Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts

Abstract

Objectives

Apical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts.

Materials and methods

Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed.

Results

Radicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions.

Conclusions

The development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin.

Clinical relevance

As M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst formation.

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Ventilator Management of Bronchopleural Fistula Secondary to Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia in a Pregnant Patient with Systemic Lupus Erythematosus

Managing mechanical ventilation in patient with bronchopleural fistula with coexisting acute respiratory distress syndrome is a challenging situation for the intensivist. We are reporting a case of a pregnant patient with systemic lupus erythematosus on immunosuppressive medications who developed methicillin-resistant Staphylococcus aureus necrotizing pneumonia complicated by bronchopleural fistula and acute respiratory distress syndrome.

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Hypoxia-based strategies for regenerative dentistry—Views from the different dental fields

Publication date: September 2017
Source:Archives of Oral Biology, Volume 81
Author(s): Anna Sonja Müller, Klara Janjić, Bledar Lilaj, Michael Edelmayer, Hermann Agis
The understanding of the cell biological processes underlying development and regeneration of oral tissues leads to novel regenerative approaches. Over the past years, knowledge on key roles of the hypoxia-based response has become more profound. Based on these findings, novel regenerative approaches for dentistry are emerging, which target cellular oxygen sensors. These approaches include hypoxia pre-conditioning and pharmacologically simulated hypoxia. The increase in studies on hypoxia and hypoxia-based strategies in regenerative dentistry highlights the growing attention to hypoxia's role in regeneration and its underlying biology, as well as its application in a therapeutic setting.In this narrative review, we present the current knowledge on the role of hypoxia in oral tissues and review the proposed hypoxia-based approaches in different fields of dentistry, including endodontics, orthodontics, periodontics, and oral surgery.



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Hypoxia-based strategies for regenerative dentistry—Views from the different dental fields

Publication date: September 2017
Source:Archives of Oral Biology, Volume 81
Author(s): Anna Sonja Müller, Klara Janjić, Bledar Lilaj, Michael Edelmayer, Hermann Agis
The understanding of the cell biological processes underlying development and regeneration of oral tissues leads to novel regenerative approaches. Over the past years, knowledge on key roles of the hypoxia-based response has become more profound. Based on these findings, novel regenerative approaches for dentistry are emerging, which target cellular oxygen sensors. These approaches include hypoxia pre-conditioning and pharmacologically simulated hypoxia. The increase in studies on hypoxia and hypoxia-based strategies in regenerative dentistry highlights the growing attention to hypoxia's role in regeneration and its underlying biology, as well as its application in a therapeutic setting.In this narrative review, we present the current knowledge on the role of hypoxia in oral tissues and review the proposed hypoxia-based approaches in different fields of dentistry, including endodontics, orthodontics, periodontics, and oral surgery.



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Dupilumab Improves General Health-Related Quality-of-Life in Patients with Moderate-to-Severe Atopic Dermatitis: Pooled Results from Two Randomized, Controlled Phase 3 Clinical Trials

Abstract

Introduction

Patients with moderate-to-severe atopic dermatitis (AD) report a multidimensional disease burden that includes impaired health-related quality-of-life (HRQoL). Changes in overall health status and specific dimensions that contribute to HRQoL were evaluated in adults with moderate-to-severe AD who participated in phase 3 clinical trials of dupilumab, which is a fully human monoclonal antibody that inhibits signaling of cytokines IL-4 and IL-13.

Methods

Two dupilumab phase 3 clinical trials of identical design included the 5-dimension 3-level EuroQol (EQ-5D) as a measure of HRQoL. EQ-5D data from the two trials were pooled in an analysis that, using analysis of covariance, compared subcutaneous dupilumab 300 mg once weekly (qw) or every 2 weeks (q2w) versus placebo for EQ-5D utility score change from baseline overall and for clinical responders. The proportions of patients who reported different levels of problems on the individual dimension of the EQ-5D were also compared by treatment group.

Results

Patients (n = 1379) were 57.9% male with a mean (SD) age of 38.3 (14.3) years; baseline EQ-5D utility scores ranged from 0.611 to 0.629 across treatment groups. EQ-5D least squares mean change from baseline at week 16 was 0.031 with placebo, and was significantly greater with dupilumab qw (0.207) and q2w (0.210) (both P < 0.0001), which exceeded the minimal clinically important difference and resulted in scores that approached population norms. Changes from baseline among patients who achieved AD clinical response were greater than changes among the total population. Improvements were driven by the individual EQ-5D dimensions with the greatest burden at baseline (i.e., pain/discomfort, anxiety/depression and usual activities).

Conclusion

In adults with moderate-to-severe AD, dupilumab resulted in improvements in HRQoL that were statistically significant relative to placebo and were clinically meaningful.

Funding

Sanofi and Regeneron Pharmaceuticals, Inc.

Trial registration

ClinicalTrials.gov identifiers, NCT02277743 and NCT02277769, EudraCT Numbers 2014-001198-15 and 2014-002619-40.

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Intratympanic steroid delivery by an indwelling catheter in refractory severe sudden sensorineural hearing loss

Publication date: Available online 13 May 2017
Source:Auris Nasus Larynx
Author(s): Diego Zanetti, Federica Di Berardino, Nader Nassif, Luca Oscar Redaelli De Zinis
ObjectiveMany studies over the last decade showed favorable outcomes with intratympanic (IT) steroid treatment, alone as salvage treatment or in combination with conventional systemic therapy (ST). However, in severe to profound sensorineural hearing loss resistant to ST, the optimal infusion mode, the type and concentration of the solution, the preferable drug, its total amount, and the duration and fractionation of the treatment are still debated. Aim of the study was to investigate the feasibility and the outcomes of a direct and constant IT delivery of dexamethasone (DEX) by means of a new indwelling catheter.MethodsA prospective case-control study in a tertiary referral university hospital. Ninety-nine subjects treated with ST only and 28 with additional IT DEX have been included in the study. A 4 Fr catheter inserted in a sub-annular fashion with a minimal postero-inferior tympanotomy through and endocanalar approach under local anesthesia. DEX 4mg/ml delivered daily, up to 7 days. Daily bone and air-conducted pure tone and speech audiometry were performed with a follow-up at 1, 3, 6 months after treatment.ResultsTwenty-one out of 28 patients (75%) refractory to ST gained on average 24.0dB±20.5dB HL after IT-DEX, compared to 35.4% (average 6.7dB±16.6dB HL) of those receiving only medical ST (p<0.001). No significant side effects were noted.ConclusionIn severe to profound sudden deafness refractory to conventional ST, the daily perfusion of 4mg/ml DEX through an intratympanic catheter is an easy, well accepted procedure that enables patients to receive a drug in the middle ear in a repeatable or sustained form, with minimal discomfort and a partial rescue (67.86%) and a speech recognition gain of 39%.



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Severely infected pneumoceles of the frontal sinus in patients with mental retardation and brain atrophy treated by endoscopic sinus surgery

Publication date: Available online 13 May 2017
Source:Auris Nasus Larynx
Author(s): Ichiro Tojima, Hirotaka Kikuoka, Takao Ogawa, Takeshi Shimizu
We herein present three cases of abnormally expanded frontal sinuses (pneumoceles) with severe infection in patients with mental retardation and brain atrophy. Two patients previously underwent laryngotracheal separation surgery, and bacteriological examinations of purulent nasal discharge revealed infections caused by drug-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As conservative medical treatments were ineffective, all three patients were treated by computed tomography-guided endoscopic sinus surgery. This navigation system is useful for safer surgery in the area of anatomic deformity. The clinical findings, possible etiologies and surgical treatment of these cases are discussed.



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