COVID-19 impact on post-traumatic stress symptoms in burning mouth syndrome: A multicentric study.

OBJECTIVES: This study investigates the psychological impact of COVID-19 on burning mouth syndrome (BMS) patients. It focuses on comparing post-traumatic stress symptoms (PTSS), post-traumatic growth (PTG), and resilience between BMS patients and Controls. METHODS: A total of 100 BMS patients and 100 Controls from five Italian centers participated in this observational cross-sectional study. They completed several assessments, including the General Health Questionnaire, Depression Anxiety and Stress Scale, Insomnia Severity Index, National Stressful Events Survey Short Scale, Impact of Event Scale-Revised, Post Traumatic Growth Inventory Short Form, and Connor-Davidson Resilience Scale. RESULTS: BMS patients had significantly higher stress, anxiety, and depression (DASS-21 score) and post-traumatic stress symptoms (IES-R-6 score), particularly in terms of intrusive thoughts. They showed lower post-traumatic growth (PTGI-SF score) compared to Controls. The resilience scale (CDRS-10) was a key predictor of PTG in both groups, explaining a significant variance in PTGI-SF scores. CONCLUSIONS: BMS patients experienced heightened post-traumatic stress, stress, anxiety, and depression during the COVID-19 pandemic, with reduced post-traumatic growth. This highlights the need to prioritize their psychological well-being, focusing on stress management and fostering post-traumatic growth in challenging times.

Evaluation of Metabolomics as Diagnostic Targets in Oral Squamous Cell Carcinoma: A Systematic Review.

In recent years, high-throughput technologies have facilitated the widespread use of metabolomics to identify biomarkers and targets for oral squamous cell carcinoma (OSCC). As a result, the primary goal of this systematic review is to identify and evaluate metabolite biomarkers and their pathways for OSCC that featured consistently across studies despite methodological variations. Six electronic databases (Medline, Cochrane, Web of Science, CINAHL, ProQuest, and Embase) were reviewed for the longitudinal studies involving OSCC patients and metabolic marker analysis (in accordance with PRISMA 2020). The studies included ranged from the inception of metabolomics in OSCC (i.e., 1 January 2007) to 30 April 2023. The included studies were then assessed for their quality using the modified version of NIH quality assessment tool and QUADOMICS. Thirteen studies were included after screening 2285 studies. The majority of the studies were from South Asian regions, and metabolites were most frequently derived from saliva. Amino acids accounted for more than quarter of the detected metabolites, with glutamate and methionine being the most prominent. The top dysregulated metabolites indicated dysregulation of six significantly enriched pathways including aminoacyl-tRNA biosynthesis, glutathione metabolism and arginine biosynthesis with the false discovery rate (FDR) <0.05. Finally, this review highlights the potential of metabolomics for early diagnosis and therapeutic targeting of OSCC. However, larger studies and standardized protocols are needed to validate these findings and make them a clinical reality.

Impact of medications on salivary flow rate in patients with xerostomia: a retrospective study by the Xeromeds Consortium.

OBJECTIVES: This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with xerostomia. MATERIAL AND METHODS: This cross-sectional multicenter study is based on data of patients referred to five oral medicine outpatient practices in Europe and USA from January 2000 and April 2014. Relevant demographic, social, medical history and current medications were collected. RESULTS: The study included 1144 patients, 972 (85%) females, with a mean (SD) age of 59 (14.1) years. In unmatched patients, the UWS flow rate was lower in patients taking a medication (vs. not taking a medication) from the following drug categories: opioid analgesics, anticonvulsants, antidepressants, antihypertensives, benzodiazepines, corticosteroids, diuretics, disease-modifying antirheumatic drugs (DMARDs) and hormones. There was a greater negative effect on SWS flow rate in patients taking (vs. not taking) anticonvulsants, antidepressants, benzodiazepines, corticosteroids, and DMARDs. In matched patients, both UWS (0.22 vs. 0.19 ml/min; p = 0.03) and SWS (0.97 vs. 0.85 ml/min; p = .017) flow rates were higher in patients on non-opioid analgesics (vs. not taking). The UWS flow rate was lower in patients taking antidepressants (vs. not taking) (0.16 vs. 0.22 ml/min p = .002) and higher (and within normal range) in patients taking sex hormones (vs. not taking) (0.25 vs. 0.16 ml/min; p = .005). On the other hand, SWS was lower in patients taking corticosteroid (vs. not taking) (0.76 vs. 1.07 ml/min; p = .002), and in patients taking DMARDs (vs. not taking) (0.71 vs. 0.98 ml/min; p = .021). Finally, differences in medians of both UWS and SWS were statistically significant in patients taking 1 or more than 1 opioid analgesic (vs. not taking, p ≤ .0001 and p = .031, respectively), 1 or more than 1 anticonvulsants (vs. not taking, p = .008 and p = .007), 1 or more than 1 antidepressants (vs. not taking, p < .0001 for both), 1 or more than 1 DMARDs (vs. not taking, p = .042, and p = .003). CONCLUSIONS: A greater negative impact on UWS and SWS flow rates was seen in patients taking more than one medication from the same drug class. Intake of antidepressants, corticosteroids and DMARDs is associated with lower whole saliva flow rates. CLINICAL RELEVANCE: Salivary flow rate can be modified by some specific medications, mostly by polypharmacy.

Evaluation of aversive behavior in Rattus norvegicus experimentally infected by two distinct strains of Toxoplasma gondii (ME49 and VEG): study of epigenetic markers.

BACKGROUND: Behavioral changes in Rattus norvegicus infected with two strains of Toxoplasma gondii (ME49 and VEG) were investigated. METHODS: Rats were evaluated for motor activity and aversion or attraction to cat urine 60 days after infection. After euthanasia, arginine-vasopressin gene methylation in the central nervous system was evaluated. RESULTS: A significant difference was observed in the methylation of the arginine-vasopressin promoter gene between rats infected with the ME49 and VEG strains. CONCLUSIONS: Although differences were not observed in many parameters, significant differences were observed in the methylation of the arginine-vasopressin promoter gene in rats infected with the two studied strains.

Evaluation of aversive behavior in Rattus norvegicus experimentally infected by two distinct strains of Toxoplasma gondii (ME49 and VEG): study of epigenetic markers

ABSTRACT Background: Behavioral changes in Rattus norvegicus infected with two strains of Toxoplasma gondii (ME49 and VEG) were investigated. Methods: Rats were evaluated for motor activity and aversion or attraction to cat urine 60 days after infection. After euthanasia, arginine-vasopressin gene methylation in the central nervous system was evaluated. Results: A significant difference was observed in the methylation of the arginine-vasopressin promoter gene between rats infected with the ME49 and VEG strains. Conclusions: Although differences were not observed in many parameters, significant differences were observed in the methylation of the arginine-vasopressin promoter gene in rats infected with the two studied strains.

Immunocytometric Analysis of Oral Pemphigus vulgaris Patients after Treatment with Rituximab as Adjuvant.

Background: B-cell depletion therapy was demonstrated to be a valid and safe alternative as an adjuvant in oral-pharyngeal pemphigus vulgaris (OPV) patients. We aimed to assess its effects on anti-desmoglein (Dsg) 1 and 3 and leukocytes subsets profile in these patients' population. Methods and Materials: We evaluated the immunologic profile of 10 OPV patients treated with RTX as adjuvant by using the ELISA testing for anti-Dsg-1 and -3 titers and the immunophenotyping for B and T-cell lymphocyte subpopulations and compared them with the PDAI score for clinical remission. Results: A significant difference in medians between baseline, end of RTX therapy, and 6 months after RTX therapy was observed in Dsg-3 titer (p < 0.001), in the CD8 (p = 0.009), and CD20 counts (p < 0.001). Multiple comparisons after Bonferroni adjustment confirmed such significant differences mainly between baseline and the end of RTX therapy and baseline and 6 months after RTX therapy. Only the anti-Dsg-3 titer at the end of RTX therapy demonstrated a slight positive correlation with the PDAI score at baseline (p = 0.046, r = 0.652). Conclusions: B-cell depletion adjuvant therapy in OPV patients demonstrated a significant impact on anti-Dsg-3 titer and B and T-cell lymphocyte subpopulations profile.

Cardiomyopathy as the first manifestation of Friedreich's ataxia.

We present the case of a female patient diagnosed in childhood with Friedreich Ataxia (FA). At the age of 6, she developed left congestive heart failure with cardiomyopathy, as evident on echocardiogram. Neurologic signs only appeared at age 7, including marked loss of muscle mass, gait instability, muscle clonus, and Babinski's signal. At age 27, she had a stroke and was hospitalized; a few days later, she had a cardiorespiratory arrest with asystole, leading to death. The autopsy disclosed severe cardiomyopathy and significant myocardial replacement with fibrosis; therefore, the cause of death was assumed to be heart failure. Compared to the literature, our case has some unique features, such as cardiac disease as the presenting manifestation instead of gait instability, which is the major initial sign in most FA cases. Since our patient was submitted to an autopsy, it was an opportunity to retrieve important data to confirm the diagnosis and to evaluate the pathophysiology of this entity, such as myocardium fibrosis and cerebellar degeneration. In summary, our case demonstrates that cardiac disease can be the first manifestation of FA, with eventual diagnostic and prognostic implications. In addition, the autopsy provided findings of severe cardiomyopathy associated with FA.

Global research trends in complex oral sensitivity disorder: A systematic bibliometric analysis of the framework.

OBJECTIVES: A systematic bibliometric analysis was performed to investigate trends in complex oral sensitivity disorder (COSD) research worldwide and compare the contributions of different countries/institutions, scientific journals, authors, keywords, and citations. METHODS: Web of Science database from 1985 to 2018 was systematically searched to identify all relevant articles using the MeSH terms "complex oral sensitivity disorder" and all synonyms used in the literature. We included original articles, review articles, letters to the editor, and book chapters in the English language and in 27 different ISI categories of medical sciences. Several bibliometric indicators were used. RESULTS: We identified 10 633 articles, of which only 3349 were eligible with only 443 being included for quantitative analyses. The annual percentage growth rate for article publication was 9.16 fractionalized articles with the most productive countries (reported only in 428 out of 443 articles) being Italy (n = 66, 15.42%) followed by USA (n = 61, 14.25%) and with Italy achieving the greatest number of citations (n = 1415). Similarly, the most productive institution for article publication was the University of Turku, Finland, with 39 (8.8%) published articles. Among the top 20 departments, 15 were affiliated with dental institutions. The most productive source was "Journal of Oral Pathology and Medicine" with 38 (8.58%) articles, whereas the most productive author was "Lopez-Jornet P" with 19 articles (6.52 fractionalized articles). CONCLUSIONS: There is an increasing trend for publications on COSD. Collaboration among different countries must improve in order to implement research on this disorder, which seems to be mainly a condition for the dental discipline.

Global research trends in complex oral sensitivity disorder: A systematic bibliometric analysis of the structures of knowledge.

OBJECTIVES: A systematic bibliometric analysis of the structure of knowledge was performed to investigate the co-word analysis, the co-citation analysis, and the social network analysis regarding complex oral sensitivity disorder (COSD). METHODS: Web of Science database from 1985 to 2018 was systematically searched to identify all relevant articles using the MeSH terms "complex oral sensitivity disorder" and all synonyms used in the literature. We included original articles, review articles, letters to the editor, and book chapters in the English language and in 27 different ISI categories of medical sciences. Several bibliometric indicators were used. RESULTS: The co-word analysis identified 741 KeyWords Plus (KWP) grouped into 4 different clusters. The terms "pain," "management," "prevalence," and "efficacy" reached the highest centrality, whereas the top 10 KWP had a frequency of 7%-29% in 443 articles. Over a period of 32 years, a complex thematic evolution occurred, going from 2 to 6 different themes, and the KWP migration rate from one cluster to another ranged from 11% to 100%. The co-citation network analysis based on the complete reference list (5932 references) of 443 articles identified only 2 clusters for journals, authors, and articles. The most prominent co-cited journal was "Oral Surgery Oral Medicine Oral Pathology" (centrality: 171.75), the most co-cited author was "Grushka M" (centrality: 330.95), and the most co-cited article was "Grushka M. Oral Surg Oral Med Oral Pathol (1987) 63:30-36" (centrality: 269.79). On the other hand, the direct citation network revealed that "Scala A et al, 2003" reached both the highest global citation score (GCS = 231) and local citation score (LCS = 161). Lastly, the social network analysis revealed an isolated collaboration among groups of authors, or countries or institutions. The worldwide collaboration analysis indicated that United States-Israel and United Kingdom-Italy were the most collaborative countries. CONCLUSIONS: The structure of knowledge of publications on COSD revealed that research in this field has been dominated by few core topics and a limited collaboration among authors and institutions from different countries. More multicenter studies on COSD are warranted in the near future when launching new projects.

Autoimmune mucocutaneous blistering diseases in the south of Italy: a 25-year retrospective study on 169 patients.

BACKGROUND: Autoimmune mucocutaneous blistering diseases (AMBDs) represent a heterogeneous group of organ-specific and potentially life-threatening diseases. We sought to determine the relationship between clinical remission and therapeutic regimens with clinical type and phenotype of AMBDs, as well as clinical outcomes achieved based on different therapeutic regimens. METHODS: A retrospective single-center study on 169 AMBDs patients, including pemphigus vulgaris (PV), mucous membrane pemphigoid (MMP), paraneoplastic autoimmune multiorgan syndrome (PAMS), and lichen planus pemphigoides (LPP), was performed from 1994 to 2019 in an oral medicine tertiary center, where we collected sociodemographic data, clinical type and phenotype, prescribed therapies, and related outcomes. RESULTS: The mean age of AMBDs patients was 55.0 ± 16.4 years. They were followed for a mean of 8.4 ± 5.8 years. The majority of these patients (62.1%) were successfully managed with conventional immunosuppressive therapy (CIST) alone. However, 37.9% of patients required additional biological treatments, either because they were non-responders or developed severe side effects from CIST, or because of the rapid and severe progression of the disease. Overall, complete clinical remission was achieved in 92.3% of patients. A statistically significant difference was noted between the frequency distribution of AMBDs patients among different therapeutic regimens (P = .002), of different clinical phenotype and type of AMBDs patients and clinical remission (P = .012 and P = .005, respectively). No difference was reported regarding clinical outcomes and different therapeutic regimens. CONCLUSIONS: AMBDs' management may be challenging, nonetheless CIST and biologic regimens introduced, when needed as reliable alternatives to CIST, result in a very high percentage of CCR.

The use of rituximab as an adjuvant in the treatment of oral pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris patients with exclusive oral involvement (OPV) treated with conventional immunosuppressive therapy may be non-responders or experience severe side effects and/or relapses. In such cases, rituximab could be used as an adjuvant in recalcitrant OPV patients. METHODS: A retrospective single-center study on patients with oral pemphigus vulgaris treated with RTX at a dose of 375 mg/m2 was performed, evaluating the complete clinical and immunological remission, side effects of RTX, and possible correlation between anti-desmoglein (Dsg) 3 antibodies and clinical remission. RESULTS: We treated 10 OPV patients, of which 60% had a moderate and 40% mild disease severity before therapy with RTX. Complete clinical remission (CCR) was achieved in 100% of OPV patients, of which 20% developed side effects and 20% experienced a relapse in a mean time of 15.2 ± 10.2 weeks. The mean time for CCR was achieved in 19.8 ± 10.3 weeks, whereas the duration of the CCR consisted in 37.4 ± 33.5 weeks. OPV patients underwent a mean follow-up of 57.2 ± 37.7 weeks. In all patients, the mean of pemphigus disease area index (PDAI) decreased from 20.3 ± 14.1 to 0.4 ± 0.0, whereas the mean Dsg3 value dropped from 157.1 ± 40.6 to 67.0 ± 26.6 after therapy with RTX. However, no correlation was found between PDAI and anti-Dsg3 antibodies before and after therapy with RTX (P > .05). CONCLUSIONS: RTX represents a valid and safe alternative as an adjuvant in OPV patients with low rate of relapses and side effects.

Assessment of oral health-related quality of life, measured by OHIP-14 and GOHAI, and psychological profiling in burning mouth syndrome: A case-control clinical study.

OBJECTIVES: To evaluate the oral health-related quality of life (OHRQoL) of patients with burning mouth syndrome (BMS) by comparing the Oral Health Impact Profile-14 (OHIP-14) and Geriatric Oral Health Assessment Index (GOHAI) tests, assessing their dependence with pain, anxiety and depression and, secondly, to analyse the changes in time after treatment with psychotropic drugs. METHODS: Twenty-six patients and 26 controls were included. The GOHAI, OHIP-14, visual analogue scale (VAS) and the Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A) were performed at baseline (time 0) and after 6 months of treatment (time 1). Descriptive statistics, the Mann-Whitney non-parametric test for two independent samples and the Wilcoxon non-parametric test for two paired samples were used. RESULTS: The scores from all outcome measurements were statistically significantly different between the cases and controls (P < .001) with a strong correlation between the GOHAI and the OHIP-14 (P < .001). The BMS patients showed a statistically significant improvement in the VAS, HAM-D and HAM-A scores from time 0 to time 1 (P < 0.001), and in the OHIP-14 scores (P < .004**) after the treatment, but no statistically significant difference in the GOHAI score (.464). CONCLUSIONS: Burning mouth syndrome patients showed poorer scores on all scales compared to the healthy subjects with a lower OHRQoL. OHIP-14 gives a greater weight to psychological and behavioural outcomes in evaluating oral health than GOHAI, and therefore, it is a more effective questionnaire in terms of the evaluation of the treatment response. The management of BMS can improve pain, anxiety and depression and the OHRQoL.

Cardiomyopathy as the first manifestation of Friedreichs ataxia

We present the case of a female patient diagnosed in childhood with Friedreich Ataxia (FA). At the age of 6, she developed left congestive heart failure with cardiomyopathy, as evident on echocardiogram. Neurologic signs only appeared at age 7, including marked loss of muscle mass, gait instability, muscle clonus, and Babinski's signal. At age 27, she had a stroke and was hospitalized; a few days later, she had a cardiorespiratory arrest with asystole, leading to death. The autopsy disclosed severe cardiomyopathy and significant myocardial replacement with fibrosis; therefore, the cause of death was assumed to be heart failure. Compared to the literature, our case has some unique features, such as cardiac disease as the presenting manifestation instead of gait instability, which is the major initial sign in most FA cases. Since our patient was submitted to an autopsy, it was an opportunity to retrieve important data to confirm the diagnosis and to evaluate the pathophysiology of this entity, such as myocardium fibrosis and cerebellar degeneration. In summary, our case demonstrates that cardiac disease can be the first manifestation of FA, with eventual diagnostic and prognostic implications. In addition, the autopsy provided findings of severe cardiomyopathy associated with FA.

Trends in International Incidence of Pediatric Cancers in Children Under 5 Years of Age: 1988-2012.

BACKGROUND: Pediatric cancer incidence has been steadily increasing over the last several decades with the largest increases reported in infants. Few evaluations have looked at international pediatric cancer incidence trends in the youngest children. The aim of this analysis was to evaluate trends in cancer incidence in children under 5 years of age, overall and by type, using data from Cancer Incidence in 5 Continents (CI5) from 1988 to 2012 (CI5 volumes VII-XI). METHODS: Rates of cancers in children ages 0-4 years were extracted from registries available in CI5 from 1988 to 2012. To overcome small numbers in individual registries, numerators and denominators were aggregated within regions corresponding to the United Nations' geoscheme. Average annual percent change (AAPC) was estimated using Poisson regression.  Robust standard errors were used in all models to correct for overdispersion in some regions, and 95% Wald confidence intervals and P values were reported. The top five cancers by increasing AAPC were ranked within each region. RESULTS: Overall, in children under 5 years, increasing incidence was seen in multiple regions for acute lymphoblastic leukemia, acute myeloid leukemia, ependymal tumors, neuroblastoma, and hepatoblastoma. Hepatoblastoma had the largest AAPC in 11 out of 15 regions and showed an increase in all regions except southern Asia. Astrocytic tumors were the only cancer that decreased over the time period. CONCLUSIONS: We evaluated 25 years of cancer incidence in children ages 0-4 years and observed increases in incidence for hepatoblastoma, leukemia, neuroblastoma, and ependymal tumors. Further etiologic evaluation will be required to explain these increases in incidence.

The usefulness of YouTube™ videos as a source of information on burning mouth syndrome.

OBJECTIVES: The aim of this review was to investigate quality assessment and quantitative information on burning mouth syndrome (BMS) on YouTube™ videos. METHODS: An electronic search of YouTube™ videos on BMS was performed using subject headings, keywords and synonyms of BMS. For each video, quality information, via the quality assessment score (QAS) and quantitative information, such as the total number of results per term searched, date of upload, clip length, view count, source category (professional, personal, educational, mixed), number of likes and dislikes and YouTube™ category were evaluated. RESULTS: The search identified 3768 videos of which only 114 were included in our analysis: the quality of videos was very poor (mean ± standard deviation = 1.76 ± 1.64). The most representative categories were "educational" with 53 (46.5%) videos scoring between 0 and 4 and "mixed" with 24 (21.1%) videos scoring between 0 and 2. Significant differences were found among all four categories in relation to length in seconds (P < 0.001), number of views (P = 0.006) and interaction index (P = 0.001), as well as between "professional" and the other categories and between "educational" and "personal" in relation to length in seconds (P < 0.001), between "educational" and "personal" (P < 0.001) and "personal" and "mixed" category in relation to interaction index (P = 0.003) and between "professional" and "personal" in relation to views per day (P = 0.015). CONCLUSIONS: A large number of videos regarding BMS have published on YouTube™, with a wide range of distribution regarding their length and views. Unfortunately, they presented unreliable information which is most often scientifically inaccurate. Health care institutions and professionals should be more actively involved in improving high-quality e-information about BMS on YouTube™.

Escalating dose of adalimumab as monotherapy to treat unusual giant and refractory oral-pharyngeal ulcerations in Crohn's disease.

Crohn's disease (CD) is a chronic, autoimmune inflammatory disease which may affect the entire gastrointestinal tract, from the oral cavity to the anus. Oral-pharyngeal ulcerations may be significant and persistent in patients with established CD, and the use of TNF-α inhibitor has demonstrated to be useful. We report a unique case of an unusual manifestation of oral CD characterized only by multiple, giant, long-lasting, relapsing ulcerations successfully treated with an escalating dose of Adalimumab at 40 mg weekly as a monotherapy.

Sleep and Orofacial Pain.

Sleep and pain share a bidirectional relationship. Therefore, it is important for practitioners managing patients experiencing either sleep and/or pain issues to recognize and understand this complex association from a neurobiological perspective involving neuroanatomic and neurochemical processes. Accounting for the influence of pain on the various aspects of sleep and understanding its impact on various orofacial pain disorders assists in developing a prudent management approach. Screening for sleep disorders benefits practitioners in identifying these individuals. Instituting evidence-based multidisciplinary management strategies using both behavioral and pharmacologic strategies enhances the delivery of appropriate care.

Management of reticular oral lichen planus patients with burning mouth syndrome-like oral symptoms: a pilot study.

OBJECTIVES: We sought to determine the efficacy of psychotropic drug in the management of BMS-like oral symptoms in patients with reticular oral lichen planus (R-OLP) refractory to conventional therapies, and its impact on anxious and depressive symptoms. MATERIALS AND METHODS: We enrolled 28 cases of symptomatic R-OLP. The Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI), the Hamilton rating scales for Depression (HAM-D) and Anxiety (HAM-A) were performed at baseline (time 0), after 2 months of topical clonazepam (time 1) and after 6 months of benzodiazepine and antidepressant drugs (time 2). RESULTS: R-OLP patients showed a statistically significant improvement in the NRS and T-PRI scores from time 0 [median: 9.0 (IQR: 7.2-10.0) and 10.5 (IQR: 7.0-13.0), respectively] to time 2 [(median: 2.0 (IQR: 2.0-3.0) (p < .001) and 3.0 (IQR: 2.0-4.7) (p < .001), respectively]. Similarly, the HAM-A and HAM-D scores showed an improvement from time 0 [(median: 15.0 (IQR: 10.2-17.8) and 13.0 (IQR: 12.0-15.0), respectively] to time 2 [median: 6.0 (IQR: 4.0-7.0) (p < .001) and 5.5 (IQR: 4.25-6.0) (p < .001), respectively]. CONCLUSIONS: Psychotropic drugs turned out to be effective in the management of BMS-like oral symptoms in R-OLP patients refractory to conventional immunosuppressive therapy, although in a long-term period.