The Influence of an Occult Infection on the Outcome of Autologous Bone Grafting During Surgical Bone Reconstruction: A Large Single-Center Case-Control Study.

BACKGROUND: Occult infections (OI) lack typical inflammatory signs, making them challenging to diagnose. Uncertainty remains regarding OI's influence on the outcome of autologous bone grafting (ABG), and evidence-based recommendations regarding an appropriate course of action are missing. Thus, we sought to determine the incidence of an OI in patients receiving ABG, evaluate whether it influences the outcome of ABG and whether associated risk factors have a further negative influence. METHODS: This study was designed as a large size single-center case-control study investigating patients treated between 01/01/2010 and 31/12/2016 with a minimum follow-up of 12 months. Patients ≥18 years presenting with a recalcitrant non-union of the lower limb receiving surgical bone reconstruction, including bone grafting, were included. A total of 625 patients were recruited, and 509 patients included in the current study. All patients received surgical non-union therapy based on the "diamond concept" including bone reconstruction using ABG. Additionally, multiple tissue samples were harvested and microbiologically analyzed. Tissue samples were microbiologically evaluated regarding an OI. Bone healing was analyzed using clinical and radiological parameters, patient characteristics and comorbidities investigated and ultimately results correlated. RESULTS: Forty-six out of 509 cases with OI resulted in an incidence of 9.04%. Overall consolidation time was increased by 15.08 weeks and radiological outcome slightly impaired (79.38% vs 71.42%), differences were at a non-significant extent. Diabetes mellitus had a significant negative influence on consolidation time (p=0.0313), while age (p=0.0339), smoking status (p=0.0337), diabetes mellitus (p=0.0400) and increased BMI (p=0.0315) showed a significant negative influence on the outcome of bone grafting. CONCLUSION: Surgeons treating recalcitrant non-unions should be aware that an OI is common. If an OI is diagnosed subsequent to ABG the majority of patients does not need immediate revision surgery. However, special attention needs to be paid to high-risk patients.

Non-Union Treatment Based on the "Diamond Concept" Is a Clinically Effective and Safe Treatment Option in Older Adults.

BACKGROUND: Patients >60 years suffering from non-unions are often unable to perform activities of daily living and often become dependent on nursing care. Evidence regarding treatment options and outcome is nonexistent. This study sought to determine the clinical effectiveness and safety of one- or two-step non-union therapy in elderly patients. METHODS: This study was a single-site retrospective database analysis of older adults with long bone non-unions treated via "diamond concept". All medical records of patients receiving surgical treatment of non-unions between 01/01/2010 and 31/12/2016 were reviewed. Clinical and radiological outcome subsequent to non-union therapy were evaluated. RESULTS: A total of 76 patients (37 patients were treated with one-step and 39 patients with Masquelet therapy) suffering from a non-union older than 60 years treated between 01/01/2010 and 31/12/2016 in our institution were included into the current study. Bone consolidation was achieved in 91.9% after one-step and 76.9% after the Masquelet therapy. Analysis of age as a risk factor in the outcome of non-union therapy revealed no significant differences in patients treated with the one-step procedure according to the "diamond concept". On the contrary, age had a significant negative influence on the outcome of the Masquelet therapy (p = 0.027). CONCLUSION: Non-union therapy according to the "diamond concept" is an effective and reliable treatment option in elderly patients. According to findings of the current study, older adults suffering from an infected non-union benefit from a two-stage procedure, whereas in patients suffering from a non-infected non-union, a one-step surgical treatment is beneficial.

Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors.

The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an additional mutation in EGFR kinase domain that confers resistance to TKIs. Crucially, oncogenic EGFR harboring both resistance mutations, T790M and C797S, can no longer be inhibited by currently approved EGFR TKIs. Here, we describe the discovery of BI-4020, which is a noncovalent, wild-type EGFR sparing, macrocyclic TKI. BI-4020 potently inhibits the above-described EGFR variants and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the molecule through macrocyclization.

Room temperature direct band gap emission characteristics of surfactant mediated grown compressively strained Ge films.

Compressively strained Ge films have been grown on relaxed Si0.45Ge0.55 virtual substrates using molecular beam epitaxy in the presence of Sb as a surfactant. Structural characterization has shown that films grown in the presence of surfactant exhibit very smooth surfaces with a relatively higher strain value in comparison to those grown without any surfactant. The variation of strain with increasing Ge layer thickness was analyzed using Raman spectroscopy. The strain is found to be reduced with increasing film thickness due to the onset of island nucleation following Stranski-Krastanov growth mechanism. No phonon assisted direct band gap photoluminescence from compressively strained Ge films grown on relaxed Si0.45Ge0.55 has been achieved up to room temperature. Excitation power and temperature dependent photoluminescence have been studied in details to investigate the origin of different emission sub-bands.

Coverage of exposed bones and joints in critically ill patients: lower extremity salvage with topical negative pressure therapy.

BACKGROUND: Soft tissue defects of the limb with exposure of tendons and bones in critically ill patients usually lead to extremity amputation. A potential treatment with topical negative pressure may allow split-thickness skin grafting to the bone, which leads to limb salvage. MATERIALS AND METHODS: We report on 21 multimorbid patients, 46 to 80 years of age, with severe lower limb soft tissue loss and infection with exposed bone following débridement with critical limb ischemia. Attempts to salvage the extremities were undertaken with repeated surgical débridement followed by vacuum-assisted closure therapy and subsequent split-thickness skin grafting procedures. RESULTS: Infection control and limb salvage were achieved in all cases with multiple débridements, topical negative pressure therapy, and skin grafts. In all patients, the exposure of tendons and bones was reversible by this strategy without a free flap transfer. DISCUSSION: The patients described in this study were severely compromised by systemic and vascular disorders, so extremity amputation had been considered owing to the overall condition and the exposure of tendons and bones. Since it was possible to salvage the affected limbs with this straightforward and simple procedure, this type of treatment should be considered as a last attempt to prevent amputation.

Expression of HIF-1 alpha in irradiated tissue is altered by topical negative-pressure therapy.

BACKGROUND AND PURPOSE: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. MATERIAL AND METHODS: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1 alpha (hypoxia-inducible factor-1 alpha), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. RESULTS: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1 alpha-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. CONCLUSION: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1 alpha expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1 alpha concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue injury, further investigations of HIF-1 alpha regulation under TNP are warranted.