Enhanced dual function of osteoclast precursors following calvarial Porphyromonas gingivalis infection.

BACKGROUND AND OBJECTIVE: Excessive osteoclast activity is a major characteristic of pathogenic bone loss in inflammatory bone diseases including periodontitis. However, beyond the knowledge that osteoclasts are differentiated from the monocyte/macrophage lineage and share common ancestry with macrophages and DC, the nature and function of osteoclast precursors are not completely understood. Furthermore, little is known about how osteoclast precursors respond to bacterial infection in vivo. We have previously demonstrated in vitro that the periodontal pathogen Porphyromonas gingivalis (Pg) plays a biphasic role on the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation. In this study, we investigated the in vivo effect of Pg infection on the regulation of osteoclast precursors, using a mouse calvarial infection model. METHODS AND RESULTS: C57BL/6 wild-type and the myeloid differentiation factor 88 knockout (MyD88-/- ) mice were infected with Pg by calvarial injection. Local and systemic bone loss, and the number and function of CD11b+ c-fms+ cells from bone marrow and spleen were analyzed. Our results show that Pg infection induces localized inflammatory infiltration and osteoclastogenesis, as well as increased number and osteoclastogenic potential of CD11b+ c-fms+ osteoclast precursors in the bone marrow and periphery. We also show that CD11b+ c-fms+ RANK+ and CD11b+ c-fms+ RANK- are precursors with similar osteoclastogenic and pro-inflammatory potentials. In addition, CD11b+ c-fms+ cells exhibit an antigen-specific T-cell immune-suppressive activity, which are increased with Pg infection. Moreover, we demonstrate that MyD88 is involved in the regulation of osteoclast precursors upon Pg infection. CONCLUSIONS: In this study, we demonstrate an enhanced dual function of osteoclast precursors following calvarial Pg infection. Based on our findings, we propose the following model: Pg infection increases a pool of precursor cells that can be shunted toward osteoclast formation at the infection/inflammation sites, while at the same time dampening host immune responses, which is beneficial for the persistence of infection and maintenance of the characteristic chronic nature of periodontitis. Understanding the nature, function, and regulation of osteoclast precursors will be helpful for identifying therapeutic interventions to aid in the control and prevention of inflammatory bone loss diseases including periodontitis.

DIAGNOSIS AND TREATMENT OF AN ENTEROCOCCUS FECALIS ABSCESS IN THE CRANIAL VAULT OF A SPOTTED EAGLE RAY (AETOBATUS NARINARI).

An adult female spotted eagle ray (Aetobatus narinari) presented for medical evaluation due to a swelling located on the dorsal head. Ultrasound revealed that the swelling originated from a large pocket of fluid in the cranial vault. The swelling was aspirated, and purulent discharge was obtained; Enterococcus faecalis was cultured. An incision was made over the swelling in an attempt to drain fluid but was unsuccessful. Multiple aspirates were performed to drain the abscess, and the animal was treated with oxytetracycline injections. The initial incision sloughed and resulted in a large defect in the cranium that allowed exhibit water to come into the cranial vault and come in contact with the protective membrane of the brain. Forty-two days after initial presentation, the defect in the cranium was healed; fluid from the cranial vault was sampled and appeared normal. During and after treatment, the ray exhibited no abnormal neurologic signs.

Successful voriconazole treatment of Talaromyces marneffei infection in an HIV-negative patient with osteolytic lesions.

Talaromyces marneffei (T. marneffei) is a dimorphic fungus that causes systemic infection in immunocompromised patients. Here, we present a case of T. marneffei infection in an immunocompetent patient with an osteolytic lesion. Diagnosis was established by fungal culture. The patient responded rapidly to intravenous voriconazole, followed by oral voriconazole. We reviewed 18 reported cases of T. marneffei infection with osteolytic lesions, which suggests a much higher rate of osteolytic lesions in immunocompetent patients than previously thought.

A novel form of intracranial coccidioidomycosis is present in dogs and exhibits characteristic clinical and magnetic resonance imaging findings.

The neurological examination findings, clinical pathology (including Coccidioides immitis IgG/IgM serology) and magnetic resonance imaging (MRI) findings in 13 dogs with a novel form of intracranial coccidioidomycosis are described in a retrospective case series, with long-term clinical resolution documented in 11/13 dogs (84.6% of cases) with oral fluconazole therapy. The medical records of the Veterinary Neurological Center in Phoenix, Arizona from the years 2000 to 2017 were utilized to search for dogs with appropriate inclusion criteria. Magnetic resonance imaging findings were highly consistent across all cases and characteristically demonstrated bilaterally symmetric T2 hyperintensity throughout the frontal lobes, caudate nuclei, and rostral internal capsule, ±faint, wispy contrast enhancement on T1-postcontrast images. These findings were in stark contrast to previously reported MRI findings in dogs with intracranial coccidioidomycosis, which were typically characterized by a focal, strongly contrast enhancing granuloma and extensive vasogenic edema, typically unilateral. Schnauzer breeds represented eight of 13 (61.5%) cases, possibly suggesting a breed predilection. Three cases underwent repeat MRI after resolution of neurological signs and documentation of a decreased Coccidioides titer in response to fluconazole therapy. All demonstrated complete resolution of previously identified lesions, but with marked, severe atrophy of the caudate nuclei and frontal lobes bilaterally. Findings from this study document a variant appearance for intracranial coccidioidomycosis that, to the author's knowledge, has not been previously described in dogs. Authors propose that, although this variant demonstrates extensive pathological changes within the forebrain, the clinical outcome and response to treatment is favorable in a majority of cases.

Epidural abscess caused by Schizophyllum commune: A rare case of rhinogenic cranial complication by a filamentous basidiomycete.

Central nervous system (CNS) infections due to filamentous basidiomycetes are extremely rare. We encountered a case of epidural abscess due to Schizophyllum commune that extended from sinusitis. A 53-year-old Japanese man presented at our hospital with a headache. Computed tomography (CT) of the cranium and sinuses showed ethmoid and sphenoid sinusitis with no intracranial abnormalities. The patient was diagnosed with acute sinusitis and underwent antibiotic treatment. However, the symptoms deteriorated, and the patient came to our hospital again with consciousness disturbance. CT scan of the cranium and sinuses showed no improvement of sinusitis after antibiotic therapy and an epidural abscess emerged in the middle cranial fossa. Therefore, emergency craniotomy and endoscopic sinus fenestration were performed. Filamentous fungal elements were observed in both rhinorrhoea and epidural abscess. The symptoms improved after the operation and administration of liposomal amphotericin B. The clinical isolate was identified as S. commune by a molecular-based method. To our knowledge, this is the first report of epidural abscess due to this fungus. Although rare, clinicians should be aware that S. commune could be a causative agent of CNS infections.

Aspergillus Osteomyelitis of the Skull.

Osteomyelitis of the craniofacial skeleton is rare, with fungal pathogens least commonly implicated. The authors present 2 patients of osteomyelitis of the skull caused by Aspergillus spp. and discuss the diagnosis, clinicopathological course, and management strategies.Late recurrence seen in this type of infection warrants long-term follow-up and a high index of suspicion for the clinical signs associated with recurrence.Such patients would benefit from their surgical debridement being planned and managed via a specialist craniofacial unit, so as to utilize the most aesthetically sensitive approach and the experience of specialists from several surgical disciplines.

[COMPUTED TOMOGRAPHIC EXAMINATION OF CRANIAL LESIONS, A PALEORADIOLOGICAL APPROACH]. / KOPONYACSONT-LAESIÓK KOMPUTERTOMOGRÁFIÁS VIZSGÁLATA ÉS PALEORADIOLÓGIAI ASPEKTUSAI.

BACKGROUND AND PURPOSE: Introducing the multidisciplinary paleoradiology research at the Institute of Diagnostic Imaging and Radiation Oncology of the Kaposvár University, highlighting the cases with potential central nervous system involvement--from the scanning methods to the 3D printing--in order to draw attention to the historical background and clinical aspects of certain pathological conditions. METHODS: The authors developed the examination protocols for three different CT scanners. Among the examined archaeological remains cranial lesions were identified in 26 cases, from which 4 cases with potential central nervous system involvement are demonstrated. The scanning parameters and the advantages of secondary image reconstructions (multiplanar reconstruction, maximum intensity projection, three-dimensional volume rendering technique) are presented with the cases. RESULTS: The authors demonstrate a case with destructive skull lesions due to syphilis from the 15th century AD, a condition rarely seen or even unknown nowadays in the modern world. With the CT images of the skull base fracture from the Iron Age, signs of healing could be verified. Using the CT images a non-invasive approach is presented in the case of the craniofacial osteosarcoma in order to visualize the local status and the direct intracranial propagation. Advantages of the 3D VRT reconstructions are shown in the case of unilateral coronal suture synostosis. CONCLUSION: Paleoradiological CT examinations serve as a non-invasive, non-destructive tool for studying archaeological remains and artifacts. The special applications provided by the imaging modality contribute to the conventional paleopathological investigations.

Microbial contamination assessment of cryostored autogenous cranial bone flaps: should bone biopsies or swabs be performed?

BACKGROUND: Autogenous cranioplasty infection requiring bone flap removal is under-recognised as a major complication causing significant morbidity. Microbial contamination of stored bone flaps may be a significant contributing factor. Current infection control practices and storage procedures vary. It is not known whether 'superficial' swabs or bone cultures provide a more accurate assessment. METHOD: Twenty-five skull flaps that were cryo-stored for more than 6 months were studied. Two swab samples (superficial and deep) and a bone biopsy sample were taken from each skull flap sample and cultured. Half blood agar and half chocolate agar plates were inoculated with the swabs for anaerobic and aerobic cultures respectively. The bone biopsy samples were cultured in brain-heart broth and subcultured similar to the swabs for 5 days. RESULTS: Incidence of microbial contamination was 20 % in the bone flaps studied. One swab culture and five bone biopsy cultures were positive for bacterial growth, all of which contained Propionibacterium acnes (p = 0.014). Positive cultures were from bone flaps stored less than 18 months, whereas no growth was obtained from bone flaps that were stored longer (p = 0.014). CONCLUSIONS: Bone biopsy culture is a more sensitive technique of assessing microbial contamination of cryo-stored autogenous bone flaps than swab cultures. The clinical implications of in vitro demonstration of microbial contamination require further study.

Isolated skull cryptococcosis in an immunocompetent patient.

A 62-year-old immunocompetent rural woman who represents an isolated cryptococcal skull infection without systematic involvement is described. Diagnosis was based on positive India ink staining, positive histopathologic examination, and positive culture. Species identification was performed by growth on Sabouraud dextrose agar and CHROMagar medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. This case describes a rare presentation of Cryptococcus neoformans infection in a human immunodeficiency virus-negative patient. The lesions were significantly improved with treatment of daily oral itraconazole 400 mg. A maintenance therapy with a low-dose itraconazole was prescribed to warrant a clinical and mycological eradication. A two-year follow-up did not show any recurrence of infection.

Titanium cranioplasty and the prediction of complications.

OBJECTIVES: Titanium cranioplasty (TC), the operative repair of a skull defect with an ergonomically manufactured plate to restore cosmesis, cranial function and reduce complications is a common neurosurgical procedure. It is technically simple but has high complication rates. This study aimed to determine the incidence and predictors of complications following TC. DESIGN: Retrospective review. SUBJECTS: All patients undergoing TC over a 42-month period in our institution. METHODS: Data was collected from the hospital database and case-notes. 3D CT reconstructions accurately measured defect size and location. Statistical analysis included correlation, independent variable analysis and descriptive methods. RESULTS: A total of 95 TCs were analysed in 92 patients (3 cases of bifrontal cranioplasty). The commonest indications for TC were bony defect following removal of infected bone flap (n = 20), acute subdural haematoma (n = 18) and post-malignant infarction (n = 11). The commonest site was frontotemporoparietal (n = 61) and the overall complication rate was 30.4%. The commonest complication was infection and the overall removal rate was 8.4%. The mean cranioplasty area was 73.26 cm(2) (range 12.78-178.26 cm(2)). There was a significant relationship between area and length of post-operative hospital stay (p = 0.008, Pearson Rank). There was no significant relationship between area and complications, removal rates or infections. There was no relationship between age and total complications, post-operative hospital stay and infections. There was a non-significant trend for older patients to have their cranioplasty removed. CONCLUSIONS: TC size is predictive of postoperative length of stay. However, the TC size is not predictive of complications or removal rate. Also, there was no association between interval since primary operation and complications. There was a non-significant trend for greater rates of TC removal in the elderly. There were no predictors of complications identified but they are common and patients should be consented accordingly.

Microbiological profile and infection potential of different cryopreserved skull flaps after decompressive hemicraniectomy. Is cryopreservation at - 80 ℃ better?

OBJECTIVE: Patterns of cryopreservation of explanted skull bone flaps have long been a matter of debate, in particular the appropriate temperature of storage. To the best of our knowledge no study to date has compared the microbiological profile and the infection potential of skull bone flaps cryostored at the same institution at disparate degrees for neurosurgical purposes. In the context of our clinical trial DRKS00023283, we performed a bacterial culture of explanted skull bone flaps, which were cryopreserved lege artis at a temperature of either - 23 °C or - 80 °C after a decompressive hemicraniectomy. In a further step, we contaminated the bone fragments in a s uspension with specific pathogens (S. aureus, S. epidermidis and C. acnes, Colony forming unit CFU 103/ml) over 24 h and conducted a second culture. RESULTS: A total of 17 cryopreserved skull flaps (8: - 23 °C; 9: - 80 °C) explanted during decompressive hemicraniectomies performed between 2019 and 2020 as well as 2 computer-aided-designed skulls (1 vancomycin-soaked) were analyzed. Median duration of cryopreservation was 10.5 months (2-17 months). No microorganisms were detected at the normal bacterial culture. After active contamination of our skull flaps, all samples showed similar bacterial growth of above-mentioned pathogens; thus, our study did not reveal an influence of the storage temperature upon infectious dynamic of the skulls.

Septicemia, meningitis, and skull osteomyelitis complicating infected cephalhematoma caused by ESBL-producing Escherichia coli.

An infected cephalhematoma is a rare condition in neonates. We report a case of an 18-day-old neonate who was diagnosed with an infected cephalhematoma caused by an extended spectrum beta-lactamase (ESBL)-producing Escherichia coli complicated with septicemia, meningitis, and skull osteomyelitis. He was successfully treated with meropenem and surgical incision and drainage. ESBL-producing E. coli may cause infection of a cephalhematoma in neonates.

Cerebral nocardiosis with osteomyelitis of skull vault complicating a primary neck lesion in an immunocompetent patient: a case report.

Nocardia infection is an uncommon and rare condition in immunocompetent patient. A case of cutaneous nocardiosis complicated with osteomyelitis of the vault scalp in a 64-year-old man, with no remarkable past medical history, is reported. Treatment with trimethoprime-sulfamethoxazole than doxycycline for 12 months led to complete resolution and no evidence of recurrence was noted. Nocardia infection should be considered even in immunocomptent patients and doxycycline is a good alternative for treatment.

Meningoencephalitis caused by Mycoplasma edwardii in a dog.

A 6-week-old, female, mixed-breed dog with a clinical history of sudden onset of neurologic signs was presented for necropsy. The dog was diagnosed with suppurative and histiocytic meningoencephalitis based on necropsy findings and histopathology. Mycoplasma sp. was isolated in pure culture from the brain and meninges and was identified as Mycoplasma edwardii using DNA sequencing.

Indirect comparison of efficacy between different antibiotic prophylaxis against the intracranial infection after craniotomy.

BACKGROUND: Many studies had shown that prophylactic use of antibiotics could significantly reduce the intracranial infection (ICI) rate of craniotomy. However, there has been no comparison of these antibiotics. METHODS: An electronic database search was performed, from inception to June 102,020. Randomized controlled trials (RCT) using different intravenous antibiotics (IVA) against the ICIs after craniotomy were considered. The primary outcome was the incidence rates of ICIs. An indirect treatment comparison (ITC) was conducted to compare the protective effect among the diverse antibiotic prophylaxis to prevent ICIs after craniotomy. Risk of potential bias was assessed. RESULTS: A total of 3214 patients after craniotomy in 11 studies were included, 159 patients experienced postoperative ICI, including 33 patients in the antibacterial group and 126 in the control group. The calculate results of meta-analysis showed that except fusidic acid, preoperative intravenous injection of cephalosporin, clindamycin, vancomycin, and penicillin can significantly reduce the incidence of ICI after craniotomy, and ITC showed there was no statistically significance difference in the rates of post craniotomy ICI between the various antibiotics. CONCLUSION: The current evidence shows that low-grade antibacterial drugs can be selected to prevent ICI after craniotomy, but this may be due to the limited number of studies per antibiotic. It still needs more high-quality, large sample RCT to confirm. SYSTEMIC REVIEW REGISTRATION: PROSPERO CRD42019133369.

Multiple intracranial cryptococcomas in an immunocompetent patient with pulmonary involvement.

Opportunistic infections affecting central nervous system (CNS) have high prevalence in developing countries and cryptococcosis is one of them. It is associated with myriad of signs symptoms and clinical behavior. Though commonly associated with AIDS/HIV infection, it has been reported to be pathogenic in immunocompetent patients. Leptomeningitis is most common presentation in CNS, but unusual tumor like mass lesions have been reported. Lungs are primary site of infection, but it can affect different organs with varied clinical presentations. Therefore, correct diagnosis and proper management is essential in such cases excluding the differentials as fatality rate can be quite high. We report such an unusual case of multiple cryptococcal mass lesions in brain in a healthy immune competent individual with bilateral pulmonary involvement.

A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction.

The control of inflammation and infection is crucial for periodontal wound healing and regeneration. M101, an oxygen carrier derived from Arenicola marina, was tested for its anti-inflammatory and anti-infectious potential based on its anti-oxidative and tissue oxygenation properties. In vitro, no cytotoxicity was observed in oral epithelial cells (EC) treated with M101. M101 (1 g/L) reduced significantly the gene expression of pro-inflammatory markers such as TNF-α, NF-κΒ and RANKL in P. gingivalis-LPS stimulated and P. gingivalis-infected EC. The proteome array revealed significant down-regulation of pro-inflammatory cytokines (IL-1ß and IL-8) and chemokine ligands (RANTES and IP-10), and upregulation of pro-healing mediators (PDGF-BB, TGF-ß1, IL-10, IL-2, IL-4, IL-11 and IL-15) and, extracellular and immune modulators (TIMP-2, M-CSF and ICAM-1). M101 significantly increased the gene expression of Resolvin-E1 receptor. Furthermore, M101 treatment reduced P. gingivalis biofilm growth over glass surface, observed with live/dead analysis and by decreased P. gingivalis 16 s rRNA expression (51.7%) (p < 0.05). In mice, M101 reduced the clinical abscess size (50.2%) in P. gingivalis-induced calvarial lesion concomitant with a decreased inflammatory score evaluated through histomorphometric analysis, thus, improving soft tissue and bone healing response. Therefore, M101 may be a novel therapeutic agent that could be beneficial in the management of P. gingivalis associated diseases.

Cerebral empyema and abscesses due to Cutibacterium acnes.

INTRODUCTION: Cutibacterium acnes is a commensal bacterium of the skin, frequently reported in prosthetic shoulder or spinal implant infections, but rarely in cranial and intracranial infections. METHODS: We retrospectively reviewed patients with intracranial samples positive to Cutibacterium acnes managed in the neurosurgical units of our hospital of Lyon, France, between 2008-2016. RESULTS: We included 29 patients, of whom 23 had empyema (with or without abscess), 17 had cranial osteomyelitis, and six only had abscess. Prior neurosurgery was reported in 28 patients, and the remaining patient had four spontaneous abscesses. Twelve patients had polymicrobial infections, including methicillin-susceptible Staphylococcus in 11 cases. The clinical diagnosis was difficult because of indolent and delayed symptoms: a CT scan or MRI was required. Thirteen patients (52%) had material at the infection site. All patients with bone flap implant or bones from biological banks had a bone flap-associated infection. Drainage was surgically performed in 25 cases or by CT scan-guided aspiration in four cases. All patients received an adapted antibiotic therapy (from three weeks to six months). The outcome was favorable in 28 patients. Three patients relapsed during the antibiotic therapy, requiring further surgery. CONCLUSION: Cutibacterium acnes can be responsible for postoperative empyema and cerebral abscesses, with particular indolent forms, which make their diagnosis difficult. They are often polymicrobial and associated with bone flap osteomyelitis. Their outcome is favorable after drainage and adapted antibiotic therapy.

Nervous signs associated with otitis and cranial osteomyelitis and with Ornithobacterium rhinotracheale infection in red-legged partridges (Alectoris rufa).

A case of nervous signs in red-legged partridges (Alectoris rufa) associated with a severe otitis and osteomyelitis is reported. The outbreak was characterized by abnormal head position, torticollis and difficulty in standing, walking and flying. Pathological, microbiological and molecular genetic data supported an association with Ornithobacterium rhinotracheale (ORT) infection. Clinical signs persisted for several days and were accompanied by weight loss leading to death. Morbidity was approximately 20% and most birds died if untreated. Lesions were mainly characterized by a severe osteomyelitis of the cranial bones and purulent inflammation of the external, middle and inner ears. O. rhinotracheale was isolated from ear samples, skull and brain stem in pure culture. Genetic characterization by pulsed-field gel electrophoresis of the clinical isolates showed that the outbreak was caused by a single strain of ORT. This appears to be the first report of otitis associated with ORT in an avian species.

An investigation of factors associated with the development of postoperative bone flap infection following decompressive craniectomy and subsequent cranioplasty.

OBJECTIVE: After a decompressive craniectomy (DC), a cranioplasty (CP) is often performed in order to improve neurosurgical outcome and cerebral blood circulation. But even though the performance of a CP subsequent to a DC has become routine medical practice, patients can in fact develop many complications from the surgery that could prolong hospitalization and lead to unfavorable prognoses. This study investigates one of the most frequent complications, bone flap infection, in order to identify prognostic factors of its development. PATIENTS AND METHODS: In this single-center study, we have retrospectively examined 329 CPs performed between 2002 and 2017. Multiple categorical and metric parameters (e.g., timing of CP, bone flap material, specific laboratory signs of infection and reason for DC) were analyzed applying unadjusted and multivariable testing. RESULTS: Bone flap infection occurred in 24 patients (7.3%). A CP performed more than six months after a DC is associated with a significantly increased risk of infection (OR = 0.308 [0.118; 0.803], p = 0.016). However, with CPs performed after twelve months, the incidence decreases, but without provable statistical impact. In addition, bone flap infection is strongly related to the neurological outcome and the material used for the skull implant, with the use of synthetic bone flaps leading to a marked increase in the rate of infection (p < 0.001). CONCLUSIONS: This study supports the hypothesis that the risk of infection is higher the longer the elapsed time between DC and CP, especially if more than six months. Based on our results, the best DC-CP time frame for keeping the infection rate low is performing the CP within the first six months after the DC. In the event that the CP cannot be performed within the first six months, a CP performed twelve months or more after the DC seems to have a favorable outcome as well.