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1.
Bone Jt Open ; 4(5): 370-377, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37203362

ABSTRACT

Aims: Using data from the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial, we sought to determine if a difference in functional outcomes exists between monopolar and bipolar hemiarthroplasty (HA). Methods: This study is a secondary analysis of patients aged 50 years or older with a displaced femoral neck fracture who were enrolled in the HEALTH trial and underwent monopolar and bipolar HA. Scores from the Western Ontario and McMaster University Arthritis Index (WOMAC) and 12-Item Short Form Health Survey (SF-12) Physical Component Summary (PCS) and (MCS) were compared between the two HA groups using a propensity score-weighted analysis. Results: Of 746 HAs performed in the HEALTH trial, 404 were bipolar prostheses and 342 were unipolar. After propensity score weighting, adequate balance between the bipolar and unipolar groups was obtained as shown by standardized mean differences less than 0.1 for each covariable. A total of 24 months after HA, the total WOMAC score and its subcomponents showed no statistically significant difference between the unipolar and bipolar groups. Similarly, no statistically significant difference was found in the PCS and MCS scores of the SF-12 questionnaire. In participants aged 70 years and younger, no difference was found in any of the functional outcomes. Conclusion: From the results of this study, the use of bipolar HA over unipolar design does not provide superior functional outcomes at 24 months postoperatively. The theoretical advantage of reduced acetabular wear with bipolar designs does not appear to influence functional outcomes in the first two years postoperatively.

2.
J Shoulder Elbow Surg ; 32(8): 1746-1760, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37080421

ABSTRACT

BACKGROUND: Calcific tendinitis is a relatively common shoulder disorder, with 7%-17% of individuals with shoulder pain having rotator cuff calcium deposits. Several nonoperative interventions, extracorporeal shockwave therapy (ESWT) and ultrasonography-guided needling (UGN), and surgical techniques have been described to treat calcific tendonitis with satisfactory outcomes. Clinical guidelines are lacking for surgical excision in cases refractory to nonoperative treatment. Several arthroscopic and open operative techniques have been described to treat calcific tendonitis with satisfactory clinical outcomes. The purpose of this systematic review of randomized controlled trials is to compare outcomes and complications of nonoperative vs. operative management of chronic calcific tendinitis of the rotator cuff, to provide evidence-based treatment guidelines for practitioners. METHODS: EMBASE, PubMed, and OVID [MEDLINE] were searched from database inception until February 20, 2022, for randomized controlled trials reporting outcomes related to operative or nonoperative management for calcific tendonitis of the shoulder. Clinical outcomes including pain on visual analog scale (VAS), Constant-Murley Shoulder Outcome Score (CMS), and resolution of calcific deposits were evaluated. Continuous data at last follow-up was pooled into mean differences using a random effects model for meta-analysis. RESULTS: A total of 27 studies (2212 nonoperative patients and 140 operative patients) met the final inclusion criteria. Pooled mean difference in VAS for ESWT was -3.83 (95% confidence interval [CI] -5.38, -2.27); P < .001), compared to -4.83 (95% CI -5.44, -4.22; P < .001) for UGN, and -4.65 (95% CI -5.47, -3.82; P < .001) for the operative interventions. Pooled mean difference in CMS score after ESWT was 18.30 (95% CI 10.95, 25.66; P < .001) compared to 22.01 (95% CI 8.17, 35.84; P = .002) for UGN, and 38.35 (95% CI 31.68, 45.02; P < .001) for the operative interventions. Eighty-five percent of patients receiving operative and 67% of patients receiving UGN management had complete radiographic resolution of calcific deposit. CONCLUSIONS: Surgical treatment of chronic calcific tendonitis of the rotator cuff results in larger improvement in functional outcome scores and comparable pain reduction to nonoperative interventions, particularly UGN. Both operative and nonoperative treatment modalities are likely to have clinically significant improvements in function and pain, and thus it is reasonable to trial UGN and ESWT as first-line treatment. Cost-effectiveness analyses will be needed to support one treatment over the other. High-quality randomized controlled trials directly comparing nonoperative interventions to operative interventions in patients prior to failing conservative treatment are needed to establish high-quality evidence-based guidelines.


Subject(s)
Rotator Cuff Injuries , Tendinopathy , Humans , Rotator Cuff/diagnostic imaging , Rotator Cuff/surgery , Randomized Controlled Trials as Topic , Tendinopathy/surgery , Tendinopathy/complications , Shoulder , Shoulder Pain/etiology , Shoulder Pain/therapy , Rotator Cuff Injuries/surgery , Rotator Cuff Injuries/complications , Treatment Outcome
3.
OTA Int ; 6(1): e231, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36760661

ABSTRACT

Introduction: Open fractures represent a major source of morbidity. Surgical site infections (SSIs) after open fractures are associated with a high rate of reoperations and hospitalizations, which are associated with a lower health-related quality of life. Early antibiotic delivery, typically chosen through an assessment of the size and contamination of the wound, has been shown to be an effective technique to reduce the risk of SSI in open fractures. The Gustilo-Anderson classification (GAC) was devised as a grading system of open fractures after a complete operative debridement of the wound had been undertaken but is commonly used preoperatively to help with the choice of initial antibiotics. Incorrect preoperative GAC, leading to less aggressive initial management, may influence the risk of SSI after open fracture. The objectives of this study were to determine (1) how often the GAC changed from the initial to definitive grading, (2) the injury and patient characteristics associated with increases and decreases of the GAC, and (3) whether a change in GAC was associated with an increased risk of SSI. Methods: Using data from the FLOW trial, a large multicenter randomized study, we used descriptive statistics to quantify how frequently the GAC changed from the initial to definitive grading. We used regression models to determine which injury and patient characteristics were associated with increases and decreases in GAC and whether a change in GAC was associated with SSI. Results: Of the 2420 participants included, 305 participants had their preoperative GAC change (12.6%). The factors associated with upgrading the GAC (from preoperative score to the definitive assessment) included fracture sites other than the tibia, bone loss at presentation, width of wound, length of wound, and skin loss at presentation. However, initial misclassification of type III fractures as type II fractures was not associated with an increased risk of SSI (P = 0.14). Conclusions: When treating patients with open fracture wounds, surgeons should consider that 12% of all injuries may initially be misclassified when using the GAC, particularly fractures that have bone loss at presentation or those located in sites different than the tibia. However, even in misclassified fractures, it did not seem to increase the risk of SSI.

4.
Bone Jt Open ; 3(8): 611-617, 2022 08.
Article in English | MEDLINE | ID: mdl-35909342

ABSTRACT

AIMS: The aim of this study was to explore the functional results in a fitter subgroup of participants in the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial to determine whether there was an advantage of total hip arthroplasty (THA) versus hemiarthroplasty (HA) in this population. METHODS: We performed a post hoc exploratory analysis of a fitter cohort of patients from the HEALTH trial. Participants were aged over 50 years and had sustained a low-energy displaced femoral neck fracture (FNF). The fittest participant cohort was defined as participants aged 70 years or younger, classified as American Society of Anesthesiologists grade I or II, independent walkers prior to fracture, and living at home prior to fracture. Multilevel models were used to estimate the effect of THA versus HA on functional outcomes. In addition, a sensitivity analysis of the definition of the fittest participant cohort was performed. RESULTS: There were 143 patients included in the fittest cohort. Mean age was 66 years (SD 4.5) and 103 were female (72%). No clinically relevant differences were found between the treatment groups in the primary and sensitivity analyses. CONCLUSION: This analysis found no differences in functional outcomes between HA and THA within two years of displaced low-energy FNF in a subgroup analysis of the fittest HEALTH patients. These findings suggest that very few patients above 50 years of age benefit in a clinically meaningful way from a THA versus a HA early after injury.Cite this article: Bone Jt Open 2022;3(8):611-617.

5.
Knee Surg Sports Traumatol Arthrosc ; 30(7): 2425-2456, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35122108

ABSTRACT

PURPOSE: The purpose of this review is to provide a summary of the techniques and outcomes of various capsular management strategies in patients undergoing hip arthroscopy for femoroacetabular impingement (FAI). The information this review provides on capsular management strategies will provide surgeons with operative guidance and decision-making when managing patients with FAI lesions arthroscopically. METHODS: Three databases MEDLINE, EMBASE, and PubMed were searched from database inception to November 2nd 2021, for literature addressing capsular management of patients undergoing hip arthroscopy for FAI. All level I-IV data on capsular management strategy as well as postoperative functional outcomes were recorded. A meta-analysis was used to combine the mean postoperative functional outcomes using a random-effects model. RESULTS: Overall, there were a total of 36 studies and 4744 patients included in this review. The mean MINORS score was 10.7 (range 8-13) for non-comparative studies and 17.6 (range 15-20) for comparative studies. Three comparative studies in 1302 patients examining the proportion of patients reaching the MCID for the mHHS score in patients undergoing interportal capsulotomy with either capsular repair or no repair found that the capsular repair group had a higher odds ratio of reaching the MCID at 1.46 (95% CI 0.61-3.45, I2 = 67%, Fig. 2, Table 3); however, this difference was not significant with a p value of 0.39. When looking at only level 1 and 2 studies, four studies in 1308 patients reporting on the mHHS score in patients undergoing capsular closure regardless of capsulotomy type, found a pooled standardized mean difference in the mHHS score of 2.1 (95% CI 1.7-2.55, I2 = 70%, Fig. 3), while four studies in 402 patients reporting on the mHHS score in patients not undergoing capsular closure regardless of capsulotomy type found a pooled standardized mean difference in the mHHS score of 1.46 (95% CI 1.2-1.7, I2 = 30%, Fig. 4). CONCLUSION: This review may demonstrate improved postoperative outcomes in patients undergoing complete capsular closure regardless of capsulotomy type based on postoperative mHHS score. Furthermore, this review may suggest improved postoperative outcomes after closure of an interportal capsulotomy. There are limited published outcome data regarding T-type capsulotomy without closure. This review provides surgeons with operative guidance on capsular management strategies when treating patients with FAI lesions arthroscopically. LEVEL OF EVIDENCE: IV.


Subject(s)
Femoracetabular Impingement , Activities of Daily Living , Arthroscopy/methods , Femoracetabular Impingement/surgery , Hip Joint/surgery , Humans , Reoperation , Treatment Outcome
7.
J Orthop Trauma ; 35(5): e165-e170, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33844665

ABSTRACT

OBJECTIVES: To evaluate if local delivery of boron can accelerate bone healing and examine if the bioactive salt impacts the osteogenic response of bone-derived osteoclasts and osteoblasts by the regulation of the Wnt/ß-catenin pathway. METHODS: Bilateral femoral cortical defects were created in 32 skeletally mature C57 mice. On the experimental side, boric acid (8 mg/kg concentration) was injected locally, whereas on the control side, saline was used. Mice were euthanized at 7, 14, and 28 days. MicroCT was used to quantify bone regeneration at the defect. Histological staining for alkaline phosphatase and tartrate-resistant acid phosphatase was used to quantify osteoblast and osteoclast activity, respectively. Immunohistochemical antibodies, ß-catenin, and CD34 were used to quantify active ß-catenin levels and angiogenesis, respectively. RESULTS: The boron group exhibited higher bone volume and trabecular thickness at 28 days on microCT. Both alkaline phosphatase activity and ß-catenin activity was significantly higher in the boron group at 7 days. In addition, CD34 staining revealed increased angiogenesis at 14 days in boron-treated groups. We found boron to have no association with osteoclast activity. CONCLUSIONS: This study shows that local delivery of boron is associated with an increase in osteoblast activity at early phases of healing. The corresponding increase in ß-catenin likely supports that boron increases osteoblast activity by the Wnt/ß-catenin pathway. Increased angiogenesis at 14 days could be a separate mechanism of increasing bone formation that is independent of Wnt/ß-catenin activation.


Subject(s)
Boron , Osteoblasts , Animals , Bone Regeneration , Cell Differentiation , Mice , Osteoclasts , Osteogenesis , Wnt Signaling Pathway
9.
J Bone Joint Surg Am ; 103(14): 1328-1334, 2021 07 21.
Article in English | MEDLINE | ID: mdl-33764913

ABSTRACT

BACKGROUND: Heterotopic ossification (HO) is a frequent complication following hip surgery. Using data from the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial, we aimed to (1) determine the prevalence of HO following total hip arthroplasty (THA) for femoral neck fracture in patients ≥50 years of age, (2) identify whether HO is associated with an increased risk of revision surgery within 24 months after the fracture, and (3) determine the impact of HO on functional outcomes. METHODS: We performed a multivariable Cox regression analysis using revision surgery as the dependent variable and HO as the independent variable. We compared Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores between participants with and those without HO at 24 months. RESULTS: Of 1,441 participants in the study, 287 (19.9%) developed HO within 24 months. HO was not associated with subsequent revision surgery. Grade-III HO was associated with statistically significant and clinically relevant deterioration in the total WOMAC score, which was mainly related to the function component of the score, compared with grade I or II. CONCLUSIONS: The impact of grade-III HO on the functional outcomes and quality of life after THA for hip fracture is clinically important, and HO prophylaxis for selected high-risk patients may be appropriate. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Femoral Neck Fractures/surgery , Ossification, Heterotopic/epidemiology , Postoperative Complications/epidemiology , Reoperation/statistics & numerical data , Arthroplasty, Replacement, Hip/statistics & numerical data , Female , Follow-Up Studies , Humans , Male , Middle Aged , Ossification, Heterotopic/diagnosis , Ossification, Heterotopic/etiology , Ossification, Heterotopic/surgery , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/surgery , Prevalence , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic , Risk Factors , Severity of Illness Index , Treatment Outcome
10.
J Orthop Trauma ; 34 Suppl 3: S29-S36, 2020 11.
Article in English | MEDLINE | ID: mdl-33027163

ABSTRACT

BACKGROUND: Total hip arthroplasty (THA) has been argued to improve health-related quality of life (HRQoL) and function in femoral neck fracture patients compared with hemiarthroplasty (HA). The HEALTH trial showed no clinically important functional advantages of THA over HA. The current analysis explores factors associated with HRQoL and function in this population. METHODS: Using repeated measures regression, we estimated the association between HRQoL and function [Short Form-12 (SF-12) physical component score (PCS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score] and 23 variables. RESULTS: THA as compared to monopolar HA, but not bipolar HA, was more likely to improve PCS scores (adjusted mean difference [AMD] 1.88 points, P = 0.02), whereas higher American Society of Anesthesiologists score (AMD -2.64, P < 0.01), preoperative use of an aid (AMD -2.66, P < 0.01), and partial weight-bearing status postoperatively (AMD -1.38, P = 0.04) demonstrated less improvement of PCS scores over time. THA improved WOMAC function scores over time compared with monopolar HA (but not bipolar HA) (AMD -2.40, P < 0.01), whereas higher American Society of Anesthesiologists classification (AMD 1.99, P = 0.01) and preoperative use of an aid (AMD 5.39, P < 0.01) were associated with lower WOMAC function scores. Preoperative treatment for depression was associated with lower functional scores (AMD 7.73, P < 0.01). CONCLUSION: Patients receiving THA are likely to receive small and clinically unimportant improvements in health utility and function compared with those receiving monopolar HA and little improvement compared with those receiving bipolar HA. Patient-specific characteristics seem to play a larger role in predicting functional improvement among femoral neck fracture patients. LEVEL OF EVIDENCE: Prognostic Level II.


Subject(s)
Arthroplasty, Replacement, Hip , Femoral Neck Fractures , Hemiarthroplasty , Femoral Neck Fractures/surgery , Humans , Quality of Life , Treatment Outcome
11.
J Orthop Trauma ; 34 Suppl 3: S15-S21, 2020 11.
Article in English | MEDLINE | ID: mdl-33027161

ABSTRACT

BACKGROUND: Hip fractures are recognized as one of the most devastating injuries impacting older adults because of the complications that follow. Mortality rates postsurgery can range from 14% to 58% within one year of fracture. We aimed to identify factors associated with increased risk of mortality within 24 months of a femoral neck fracture in patients aged ≥50 years enrolled in the FAITH and HEALTH trials. METHODS: Two multivariable Cox proportional hazards regressions were used to investigate potential prognostic factors that may be associated with mortality within 90 days and 24 months of hip fracture. RESULTS: Ninety-one (4.1%) and 304 (13.5%) of 2247 participants died within 90 days and 24 months of suffering a femoral neck fracture, respectively. Older age (P < 0.001), lower body mass index (P = 0.002), American Society of Anesthesiologists (ASA) class III/IV/V (P = 0.004), use of an ambulatory aid before femoral neck fracture (P < 0.001), and kidney disease (P < 0.001) were associated with a higher risk of mortality within 24 months of femoral neck fracture. Older age (P = 0.03), lower body mass index (P = 0.02), use of an ambulatory aid before femoral neck fracture (P < 0.001), and having a comorbidity (P = 0.04) were associated with a higher risk of mortality within 90 days of femoral neck fracture. CONCLUSIONS: Our analysis found that factors that are indicative of a poorer health status were associated with a higher risk of mortality within 24 months of femoral neck fracture. We did not find a difference in treatment methods (internal fixation vs. joint arthroplasty) on the risk of mortality. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Arthroplasty, Replacement, Hip , Femoral Neck Fractures , Hip Fractures , Aged , Femoral Neck Fractures/surgery , Fracture Fixation, Internal , Hip Fractures/surgery , Humans , Retrospective Studies , Risk Factors
12.
J Orthop Trauma ; 34 Suppl 3: S22-S28, 2020 11.
Article in English | MEDLINE | ID: mdl-33027162

ABSTRACT

BACKGROUND: Hip fracture trials often suffer substantial loss to follow-up due to difficulties locating and communicating with participants or when participants, or their family members, withdraw their consent. We aimed to determine which factors were associated with being unable to contact FAITH and HEALTH participants for their 24-month follow-up and to also determine which factors were associated with their withdrawal of consent. METHODS: We conducted 2 multivariable logistic regression analyses to determine which factors were predictive of being unable to contact participants at 24 months postfracture and withdrawal of consent within 24 months of their fracture. Results were reported as odds ratios, 95% confidence intervals, and associated P-values. All tests were 2-tailed with alpha = 0.05. RESULTS: We were unable to contact 123 of 2520 participants (4.9%) for their 24-month follow-up visits and 124 (4.9%) withdrew their consent from the trial. Being non-White (P = 0.003), enrolled from a non-European hospital (P < 0.001), and treated with arthroplasty (P < 0.001) were associated with an increased odds of not completing the 24-month follow-up visit. Being enrolled from a hospital in the United States (P = 0.02), from a hospital in Oceania, India, or South Africa (P < 0.001) as compared to a European hospital, and treated with arthroplasty (P < 0.001) were associated with an increased odds of consent withdrawal. DISCUSSION: Certain factors may be predictive of loss to follow-up in hip fracture trials. We suggest that the identification of such factors may be used to inform and improve retention strategies in future orthopaedic hip fracture trials. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Hip Fractures , Orthopedics , Follow-Up Studies , Hip Fractures/epidemiology , Hip Fractures/surgery , Humans , India , Odds Ratio , United States
13.
Injury ; 51(11): 2449-2459, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32829895

ABSTRACT

The Wnt/ß-catenin signaling pathway is critical for bone differentiation and regeneration. Tideglusib, a selective FDA approved glycogen synthase kinase-3ß (GSK-3ß) inhibitor, has been shown to promote dentine formation, but its effect on bone has not been examined. Our objective was to study the effect of localized Tideglusib administration on bone repair. Bone healing between Tideglusib treated and control mice was analysed at 7, 14 and 28 days postoperative (PO) with microCT, dynamic histomorphometry and immunohistology. There was a local downregulation of GSK-3ß in Tideglusib animals, resulting in a significant increase in the amount of new bone formation with both enhanced cortical bone bridging and medullary bone deposition. The bone formation in the Tideglusib group was characterized by early osteoblast differentiation with down-regulation of GSK-3ß at day 7 and 14, and higher accumulation of active ß-catenin at day 14. Here, for the first time, we show a positive effect of Tideglusib on bone formation through the inactivation of GSK-3ß. Furthermore, the findings suggest that Tideglusib does not interfere with precursor cell recruitment and commitment, contrary to other GSK-3ß antagonists such as lithium chloride. Taken together, the results indicate that Tideglusib could be used directly at a fracture site during the initial intraoperative internal fixation without the need for further surgery, injection or drug delivery system. This FDA-approved drug may be useful in the future for the prevention of non-union in patients presenting with a high risk for fracture-healing.


Subject(s)
Pharmaceutical Preparations , beta Catenin , Animals , Bone Regeneration , Bone and Bones , Glycogen Synthase Kinase 3 beta , Humans , Mice
14.
Bone ; 138: 115491, 2020 09.
Article in English | MEDLINE | ID: mdl-32569871

ABSTRACT

Genetic studies have been instrumental in the field of orthopaedics for finding tools to improve the standard management of fractures and delayed unions. The Wnt signaling pathway that is crucial for development and maintenance of many organs also has a very promising pathway for enhancement of bone regeneration. The Wnt pathway has been shown to have a direct effect on stem cells during bone regeneration, making Wnt a potential target to stimulate bone repair after trauma. A more complete view of how Wnt influences animal bone regeneration has slowly come to light. This review article provides an overview of studies done investigating the modulation of the canonical Wnt pathway in animal bone regeneration models. This not only includes a summary of the recent work done elucidating the roles of Wnt and ß-catenin in fracture healing, but also the results of thirty transgenic studies, and thirty-eight pharmacological studies. Finally, we discuss the discontinuation of sclerostin clinical trials, ongoing clinical trials with lithium, the results of Dkk antibody clinical trials, the shift into combination therapies and the future opportunities to enhance bone repair and regeneration through the modulation of the Wnt signaling pathway.


Subject(s)
Fractures, Bone , beta Catenin , Animals , Bone Regeneration , Fracture Healing , Stem Cells/metabolism , Wnt Signaling Pathway , beta Catenin/metabolism
15.
Mil Med ; 185(Suppl 1): 77-81, 2020 01 07.
Article in English | MEDLINE | ID: mdl-32074299

ABSTRACT

INTRODUCTION: Acute compartment syndrome (ACS) is a well-recognized and common emergency. Undiagnosed ACS leads to muscle necrosis, limb contracture, intractable pain, and may even result in amputation. METHODS: Three devices (Synthes, Stryker, and MY01) were compared in a pre-clinical rat abdominal compartment syndrome simulation. Simultaneous measurements of intracompartmental pressures allowed concurrent comparison among all devices. RESULTS: Large variations from the reference values are seen with the Synthes and Stryker devices. Variances are large in these two devices even under ideal conditions. The MY01 device was the truest indicator of reference pressure in this ACS model (over 600% more accurate). CONCLUSIONS: The MY01 device was the most accurate device in tracking pressure changes in this rat model of abdominal compartment syndrome.


Subject(s)
Compartment Syndromes/classification , Equipment Design/standards , Pressure , Weights and Measures/standards , Animals , Compartment Syndromes/diagnosis , Compartment Syndromes/physiopathology , Disease Models, Animal , Equipment Design/statistics & numerical data , Hemorrhage/physiopathology , Hemorrhage/surgery , Rats, Sprague-Dawley , Weights and Measures/instrumentation , Wounds and Injuries/complications
16.
Tissue Eng Part A ; 25(7-8): 554-562, 2019 04.
Article in English | MEDLINE | ID: mdl-30187830

ABSTRACT

IMPACT STATEMENT: A variety of biological, mechanical, and physical therapeutic modalities of varying complexity, efficacy, cost, and safety profile have been developed to enhance bone healing. There have been sporadic reports of spontaneous bone formation after repeated cold exposure. In this study we report for the first time, the anabolic effect of cold exposure on bone healing in vivo resulting in a doubling of bone volume. Although the precise mechanism is not fully understood, cold is well known to stimulate osteoclastogenesis and modulate inflammation. The impact of this finding is considerable for tissue regeneration because cold application is noninvasive, safe, and easily implemented.


Subject(s)
Osteoclasts/cytology , Anabolic Agents , Animals , Bone Regeneration/physiology , Cryotherapy , Hypoxia/metabolism , Inflammation/metabolism , Mice , Neovascularization, Physiologic/physiology , Osteoclasts/metabolism , Osteogenesis/physiology
17.
Angew Chem Int Ed Engl ; 55(18): 5452-6, 2016 04 25.
Article in English | MEDLINE | ID: mdl-27010510

ABSTRACT

Metabolic sugar labeling followed by the use of reagent-free click chemistry is an established technique for in vitro cell targeting. However, selective metabolic labeling of the target tissues in vivo remains a challenge to overcome, which has prohibited the use of this technique for targeted in vivo applications. Herein, we report the use of targeted ultrasound pulses to induce the release of tetraacetyl N-azidoacetylmannosamine (Ac4 ManAz) from microbubbles (MBs) and its metabolic expression in the cancer area. Ac4 ManAz-loaded MBs showed great stability under physiological conditions, but rapidly collapsed in the presence of tumor-localized ultrasound pulses. The released Ac4 ManAz from MBs was able to label 4T1 tumor cells with azido groups and significantly improved the tumor accumulation of dibenzocyclooctyne (DBCO)-Cy5 by subsequent click chemistry. We demonstrated for the first time that Ac4 ManAz-loaded MBs coupled with the use of targeted ultrasound could be a simple but powerful tool for in vivo cancer-selective labeling and targeted cancer therapies.


Subject(s)
Azides/administration & dosage , Breast Neoplasms/diagnostic imaging , Click Chemistry/methods , Drug Delivery Systems/methods , Hexosamines/administration & dosage , Microbubbles , Animals , Azides/analysis , Azides/metabolism , Breast/diagnostic imaging , Breast/metabolism , Breast Neoplasms/metabolism , Carbocyanines/analysis , Cell Line, Tumor , Female , Fluorescent Dyes/analysis , Hexosamines/analysis , Hexosamines/metabolism , Mice, Inbred BALB C , Optical Imaging/methods , Ultrasonography, Mammary
18.
J Ultrasound Med ; 34(8): 1363-72, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26206822

ABSTRACT

OBJECTIVES: A protocol was designed to produce albumin-coated microbubbles (MBs) loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug delivery studies. METHODS: Microbubbles resulted from the sonication of 5% bovine serum albumin and 15% dextrose solution. Functionalized NPs were produced by mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates. Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs were produced and compared. Statistical evaluations were based on quantitative analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB fabrication): MB diameter using a circle detection routine based on the Hough transform, MB number density using a hemocytometer, and NP-loading yield based on MB counts from fluorescence and light microscopic images. Loading capacity of the albumin-coated MBs was evaluated by fluorescence. RESULTS: Loaded MB sizes were stable over 6 days after production and were not significantly different from that of time-matched unloaded MBs. Number density evaluation showed that only 1/1 NP/MB volume ratio and unloaded MB number densities were stable over time, and that the 1/1 MB number density evaluated at each time point was not significantly different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had unstable number densities that were significantly different from that of unloaded MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP-loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested that the 1/1 MBs had a loading capacity of 3700 NPs/MB. CONCLUSIONS: A protocol was developed to load albumin MBs with functionalized PLA NPs for further drug delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to produce stable loaded MBs with a loading capacity of 3700 NPs/MB.


Subject(s)
Coated Materials, Biocompatible/chemical synthesis , Delayed-Action Preparations/chemistry , Nanocapsules/chemistry , Polyesters/chemistry , Serum Albumin/chemistry , Sonication/methods , Coated Materials, Biocompatible/radiation effects , Delayed-Action Preparations/radiation effects , Drug Design , Materials Testing , Microbubbles , Nanocapsules/administration & dosage , Nanocapsules/radiation effects , Serum Albumin/radiation effects , Ultrasonic Waves
19.
Nat Prod Commun ; 9(2): 257-60, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24689304

ABSTRACT

The chemical composition of Populus balsamifera essential oils obtained from spring buds, fall buds, and young leaves were determined by GC and GC-MS analyses. The major constituent, (+)-alpha-bisabolol, a rare sesquiterpene, was isolated from spring oil using reverse-phase preparative HPLC. The cytotoxic activity of balsam poplar oils and isolated (+)-alpha-bisabolol was assessed in vitro against human lung carcinoma (A549) and colorectal adenocarcinoma (DLD-1) cell lines. Essential oils were cytotoxic with IC50 ranging from 35 to 50 microg/mL. (+)-alpha-Bisabolol exhibited pronounced activity (IC50 14 microg/mL) against both cancer cell lines. It also exhibited interesting cytotoxic activity (IC50 23 microg/mL) against human glioma (U251), higher than the one observed for (-)-alpha-bisabolol (IC50 34 microg/mL), which is known for its apoptosis-inducing effect against glioma cells.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Oils, Volatile/analysis , Oils, Volatile/pharmacology , Populus/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Chromatography, High Pressure Liquid , Humans
20.
Can J Neurol Sci ; 40(5): 705-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23968945

ABSTRACT

OBJECTIVES: The Neuromuscular Registry of Saguenay-Lac-Saint-Jean (SLSJ), Québec, Canada was established for epidemiological surveillance of neuromuscular disorders including amyotrophic lateral sclerosis (ALS). The objectives of this study are to analyze the ALS clinical characteristics of the SLSJ population and to determine the incidence rate over time by five year periods since 1985. METHODS: The Registry was validated by a review of the medical records maintained at the CSSS de Chicoutimi, the regional university hospital and, by the estimation of the number of hospitalizations for ALS patients using the Quebec Hospital inpatient database (MED-ECHO). RESULTS: A total of 109 patients were included. Overall, the clinical features of ALS observed in SLSJ population are similar to those described in the literature. We observed a significant increase in the incidence rate of ALS during the 2005-2009 period compared with the previous periods. This is due to a significant increase in the incidence rate among the ≥65 years old group, from 4.68 per 100,000 persons/year (CI 95% 2.88-6.48) during 1985-2004 period to 12.22 (CI 95% 7.43-17.02) during 2005-2009 period. CONCLUSION: Given the small size of the SLSJ population, a longer observation period will be needed to confirm a new steady state incidence of ALS in this region.


Subject(s)
Amyotrophic Lateral Sclerosis/epidemiology , Epidemiological Monitoring , Adult , Age Factors , Age of Onset , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Quebec/epidemiology , Registries , Retrospective Studies
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