Elevated IL-8 and sTNFR I/II levels indicate an association between CRPS I and an inflammatory process. Normal WBC, CRP, and IL-6 give evidence for localized inflammation. The hypothesis of neurogenic-induced inflammation mediated by neuropeptides is supported by elevated substance P levels.

Recurrent Respiratory Papillomatosis(RRP) is a rare disease with severe morbidity. Treatment is surgical. Prevailing viewpoint is that prophylactic HPV vaccines do not have therapeutic benefit due to their modus operandi. Studies on HPV vaccination alongside surgery were meta-analysed to test effect on burden of disease. Databases were accessed Nov and Dec 2021 [PubMed, Cochrane, Embase and Web of Science]. Main outcome measured was: Mean paired differences in the number of surgeries or recurrences per month. Analyses was performed using: Random effect maximal likelihood estimation model using the Stata module Mataan(StataCorp. 2019. Stata Statistical Software: Release 16. College Station, TX:StataCorp LLC.) Our results found n = 38 patients, suitable for syntheses with one previous meta-analyses (4 published, 2 unpublished studies) n = 63, total of n = 101 patients. Analyses rendered an overall reduction of 0.123 recurrences or surgeries per month (95% confidence interval [0.064, 0.183]). Our meta-analyses concludes that HPV vaccine is a beneficial adjunct therapy alongside surgery

Trochanteric femoral fractures are frequently associated with severe osteoporosis in elderly patients. The failure of devices intended to repair trochanteric fractures, such as the gamma locking nail (GLN), might be related to reduced bone density. Osteoporosis may also influence pain and walking ability because of low stability in the fracture area. In 74 patients (mean age 76 ± 16.5 years), the stability and clinical outcome following treatment with GLN were prospectively evaluated and recorded after 9 (n = 43) and 24 months (n = 34). Vertebral bone mineral density (BMD) was measured via quantitative computed tomography (QCT) at time of operation. Mechanical failure of GLN was recorded by radiographs of the hip. Assessment of outcome included the Harris Hip Score. Regression analysis was done to show the influence of age and BMD on clinical outcome. 9 months after treatment, complete fracture healing without dislocation of the lag screw of the GLN was observed even in patients with low BMD (< 55 mg/cm 3 trabecular BMD). Clinical outcome assessed by the Harris Hip Score was independent of BMD at both follow-ups. At the first follow-up, outcome depended on the patient's age, with younger patients (< 70 years) showing better results than elderly patients. The stability of fracture also seemed to influence the outcome.Our results indicate that stabilization of unstable osteoporotic fractures with GLN is associated with few complications and can be accomplished with identical clinical and radiologic results seen in patients with high BMD. The critical factor influencing outcome is patient's age, stability of fracture and not BMD.

BackgroundCholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies.MethodsWe isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry.ResultsUnder standard culture conditions, we detected a tissue-independent higher expression of IL-1β and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1β, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation.ConclusionWe propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence.