Oral Candida carriage and resistance against common antifungal agents in hematopoietic stem cell transplantation recipients.

PURPOSE: Allogeneic hematopoietic stem cell transplant (HSCT) recipients receiving long-term and high-dose immunosuppressive medications suffer commonly from oral candida infections. This prospective cohort study examined oral fungal carriage in HSCT recipients and screened the susceptibility against commonly used antifungal agents. An increasing oral occurrence of Candida spp. and the development of resistance against clinically administered fluconazole were hypothesized. METHODS: Two hundred HSCT recipients were included and followed up for 2 years post-HSCT. Oral microbiological specimens were analyzed with matrix-assisted laser desorption/ionization-time of flight mass spectrometry assays (MALDI-TOF). The colorimetric method was applied for the susceptibility testing by commercially available Sensititre YeastOne (SYO®, TREK Diagnostics Systems, Thermo-Fisher, UK). RESULTS: The prevalence of oral Candida spp. carriage increased statistically significantly after a year post-HSCT being 30, 26, 35, 44, and 47%, pre-HSCT, 3, 6, 12, and 24 months post-HSCT, respectively. Altogether, 169 clinical oral Candida strains were isolated. Fourteen Candida spp. were identified, and C. albicans was predominant in 74% of the isolates pre-HSCT with a descending prevalence down to 44% 2 years post-HSCT. An increasing relative proportion of non-albicans species post-HSCT was evident. No development of resistance of C. albicans against fluconazole was found. Instead, a shift from C. albicans towards non-albicans species, especially C. dubliensis, C. glabrata, and relatively seldom found C. krusei, was observed. CONCLUSION: Oral Candida carriage increases after HSCT. Instead of the expected development of resistance of C. albicans against fluconazole, the relative proportion of non-albicans strains with innate resistance against azole-group antifungals increased.

Expression of advanced glycation end products and their receptors in diabetic periodontitis patients.

AIM: The systematic review aimed to compare the levels of advanced glycation end products (AGEs) and RAGE (AGE receptors) expression in diabetic periodontitis patients with non-diabetic periodontitis patients and to identify the relationship of AGE and RAGE levels with periodontal disease severity. MATERIALS AND METHODS: The literature search was carried out according to PRISMA guidelines by two independent researchers using four online databases: PubMed, Scopus, Web of Science Core Collection, and Pro-Quest. Relevant studies published between 2000 and March 2023 were included in this review. The association of diabetes and AGE/RAGE levels on periodontal health, periodontal pocket depth (PPD), and clinical attachment loss (CAL) was studied. RESULTS: Sixteen cross-sectional studies, including 2794 patients (age range 15-75 years), were identified in the final stage. An elevated AGE level was observed among patients with diabetes and chronic periodontal disease compared to the non-diabetic group. Furthermore, the levels of AGE and RAGE are associated with CAL and PPD. Potential confounding factors like genetic and methodological differences were also responsible for AGE and RAGE variation. CONCLUSION: Levels of AGEs and RAGE expressions in diabetic periodontitis patients differ from non-diabetic periodontitis patients. The differences may impact the course and severity of periodontal disease.

Oral active matrix metalloproteinase-8 immunotest may be less accurate in haemato-oncologic patients.

OBJECTIVES: This study examines the associations of active matrix metalloproteinase-8 (aMMP-8) point-of-care immunotest (Periosafe) outcomes with oral health of patients with haemato-oncologic diseases. METHODS: Adult patients diagnosed with haematological diseases aimed to be treated with haematopoietic stem cell transplantation (HSCT) between 2018 and 2019 were included in the study. Clinical and radiological dental examination were taken immediately prior to transplantation. The presence of oral foci of infections, caries or periodontitis was examined and compared with the outcomes of aMMP-8 immunotest. RESULTS: Acute oral infection foci were present in 11.9%, chronic in 44.1% and periodontitis in 42.0% of the 143 subjects. aMMP-8 immunotest was positive in 13.3% of all the 143 subjects. Among subjects with periodontitis (n = 60), the aMMP-8 immunotest was also positive in 13.3% of these subjects. However, the subjects with positive aMMP-8 immunotest (n = 19) had more often acute or chronic infection foci and more than one of the examined dental treatment needs compared with subjects with negative immunotest (all p < 0.05). There were no differences in age, sex, hyposalivation, DMFT-index values nor with plasma levels of leukocytes, neutrophils or C-reactive protein between subjects with positive or negative aMMP-8 immunotest. CONCLUSIONS: aMMP-8 immunotest accuracy might be reduced, in relation to periodontitis, in haemato-oncologic patients.

Active MMP-8 point-of-care (PoC)/chairside enzyme-test as an adjunctive tool for early and real-time diagnosis of peri-implantitis.

OBJECTIVE: The aim of this study was to investigate the utility of the active matrix metalloproteinase (aMMP-8)-point-of-care (PoC) test as a quantitative real-time chair-side diagnostic tool for peri-implant diagnosis, as well as assess the potentially developing and ongoing risk relative to the traditional clinical methods. BACKGROUND: Current peri-implant and periodontal disease diagnoses rely on clinical and radiological examinations. This case-control study investigated the applicability of aMMP-8-PoC immunotest for quantitative real-time diagnosis and monitoring of dental implants in health and disease. METHODS: Sixty-eight patients visiting a specialist clinic for maintenance following dental implant placement underwent assessment of their peri-implant health. aMMP-8-PoC peri-implant sulcular fluid (PISF) lateral-flow immunotests were performed using ImplantSafe® technology quantitated by ORALyzer®. In addition, the PISF samples were analyzed for total MMP-8, calprotectin, and interleukin (IL)-6 by enzyme-linked immunosorbent assays (ELISA), aMMP-8 by western immunoblot, and MMP-2 and MMP-9 by gelatin zymography. RESULTS: The aMMP-8-PoC test promptly recorded and reflected peri-implant disease, differentiating it clearly from health. X-ray findings (bone loss > 2 mm), peri-implant pocket depth ≥ 3 mm, and bleeding on probing were significantly more prevalent among implants positive for the aMMP-8-PoC test. aMMP-8/ORALyzer analysis was more precise in recording disease than total MMP-8, calprotectin, IL-6, MMP-2, and MMP-9. CONCLUSIONS: The aMMP-8-PoC test can be conveniently implemented to alert for and detect active collagenolysis affecting peri-implant tissues, both in the early and advanced stages of the disease. Active and fragmented MMP-8 exhibits a strong and significant association with peri-implantitis as compared to total MMP-8 and other biomarkers and can be utilized as the POC/chairside biomarker of choice in the new classification of peri-implantitis.

Conceptual changes in ameloblastoma: Suggested re-classification of a "veteran" tumor.

OBJECTIVES: The merging of ameloblastoma (AM) with mural unicystic ameloblastoma (UAM-M) was suggested by the 2017 WHO based on similar treatment needs. In an international multicenter study, we investigated the characteristics of their merged product (merged-AM) and raised the possibility of unifying AM and UAM (total-AM). MATERIALS AND METHODS: AM and UAM (luminal/intraluminal/mural), separate and combined, were analyzed for demographic/clinical/radiological features. ANOVA and chi-square tests were followed by univariate and multivariate analyses, and significance was set at p < .05. RESULTS: The patients' mean age was 39.6 ± 20.3 years in merged-AM (147 AM, 76 UAM-M), 45.1 ± 19.4 years in AM (p = .009). Merged-AM comprised 51.3% multilocular/48.7% unilocular tumors, AM comprised 72.5%/27.5%, respectively (p < .001). Merged-AM was associated with impacted teeth in 30.8%, AM in 18% (p = .023). The probability of merged-AM for multilocularity increased by 2.4% per year of age (95%CI 0.6-4.2, p = .009). Association with impacted teeth decreased by 7.9% per year of age (95%CI 1.9-14.39, p = .009). Merged-AM did not differ from total-AM (p > .05). CONCLUSIONS: Merged-AM partially differed from AM, but differences appeared to diminish in an age/time-wise manner. Merged-AM and total-AM were nearly indistinguishable. Therefore, AM and UAM may be considered a continuous spectrum of one type of tumor, further necessitating revision of the treatment approaches.

Bilberry (Vaccinium myrtillus L.) Powder Has Anticarcinogenic Effects on Oral Carcinoma In Vitro and In Vivo.

Previous studies indicate that bilberry with high amounts of phenolic compounds can inhibit carcinogenic processes of colorectal cancer in vitro and in vivo. However, no studies have focused on the effects of bilberry on oral cancer. In this study, we aimed to examine the effects of bilberry powder on oral squamous cell carcinoma (OSCC) cells using both in vitro and in vivo assays. The effects of 0, 1, 10, and 25 mg/mL of whole bilberry powder on the viability, proliferation, migration, and invasion of OSCC (HSC-3) cells were examined and compared with 0.01 mg/mL of cetuximab. Two oral keratinocyte cell lines served as controls. Tumor area was analyzed in zebrafish microinjected with HSC-3 cells and treated with 2.5, 10, or 25 µg/mL of bilberry powder. Metastases in the head or tail areas were counted. Bilberry powder inhibited the viability, proliferation, migration, and invasion of HSC-3 cells (p < 0.05), which was more pronounced with higher concentrations. Cetuximab had no effect on HSC-3 cell migration or invasion. Compared to controls, the tumor area in zebrafish treated with bilberry powder (10 and 25 µg/mL) was reduced significantly (p = 0.038 and p = 0.021, respectively), but the number of fish with metastases did not differ between groups. Based on our in vitro and in vivo experiments, we conclude that whole bilberry powder has anti-tumor effects on OSCC cells.

Human leukocyte antigens are associated with salivary level of active MMP-8.

OBJECTIVES: This case control study examined the associations of HLA antigens and periodontitis with the salivary level of active MMP-8 (aMMP-8). MATERIALS AND METHODS: A total of 202 subjects, registered as Swiss bone marrow donors, participated in the study. HLA-A, -B, and -C types were determined by serology or PCR. Saliva samples were collected from subjects, followed by a periodontal examination. The salivary level of aMMP-8 was determined with immunofluorometric assay. RESULTS: The mean salivary level of aMMP-8 was directly comparable to the grade of periodontitis and increased from healthy to mild/moderate to severe (125.0 ± 132.1, 200.6 ± 170.2, 290.1 ± 202.3 ng/ml; p < 0.001 between each group, respectively). The only association between the HLA types and the salivary level of aMMP-8 was observed in subjects with HLA-A11. Subjects with healthy periodontium and HLA-A11 had a lower level of aMMP-8 (49.2 ± 32.5 ng/ml) compared with subjects without HLA-A11 (123.6 ± 119.2; p = 0.048). Among subjects with periodontitis, a higher level of aMMP-8 (394.2 ± 255.6 ng/ml) was observed in subjects with HLA-A11 compared with subjects without HLA-A11 (201.1 ± 146.1 ng/ml; p < 0.002). This finding was statistically significant also after adjusting for sex, age, smoking, tooth brushing and the number of medications (p < 0.05). CONCLUSIONS: HLA-A11 is associated with the salivary level of aMMP-8 which contributes to the subject's immune and inflammatory response in periodontium.

Anticancer Effects of Lingonberry and Bilberry on Digestive Tract Cancers.

Wild berries are part of traditional Nordic diets and are a rich source of phytochemicals, such as polyphenols. Various berry treatments have shown to interfere with cancer progression in vitro and in vivo. Here, we systematically reviewed the anticancer effects of two Nordic wild berries of the Vaccinium genus, lingonberry (Vaccinium vitis-idaea) and bilberry (Vaccinium myrtillus), on digestive tract cancers. The review was conducted according to the PRISMA 2020 guidelines. Searches included four databases: PubMed, Scopus, Web of Science, and CAB abstracts. Publications not written in English, case-reports, reviews, and conference abstracts were excluded. Moreover, studies with only indirect markers of cancer risk or studies with single compounds not derived from lingonberry or bilberry were not included. Meta-analysis was not performed. The majority (21/26) of studies investigated bilberry and colorectal cancer. Experimental studies on colorectal cancer indicated that bilberry inhibited intestinal tumor formation and cancer cell growth. One uncontrolled pilot human study supported the inhibitory potential of bilberry on colorectal cancer cell proliferation. Data from all 10 lingonberry studies suggests potent inhibition of cancer cell growth and tumor formation. In conclusion, in vitro and animal models support the antiproliferative and antitumor effects of various bilberry and lingonberry preparations on digestive tract cancers.

Dissociations of oral foci of infections with infectious complications and survival after haematopoietic stem cell transplantation.

INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) recipients are at increased risk for severe infections. This study examined the associations of common oral infections with survival and infectious complications in HSCT recipients. MATERIALS AND METHODS: All autologous and allogeneic HSCT recipients transplanted in the University Hospital of Basel, Switzerland, between 2008 and 2016 and referred to oral infection control pre-HSCT were included in this retrospective case-control study. All patients had a clinical and a panoramic radiological dental examination taken immediately prior to HSCT. Presence of acute or chronic oral foci of infections, decayed, missing or filled tooth index (DMFT) and radiological attachment loss (RAL) were examined. Survival and infections of the subjects were followed up for 6 months post-HSCT. RESULTS: Altogether 341 allogeneic and 125 autologous HSCT recipients were included in the study. Within 6 months post-HSCT, 47 (14%) of the allogeneic and 4 (3%) of the autologous recipients died. Oral foci of infections (acute or chronic), DMFT or periodontitis pre-HSCT were not associated with survival 6 months post-HSCT. Oral foci of infections were also not associated with hospital treated infectious diseases or blood culture positive bacteremia during the 6 month follow-up period. Untreated oral foci of infections were not associated with survival or severe infectious complications within 6 months post-HSCT. CONCLUSION: The results of this study suggest that radical dental interventions to chronic oral infections could be postponed until post-HSCT.

Common oral diseases, hyposalivation and survival post-HSCT, a longitudinal study.

OBJECTIVES: Haematopoietic stem cell transplantation (HSCT) recipients are at risk of side effects within the oral cavity. The purpose of this study was to examine progression of common oral diseases and hyposalivation and their associations with survival in allogeneic HSCT recipients. METHODS: Two hundred and sixty nine adult HSCT recipients treated with HSCT between 2008 and 2016 were included in this study. The associations of caries, decayed, missing, filled teeth (DMFT) index, radiological attachment loss and stimulated salivary flow rate with 6-month survival and the progression of the oral disorders within 2 years were examined. RESULTS: Forty HSCT recipients (14.8%) deceased within 6 months post-HSCT. Among the deceased recipients, hyposalivation and caries were more common pre-HSCT than in recipients who survived over 6 months (P < 0.05). HSCT recipients with hyposalivation pre-HSCT had higher risk of death (HR: 1.90, 95% CI:1.00-3.60; P = 0.044) within 6 months post-HSCT compared with recipients without hyposalivation. Hyposalivation pre-HSCT was associated with a higher DMFT index score (P < 0.05) and a smaller number of teeth (P < 0.005) 24 months post-HSCT in comparison with those without hyposalivation. CONCLUSIONS: Hyposalivation and caries were associated with a lower rate of survival in HSCT recipients. Additionally, hyposalivation predisposed to deterioration of oral health post-HSCT.

Common oral diseases in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pre-HSCT.

OBJECTIVES: The purpose of this study was to compare the prevalence of common oral diseases between allogeneic haematopoietic stem cell transplantation (HSCT) recipients and healthy controls. MATERIALS AND METHODS: A total of 143 adult allogeneic HSCT recipients who were treated for haematological malignancies between 2008 and 2016 were included in the study. The HSCT recipients were age and sex matched with healthy controls. A dental examination was performed on the HSCT recipients prior to HSCT. Differences in stimulated saliva flow rate (SSFR), decayed, missing and filled teeth (DMFT) index, number of teeth, number of caries lesions, and measures of current or previous periodontitis (radiological attachment loss >3 mm or probing pocket depth ≥4 mm) between HSCT recipients and controls were examined. RESULTS: Stimulated saliva flow rate, DMFT index and the number of caries lesions were poorer in the HSCT recipients pre-HSCT compared to controls (all P-values <0.05). No statistically significant differences in the measures of current or previous periodontitis were observed. CONCLUSIONS: Stimulated saliva flow rate was low and caries was common in HSCT recipients prior to HSCT. Efficient preventive strategies are important in order to maintain the oral health of these patients.

Determinants of stimulated salivary flow among haematopoietic stem cell transplantation recipients.

OBJECTIVES: The aetiology of hyposalivation in haematopoietic stem cell transplantation (HSCT) recipients is not fully understood. This study examined the effects of treatment-related aetiological factors, particularly medications, on stimulated salivary flow in HSCT recipients. SUBJECTS AND METHODS: Adult HSCT recipients (N = 118, 66 males, 27 autologous and 91 allogeneic transplants) were examined. Stimulated whole salivary flow rates (SWSFR) were measured before HSCT and at 6 and 12 months post-HSCT. Linear regression models were used to analyse the associations of medications and transplant-related factors with salivary flow rates, which were compared to salivary flow rates of generally healthy controls (N = 247). RESULTS: The SWSFR of recipients were lower pre-HSCT (mean ± standard deviation, 0.88 ± 0.56 ml/min; P < 0.001), 6 months post-HSCT (0.84 ± 0.61; P < 0.001) and 12 months post-HSCT (1.08 ± 0.67; P = 0.005) than the SWSFR of controls (1.31 ± 0.65). In addition, hyposalivation (<0.7 ml/min) was more frequent among HSCT recipients pre-HSCT (P < 0.001), 6 months post-HSCT (P < 0.001) and 12 months post-HSCT (P = 0.01) than among controls. The SWSFR was observed to improve over time being significantly higher 12 months post-HSCT compared to pre-HSCT (P < 0.001). The observed decrease of salivary flow could not be explained by the examined transplant-related factors and medications. CONCLUSIONS: Decreased stimulated salivary flow rates could not be explained by the examined factors alone; these findings indicate that hyposalivation in HSCT recipients exhibits a multifactorial aetiology. CLINICAL RELEVANCE: All HSCT recipients should be considered to be at high risk of hyposalivation and consequent oral diseases, and they should be treated accordingly.

Associations of HLA-A, -B and -DRB1 types with oral diseases in Swiss adults.

Human leukocyte antigens (HLA) are crucial components of host defense against microbial challenge but the associations of HLA types with oral infectious diseases have not been studied in detail. This prospective cross-sectional study examined associations of HLA-A, -B and -DRB1 types with common oral diseases in a healthy Swiss adult population. 257 subjects (107 m, 150 f, mean age: 43.5 yr; range: 21-58 yr) with known HLA-A, -B and -DRB1 profiles and comprehensive medical records were included. A thorough anamnesis was followed by oral examinations including saliva flow measurements, the DMFT score for cariological status, complete periodontal status with plaque and bleeding indexes as well as assessment of mucosal alterations and temporomandibular dysfunction (TMD). Student's t-test and Pearson chi-square test were utilized to compare the oral diseases between HLA positive and negative subjects. Bonferroni correction for multiple comparisons was used and PBonf<0.05 was considered statistically significant. HLA types -B15 (PBonf = 0.002), -B51 (PBonf = 0.02) and -DRB1*12 (PBonf = 0.02) were associated with less periodontal disease manifestations. HLA-A32 had a positive association with TMD dysfunction (PBonf = 0.012). No other statistically significant associations were observed. In conclusion, HLA types may contribute to the development of oral diseases in generally healthy Caucasian adults.