Phagocytic cells and Streptococcus pyogenes in invasive infections : an inflammatory relationship

Severe Streptococcus pyogenes infections, such as streptococcal toxic shock syndrome and necrotizing soft tissue infections, are rare but life threatening conditions. They are characterized by high bacterial load and a hyper-inflammatory state. The aim of this thesis was to investigate interactions between S. pyogenes and the phagocytic cells neutrophils and macrophages and how this correlates to cell activation and inflammation. First, we investigated high mobility group box 1 (HMGB1), a marker of inflammation and necrosis, as a potential biomarker and mediator of tissue pathology in S. pyogenes tissue infections. Analysis of tissue biopsies collected from patients with streptococcal soft tissue infections of varying severity showed that HMGB1 was present in the tissue, and that the amount correlates with severity. Further investigations showed that HMGB1 co-localized with IL-1β suggesting the potential for immunostimulatory complexes to form at the site of infection. HMGB1 was also demonstrated to act as a chemoattractant for neutrophils. Next, we assessed neutrophil activation and degranulation in response to different bacterial species, focusing on the release of the sepsis-associated factors heparin-binding protein (HBP) and resistin. Stimulations of neutrophils showed that streptococcal strains were potent inducers of neutrophil activation and degranulation. The results also showed a difference in signaling requirements for the release of HBP and resistin, respectively. While HBP release was mainly dependent on a previously described mechanism involving dual ligation of integrins and Fc-receptors, the release of resistin appeared to be multifactorial and involve multiple bacterial structures and host signaling pathways. Finally, we set out to define the macrophage phenotype present at the site of infection. Using a multi-parameter imaging workflow, we were able to assess the phenotype of macrophages present at the site of infection, in tissue from patients with severe S. pyogenes soft tissue infections as well as infected organotypic skin tissue models. These investigations showed that macrophages in S. pyogenes infected tissue displayed a shift towards a more anti- inflammatory M2-like phenotype, in spite of the hyper-inflammatory environment in the tissue. Gene expression analysis of infected patient tissue, skin tissue models as well as a murine model of severe streptococcal soft tissue infection showed an overrepresentation of signaling pathways associated with anti-inflammatory macrophage polarization. Taken together these findings highlight the complex pathophysiology of severe S. pyogenes infections, where on the one hand the bacteria and mediators present in the infected tissue potently activates neutrophils. While macrophages on the other hand, display a more anti- inflammatory phenotype upon infection, potentially promoting intracellular survival and persistence of S. pyogenes. Emphasizing the importance of careful patient characterization with regards to immune status, to ensure optimal treatment

Effect of perioperative dexamethasone on surgical site healing in patients with facial fractures

Background and purpose Short-term glucocorticoids (GCs) are frequently used in association with oral and maxillofacial surgery to prevent postoperative pain, edema, and nausea. However, the influence on tissue repair and the anti-inflammatory and immunosuppressive features of GCs may have an adverse impact on healing of the surgical site. The main aim of this study was to determine the occurrence of disturbance in surgical wound healing (DSWH) and pulp necrosis (PN) after surgical treatment of facial fractures and the influence of perioperative administration of GCs on these complications. Patients This study comprised four populations of patients (Studies I-IV) treated for facial fractures. For Study I, the medical records of 280 consecutive patients who had undergone open reduction of different types of facial fractures or reconstruction of orbital wall fracture were assembled retrospectively. Prospective Studies II-IV consisted of patients with mandibular fractures (n=41) (Study II) and patients with a simple zygomatic complex (ZC) fractures (n=64) (Study III). The fourth population (n=24) (Study IV) was extracted from the population of patients with mandibular fractures recruited for Study II. Methods In the retrospective study (Study I), the outcome variable was DSWH, which was established when any kind of aberrant wound healing and/or sign of infection in the surgical site occurred. The primary predictor variable was the perioperative use of GC. Patients recruited for Studies II and III were randomly assigned to one of two groups. Patients in the study group received dexamethasone (DXE) (Oradexon®), whereas patients in the control group received no GC. The main outcome variables were DSWH (Studies II-III) and PN of teeth in the area of mandibular fracture (Study IV). The primary predictor variable was the perioperative use of DXE. Results In patients with ZC fractures (Study III), DSWH was significantly associated with perioperative use of DXE as well as with intraoral surgical approach. In patients operated on for different types of facial fractures (Study I), DSWH was associated significantly with intraoral surgical approach. DSWH occurred more frequently in patients receiving GCs, however, without statistical significance. In patients undergoing intraoral surgery for mandibular fractures (Study II), DSWH occurred more frequently in the DXE group. Also PN occurred more frequently in the DXE group (Study IV). The delay of DSWH was notably longer in the DXE groups (Study I-III). Particularly PN (Study IV) was observed much later in the DXE group. Conclusions Perioperative DXE cannot be recommended in association with surgery of ZC fractures. Moreover, GCs should be used with caution in association with surgery of other facial fractures as well, particularly when the intraoral approach is used.Lyhytaikaista glukokortikoidihoitoa käytetään leikkauksen jälkeisen kivun ja pahoinvoinnin ehkäisyyn ja suun ja leukojen alueen kirurgiassa erityisesti myös turvotuksen ehkäisyyn. Glukokortikoidit kuitenkin vaikuttavat monin tavoin kudosten paranemiseen, immuunipuolustukseen ja ne myös lamaavat elimistön tulehdusreaktiota. Siten lyhytaikaisella glukokortikoidihoidolla voi olla vaikutusta leikkausalueen paranemiseen. Tutkimus koostui kasvomurtumien vuoksi leikatuista potilaista. Tutkimuksessa selvitettiin leikkaushaavan paranemista ja glukokortikoidien vaikutusta siihen kolmessa populaatiossa: usean tyyppisissä kasvomurtumissa, alaleuan murtumissa ja poskiluun murtumissa. Neljännessä populaatiossa tarkasteltiin hampaan ytimen kuolioitumista alaleuan murtumapotilailla. Leikkaushoidon aikainen deksametasoni kahdeksankertaisti leikkaushaavan paranemisongelmat poskiluumurtumapotilailla ja yhteys oli tilastollisesti merkitsevä. Leikkaushaavan paranemisongelmat olivat myös yleisempiä muilla kasvomurtumapotilailla, jotka saivat glukokortikoideja, mutta tilastollista yhteyttä ei todettu. Lisäksi hampaan ytimen kuolio alaleuan murtuma-alueen hampaissa oli yleisempää potilailla, jotka saivat deksametasonia. Leikkausalueen paranemisongelmat ilmenivät myöhemmin niillä potilailla, jotka olivat saaneet glukokortikoideja, kuin niillä, jotka eivät saaneet. Suun limakalvolle tehty leikkausavaus liittyi paranemisongelmiin. Leikkaushoidon aikaista glukokortikoidihoitoa ei voida suositella poskiluumurtumapotilailla. Myös muiden kasvojen alueen murtumaleikkausten yhteydessä glukokortikoidihoitoon on syytä suhtautua varauksella, erityisesti, jos leikkaushaava tehdään suun limakalvolle

Temporomandibular Dysfunction After Surgery of Mandibular Fractures Not Involving the Mandibular Condyle : A Prospective Follow-Up Study

Purpose: Facial trauma can lead to temporomandibular dysfunction (TMD). The aim of this study was to clarify the occurrence and characteristics of TMD in patients surgically treated for mandibular fractures not involving the mandibular condyle. Materials and Methods: This prospective single-center follow-up study was composed of patients who underwent surgery for non-condylar mandibular fracture. Patients were evaluated at presentation and 6 months after surgery to assess the function of the masticatory system using the Helkimo index. Specifically, this index incorporates 2 complementary subindices: the subjective symptomatic (anamnestic) index (A(i)) and the objective clinical dysfunction index (D-i). The A(i) score was recorded at presentation and 6-month follow-up. The D-i score was recorded at 6-month follow-up. Results: Thirty-one patients completed the study. All patients were men (mean age, 26.2 yr; range, 18 to 47 yr). Four (12.9%) developed severe symptoms of dysfunction during the study period according to the A(i). Clinical findings (D-i) were observed in 25 patients (80.6%), but these were not associated with symptoms of dysfunction. Conclusions: TMD is common 6 months after surgery in patients with non-condylar mandibular fractures. Patients with such fractures should be evaluated for dysfunction during follow-ups and referred for further treatment if necessary. (C) 2019 American Association of Oral and Maxillofacial SurgeonsPeer reviewe

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

Hammasvamma - mitä teen?

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

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