Correlations between Immune Response and Etiopathogenic Factors of Medication-Related Osteonecrosis of the Jaw in Cancer Patients Treated with Zoledronic Acid.

Impairment of the immune response in MRONJ (medication-related osteonecrosis of the jaws) is one of the still unclear etiopathogenic mechanisms of this condition encountered in cancer patients treated with bisphosphonates, with negative effects on the patient's quality of life. The aim of the present study was to correlate the immune response with etiopathogenic factors via immunohistochemical evaluation of the maxillary tissues in zoledronic acid osteonecrosis. The retrospective study included a group of 51 patients with various types of cancers, diagnosed with stage 2 or 3 MRONJ at zoledronic acid and treated surgically. Immunohistochemical expressions of αSMA, CD3, CD4, CD8, CD20, CD79α, CD68, CD204, and tryptase were evaluated. Immunohistochemical markers expressions were statistically analyzed according to the duration of the treatment, the trigger factor, the location of the MRONJ, and the healing status. Analysis of the immune response included T lymphocytes, B lymphocytes, plasma cells, macrophages, and mast cells. The duration of treatment significantly influenced the immunohistochemical expression of most markers (p < 0.05). For an increasing trend in treatment duration, a decreasing trend in marker score was observed, suggesting an inverse correlation. The expression of the markers was different depending on the trigger factor, on MRONJ localization (maxilla/mandible), and the healing status, being more intense in patients cured per primam compared to those who had relapses. The patient's immune response was negatively influenced by the duration of the treatment, the trigger factor, the location of the lesion in the mandible, and the recurrence of MRONJ.

Risk Factors for Medication-Related Osteonecrosis of the Jaw-A Binomial Analysis of Data of Cancer Patients from Craiova and Constanta Treated with Zoledronic Acid.

MRONJ (Medication-Related Osteonecrosis of the Jaw) is a condition observed in a subset of cancer patients who have undergone treatment with zoledronic acid in order to either prevent or treat bone metastases. The primary aim of this research was to establish the importance of risk factors in the development of medication-related osteonecrosis of the jaw in cancer patients receiving zoledronic acid therapy for bone metastases. The present study is an observational retrospective investigation conducted at two university centers, namely, Craiova and Constanța, and included cancer patients treated with zoledronic acid. The medical records of the patients were obtained over a four-year timeframe spanning from June 2018 to June 2022. The data analysis was carried out between January 2021 and October 2022. Patients were treated for cancer, bone metastases, and MRONJ according to the international guidelines. The research investigated a cohort of 174 cancer patients (109 females and 65 males) aged between 22 and 84 years (with a mean age 64.65 ± 10.72 years) seeking treatment at oncology clinics situated in Craiova and Constanța. The study conducted a binomial logistic regression to analyze ten predictor variables, namely, gender, age, smoking status, treatment duration, chemotherapy, radiotherapy, endocrine therapy, presence of diabetes mellitus (DM), obesity, and hypertension (HT). The results of the analysis revealed that only five of the ten predictor variables were statistically significant for MRONJ occurrence: duration of treatment (p < 0.005), chemotherapy (p = 0.007), and hypertension (p = 0.002) as risk factors, and endocrine therapy (p = 0.001) and obesity (p = 0.024) as protective factors.

Clinical and Histopathological Aspects of MRONJ in Cancer Patients.

Medication-related osteonecrosis of the jaw (MRONJ) is a major complication of bisphosphonate treatment in cancer patients, and its etiology is not completely clarified. The study's goal is to find connections between the clinical and histopathological characteristics of osteonecrosis and bisphosphonates in a cohort of cancer patients who had osteonecrosis treated surgically. The retrospective study includes 51 patients of both sexes, aged 46 to 85 years, who underwent surgical treatment for MRONJ in two oral and maxillofacial surgery clinics (Craiova and Constanța). Demographic, clinical, and imaging data from the records of patients with osteonecrosis were analyzed. The surgical treatment removed the necrotic bone, and the harvested fragments were analyzed from a histopathological perspective. The histopathological examination data were evaluated and statistically processed to look for viable bone, granulation tissue, bacterial colonies, and inflammatory infiltrate. In the study groups, MRONJ was found particularly in the posterior regions of the mandible. Tooth extraction, but also periapical or periodontal infections, represented the trigger factors in most of the cases. The surgical therapy consisted of sequestrectomy or bone resection, and the histopathological examination of the fragments revealed osteonecrosis-specific features, such as the lack of bone cells, the development of an inflammatory infiltrate, and the existence of bacterial colonies. MRONJ in cancer patients receiving zoledronic acid is a severe complication that significantly lowers quality of life. Since these patients are not usually monitored by the dentist, they are identified in advanced stages of MRONJ. For these patients, thorough dental monitoring could reduce the incidence of osteonecrosis and its related complications.

Osseointegration evaluation of an experimental bone graft material based on hydroxyapatite, reinforced with titanium-based particles.

Bone graft materials are more and more frequently used in dentistry for improving the periodontal support and for creating a bone support favorable for the insertion of dental implants. The experimental study carried out on laboratory animals aimed to evaluate the biocompatibility and the manner of integration of an experimental bone augmentation material, based on hydroxyapatite (HAp), reinforced with titanium-based particles by comparison with a commercial synthetic graft material already existing on the profile market, also based on HAp. We noticed a common pattern of evolution, although there were differences related to the speed of new bone tissue formation and implicitly the morphological elements captured at the two moments of time. In the presence of both synthetic materials, ossification also begins from the center of the cavity at distance from the margins of the bone defect, with a common pattern with an appearance with the presence of osteon-like structures. The experimental material generally determined a more intense initial inflammatory reaction, followed by the generation of a repair bone tissue with a denser appearance but with a less uniform structure and a greater number of residual particles.

Oral and Periodontal Implications of Hepatitis Type B and D. Current State of Knowledge and Future Perspectives.

Periodontitis is characterized by low-grade inflammation of the periodontal tissues, the structures that support and connect the teeth to the maxilla and mandible. This inflammation is caused by the accumulation of subgingival bacterial biofilm and gradually leads to the extensive damage of these tissues and the consequent loss of teeth. Hepatitis B is a major global health concern; infection with the hepatitis B virus causes significant inflammation of the liver and the possibility of its gradual evolution to cirrhosis. Hepatitis D, caused by infection with the delta hepatitis virus, is manifest only in patients already infected with the type B virus in a simultaneous (co-infected) or superimposed (superinfected) manner. The dental and periodontal status of patients with hepatitis B/D could exhibit significant changes, increasing the risk of periodontitis onset. Moreover, the progression of liver changes in these patients could be linked to periodontitis; therefore, motivating good oral and periodontal health could result in the prevention and limitation of pathological effects. Given that both types of diseases have a significant inflammatory component, common pro-inflammatory mediators could drive and augment the local inflammation at both a periodontal and hepatic level. This suggests that integrated management of these patients should be proposed, as therapeutical means could deliver an improvement to both periodontal and hepatic statuses. The aim of this review is to gather existing information on the proposed subject and to organize significant data in order to improve scientific accuracy and comprehension on this topic while generating future perspectives for research.

Periodontitis, Metabolic and Gastrointestinal Tract Diseases: Current Perspectives on Possible Pathogenic Connections.

Comprehensive research conducted over the past decades has shown that there is a definite connection between periodontal and systemic conditions, leading to the development and consolidation of the "periodontal medicine" concept. The 2018 classification of periodontal conditions uses this concept as a key element of the precise diagnosis of and individualized therapeutical protocols for periodontitis patients. The topic of this review is the pathogenic connections that exist between periodontal disease and metabolic/digestive tract conditions. It is important to remember that the oral cavity is a key element of the digestive tract and that any conditions affecting its integrity and function (such as periodontitis or oral cancer) can have a significant impact on the metabolic and gastrointestinal status of a patient. Thus, significant diseases with links to metabolic or digestive disruptions were chosen for inclusion in the review, such as diabetes mellitus, hepatic conditions and gastric cancers. Periodontal pathogenic mechanisms share several significant elements with these conditions, including mutual pro-inflammatory mediators, bacterial elements and genetic predisposition. Consequently, periodontal screening should be recommended for affected patients, and conversely, periodontitis patients should be considered for careful monitoring of their metabolic and digestive status.

Correlations between periodontal indices and osteoporosis.

In the pathogenesis of chronic periodontitis, there are general systemic factors which play a major role, such as osteoporosis, with menopause as the most common etiological factor, and other pathological determining conditions for osteoporosis as well (ovary, thyroid and malignant tumors). The aim of the present study was to assess the correlations between periodontal indices and osteoporosis. The study was performed on 35 patients with periodontal disease aged between 45 and 79 years. These patients were divided into two groups: a study group with osteoporosis and periodontal disease (n=25) and a control group with periodontal disease (n=10) only. The periodontal assessment included community periodontal index (CPI), gingival inflammation index (GI), plaque index (PI), body mass index (BMI), bone mineral density (BMD), tooth mobility and tooth loss. Osteoporosis was assessed by dual-energy X-ray absorptiometry. Results were statistically analyzed with Microsoft Excel software and XLSTAT. The results showed that patients in the study group had higher values of periodontal indices, and a highly significant inverse correlation was observed between the CPI and the tooth loss. Inverse correlations between BMI and tooth mobility, as well as BMI and CPI were determined for the study group. In conclusion, the positive association between BMD and GI shows that the gingival index can be a predictive factor in the occurrence of osteoporosis.

Non-Surgical Periodontal Therapy Could Improve the Periodontal Inflammatory Status in Patients with Periodontitis and Chronic Hepatitis C.

Non-surgical periodontal therapy (NSPT) is the first essential step for the management of any periodontitis patient. This study aims to evaluate the impact of NSPT on pro-inflammatory mediators' regulation and on clinical parameters in periodontitis patients who suffer from chronic hepatitis C. At baseline, selected patients were clinically evaluated for their periodontal status. A subsequent quantitative assessment of C-reactive protein and pentraxin-3 in samples of gingival fluid was performed by Enzyme-Linked Immunosorbent Assay (ELISA). Afterwards, NSPT was performed. Three months after NSPT, the clinical and ELISA assessments were repeated. The results show an improvement of the clinical parameters in periodontitis patients at the three-month recall. In chronic hepatitis C patients with periodontitis, the gingival fluid levels of pro-inflammatory markers reduced significantly. The targeted markers also expressed significant correlations with the clinical parameters used for the assessment of periodontitis' severity. The results suggest that, while chronic hepatitis C patients exhibited a more negative periodontal status at baseline as compared to non-hepatitis ones, NSPT is effective in decreasing the local periodontal inflammatory reaction and in proving the periodontal status of this type of patients. Given the limitation of the study, periodontal screening and NSPT should be included in the integrated therapeutical approach of chronic hepatitis C patients, for its impact on the local inflammatory response.

Immunohistochemical evaluation of D2-40, Galectin-3, Maspin and MCM7 expression in palate squamous cell carcinomas.

Squamous cell carcinoma (SCC) is the most frequent cancer in oral cavity and its prognosis has exhibited little improvement in the last decades. Although much less common palate SCCs manifests a higher local aggression invading very quickly the adjacent muscles and jawbones, thus being able frequently to lead to dysfunctions in chewing, swallowing, and speech. To elucidate what underlies such local aggression, we investigated the immunohistochemical expression in palate SCCs of Podoplanin (D2-40), Galectin-3 (Gal-3), mammary serine protease inhibitor (Maspin) and minichromosome maintenance complex component 7 (MCM7), markers that are known to be involved in tumor invasiveness. We found a progressive increase in reactivity for D2-40 and MCM7 from the normal epithelium toward dysplastic epithelium and respectively to SCC, which suggests the intervention of these markers in the early stages of squamous cell carcinogenesis in the palate. The highest D2-40, Gal-3 and MCM7 reactivity was observed in basaloid and in poorly differentiated (G3) palate SCCs, while for Maspin the well-differentiated (G1) palate SCCs were the most reactive. The first three markers mentioned above were most intensely expressed at the invasion front, while the Maspin reactivity was low or absent at this level. Statistically, we found significant stratification on localization, grading, muscle invasion, and survival for all investigated markers, but with very high direct correlations between D2-40, Gal-3, and MCM7 immunoreactive score (IRS) values, while between the Maspin and each of the previous markers there were very high inverse correlations. Overall, all these investigate markers proved to be responsible for the local invasiveness and regional lymph node metastasis, thus allowing a prognostic and therapeutic stratification of patients with palate SCCs.

Use of optical coherence tomography in orthodontics.

Optical coherence tomography (OCT) is a modern imaging method with applicability in orthodontics. In recent years, there has been an increasing trend in the use of ceramic brackets. The aim of the present study was to investigate the effects of bonding metallic and ceramic brackets on tooth enamel, using optical coherence tomography. For this purpose, 20 permanent teeth we bonded and were subsequently debonded using a side cutter or anterior bracket removal pliers. Using the OCT technique, the enamel, the amount of adhesive remaining and the bracket fragments remaining on the tooth surface were analyzed following the debonding procedure. It was demonstrated that enamel cracks were present only in the samples bonded with ceramic brackets. At the same time, it was noted that the type of pliers did not affect the incidence and extent of damage to the enamel. The type of debonding technique (using the side cutter or the anterior removal pliers) used did not markedly affect the amount of adhesive remaining on the teeth. Thus, as demonstrated herein, by analyzing the enamel structure through the use of OCT, the quality of the processes and the materials used for manufacturing brackets can be increased.

Evaluation Through the Optical Coherence Tomography Analysis of the Influence of Non-Alcoholic Fatty Liver Disease on the Gingival Inflammation in Periodontal Patients.

PURPOSE: The purpose of this ex vivo study is to exhibit the inflammatory changes that occur within the gingival tissue by using optical coherence tomography (OCT) in periodontal patients with non-alcoholic fatty liver disease (NAFLD) and if NAFLD could influence the local periodontal inflammation. PATIENTS AND METHODS: Gingival tissue samples obtained from patients were divided into three groups - P (periodontitis), NAFLD+P (NAFLD+periodontitis) and H (healthy) groups - and were scanned using an OCT light beam, in order to perform a qualitative and quantitative analysis of images. The value of average pixel density has been associated with the degree of inflammation. RESULTS: The highest average pixel density was found in patients from the H group, while the lowest value of average pixel density was recorded in gingival tissue samples collected from patients with NAFLD+P. The image assessments from NAFLD+P group delivered lower values of average pixel density than those of P group, suggesting a possible influence of this disease on the inflammatory tissular changes produced by periodontal disease. CONCLUSION: After comparing the OCT analysis results obtained for the three groups of patients, we can consider that NAFLD may be an aggravating factor for the inflammation of periodontal disease.

Analysis of the distribution and expression of some tumor invasiveness markers in palate squamous cell carcinomas.

Oral cancer remains an important global health issue and despite recent diagnostic and therapeutic advances, it continues to have an unfavorable prognostic and decreased survival. Although palatal tumors represent one of the rarest locations of oral squamous cell carcinomas (SCCs), they are among the most aggressive local tumors, leaving behind important morpho-functional disabilities. In order to explain such local aggressiveness, the present study aims to investigate the immunohistochemical expression in palate SCCs of some markers known to be involved in the process of tumor invasiveness, such as Wiskott-Aldrich syndrome like (WASL), Claudin-1 (CLDN1), Integrin beta-6 (ITGB6) and c-Mesenchymal to epithelial transition protein (c-Met). We have found here a higher tumor WASL and CLDN1 reactivity in well-differentiated (G1) palate SCCs, and regardless the histological type, degree of differentiation or tumor topography, an overexpression at the invasion front, and in those palate' SCC cases with muscular invasiveness and with lymph node (LN) dissemination. ITGB6 and c-Met had a higher reactivity in moderately differentiated (G2) palate SCCs, especially at the periphery of tumor proliferations, at the invasion front and in those high invasive cases and as well as in those that associated LN dissemination. All four investigated markers were also positive at the level of LN metastatic proliferations. None of the markers could statistically stratify on age group and pain, and on bone and perineural invasion while all of them statistically stratified on survival and grading. We concluded that these markers have a prognostic role allowing the identification of those cases with an unfavorable clinical evolution and decreased survival.

Palate Squamous Cell Carcinomas:A Ten-Year Single Institute Experience.

The literature date estimated that about 5% of all oral cavity cancers are hard palate cancers while soft palate cancers account for about 5-12% of oropharyngeal cancers. Although rare, usually these tumors had a more aggressively behavior than other oral cancer sites. That is why our study aimed to investigate comparatively the epidemiological, clinical and histopathological peculiarities of the two palatal sites of oral squamous cell carcinomas. We conducted a retrospective study limited to a period of 10 years in a single medical institution to investigate the morphoclinical profile of such tumors. We found that patients with hard palate SCCs had an average age slightly larger compared to those who developed soft palate tumors. Also, those with hard palate tumors are mostly diagnosed in less advanced stages compared to those at the level of the soft palate, and implicitly the former had a longer survival time. Histopathologically the most encountered hard palate SCC were the conventional well-differentiated tumor, and from the peculiar SCC variant the papillary and verrucous forms while for the soft palate SCC prevailed the moderate and poor differentiated conventional SCC and from the peculiar SCC variant the basaloid and acantholytic forms. In conclusion hard palate tumors differ in many aspects from those of the soft palate, and thus specification of the origin tumor site become important for the assessment of prognosis, treatment and survival outcome of such patients.

Craniofacial morphology aspects in children with isolated growth hormone deficiency - a cephalometric study.

Craniofacial and dental morphology is influenced by different circulating hormones, but it is of particular importance that there is growth hormone (GH) in normal craniofacial and teeth development. Craniofacial morphometry studies in children with GH deficiency show different changes in certain anthropometric variables in the sense of reducing their values compared to normal children's developmental norms in different stages of childhood and adolescence. Therefore, the early establishment of GH replacement therapy can correct craniofacial morphological changes induced by GH deficiency. In our study, we evaluated different anthropometric craniofacial variables at children with GH deficiency and we established some anthropometric and morphological characteristics associated with this pathology.

Histological findings from rat calvaria defect augmented with platelet-rich fibrin by using two consecutive periosteal incisions.

BACKGROUND AND OBJECTIVES: Platelet-rich fibrin (PRF) is a new generation of biomaterial that proved to be an effective tool in numerous clinical uses. This study aims at expanding the range effectiveness of PRF in promoting bone healing by histological evaluation. MATERIALS AND METHODS: We performed a pair of two calvaria defects on 35 Wistar rats. The left defect was left empty as a control and the right defect was augmented with PRF. After 45 days, the experiment was terminated and the calvaria were collected and underwent morphological and histological analysis. RESULTS: New bone formations have been shown to be prevalent in the PRF augmented defect. CONCLUSIONS: PRF increases the body's natural ability to heal and regenerate bone.

The prognostic value of CXCR4, α-SMA and WASL in upper lip basal cell carcinomas.

Lip cancers account for 10-12% of the total head and neck cancers and, although squamous cell carcinoma is by far the most common lower lip cancer, the basal cell carcinoma (BCC) seems to be more common for the upper lip. Most BCCs have a clinically indolent behavior, but there are also local aggressive and∕or metastatic cases, with the incidence of such cases being estimated at about 1-10% of all cases of BCC. Many of the molecular mechanisms underlying this aggression are still unknown, which is why our study aimed to investigate the potential prognosis of a few markers, such as C-X-C chemokine receptor type 4 (CXCR4), alpha-smooth muscle actin (α-SMA) and Wiskott-Aldrich syndrome like (WASL) in upper lip BCCs. For this purpose, 24 basocellular cancers with this localization have been investigated immunohistochemically, histopathologically belonging to the next varieties: superficial, nodular, micronodular, adenoid cystic, keratotic, sclerodermiform and mixed. Regardless of the histopathological subtype, for all invasive cases we have recorded an increased reactivity of the three markers especially in the invasion front, reactivity also present at the stroma level, especially at the stroma-parenchyma interface. The most intense immunoreactivity was obtained for the micronodular and sclerodermiform subtypes, confirming their biological behavior to be more aggressive than the rest of the investigated strains. All these results confirm the prognostic value of the CXCR4∕α-SMA∕WASL panel in assessing the biological behavior of the upper lip BCC.

A patient with pilomatricoma in the parotid region: case report and review of the literature.

Pilomatricoma is a benign skin tumor originating from the matrix cells of the hair follicles. Sometimes, its diagnosis can be difficult, especially in the preauricular region, where in the differential diagnosis, in addition to other dermal and subcutaneous masses, primary and secondary parotid gland tumor lesions must be also considered. A 34-year-old female was referred to our Institution with a right preauricular swelling over 12 months, which enlarged in the last two months. The ultrasonography confirms the origin of the tumoral mass in the skin of the preauricular region and not from the superficial lobe of the right parotid gland. The patient underwent complete tumor excision and the histopathology and immunohistochemical exams confirmed the diagnosis of a conventional pilomatricoma evolving to a late regressive lesion. She was discharged considered as cured and no recurrences were reported within a period of eight months of follow-up. This is the first reported case in the last 30 years, in this location, in the Department of Oral and Maxillofacial Surgery our Institution. Regarding the rarity of these tumors, especially in this location, we must keep in mind to consider a broader differential diagnosis that includes both tumoral and non-tumoral skin lesion and also parotid gland lesions.

Optical coherence tomography assessment of gingival epithelium inflammatory status in periodontal - Systemic affected patients.

INTRODUCTION: Optical coherence tomography (OCT) is an imaging tool used in various medical fields (ophthalmology, dermatology), which allows the observation of morphological particularities on the surface of tissues or internal constructive details of about 2-3mms in depth. In periodontology, it has been used as an experimental tool for periodontal pocket analysis (depth, calculus deposits) but not for the assessment of periodontal inflammation in the gingival tissues, which has been the subject of our in-vitro study. MATERIAL AND METHOD: Gingival samples were collected from three types of patients: patients with periodontal disease; patients with periodontal disease and a systemic comorbidity; periodontal and systemic healthy patients. The samples were scanned with an OCT light beam, resulting two-dimensional images of the gingival tissue (full thickness epithelium and partial connective tissue). The images were assessed using dedicated software, which allowed the quantification of pixels on a given segment in the epithelium. The average pixel densities were then calculated for each patient group and statistically analyzed. RESULTS: The resulted pixel densities were highest for the control group samples, while the lowest pixel densities were found in samples originating from periodontal patients with diabetes mellitus. For the other possible periodontal comorbidity, chronic hepatitis C, image assessment also exhibited lower pixel densities than those of the periodontal group, suggesting that this condition could also have an added effect on the tissular changes induced by periodontal disease. CONCLUSION: OCT has proven that in an in-vitro environment it can be a useful tool for the assessment of periodontal inflammation in gingival samples of periodontal patients. In terms of inflammatory tissular changes observed by OCT analysis, chronic hepatitis C could be regarded as possible periodontal disease's comorbidity.

Immunoexpression of p53 and COX-2 in basal cell carcinoma.

Basal cell carcinoma (BCC) is a variety of cutaneous carcinoma associated with an excellent prognosis because it rarely metastasizes, but it can cause significant local destruction and morbidity if surgical excision is not made. In this study, we examined the immunohistochemical expression of p53 and cyclooxygenase-2 (COX-2) in 51 BCCs, nodular and infiltrative subtypes, with various Clark levels. The immunoexpression of p53 was identified in 74.5% BCC cases and COX-2 reactions in 88.2% of cases. The scores of p53 reactions revealed significant differences depending on Clark level and borderline significance with tumor type, the high positive scores being associated to infiltrative tumors and high Clark level. No differences were revealed between COX-2 scores with both Clark level and tumor type. The analysis of the percentage values of p53 and COX-2 indicated a positive linear correlation. The positivity of p53 and COX-2 in a large proportion of BCCs, regardless of histological type and of depth of invasion, supports the two markers involvement in tumor progression.

Intramuscular human Dirofilaria repens infection of the temporal region - case report and review of the literature.

Dirofilariasis is a zoonotic worldwide-distributed disease, especially in regions with warm to temperate climate, where it recently recorded a significant increase of prevalence. A 61-year-old female, a dog owner, residing in the Southwest of Romania, near a swamp, developed a painless nodule in the left temporal region. The contrast-enhanced computed tomography (CT) scan revealed a temporal intramuscular cystic lesion. The surgical exploration confirmed the lesion as with intramuscular localization. The histopathology and biochemistry investigations established as a cause of the lesion an infestation with Dirofilaria repens species. The patient underwent an anthelmintic treatment with Diethylcarbamazine and the clinical and radiological follow-up did not revealed any recurrences within a period of 15 months after surgery. This is the second case reported in Craiova (Romania), the seventh worldwide reported case with localization in the temporal region, and the second one with intramuscular development in this region. The existence of such cases should alert the clinician to include parasitosis in the differential diagnosis of atypical space-occupying lesions of the head regions.