Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains

Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, micro-computed tomography (μCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. μCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Analgesic Effects of Ultrasound‐Guided Iliohypogastric/Ilioinguinal Nerve Block Combined with Lateral Femoral Cutaneous Nerve Block in Total Hip Arthroplasty via Direct Anterior Approach: A Retrospective Cohort Study

ObjectiveThis study aimed to explore the efficacy and safety of the combination of lateral femoral cutaneous nerve blocks (LFCNB) and iliohypogastric/ilioinguinal nerve blocks (IHINB) on postoperative pain and functional outcomes after total hip arthroplasty (THA) via the direct anterior approach (DAA).MethodsIn this retrospective cohort study, patients undergoing THA via the DAA between January 2019 and November 2019 were stratified into two groups based on their date of admission. Sixty‐seven patients received LFCNB and IHINB along with periarticular infiltration analgesia (PIA) (nerve block group), and 75 patients received PIA alone (control group). The outcomes included postoperative morphine consumption, postoperative pain assessed using the visual analogue scale (VAS), the QoR‐15 score, and functional recovery measured as quadriceps strength, time to first straight leg rise, daily ambulation distance, and duration of hospitalization. The Oxford hip score and the UCLA activity level rating were assessed at 1 and 3 months after surgery. In addition, postoperative complications were recorded. Patients were also compared based on the type of incision used during surgery (traditional longitudinal or “bikini” incision).ResultsPatients in the nerve block group showed significantly lower postoperative morphine consumption, lower resting VAS scores within 12 h postoperatively, lower VAS scores during motion within 24 h postoperatively, and better QoR‐15 scores on postoperative day 1. These patients also showed significantly better functional recovery during hospitalization. At 1‐month and 3‐month outpatient follow up, the two groups showed no significant differences in Oxford hip score or UCLA activity level rating. There were no significant differences in the incidence of postoperative complications. Similar results were observed when patients were stratified by type of incision, except that the duration of hospitalization was similar.ConclusionCompared to PIA alone, a combination of LFCNB and IHINB along with PIA can improve early pain relief, reduce morphine consumption, and accelerate functional recovery, without increasing complications after THA via the DAA.     

Treatment of Recurrent Hemarthrosis Following Total Knee Arthroplasty Using Surgical Interventions

BackgroudRecurrent hemarthrosis following total knee arthroplasty (TKA) is a rare complication. Its pathophysiology and standard treatments have not yet been established. In this study, we report 7 cases of recurrent hemarthrosis after TKA in which failure of the initial conservative treatment was followed by angiographic embolization; in 1 of the 7 cases, arthroscopic electrocauterization was also performed after treatment failure with selective embolization.MethodsFrom January 2015 to May 2018, 7 patients visited our hospital due to recurrent hemarthrosis after TKA. Their medical records and serologic test results were reviewed to check for the presence of any bleeding disorder and history of anticoagulant use. Implant malalignment and instability were checked using X-ray. In all cases, the conservative treatment failed, so interventional angiography with selective embolization was performed, which was also followed by arthroscopic electrocauterization if the outcome was unsatisfactory.ResultsThe interval between TKA and the onset of hemarthrosis ranged from 3 to 76 months (average, 34.1 months). There was no coagulopathy and instability. All patients underwent conservative treatment at an interval of 4.3 months and the rate of relapse was 3.1 on average. On the interventional angiography, 6 cases showed vascular blush, and 1 case had pulsatile bleeding. The average duration for interventional angiography was 90.9 minutes. The average length of follow-up was 38.8 months. Embolization was successfully performed in 4 cases. In 2 of 3 failed cases, the symptoms improved without further treatment. In the remaining 1 failed case, the patient had a relapse of hemarthrosis, so an arthroscopic procedure was performed, which led to identification of the suspicious bleeding point by using preoperative angiographic findings. Electrocauterization was performed and active bleeding was stopped. All cases with recurrent hemarthrosis achieved improvement.ConclusionsInterventional angiography was used to aid in the diagnosis of recurrent hemarthrosis, and therapeutic selective embolization provided satisfactory clinical results. Even if selective embolization fails, interventional angiography may be helpful for further surgical procedures because it reveals vascular blush of a bleeding site. Therefore, interventional angiography and selective embolization should be considered to be a useful treatment for recurrent hemarthrosis after TKA.     

Culture-Expanded Autologous Adipose-Derived Mesenchymal Stem Cell Treatment for Osteonecrosis of the Femoral Head

BackgroudOutcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH.MethodsEighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint.ResultsPreoperatively, the necrotic lesion extent was 63.0% (38.4%–96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2).ConclusionsOur outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.     

An aqueous extract of Platycodi radix inhibits LPS-induced NF-kappaB nuclear translocation in human cultured airway epithelial cells

We investigated the effects of aqueous extract from Platycodi radix (AEPR), a traditional drug used to treat acute lung inflammatory disease, on lipopolysaccharide (LPS)-induced inflammation in A549 human cultured airway epithelial cells. Nuclear factor-kappaB (NF-kappaB) and its inhibitory regulator, inhibitory kappaB (I-kappaB), play crucial roles in LPS-induced inflammatory response. We show that LPS-induced nuclear translocation of NF-kappaBp65 is inhibited by AEPR. LPS-induced expression of I-kappaBalpha, which is expressed by LPS-induced activation of NF-kappaB, is inhibited by AEPR as well. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), are repressed by AEPR. We also found that expression of heat shock protein 70 (Hsp70), which has an anti-inflammatory activity, is increased by AEPR plus LPS. These results suggest that AEPR may act as a therapeutic agent for inflammatory disease through regulating the activity of NF-kappaB and expression of inflammatory genes.     

Problem case: two-dimensional enlargement of the upper lip after excision of a vascular malformation

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Problem case: two-dimensional enlargement of the upper lip after excision of a vascular malformation