Long-Term Outcomes Following Single-Stage Reamed Intramedullary Exchange Nailing in Apparently Aseptic Femoral Shaft Nonunion with Unsuspected Proof of Bacteria

Background: The aim of this study was to evaluate detection rates and risk factors for unsuspected proof of bacteria, as well as clinical and radiologic outcomes following femoral shaft nonunion without clinical signs of infection treated by a single-stage surgical revision procedure including reamed intramedullary exchange nailing. Methods: A retrospective cohort study was performed in a European level I trauma center between January 2015 and December 2022. Fifty-eight patients were included who underwent reamed intramedullary exchange nailing as a single-step procedure for surgical revision of posttraumatic diaphyseal femoral nonunion without any indications of infection in medical history and without clinical signs of local infection. Clinical details of the patients were analyzed and functional and radiologic long-term outcomes were determined. Results: In all patients, with and without proof of bacteria osseous, healing could be observed. The physical component summary of the SF-12 demonstrated significantly better results at least one year after the final surgical revision in case of a negative bacterial culture during exchange nailing. Conclusions: Clinical long-term outcomes demonstrated a trend towards better results following femoral shaft nonunion revision if there was no evidence for the presence of low-grade infected nonunion. In this case, a single-stage surgical procedure may be recommended

Radiographic cortical thickness parameters as predictors of rotational alignment in proximal tibial shaft fractures: a cadaveric study

AIM The treatment of tibial fractures with an intramedullary nail is an established procedure. However, torsional control remains challenging using intraoperatively diagnostic tools. Radiographic tools such as the Cortical Step Sign (CSS) and the Diameter Difference Sign (DDS) may serve as tools for diagnosing a relevant malrotation. The aim of this study was to investigate the effect of torsional malalignment on CSS and DDS parameters and to construct a prognostic model to detect malalignment. METHODS A proximal tibial shaft fracture was set in human tibiae. Torsion was set stepwise from 0° to 30° in external and internal torsion. Images were obtained with a C-arm and transferred to a PC for measuring the medical cortical thickness (MCT), lateral cortical thickness (LCT), tibial diameter (TD) in AP and the anterior cortical thickness (ACT) as well as the posterior cortical thickness (PCT) and the transverse diameter (TD) of the proximal and the distal main fragment. RESULTS There were significant differences between the various degrees of torsion for each of the absolute values of the examined variables. The parameters with the highest correlation were TD, LCT and ACT. A model combining ACT, LCT, PCT and TD lateral was most suitable model in identifying torsional malalignment. The best prediction of clinically relevant torsional malalignment, namely 15°, was obtained with the TD and the ACT. CONCLUSION This study shows that the CSS and DDS are useful tools for the intraoperative detection of torsional malalignment in proximal tibial shaft fractures and should be used to prevent maltorsion

Growth factor-mediated augmentation of long bones: evaluation of a BMP-7 loaded thermoresponsive hydrogel in a murine femoral intramedullary injection model

Background Due to our aging population, an increase in proximal femur fractures can be expected, which is associated with impaired activities of daily living and a high risk of mortality. These patients are also at a high risk to suffer a secondary osteoporosis-related fracture on the contralateral hip. In this context, growth factors could open the field for regenerative approaches, as it is known that, i.e., the growth factor BMP-7 (bone morphogenetic protein 7) is a potent stimulator of osteogenesis. Local prophylactic augmentation of the proximal femur with a BMP-7 loaded thermoresponsive hydrogel during index surgery of an osteoporotic fracture could be suitable to reduce the risk of further osteoporosis-associated secondary fractures. The present study therefore aims to test the hypothesis if a BMP-7 augmented hydrogel is an applicable carrier for the augmentation of non-fractured proximal femurs. Furthermore, it needs to be shown that the minimally invasive injection of a hydrogel into the mouse femur is technically feasible. Methods In this study, male C57BL/6 mice (n = 36) received a unilateral femoral intramedullary injection of either 100 μl saline, 100 μl 1,4 Butan-Diisocyanat (BDI)-hydrogel, or 100 μl hydrogel loaded with 1 μg of bone morphogenetic protein 7. Mice were sacrificed 4 and 12 weeks later. The femora were submitted to high-resolution X-ray tomography and subsequent histological examination. Results Analysis of normalized CtBMD (Cortical bone mineral density) as obtained by X-ray micro-computed tomography analysis revealed significant differences depending on the duration of treatment (4 vs 12 weeks; p < 0.05). Furthermore, within different anatomically defined regions of interest, significant associations between normalized TbN (trabecular number) and BV/TV (percent bone volume) were noted. Histology indicated no signs of inflammation and no signs of necrosis and there were no cartilage damages, no new bone formations, or new cartilage tissues, while BMP-7 was readily detectable in all of the samples. Conclusions In conclusion, the murine femoral intramedullary injection model appears to be feasible and worth to be used in subsequent studies that are directed to examine the therapeutic potential of BMP-7 loaded BDI-hydrogel. Although we were unable to detect any significant osseous effects arising from the mode or duration of treatment in the present trial, the effect of different concentrations and duration of treatment in an osteoporotic model appears of interest for further experiments to reach translation into clinic and open new strategies of growth factor-mediated augmentation

SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia.

The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking. SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase that cleaves physiological dNTPs into deoxyribonucleosides and inorganic triphosphate. Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog derivatives through the depletion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells. Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic reduction of Ara-CTP in leukemic cells. Loss of SAMHD1 activity-through genetic depletion, mutational inactivation of its triphosphohydrolase activity or proteasomal degradation using specialized, virus-like particles-potentiates the cytotoxicity of Ara-C in AML cells. In mouse models of retroviral AML transplantation, as well as in retrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was inversely correlated with SAMHD1 expression. These results identify SAMHD1 as a potential biomarker for the stratification of patients with AML who might best respond to Ara-C-based therapy and as a target for treating Ara-C-refractory AML

Patients with complex proximal tibial fractures overestimate the prognosis of their injury

PURPOSE To investigate, if patients with complex proximal tibial fracture have realistic expectations on open reduction and internal fixation. METHODS 114 patients (mean 49 years, SD ± 13) with closed AO-type B and C proximal tibial fracture were grouped (group B, respectively C). Prior to surgery expectations concerning knee function, pain, return to work/sports, and the risk for osteoarthritis was assessed with the Hospital for Special Surgery-Knee Surgery Expectations Survey (HFSS-KSE) and a non-validated ten-item survey. RESULTS 92% of patients expected at least an almost natural knee postoperatively. All items regarding restoring knee function were ranked to be at least important in both groups. 65% in group B and 47% in group C expected at most occasional pain. 83% in group B and 67% in group C expected full return to work without any limitations. Patients with low physical work intensity expected significantly shorter incapacity to work in both groups (7.8, respectively 8.9~weeks). 71% in group B and 60% in group C expected to return to sports with at most small limitations. 33% in group B and 22% in group C assumed risk for osteoarthritis will be prevented by surgery. CONCLUSION Expectations on surgery for complex proximal tibial fracture are high regardless of fracture type. The prognosis of many health and lifestyle domains was overestimated. The risk for osteoarthritis was underestimated. This study should sensitize surgeons to discuss realistic expectations. This may help to improve patient comprehension what leads to sensible expectations, resulting in improved patients´ satisfaction. LEVEL OF EVIDENCE IV. TRIAL REGISTRATION NUMBER 14104, Date of registration: 06/2015

Nanoscale Ion-Exchange Materials: From Analytical Chemistry to Industrial and Biomedical Applications

Nano-sized ion exchangers (NIEs) combine the properties of common bulk ion-exchange polymers with the unique advantages of downsizing into nanoparticulate matter. In particular, being by nature milti-charged ions exchangers, NIEs possess high reactivity and stability in suspensions. This brief review provides an introduction to the emerging landscape of various NIE materials and summarizes their actual and potential applications. Special attention is paid to the different methods of NIE fabrication and studying their ion-exchange behavior. Critically discussed are different examples of using NIEs in chemical analysis, e.g., as solid-phase extraction materials, ion chromatography separating phases, modifiers for capillary electrophoresis, etc., and in industry (fuel cells, catalysis, water softening). Also brought into focus is the potential of NIEs for controlled drug and contrast agent delivery

The role of low-grade infection in the pathogenesis of apparently aseptic tibial shaft nonunion

PURPOSE Aim of this study was to determine the rate of low-grade infection in patients with primarily as aseptic categorized tibial shaft nonunion and lack of clinical signs of infection. METHODS In a retrospective study between 2006 and 2013, all patients who underwent revision surgery for treatment of tibial shaft nonunion without clinical evidence of infection were assessed. Bacterial cultures harvested during nonunion revision, C-reactive protein (CRP) and/or white blood cell (WBC) values at hospital admission, outcome, and epidemiological data were analyzed. RESULTS In 88 patients with tibial shaft nonunion without any clinical signs of infection, bacterial samples remained negative in 51 patients. In 37 patients, microbiological diagnostic studies after long-term culturing demonstrated positive bacterial cultures whereas after short-term culturing for 2 days only 17 positive cultures were observed. In 12 cases a mixed culture with 2.3 different bacteria on average was detected. Among patients with negative bacterial cultures bone healing was achieved after 13.2 months. Nonunion with positive bacterial cultures required 19 (range 2-42) months until osseous healing (p = 0.009). Furthermore, nonunion with positive bacterial cultures require statistically more surgical revisions to achieve healing (2.9 ± 0.5 vs. 1.3 ± 0.1 additional procedure; (p = 0.003). Hematological studies carried out before surgical intervention did not demonstrate significant differences in CRP values (negative vs. positive cultures: 0.3 (range 0.3-2.8) mg/dl vs. 0.5 (range 0.3-5.7) mg/dl (p = 0.181) and in WBC values (negative vs. positive cultures: 7.4 (range 3.5-11.9) /nl vs. 7.3 (range 3.7-11.1) /nl (p = 0.723). Limitations of this study may include the varying amount of the at least four samples for microbiological diagnostics as well as the circumstance that for diagnosing low-grade infection swabs and tissue samples were included in this evaluation as being equivalent. CONCLUSION The pathogenesis of nonunion may originate from low-grade infection even in patients without clinical signs of infection. In addition, nonunion with positive bacterial cultures require statistically more surgical revisions to achieve healing. Therefore, during any revision surgery, multiple bacterial samples are intended to be harvested for long-term culturing. Particularly, in tibial shaft nonunion following Gustilo-Anderson type III open fractures, low-grade infection should be suspected. TRIAL REGISTRATION NUMBER DRKS00014657. DATE OF REGISTRATION 04/26/2018 retrospectively registered