Inflammatory bowel disease and periodontitis: A retrospective chart analysis.

OBJECTIVES: This study examined the variation in prevalence of periodontitis among different sexes, age groups, smoking status, and oral hygiene adherence in patients affected by either Crohn's disease (CD) or ulcerative colitis (UC). MATERIALS & METHODS: This study was a retrospective chart analysis that collected data from the School of Dentistry's Oral Health Clinic at the University of Alberta, Edmonton, Canada. Patients' electronic health records between the years of 2013 and 2019 were analyzed. Multiple keywords such as IBD, CD, UC, and periodontal disease with various spelling combinations were used for searching and gathering pertinent data, which was then further assessed. After applying the inclusion and exclusion criteria, a total of 80 patient charts were included. These patient charts were thoroughly screened to gather information such as age, sex, smoking status, and a variety of periodontal parameters. Collected data were analyzed using SPSS software by using Pearson's χ2 , Pearson's correlation, and Mann-Whitney U-test. RESULTS: IBD had an impact on the severity of periodontitis in patients between the ages of 50 and 64 years with higher odds ratio (OR). Biological sex or history of smoking in IBD patients did not have higher odds of developing periodontitis. Plaque score derived from this retrospective study was used to estimate the patient's oral hygiene status and showed no impact. Also, prevalence of periodontitis did not differ between UC and CD. We anticipated some of these findings because of the retrospective nature of the study. CONCLUSIONS: Within the limitation of the retrospective study, IBD patients in the 50-64 age group years showed a higher odds ratio for a greater prevalence of periodontitis. Thus, a closer periodontal recall and evaluation in these patients is recommended for early diagnosis and preventive care. It is advised that periodontists work closely with gastroenterologists to maintain periodontal health in IBD-affected individuals.

Differential Signature of the Microbiome and Neutrophils in the Oral Cavity of HIV-Infected Individuals.

HIV infection is associated with a wide range of changes in microbial communities and immune cell components of the oral cavity. The purpose of this study was to evaluate the oral microbiome in relationship to oral neutrophils in HIV-infected compared to healthy individuals. We evaluated oral washes and saliva samples from HIV-infected individuals (n=52) and healthy controls (n=43). Using 16S-rRNA gene sequencing, we found differential ß-diversity using Principal Coordinate Analysis (PCoA) with Bray-Curtis distances. The α-diversity analysis by Faith's, Shannon, and observed OTUs indexes indicated that the saliva samples from HIV-infected individuals harbored significantly richer bacterial communities compared to the saliva samples from healthy individuals. Notably, we observed that five species of Spirochaeta including Spirochaetaceae, Spirochaeta, Treponema, Treponema amylovorum, and Treponema azotonutricum were significantly abundant. In contrast, Helicobacter species were significantly reduced in the saliva of HIV-infected individuals. Moreover, we found a significant reduction in the frequency of oral neutrophils in the oral cavity of HIV-infected individuals, which was positively related to their CD4+ T cell count. In particular, we noted a significant decline in CD44 expressing neutrophils and the intensity of CD44 expression on oral neutrophils of HIV-infected individuals. This observation was supported by the elevation of soluble CD44 in the saliva of HIV-infected individuals. Overall, the core oral microbiome was distinguishable between HIV-infected individuals on antiretroviral therapy compared to the HIV-negative group. The observed reduction in oral neutrophils might likely be related to the low surface expression of CD44, resulting in a higher bacterial diversity and richness in HIV-infected individuals.

Galectin-9 expression defines exhausted T cells and impaired cytotoxic NK cells in patients with virus-associated solid tumors.

BACKGROUND: We have previously reported that the upregulation of galectin-9 (Gal-9) on CD4+ and CD8+ T cells in HIV patients was associated with impaired T cell effector functions. Gal-9 is a ligand for T cell immunoglobulin and mucin domain-3, and its expression on T cells in cancer has not been investigated. Therefore, we aimed to investigate the expression level and effects of Gal-9 on T cell functions in patients with virus-associated solid tumors (VASTs). METHODS: 40 patients with VASTs through a non-randomized and biomarker-driven phase II LATENT trial were investigated. Peripheral blood mononuclear cells and tumor biopsies were obtained and subjected to immunophenotyping. In this trial, the effects of oral valproate and avelumab (anti-PD-L1) was investigated in regards to the expression of Gal-9 on T cells. RESULTS: We report the upregulation of Gal-9 expression by peripheral and tumor-infiltrating CD4+ and CD8+ T lymphocytes in patients with VASTs. Our results indicate that Gal-9 expression is associated with dysfunctional T cell effector functions in the periphery and tumor microenvironment (TME). Coexpression of Gal-9 with PD-1 or T cell immunoglobulin and ITIM domain (TIGIT) exhibited a synergistic inhibitory effect and enhanced an exhausted T cell phenotype. Besides, responding patients to treatment had lower Gal-9 mRNA expression in the TME. Translocation of Gal-9 from the cytosol to the cell membrane of T cells following stimulation suggests persistent T cell receptor (TCR) stimulation as a potential contributing factor in Gal-9 upregulation in patients with VASTs. Moreover, partial colocalization of Gal-9 with CD3 on T cells likely impacts the initiation of signal transduction via TCR as shown by the upregulation of ZAP70 in Gal-9+ T cells. Also, we found an expansion of Gal-9+ but not TIGIT+ NK cells in patients with VASTs; however, dichotomous to TIGIT+ NK cells, Gal-9+ NK cells exhibited impaired cytotoxic molecules but higher Interferon gamma (IFN-γ) expression. CONCLUSION: Our data indicate that higher Gal-9-expressing CD8+ T cells were associated with poor prognosis following immunotherapy with anti-Programmed death-ligand 1 (PD-L1) (avelumab) in our patients' cohort. Therefore, for the very first time to our knowledge, we report Gal-9 as a novel marker of T cell exhaustion and the potential target of immunotherapy in patients with VASTs.

Clinicopathologic correlation: mixed-density lesion in the posterior mandible.

A middle-aged man presented for evaluation of a mixed-density lesion of the left posterior mandible. This clinicopathologic correlation presents the radiographic, clinical, and histopathologic findings; differential diagnosis; and treatment plan for this case. The lesion was deemed to be of bacteriologic origin, likely a polymicrobial infection containing actinomycetes. Clinical care and follow-up for the patient are discussed.

Rare dental manifestation in Simpson-Golabi-Behmel syndrome.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked recessive overgrowth disorder with prominent craniofacial manifestations. Macrodontia is also an uncommon dental anomaly that can be an isolated finding and has been associated with numerous systemic conditions and syndromes. This case report describes this previously unreported dental anomaly, macrodontia, in a patient with SGBS, which may broaden the phenotype of this syndrome. A brief review of the literature on orofacial findings associated with SGBS is also presented.

Clinicopathologic correlation: palatal mass interfering with seating of a maxillary denture.

This paper is a clinicopathologic correlation regarding a 61-year-old patient with an ill-fitting maxillary denture. Examination revealed a firm, nontender palatal mass. Descriptions of the clinical findings, work-up, differential diagnosis, histological observations, and diagnosis of the lesion are presented.

Proliferative verrucous leukoplakia: an elusive disorder.

UNLABELLED: Proliferative Verrucous Leukoplakia (PVL) is a multifocal form of progressive leukoplakia with a high rate of malignant transformation that requires early recognition by oral health care providers for proper management. BACKGROUND AND PURPOSE: PVL will frequently appear as an innocuous white lesion or lesions that can easily be overlooked or considered clinically insignificant, yet it has a high rate of malignant transformation. There is limited in-depth knowledge about the pathobiology of PVL. Oral health care providers lack familiarity with this lesion; consequently the intent of this article is to increase awareness of the clinical aspects of PVL. METHODS: Case reports, case series and review articles provide a profile of PVL. CONCLUSION: It is essential that health care providers performing intraoral examinations are aware that PVL is a distinct and rare form of multifocal oral leukoplakia. PVL commonly affects females above the age of 62. Currently, little is known about its etiopathogenesis. Additionally, no specific treatment modality has proven to be effective in aborting its progression. Because of its high recurrence potential and relentless progression to squamous cell carcinoma, all recurrent and multifocal white lesions of the oral cavity should be viewed with suspicion.

Oral lichen planus.

Oral lichen planus (OLP) is a chronic, immune-mediated condition commonly affecting middle-aged women. The cause of OLP remains obscure. Strict clinical and histologic criteria need to be met to arrive at a definite diagnosis, thereby ruling out other conditions that may mimic OLP clinically and/or histologically. Although OLP is considered a premalignant condition, the risk for neoplastic change seems low.

Melorheostosis: report of two cases affecting the jaw.

Melorheostosis is a rare sclerosing bone dysplasia that is characterized by a localized, diffuse thickening of the cortical bone. This condition usually affects the appendicular skeleton and associated soft tissue and rarely affects the craniofacial complex. The etiology of this condition is obscure. Diagnosis of melorheostosis relies on clinical, radiographic, and histological correlation. Only 8 cases of melorheostosis involving the craniofacial complex have been reported. We report 2 new cases of isolated melorheostosis involving the maxilla and mandible, together with differential diagnostic considerations. To our knowledge, involvement of the maxilla only has not been previously reported.

Basal cell adenocarcinoma of the oral minor salivary glands: review of the literature and presentation of two cases.

Basal cell adenocarcinoma (BCA) is an unusual salivary gland malignancy that very rarely affects the minor glands. Here we present 2 cases of BCA arising in the minor salivary glands of the left cheek and junction of the hard and soft palate, respectively. The patients were both women aged 66 and 42 years. The tumors assumed a tubular-trabecular and a solid-membranous pattern, respectively. Both tumors showed immunopositivity for S-100, Bcl-2, and cytokeratin 7. One tumor was also immunopositive for epithelial membrane antigen and carcinoembryonic antigen, and the other tumor was reactive with p53 and vimentin. Both tumors were surgically removed. A comprehensive literature review revealed only 21 previously reported cases of BCA of oral minor salivary glands. This is an exceptionally rare salivary gland tumor, which, despite its low-grade behavior, demands complete surgical removal with adequate margins. Immunohistochemical studies may complement a thorough histopathologic analysis in discriminating BCA from other salivary gland tumors.

Hypoxia-inducible factor-1alpha polymorphisms and TSC1/2 mutations are complementary in head and neck cancers.

BACKGROUND: Polymorphisms or mutations in hypoxia inducible factor-1 alpha (HIF-1alpha) that increases its activity and stability under normoxia have recently been identified. Likewise, disruption of the TSC1/TSC2 complex through loss of TSC1 or TSC2 has been shown to result in abnormal accumulation of HIF-1alpha. Here, we investigate the novel polymorphisms in exon 12, that approximate the oxygen-dependent degradation domain of HIF-1alpha in five cell lines and 28 patients with oral squamous carcinomas. Moreover, we assess for the presence of polymorphisms and mutations in TSC1 and TSC2, to ascertain if dysregulation of such might complement HIF-1alpha expression. RESULTS: Denaturing high pressure liquid chromatography (DHPLC) analysis on PCR fragments in exon 12 of HIF-1alpha from 28 patients with OSCC revealed that 6 of 28 patients had mismatched heteroduplex patterns. Genomic DNA was extracted from peripheral blood leukocytes and direct sequencing showed that in 5 of the six cases these changes represented polymorphisms while, one case was a somatic mutation. Analyses of TSC1 and TSC2 revealed heteroduplexes in exons: TSC1 exon 17; TSC2 exons 36, 40, and 41. The relative levels of HIF-1alpha were significantly greater for tumors possessing a HIF-1alpha polymorphism or mutation within exon 12, whereas tumors possessing a deletion or polymorphism in TSC1/TSC2 displayed a trend for higher levels of HIF-1alpha. Western blot analyses for HIF-1alpha, TSC1 and TSC2 in five SCC cell lines revealed high levels of HIF-1alpha in SCC cells possessing TSC1 and/or TSC2 mutations. Wild-type TSC2 cells targeted with siRNA to TSC2 exhibited increased levels of HIF-1alpha. Transfection of a HIF-1alpha mutant produced higher levels of HIF-1alpha in TSC1/TSC2 mutant cell lines than in wild type cells. TSC1/TSC2 mutant cell lines administered Rapamycin blocked S6 phorphorylation and diminished the levels of HIF-1alpha to those observed in cell lines with wild type TSC1/TSC2. CONCLUSION: Dysregulation of the TSC1/TSC2 complex by mutation compliments HIF-1alpha polymorphisms in the expression of HIF-1alpha in SCC of the head and neck, and may provide biomarkers to predict responses to specific therapies and overall disease prognosis.