Production of Carcinogenic Acetaldehyde by Oral Microbiome

Oral cancer is the seventh most common cancer worldwide and its incidence is increasing. The most important risk factors for oral cancer are chronic alcohol consumption and tobacco smoking, up to 80 % of oral carcinomas are estimated to be caused by alcohol and tobacco. They both trigger an increased level of salivary acetaldehyde, during and after consumption, which is believed to lead to carcinogenesis. Acetaldehyde has multiple mutagenic features and it has recently been classified as a Group 1 carcinogen for humans by the International Agency for Research on Cancer. Acetaldehyde is metabolized from ethanol by microbes of oral microbiota. Some oral microbes possess alcohol dehydrogenase enzyme (ADH) activity, which is the main enzyme in acetaldehyde production. Many microbes are also capable of acetaldehyde production via alcohol fermentation from glucose. However, metabolism of ethanol into acetaldehyde leads to production of high levels of this carcinogen. Acetaldehyde is found in saliva during and after alcohol consumption. In fact, rather low ethanol concentrations (2-20mM) derived from blood to saliva are enough for microbial acetaldehyde production. The high acetaldehyde levels in saliva after alcohol challenge are explained by the lack of oral microbiota and mucosa to detoxify acetaldehyde by metabolizing it into acetate and acetyl coenzymeA. The aim of this thesis project was to specify the role of oral microbes in the in vitro production of acetaldehyde in the presence of ethanol. In addition, it was sought to establish whether microbial metabolism could also produce acetaldehyde from glucose. Furthermore, the potential of xylitol to inhibit ethanol metabolism and acetaldehyde production was explored. Isolates of oral microbes were used in the first three studies. Acetaldehyde production was analyzed after ethanol, glucose and fructose incubation with gas chromatography measurement. In studies I and III, the ADH enzyme activity of some microbes was measured by fluorescence. The effect of xylitol was analyzed by incubating microbes with ethanol and xylitol. The fourth study was made ex vivo and microbial samples obtained from different patient groups were analyzed. This work has demonstrated that isolates of oral microbiota are able to produce acetaldehyde in the presence of clinically relevant ethanol and glucose concentrations. Significant differences were found between microbial species and isolates from different patient groups. In particular, the ability of candidal isolates from APECED patients to produce significantly more acetaldehyde in glucose incubation compared to healthy and cancer patient isolates is an interesting observation. Moreover, xylitol was found to reduce their acetaldehyde production significantly. Significant ADH enzyme activity was found in the analyzed high acetaldehyde producing streptococci and candida isolates. In addition, xylitol was found to reduce the ADH enzyme activity of C. albicans. Some results from the ex vivo study were controversial, since acetaldehyde production did not correlate as expected with the amount of microbes in the samples. Nevertheless, the samples isolated from patients did produce significant amounts of acetaldehyde with a clinically relevant ethanol concentration.Suusyöpä on maailmanlaajuisesti seitsemänneksi yleisin syöpä ja sen ennuste on varsin huono. Viiden vuoden kuluttua sairastumisesta vain noin puolet potilaista on elossa. Suusyövän tärkeimmät riskitekijät ovat alkoholi ja tupakka ja on arveltu, että ne selittävät noin 80% kaikista suusyövistä. Alkoholin nauttiminen ja tupakointi lisäävät karsinogeenisen asetaldehydin määrää syljessä. Asetaldehydillä on useita mutageenisiä ominaisuuksia ja maailman syöpäjärjestö (International Agency for Research on Cancer, IARC) on todennut alkoholin nauttimisen aiheuttaman asetaldehydin olevan 1-luokan karsinogeeni. Asetaldehydiä syntyy suuhun alkoholista suun mikrobien alkoholidydrogenaasi(ADH)-entsyymin avulla. Tupakan savu sisältää asetaldehydiä, joka liukenee sylkeen tupakoinnin aikana. Väitöskirjan osatöiden tarkoituksena oli kartoittaa tarkemmin, mitkä suun mikrobit asetaldehydiä etanolista tuottavat sekä tutkia mikrobien kykyä tuottaa asetaldehydiä myös glukoosista. Erityisesti keskityttiin suun streptokokkeihin sekä Candida-hiivoihin. Candida-näytteitä oli kerätty apeced (autoimmuuni-polyendokrinopatia-candidoosi-ektodermi-dystrofia) potilasryhmältä, suusyöpäpotilailta sekä terveiltä verrokeilta. Lisäksi tavoitteena oli selvittää, voidaanko ksylitolin avulla vähentää asetaldehydin syntymistä. Viimeisessä osatyössä kerättiin näytteitä suusyöpä- ja lichen planus - potilailta sekä terveiltä verrokeilta. Näytteistä analysoitiin mikrobit sekä mitattiin niiden kyky tuottaa asetaldehydiä etanolista. Kaikissa osatöissä osoitettiin, että suun mikrobit kykenevät tuottamaan mutageenisiä pitoisuuksia asetaldehydiä kliinisesti merkittävästä etanolimäärästä. Merkittäviä eroja mikrobien välillä oli havaittavissa, lähes kaikki Candida-kannat tuottivat selvästi enemmän asetaldehydiä verrattuna streptokokkeihin. Apeced-potilasryhmän Candida-kannat tuottivat lisäksi merkittävästi enemmän asetaldehydiä glukoosista verrattuna muihin analysoituihin Candida-kantoihin. Apeced-potilailla on keskimääräistä selvästi suurempi riski sairastua suusyöpään, potilaat saavat suusyövän verrattain nuorina; 27 44-vuotiaina. Todennäköistä on, että alkoholi ja tupakka eivät ole tämän potilasryhmän kohdalla tärkeimmät etiologiset tekijät. Kyseisillä potilailla suusyöpä on kehittynyt kroonisen Candida-infektion kohdalle ja on oletettavaa, että Candida-infektio liittyy suusyövän etiologiaan APECED-potilailla. Ksylitoli laski Candida-kantojen asetaldehydi-tuottoa keskimäärin 84 %. Asetaldehydimäärän väheneminen on merkittävää ja se johtuu todennäköisesti ksylitolin kyvystä vähentää mikrobien ADH-entsyymiaktiivisuutta. Tutkimus tehtiin in vitro ja todettu ilmiö tulee varmistaa kliinisessä tutkimuksessa

Effect of social distancing during the COVID-19 pandemic on the occurrence of maxillofacial fractures in a Finnish Tertiary Trauma Centre

Objectives To evaluate the effects of the COVID-19 pandemic on the occurrence of facial fractures in a tertiary trauma centre. Materials and methods All facial fracture patients evaluated by an oral and maxillofacial surgeon during the first stage of the pandemic in spring 2020 were included in the study and compared to the corresponding periods in 2017 and 2018. Differences in age, sex, timespan from accident to diagnosis of facial fracture, injury mechanism, fracture type, treatment method, associated injuries (AIs), and alcohol consumption at the time of injury were analyzed between the forementioned time periods. Results The total number of patients (n = 107) during the COVID restriction period did not differ from the previous years (116 and 113 patients in 2017 and 2018, respectively, p=.368). Injury mechanism was less often assault during 2020 compared with previous years (14.0% in 2020 versus 31.8% in 2018 and 30.2% in 2017). Non-intracranial AIs were more common in the COVID period (28% in 2020 versus 14.2% in 2018 and 21.6%). The distribution was statistically significant (p=.041). Alcohol use prior to injury varied between years (p=.023). Alcohol was more often related to the injuries in 2020 compared to the previous years. Conclusions COVID restrictions did not affect the overall facial fracture occurrence, but there was a significant decrease in assaults. The proportion of alcohol-related injuries did not decrease despite restrictions.Peer reviewe

Severe infections after teeth removal - are we doing enough in preventing them?

The present study clarified features and prehospital care in patients with severe infection after teeth removal. Patients who were hospitalized for infection following teeth removal were included in this study. Background variables and infection severit

Health status in patients hospitalised for severe odontogenic infections

Objective Previous findings refer to certain predisposing medical conditions that compound the risk of developing severe and potentially lethal acute odontogenic infections (OI). The objective of this study was to clarify this rationale and infection severity in general. Material and methods Records of patients aged >= 18 years requiring hospital care for deep OI were retrospectively investigated. The main outcome variable was need for intensive care unit (ICU) treatment. Additional outcome variable was occurrence of infection complications and/or distant infections. Several parameters describing patients' prior health and recent dental treatment were set as independent variables. Results Of the 303 acute OI patients included, 71 patients (23%) required treatment in the ICU, with no significant difference between previously healthy and patients with disease history. OIs originating from teeth in the mandible compared with maxilla had 7.8-fold risk (p = .007) for ICU treatment in binary logistic regression analyses. Elevated levels of infection parameters at hospital admission predicted further ICU stay. Infection complications and/or distant infections occurred in 7.6% of patients, of which septicaemia and pneumonia were the most common. The mortality rate was 0.3%. Infection complications and/or distant infections occurred significantly more often in smokers (p = .001) and in patients with excessive consumption of alcohol or drugs (p = .025), however smoking showed 3.5-folded independent risk for infection complications and/or distant infections (p = .008) in logistic regression. Conclusions Severe OIs often occur in previously healthy patients. Smokers in particular are prone to the most serious OIs.Peer reviewe

Effect of COVID-19 pandemic on orofacial and respiratory infections in ear, nose, and throat and oral and maxillofacial surgery emergency departments : a retrospective study of 7900 patients

Objectives The study purpose was to evaluate the effects of the COVID-19 pandemic on the rate and disease profile of orofacial and respiratory infections in oral and maxillofacial surgery (OMFS) and ear, nose, and throat (ENT) emergency units. Materials and methods Records of patients with orofacial or respiratory infection, or infectious symptoms, diagnosed in the OMFS or ENT Emergency Departments of the Helsinki University Hospital, Helsinki, Finland between 1st March and 30th October 2020 and the corresponding periods in 2018 and 2019 were reviewed. The main outcome variable was the occurrence of studied infections during the evaluated periods. Other study variables were age, gender, residence area, speciality, specific cause for the emergency department visit and admission to ward. Results There was a significant 37% decrease in the number of infection patients in 2020 compared to the years 2019 and 2018 (1894 vs. 2929 and 3077, respectively, p < .001). A mean decrease of 51% (from 1319 and 1249 patients in 2018 and 2019, respectively, to 592 patients in 2020) was seen in the "Other ENT respiratory infection" category. ENT patients were 51% less likely to be admitted to the ward in 2020 compared to 2019 and 2018 (p = .013). Conclusion A significant decrease was observed in the volume of emergency department visits for orofacial and respiratory infections during the COVID-19-pandemic in 2020 compared to the non-COVID periods.Peer reviewe

Hammasvamma - mitä teen?

Pysyvän hampaan irtoaminen vaatii välitöntä hoitoa, ja lääkärinkin kannattaa osata asettaa hammas paikalleen. Hammasvammapotilas tutkitaan huolellisesti myös kasvomurtumien varalta

TLR1-10 aktiivisuuden korrelaatio suun lichen planusta ja suusyöpää sairastavilla

Synnynnäistä immuunipuolustusta muodostavat elimistön fyysiset esteet kuten iho, hengitystiet ja ruuansulatuskanava, sekä ensilinjan immuunipuolustuksen epäspesifiset solut, kuten monosyytit/makrofagit, neutrofiilit, basofiilit, eosinofiilit ja NK-solut (Natural killer cells). Synnynnäisen immuunipuolustuksen leukosyytit tunnistavat normaalissa toiminnassa elimistön ulkopuoliset kohteet toll-like reseptoreillaan, ja esimerkiksi NK-solut tunnistavat elimistön omia soluja, jotka ovat viruksen infektoimia tai tuumorigeenisiä. Eri kudosten soluilla on sisäisiä mekanismeja, jotka yleensä vievät väärin toimivan solun apoptoosiin esimerkiksi p53-geenin aktivoimana. Sisäiset säätelymekanismit voivat pettää mutaatioiden aiheuttamien geneettisten muutosten vuoksi johtaen pahimmillaan syöpään. Suun limakalvoilla esiintyvä punajäkälä eli oral lichen planus (OLP) on inflammatorinen, verrattaen yleinen immunoreaktiivinen sairaus. OLP on alatyyppi Lichen planukselle, joka voi ilmetä tyypillisesti ranteiden ja nilkkojen seudun iholla tai kaikilla elimistön limakalvoilla, kuten nielussa, ruokatorvessa, korvissa tai sukuelimissä. OLP voi olla osin ulseratiivista, erosiivista tai koostua punertavista atrofisista alueista. Tämän tutkimuksen tavoitteena oli kuvailla TLR-reseptoreiden aktivoitumista sairauden eri vaiheissa. Tätä tietoa voidaan hyödyntää tulevaisuudessa lääkehoidon kehittämiseen ja autoimmuunisairauden muodostumisen, sekä malignisoitumisen mekanismien selvittämiseen. Tutkimukseen on kerätty kudosnäytteet potilaista, jotka ovat käyneet Suu- ja leukasairauksien osastolla Helsingin yliopistollisessa sairaalassa, ja Helsingin Yliopistollisessa hammasklinikassa vuosina 2007 – 2011. Tilastollisen merkitsevyyden rajana pidettiin p < 0,05 Tutkimustulosten perusteella useilla TLR-reseptoreilla oli kohonneet aktiivisuustasot premalignissa koeryhmässä. TLR 6 ja 10 -aktiivisuudet olivat ryhmässä suurimmat syöpäpotilaiden koeryhmässä, ja TLR4 oli ainoa reseptori, joka oli aktiivisin premalignissa koeryhmässä. TLR2 ei ollut aktiivinen minkään kudosleikkeen endoteelikerroksessa ja syytä sen inaktiivisuudelle tulisi tutkia lisää. TLR10 on vielä varsin hiljattain löydetty reseptori, jonka toimintaa on vielä syytä tutkia syöpäsairauksiss

Preoperative C-reactive protein to albumin ratio and oral health in oral squamous cell carcinoma patients

BackgroundThe C-reactive protein to albumin (CRP/alb) ratio can predict early survival of a hospitalized patient. We evaluated factors that influence the preoperative CRP/alb ratio in oral squamous cell carcinoma (OSCC) patients and in particular clarified the role of oral health to this ratio.Materials and methodsData from surgically treated OSCC patients were collected retrospectively. The outcome variables were preoperative CRP/alb ratio, CRP level, and alb level. The studied predictors were total number of teeth, periodontal stability, marginal bone loss, tumour stage, T-class, lymph node status, and site. The statistical significance of age, sex, comorbidity combination of age and disease history (Charlson Comorbidity Index [CCI]), smoking, and alcohol history for outcome variables were evaluated. Patient 3-month mortality and occurrence of postoperative infections were recorded.ResultsA total of 159 patients were included in the study. The early mortality was 3.8%. CRP/alb was higher in these patients than in those who survived. The only independent variables for CRP/alb changes were CCI and heavy alcohol use. The CRP/alb ratio was significantly lower in non-heavy alcohol users (odds ratio [OR] 0.114, 95% confidence interval [CI] 0.024-0.541; adjusted p = 0.006) than in other patients. Patients with CCI 0-1 were more likely to have a lower CRP/alb ratio than patients with CCI >= 5 (OR 0.033, 95% CI 0.004-0.284; adjusted p = 0.002). In addition, high CRP/alb ratio associated with postoperative infections (p = 0.026).ConclusionsThe CRP/alb ratio was high in OSCC patients with combined comorbities of age and disease history and in patients with heavy alcohol use. Oral health or tumour-related variables did not independently affect the CRP/alb ratio. The CRP/alb ratio appears suitable for prediction of OSCC patient early survival.Peer reviewe

Deep odontogenic infections-identifying risk factors for nosocomial pneumonia

Objectives To evaluate occurrence and risk factors for pneumonia in patients with deep odontogenic infection (OI). Materials and methods All patients treated for deep OIs and requiring intensive care and mechanical ventilation were included. The outcome variable was diagnosis of nosocomial pneumonia. Primary predictor variables were re-intubation and duration of mechanical ventilation. The secondary predictor variable was length of hospital stay (LOHS). The explanatory variables were gender, age, current smoking, current heavy alcohol and/or drug use, diabetes, and chronic pulmonary disease. Results Ninety-two patients were included in the analyses. Pneumonia was detected in 14 patients (15%). It was diagnosed on postoperative day 2 to 6 (median 3 days, mean 3 days) after primary infection care. Duration of mechanical ventilation (p = 0.028) and LOHS (p = 0.002) correlated significantly with occurrence of pneumonia. In addition, re-intubation (p = 0.004) was found to be significantly associated with pneumonia; however, pneumonia was detected in 75% of these patients prior to re-intubation. Two patients (2%) died during intensive care unit stay, and both had diagnosed nosocomial pneumonia. Smoking correlated significantly with pneumonia (p = 0.011). Conclusion Secondary pneumonia due to deep OI is associated with prolonged hospital care and can predict the risk of death. Duration of mechanical ventilation should be reduced with prompt and adequate OI treatment, whenever possible. Smokers with deep OI have a significantly higher risk than non-smokers of developing pneumonia.Peer reviewe