Πέμπτη 17 Νοεμβρίου 2022

FasL is a catabolic factor in alveolar bone homeostasis

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Abstract

Aim

Fas ligand (FasL) belongs to the tumor necrosis factor (TNF) superfamily regulating bone turnover, inflammation, and apoptosis. The appendicular and axial skeleton phenotype of mature Fasl gld mice was reported. The impact of FasL on the alveolar bone providing support for the teeth at mature stages under healthy and induced inflammatory conditions remains unknown.

Materials and methods

We performed a phenotypical analysis of mice carrying the homozygous Fasl gld mutation and wild-type (WT) mice (C57BL/6) under healthy conditions and upon ligature-induced periodontitis. After 12 days, μCT analysis revealed the distance between the cement enamel junction and the alveolar bone crest (CEJ-ABC). Additional structural parameters like the bone volume fraction (BV/TV) and the periodontal ligament space volume (PLS.V) were measured. Histological analyses were performed to visualize the catabolic changes at the defect site.

Results

We report that healthy Fasl gld mice have more periodontal bone than wild-type littermates. Fasl gld had no significant effect on inflammatory osteolysis compared to WT controls with ligatures. Histology revealed eroded surfaces at the root and in the interproximal bone in both strains.

Conclusions

These findings suggest that FasL is a catabolic factor in alveolar bone homeostasis, however, FasL does not affect the inflammatory osteolysis.

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Mediterranean Diet component oleic acid increases protective lipid‐mediators and improves trabecular bone in a Porphyromonas‐gingivalis‐inoculation‐model

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Abstract

Background

Therapeutic modulation of bacterial-induced inflammatory host response is being investigated in gingival inflammation and periodontal disease pathology. Therefore, dietary intake of monounsaturated fatty acid (FA) oleic acid (OA (C18:1)), main-component of Mediterranean-style diets, and Western-style diet component saturated FA palmitic acid (PA (C16:0)) were investigated for their modifying potential in a P.gingivalis-oral-inoculation-model.

Methods

Normal-weight C57BL/6-mice received OA-or PA-enriched diets (PA-ED, OA-ED, PA/OA-ED) or normal-standard-diet for 16 weeks and were inoculated with P.gingivalis/placebo (n=12/group). Gingival inflammation, alveolar bone structure, circulating lipid mediators and in vitro cellular response were determined.

Results

FA-treatment of P.gingivalis-LPS-incubated gingival fibroblasts (GFb) modified inflammatory activation, which only PA exacerbated with concomitant TNF-α-stimulation. Mice exhibited no signs of acute inflammation in gingiva or serum and no inoculation-and nutrition-associated changes of crestal alveolar bone. However, following P.gingivalis-inoculation, OA-ED improved oral trabecular bone-micro-architecture and enhanced circulating pro-resolving mediators Resolvin D4 (RvD4) and 4-hydroxydocosahexaenoic acid (4-HDHA), whereas PA-ED did not. In vitro-experiments demonstrated significantly improved differentiation in RvD4-and 4-HDHA-treated primary osteoblast-cultures and reduced expression of osteoclastogenic factors in GF. Further, P.gingivalis-infection of OA-ED animals led to a serum composition that suppressed osteoclastic differentiation in vitro.

Conclusions

Results underline preventive impact of Mediterranean-style-OA-EDs by indicating their pro-resolving nature beyond anti-inflammatory properties.

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Is drug‐induced sleep endoscopy associated with better outcomes after soft tissue surgery for sleep apnea? A systematic review and meta‐analysis

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Abstract

Objectives

The aim was to estimate the effect of drug-induced sleep endoscopy (DISE) on surgical outcomes after soft tissue surgery for obstructive sleep apnea (OSA).

Design and setting

Systematic review and meta-analysis.

Participants

Adult patients with OSA and candidates for soft tissue surgery, with and without preoperative DISE, were included.

Main outcomes measures

A systematic literature search of Medline, Web of Science, and Cochrane databases was performed from inception to December 31, 2021. Studies directly comparing patients with and without preoperative DISE were included. Success rate, change in apnea-hypopnea index (AHI), change in minimum SpO2 and change in Epworth Sleepiness Scale (ESS) score were extracted. Random-effect models were used to pool estimates.

Results

Seven out of 619 articles were included, representing 791 patients (389 in the DISE group and 402 in the no DISE group). DISE was neither associated with a higher success rate (pooled OR 1.34, 95% CI 0.69 – 2.59, p=0.39) after soft tissue surgery for OSA, nor a significant change in AHI (-4.69 events/hour, 95% CI -11.10 – 1.72, p=0.15), minimal SpO2 (mean increase of 2.02%, 95% CI -0.26 – 4.29, p=0.08) and ESS (mean difference of 1.29, 95% CI -0.48 – 3.05, p=0.15) when compared to patients without preoperative DISE.

Conclusions

Soft tissue surgery does not give better results after DISE compared to when DISE is not performed. However, given the overall low level of evidence of included studies, future well-conducted studies should confirm or overturn these results and clarify the added value of DISE.

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Post‐operative survival in head & neck cancer patients with elevated troponins

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Abstract

Objective

The strenuous demands of head and neck cancer surgery (HNS) place patients at increased risk of myocardial injury. Troponin positivity (TP) post-operatively is a predictor of increased complications and mortality. The present study is the first to investigate the effects of TP on potential delays in adjuvant treatment and disease-specific survival.

Methods

All patients undergoing HNS from 2014 to 2016 had troponins measured at a single academic center. Relevant patient data was extracted on retrospective chart review.

Results

Of 166 patients, 26 (15.6%) developed TP post-operatively. There was no significant difference between cohorts for baseline characteristics except for age. Overall and disease-specific survival for TP patients were respectively 45.9% and 57.4% at 3 years. There was no significant difference between cohorts for overall & disease-specific survival, and time to adjuvant therapy.

Conclusion

No significant association was found between TP and overall & disease-specific survival, and time to adjuvant therapy.

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Oncologic Outcomes After Clinically Node-Negative Salvage Laryngectomy

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This cohort study investigates the association of elective nec k dissection vs observation with oncologic outcomes among patients who received clinically node-negative salvage total laryngectomy.
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Multimodale Therapie bei lokal fortgeschrittenem kutanem Plattenepithelkarzinom

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Laryngorhinootologie
DOI: 10.1055/a-1949-2936

Die Therapieoptionen für lokal fortgeschrittene oder metastasierte Plattenepithelkarzinome waren bisher stark begrenzt und nicht standardisiert. Durch die Zulassung des monoklonalen Antikörpers Cemiplimab, der gegen den programmed death-1-Rezeptor (PD-1) gerichtet ist, hat sich die Prognose der betroffenen Patienten deutlich gebessert, wobei z.T. anhaltende Komplettremissionen erzielt werden können.In der vorgestellten Kasuistik wurde ein multimorbider, 81-jähriger Patient aufgrund eines ausgedehnten Plattenepithelkarzinoms frontoparietal mit Schädelkalotteninfiltration und Einbruch nach intrakraniell zunächst mit Cemiplimab behandelt. Immunvermittelte Nebenwirkungen sind nicht aufgetreten. Bei klinischer und radiologischer Remission wurde der Restbefund interdisziplinär operativ versorgt, wobei die defekte Schädelkalotte rekonstruiert wurde. Histologisch wurde eine pathologische Komplettremissio n des Plattenepithelkarzinoms nachgewiesen. 6 Monate postoperativ ergab sich kein Anhalt für ein Lokalrezidiv oder Metastasen.Dieser Fall zeigt exemplarisch einen Patienten, der trotz seines hohen Alters und Ko-Morbidität von der Therapie mit Cemiplimab profitiert hat. Darüber hinaus demonstriert dieser Fall die Relevanz eines interdisziplinären/multimodalen Therapieregimes im Management dieser in der Inzidenz deutlich ansteigenden Tumorentität.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Staphylococcus aureus Carrier Types are not Evidence of Population Heterogeneity

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Abstract
Asymptomatic colonization by Staphylococcus aureus is a precursor for infection, so identifying the mode and source of transmission which leads to colonization could help target interventions. Longitudinal studies have shown that some people are persistently colonized for years, while others seem to carry S. aureus for weeks or less, and conventional wisdom attributes this disparity to an underlying risk factor in the persistently colonized. We analyze published data with mathematical models of acquisition and carriage to compare this hypothesis with alternatives. The null model assumes a homogeneous population and still produces highly variable colonization durations (mean of 1.94 years, 5th percentile 0.1 years, 95th percentile 5.8 years). Simulations show that this inherent variability, combined with censoring in longitudinal cohort studies, i s sufficient to produce the appearance of "persistent carriers," "intermittent carriers," and "noncarriers" in data. Our estimates for colonization duration exhibit sensitivity to the assumption that false positives can occur despite being rare, but our model-based approach simultaneously estimates specificity and sensitivity along with epidemiological parameters. Our results show it is plausible that S. aureus colonizes people indiscriminately, and improved understanding of the types of exposures which result in colonization is essential.
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