A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients

BACKGROUND: Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). METHODS: The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. RESULTS: The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). CONCLUSIONS: Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole

Healing of fracture nonunions treated with low-intensity pulsed ultrasound (LIPUS): A systematic review and meta-analysis

Introduction: Bone fractures fail to heal and form nonunions in roughly 5% of cases, with little expectation of spontaneous healing thereafter. We present a systematic review and meta-analysis of published papers that describe nonunions treated with low-intensity pulsed ultrasound (LIPUS). Methods: Articles in PubMed, Ovid MEDLINE, CINAHL, AMED, EMBASE, Cochrane Library, and Scopus databases were searched, using an approach recommended by the Methodological Index for Non-Randomized Studies (MINORS), with a Level of Evidence rating by two reviewers independently. Studies are included here if they reported fractures older than 3 months, presented new data with a sample N ≥ 12, and reported fracture outcome (Heal/Fail). Results: Thirteen eligible papers reporting LIPUS treatment of 1,441 nonunions were evaluated. The pooled estimate of effect size for heal rate was 82% (95% CI: 77-87%), for any anatomical site and fracture age of at least 3 months, with statistical heterogeneity detected across all primary studies (Q = 41.2 (df = 12), p &lt; 0.001, Tau2 = 0.006, I2 = 71). With a stricter definition of nonunion as fracture age of at least 8 months duration, the pooled estimate of effect size was 84% (95% CI: 77% − 91.6%; heterogeneity present: Q = 21 (df = 8), p &lt; 0.001, Tau2 = 0.007, I2 = 62). Hypertrophic nonunions benefitted more than biologically inactive atrophic nonunions. An interval without surgery of &lt;6 months prior to LIPUS was associated with a more favorable result. Stratification of nonunions by anatomical site revealed no statistically significant differences between upper and lower extremity long bone nonunions. Conclusions: LIPUS treatment can be an alternative to surgery for established nonunions. Given that no spontaneous healing of established nonunions is expected, and that it is challenging to test the efficacy of LIPUS for nonunion by randomized clinical trial, findings are compelling. LIPUS may be most useful in patients for whom surgery is high risk, including elderly patients at risk of delirium, or patients with dementia, extreme hypertension, extensive soft-tissue trauma, mechanical ventilation, metabolic acidosis, multiple organ failure, or coma. With an overall average success rate for LIPUS &gt;80% this is comparable to the success of surgical treatment of non-infected nonunions

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Impairment of maturation of BMP-6 (35 kDa) correlates with delayed fracture healing in experimental diabetes

Background: Although it is known that diabetes interferes with fracture healing, the mechanisms remain poorly understood. The aim of this study was to investigate the correlation of BMP-6 and BMP-9 with the impairment in fracture healing in diabetes, by analyses of the difference in size and calcification of the callus, mechanical endurance, and expressing BMP-6 and BMP-9 in the callus, using a clinical related diabetic rodent model.Methods: We evaluated femur fracture healing by quantification of size and calcification of the callus by X-ray, histological and histochemical images, loading capacity of the fractured bone, and amount of BMP-6 in the callus and the bones using Western blot assay.Results: Significant upregulation of BMP-6 in the callus and the fractured bones of both non-diabetic and the diabetic animals was observed, at the end of the second and the fourth weeks after fracture. However, significantly lower levels of BMP-6 at 35 kDa with smaller sizes of calcified callus and poor loading capacity of the healing bones were detected in the diabetic animals, compared to the non-diabetic controls. The impairment of the maturation procedure of BMP-6 (35 kDa) from precursors may be underlying the downregulation of the BMP-6 in diabetic animals.Conclusions: It could be concluded that the delayed fracture healing in the diabetic animals is correlated with deficiency of BMP-6 (35 kDa), which may be caused by impairment of maturation procedure of BMP-6 from precursors to functioning format. This is a primary study but an important step to explore the molecular pathogenesis of impairment of fracture healing in diabetes and to molecular therapeutic approach for the impairment of fracture healing.</p

Novel use of an exchange catheter to facilitate intubation with an Aintree catheter in a tall patient with a predicted difficult airway: a case report

<p>Abstract</p> <p>Introduction</p> <p>The Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) has been shown to successfully facilitate difficult intubations when other methods have failed. The Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) has a fixed length of 56 cm, and it has been suggested in the literature that it may be too short for safe use in patients who are tall.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old, 180 cm tall Caucasian woman with a predicted difficult airway who presented to our facility for an emergency cesarean section. After several failed intubation attempts via direct laryngoscopy, an airway was established with a laryngeal mask airway. After delivery of a healthy baby, our patient's condition necessitated tracheal intubation. A fiber-optic bronchoscope loaded with an Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) was passed through the laryngeal mask airway into the trachea until just above the carina, but was too short to safely allow for the passage of an endotracheal tube.</p> <p>Conclusions</p> <p>We present a novel technique in which the Aintree intubating catheter (Cook^®Medical Inc., Bloomington, IN, USA) was replaced with a longer (100 cm) exchange catheter, over which an endotracheal tube was passed successfully into the trachea.</p

Protein Modification by Deamidation Indicates Variations in Joint Extracellular Matrix Turnover

As extracellular proteins age, they undergo and accumulate nonenzymatic post-translational modifications that cannot be repaired. We hypothesized that these could be used to systemically monitor loss of extracellular matrix due to chronic arthritic diseases such as osteoarthritis (OA). To test this, we predicted sites of deamidation in cartilage oligomeric matrix protein (COMP) and confirmed, by mass spectroscopy, the presence of deamidated (Asp64) and native (Asn64) COMP epitopes (mean 0.95% deamidated COMP (D-COMP) relative to native COMP) in cartilage. An Asp64, D-COMP-specific ELISA was developed using a newly created monoclonal antibody 6-1A12. In a joint replacement study, serum D-COMP (p = 0.017), but not total COMP (p = 0.5), declined significantly after replacement demonstrating a joint tissue source for D-COMP. In analyses of 450 participants from the Johnston County Osteoarthritis Project controlled for age, gender, and race, D-COMP was associated with radiographic hip (p < 0.0001) but not knee (p = 0.95) OA severity. In contrast, total COMP was associated with radiographic knee (p < 0.0001) but not hip (p = 0.47) OA severity. D-COMP was higher in soluble proteins extracted from hip cartilage proximal to OA lesions compared with remote from lesions (p = 0.007) or lesional and remote OA knee (p < 0.01) cartilage. Total COMP in cartilage did not vary by joint site or proximity to the lesion. This study demonstrates the presence of D-COMP in articular cartilage and the systemic circulation, and to our knowledge, it is the first biomarker to show specificity for a particular joint site. We believe that enrichment of deamidated epitope in hip OA cartilage indicates a lesser repair response of hip OA compared with knee OA cartilage

High rate of complications with exchange nailing for femoral nonunions

Objectives: To evaluate rates of nonunion repair, osseous healing, and outcomes in femoral nonunions with contemporary healing. Design: Retrospective review. Setting: Five academic level 1 trauma centers. Patients/Participants: This study includes adult patients (age older than 18) seen at one of the participating institutions between 2012 and 2019 who sustained a femur fracture (OTA/AO 31, 32, 33) initially treated with intramedullary fixation that developed nonunion and were treated with exchange nailing for the index nonunion surgery. Seventy-nine patients with femoral nonunion met inclusion criteria. Intervention: Exchange nailing for treatment of femoral nonunion. Main Outcome Measurements: The primary outcome measure was radiographic osseous union. We further analyzed union rates by OTA/AO classification, nonunion type, implants used, graft used, time from the initial procedure, and infection status. Results: Seventy-nine patients met inclusion criteria. Rates of osseous union were similar by OTA/AO classification (P = 0.48), nonunion type (hypertrophic, oligotrophic, atrophic) (P = 0.52), implant/biologic used (P = 0.45), and time from the initial procedure until exchange nail procedure (P = 0.09). Forty-two patients had inflammatory laboratory markers (C-reactive protein, erythrocyte sedimentary rate) and cultures obtained during the first nonunion surgery with no significant differences in union (P = 0.29) based on laboratory and culture results. However, a considerable number of complications were encountered (n = 32; 41%). Common complications included reoperation (n = 30; 38%) secondary to recalcitrant nonunion, readmission, implant failure, and infection. Conclusions: This large, multicenter study with modern implants, instruments, and techniques for exchange nailing of femoral nonunions demonstrates high rates of reoperation (n = 30; 38%), but higher rates of osseous healing (n = 68; 86% healed) than previously reported data in the literature

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article