospective cohort. Subjects and Methods: The study comprise of 203 histopathologically diagnosed surgically operated cases of OSCC retrieved from the departmental archives. The OSCC cases were subgrouped into two, OSCC with OSMF (Group I) and OSCC without OSMF (Group II). The evaluation of hypoxia and angiogenesis was carried out by immunohistochemical markers, HIF-1α and CD105. MVD is the parameter of angiogenesis expressed by CD105. Statistical Analysis Used: Differences in CD105, and HIF-1α immunoreactivity between study groups were done using descriptive statistics using "Kruskal-Wallis test," "Mann-Whitney test." Statistical significance was set at P < 0.05. Results: On comparison of MVD in Group I and II, statistically significant difference was found in MVD (8.88 ± 3.41, 16.13 ± 5.86, P = 0.0001). The HIF1-α expression was less in Group I (6.85 ± 2.62) as compare to Group II (7.22 ± 3.08) but the difference was statistically nonsignificant (P = 0.35). Conclusions: The OSCC with OSMF is not only clinicopathologically distinct entity of OSCC but also diverse in its molecular pathogenesis as explicited by distinct expression of HIF-1 α and CD105.

Prevalence of Trismus and Its Impact on Oral Health-Related Quality of Life in Patients Treated for Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma, one of the most common malignancies, has a poor prognosis due to impairment in oral functions secondary to treatment. Trismus one of the major causes of impairment of oral function. The present study investigated the prevalence of trismus and its impact on oral health-related quality of life (OHRQoL) in patients treated for oral squamous cell carcinoma (OSCC). The maximum inter-incisal mouth opening of hundred OSCC patients was recorded at post-treatment and 3 months post-treatment. OHRQoL questionnaire (OHIP-14) was intervened to assess the OHRQoL of patients post-treatment and 3 months follow-up, with emphasis on correlation with grades of trismus. The prevalence of trismus was 16% pre-treatment, 72% post-treatment, and 62% at 3 months after treatment. The overall OHIP-14 scores indicated that patients with trismus reported greater impairment of OHRQoL than those without trismus at the end of treatment and 3 months follow-up. At the end of treatment, patients with severe trismus demonstrated a higher mean OHIP-14 score (23.47 ±3.34) than those with moderate (17.72 ±2.83) and mild trismus (12.66 ±3.84) with statistically significant differences (p <0.001). Equivalent results were obtained at 3 months follow-up period. Patients with trismus suffer greater impairment of OHRQoL. The findings demand the need of identifying risk factors for developing trismus and early institution of newer/modified treatment approaches for better OHRQoL in OSCC survivors.
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Exploring the role of immunotherapeutic drugs in autoimmune diseases: A comprehensive review.

Autoimmune diseases are group of disorders where an immune response is mounted against the self. The prevalence and burden of this well established and recognised entity is on the rise. Irrespective of being a systemic or organ specific autoimmune disorder, the common underlying mechanism of action, is the imbalance in immune system resulting in loss of tolerance to self-antigens. The oral cavity is no alien to these disorders or to their influences. Pemphigus group of lesions, systemic lupus erythematosus, psoriasis and even Sjogren's syndrome are some of the established autoimmune disorders with prominent oral manifestations. Though these diseases are well documented and enumerated, however addressing them is where the dilemma lies. Science, research and discoveries are a crucial part of medical discipline which help in looking beyond the horizon. With the introduction of selective targeted immunotherapies for autoimmune diseases as a treatment modality either in solitary or in combination with the conventional immunosuppressive treatments, are emerging as a promising elixir for patients enduring them. However, being unique, exploration of these biologics from its inception, to its mechanism of action, recognition of its application and evaluation of its safety norms are equally vital. Therefore, this review aims to provide a comprehensive particular on the novel biologics, the immunotherapies in autoimmune disorders targeting the different cells, their receptors or cytokines of the immune system.

Oral and general health-related quality of life in oral squamous cell carcinoma patients- comparative analysis of different treatment regims.

BACKGROUND: Modern aggressive oncological treatment options for oral squamous cell carcinoma (OSCC) are inevitably associated with impaired general health-related quality of life (HRQoL) and oral HRQoL (OHRQoL). However, there is dire need for prospective and concomitant assessment of HRQoL and OHRQoL after different treatment regims. Hence, present study was designed to investigate HRQoL and OHRQoL in patients treated for OSCC using various modalities. METHODS: 135 OSCC patients were grouped according to treatment rendered into Group A: surgery only; Group B: post-surgical radiotherapy (PRT); and Group C: post-surgical chemo-radiation (PCRT). The 12-item Short Form Health Survey (SF-12) and Oral Health Impact Profile-14 (OHIP-14) were intervened to assess HRQoL and OHRQoL respectively at 1-month and 6-months post-treatment. RESULTS: At 1-month post-treatment, patients who received PCRT showed significantly lower mean values for physical and mental domains of SF-12 and higher mean subscales and overall OHIP-14 (24.57 â€‹± â€‹2.62) score than those treated by surgery alone (10.55 â€‹± â€‹2.26) and PRT (20.20 â€‹± â€‹3.80), with largest differences between PCRT and surgery alone groups (p â€‹< â€‹0.001). Social functioning, general health and bodily pain of SF-12 and functional limitations, physical pain and physical disability amongst OHIP-14 domains were greatly affected. Although few physical domains of SF-12 showed significant improvement, mental domains remained a greater problem after 6 months. However, OHRQoL was significantly poor in all the three study groups (p â€‹< â€‹0.001). CONCLUSION: Irrespective of the post-treatment duration, patients who received PCRT had worse HRQoL and OHRQoL. There is a need to identify factors associated with impaired HRQoL and OHRQoL to customize better therapeutic decisions.

Oro-facial opportunistic infections and related pathologies in HIV patients: A comprehensive review.

Among all the viral infections, acquired immunodeficiency syndrome (AIDS) is considered as one of the most morbid infections caused by the human immunodeficiency virus (HIV). The prime reason for the pathogenesis is the profound immunosuppression that leads to lethal opportunistic infections (OI), neurological disorders, unexpected malignancies and pathologies of the orofacial region. Patients with OI whose HIV status is unknown have shown a mortality rate higher than those with known HIV status. Among HIV-associated infections, orofacial lesions contribute a major proportion of the OI attributed to the plethora of micro-organisms present in the oral cavity. Apart from serious clinical manifestations, opportunistic infections also lead to significant impairment of quality of life. These lesions not only indicate the HIV infection but also among the clinical manifestations, which often occur early in the course of disease. World Health Organization has also provided policies for treatment/prevention of oral lesions, strengthening the promotion and care of oral health in HIV/AIDS patients. The present review provides comprehensive information about orofacial OI in HIV/AIDS patients and emphasis was also given to the malignancies associated with EB and HTLV virus.

Denture induced mechanotransduction can contribute to oral carcinogenesis.

Mechanical stresses in the form of substrate rigidity, hydrostatic pressure, compressive, tensile and shear stress has been regarded as an important motive for the epithelial carcinogenesis brought about by the activation of Hippo signaling pathways. Masticatory forces generated in edentulous patients with dentures are transferred directly to the palatal mucosa (maxillary denture) and alveolar mucosa (mandibular denture). Thus, the oral mucosa present underneath the dentures experiences compressive, shear and tensile stresses on a day-to-day basis. These stresses can induce carcinogenesis by mechano-transduction and subsequent activation of numerous carcinogenesis relevant signaling pathways such as the HIPPO pathway. With this contention in mind, we proposed a hypothesis, which explains the pathogenesis for the presence of oral squamous cell carcinoma in denture wearer patients. Efforts were made to envisage the appropriate experimentations for the evaluation of the hypothesis. As a therapeutic implication, flexible dentures, soft denture, or medicated dentures could be prescribed for the high-risk groups having potentially malignant lesions in the oral cavity.

Oral Psychosomatic Disorders in Family Caregivers of Oral Squamous Cell Carcinoma Patients.

OBJECTIVE: To investigate the oral psychosomatic disorders (PSDs) in family caregivers (FCs) of oral cancer (OC) patients and to evaluate the correlation between these oral PSDs to severity of depression anxiety and stress. METHODS: A total of 50 participants were included each in first degree relative (FDR), second degree relative (SDR) and control group. All the participants completed DASS-21 questionnaire and were subjected to thorough clinical history and oral examination. RESULTS: All the FCs reported statistically significant higher mean levels of depression, anxiety and stress compared to controls (p˂0.001). A significantly greater number of FCs (40.00%) reported oral PSDs than control group (12.00%). Most prevalent oral PSD in FCs was aphthous stomatitis followed by oral lichen planus, bruxism, burning mouth syndrome and myofascial pain dysfunction syndrome. Moreover, there was a preponderance of these diseases in FDR (60.86%) compared to SDR (26.08%). FCs with moderate to very severe depression, anxiety and stress showed higher prevalence of these oral PSDs compared to the ones with mild depression, anxiety and stress. CONCLUSION: The observations of higher prevalence of oral PSDs in FCs with psychological alterations can enhance healthcare professionals' awareness to better understand FCs' oral healthcare needs.
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Tumor associated tissue eosinophilia in oral squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) still lacks the valid prognosticator for survival. Tumor associated tissue eosinophilia (TATE) have been widely investigated in the literature but still there is no consensus viewpoint on its role as prognostic marker. With this view in mind, a systematic review and meta-analysis of studies that evaluated the overall risk of elevated TATE and survival in OSCC was conducted. METHODOLOGY: A systematic literature search conducted to identify studies that have evaluated TATE in OSCC. Overall survival (OS), Disease Free Survival (DFS) Hazard ratio (HR) with 95% confidence interval) was extracted. HR was extrapolated if direct HR was not given in publication. Studies were pooled and combined hazard ratios (HRs) of High TATE for OS and DFS were calculated. RESULTS: 6 out of 874 articles were found eligible for systematic review and meta-analysis. High TATE was predictor of OS (pooled HR 0.45 (95% CI, 030-0.65, P â€‹< â€‹0.0001)) and DFS (pooled HR 2.33 (95% CI, 0.74-7.37)) in OSCC patients. CONCLUSION: High TATE positively predicts OS and DFS in OSCC and thus can be regarded as an important survival prognosticator. Standardization of counting and reporting methodology for TATE count is recommended on future cohort studies.

Analysis of 100 most cited articles on forensic odontology.

OBJECTIVES: Bibliometric analysis of best-cited papers brings awareness about the influential publications and trends in the literature on a particular topic. This will help not only the researchers and academicians but also the students for selecting quality landmark articles. With this view in mind a bibliometric analysis was performed to identify the 100 top-cited papers on Forensic Odontology (FO) in the literature. MATERIALS AND METHODS: A search was performed using Scopus database in August 2019. The articles were further reviewed and basic standard information related to bibliometric analysis was recorded. RESULTS: The 100 most cited articles were published from 1985 to 2014 (77% published after 2001). The most frequently cited article received 259 citations, whereas the least received 31 (mean citations 58.78 ± 33.14). There were 16 different journals with Forensic Science International having the most number of articles (n = 36). One author had 16 articles while 8 authors had 4 or more articles published in the top 100 list. Belgium was the country with most number of articles (n = 17) followed by United States (n = 16). In terms of document type, 87 were original research, 7 conference papers and 6 reviews. Five organizations funded 5 of the top 100 articles. Katholieke Universiteit Leuven, Belgium affiliated the most documents (n = 16). Majority of the papers were related to age estimation (46) followed by victim identification (30), mass disaster (9), bite mark analysis (8), sex determination (5), race determination (4), dental DNA analysis (3), palatal rugae pattern (2) and lip prints (1). CONCLUSION: This is first of its kind citation analysis of the 100 most cited articles in the field of FO. The results of this paper will help the researchers, academicians and students for appropriate article referrals.

Clinical efficacy of mouth exercising devices in oral submucous fibrosis: A systematic review.

BACKGROUND: The management of oral submucous fibrosis (OSF) is primarily focused towards minimizing patient's symptoms and to prevent cancer development. Mouth exercise physiotherapy independently or in combination with other modalities is considered to be a mainstay for increasing the mouth opening (MO). The present systematic review was performed to identify different mouth exercising devices (MEDs) used and to provide detailed information on the fabrication and clinical efficacy of these devices among OSF patients. METHODS: PubMed, Scopus, Web of Science, Google Scholar and CINAHL were searched for relevant literature until February 2019 and the information was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All full text papers describing use of MED in OSF patients were considered eligible. RESULTS: Initial search resulted in 88 hits. After removing duplicates and screening of titles and abstracts, five papers that met the inclusion criteria were included. We identified five MEDs used for increasing the MO in OSF patients. Only one study administered additional treatment with topical steroids, oral antioxidants and ice-cream stick regime. The follow-up across studies ranged from 8 weeks to 6 months. Majority of the studies reported significant improvement in the MO without any relapse and side effects. CONCLUSIONS: MED could play an important role in the management of OSF. Limited researches in this area suggest a dire need for the further investigations using randomized controlled trials.

Transverse Ridge of Premolars and Oblique Ridge of Maxillary Molars are in Divine Golden Ratio.

AIMS: In premolars and molars, transverse ridge (TR) and oblique ridge (OR) play major roles in providing strength and stability to the cusps in particular and tooth as a whole. Hence, they could be divided at the central groove or the transverse groove in a divine golden ratio. MATERIALS AND METHODS: Twenty pairs of maxillary and mandibular casts were retrieved from the Department of Orthodontics. The lengths of buccal triangular ridge (BTR), lingual triangular ridge (LTR) and TR of maxillary and mandibular first and second premolars were measured. Similarly, lengths of distal cuspal ridge of mesiopalatal cusp, triangular ridge of distobuccal cusp (DBTR) and OR of the maxillary first and second molars were measured using a brass wire and a Vernier caliper. The TR:BTR, BTR:LTR, OR:distal ridge of mesiopalatal cusp (MPDR), and MPDR:DBTR ratios were calculated to find out the possibility of golden ratio. RESULTS: Transverse ridges of the premolars and OR of the maxillary first and second molars were divided at the central groove in a divine golden ratio. The mean TR/BTR ratio for maxillary first premolar was 1.61 ± 0.007, whereas the mean BTR/LTR ratio was 1.63 ± 0.02. The mean TR/BTR ratio for maxillary second premolar was 1.61 ± 0.01, whereas the mean BTR/LTR ratio was 1.62 ± 0.04. The TR/BTR and BTR/LTR ratios for mandibular first premolar were 1.6 ± 0.008 and 1.64 ± 0.02, respectively. Similarly, the mean TR/BTR ratio for mandibular second premolar was 1.61 ± 0.01, whereas the mean BTR/LTR ratio was 1.63 ± 0.02. CONCLUSION: The ORs of maxillary first molar ridge and TR of maxillary and mandibular premolars are divided into two parts at transverse and central grooves, respectively, in a divine ratio. CLINICAL RELEVANCE: The ORs of maxillary first molar ridge and TR of maxillary and mandibular premolars are divided into two parts at transverse and central grooves, respectively, in a divine ratio. This signifies the strength and stability of the occlusal table in the posterior teeth, as the golden ratio is the mark of functional excellence. Golden ratio should be taken into consideration while restoration or fabrication of the posterior teeth.

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.

Bibliographic Analysis of Oral Precancer and Cancer Research Papers from Saudi Arabia.

OBJECTIVE: Oral cancer and precancers are a major public health challenge in developing countries. Researchers in Saudi Arabia have constantly been directing their efforts on oral cancer research and have their results published. Systematic analysis of such papers is the need of the hour as it will not only acknowledge the current status but will also help in framing future policies on oral cancer research in Saudi Arabia. METHOD: The search string "oral cancer" OR "Oral Squamous Cell Carcinoma" OR "oral premalignant lesion" OR "oral precancer" OR "Oral Potentially malignant disorder" AND AFFIL (Saudi AND Arabia ) was used for retrieval of articles from Scopus database. Various tools available in Scopus database were used for analyzing the bibliometric related parameters. RESULTS: The search revealed a total of 663 publications based on the above query. Maximum affiliations were from King Saud University (163) followed by Jazan University (109) and then King Abdulaziz University (106). A large number of international collaborations were observed, the maximum with India (176) and the USA (127). The maximum number of articles were published in the Asia Pacific Journal of Cancer Prevention (34) followed by the Journal of Contemporary Dental Practice (33) and Journal of Oral Pathology and Medicine (19). CONCLUSION: Saudi researchers are directing their efforts towards the public health menace of oral cancer. However, it was also observed that some institutions have emerged as front runners in research, whereas others are contributing significantly less. The health department should encourage and take necessary steps to increase the involvement of other institutions.