Automatic Detection of Perilunate and Lunate Dislocations on Wrist Radiographs Using Deep Learning.

SUMMARY: Delayed or missed diagnosis of perilunate or lunate dislocations can lead to significant morbidity. Advances in computer vision provide an opportunity to improve diagnostic performance. In this study, a deep learning algorithm was utilized for detection of perilunate and lunate dislocations on lateral wrist radiographs. A total of 435 lateral wrist radiographs were labeled as normal or pathologic (perilunate or lunate dislocation). The lunate in each radiograph was segmented with a rectangular bounding box. Images were partitioned into training and test sets. Two neural networks, consisting of an object detector followed by an image classifier, were applied in series. First, the object detection module was used to localize the lunate. Next, the image classifier performed a binary classification for normal or pathologic. The accuracy, sensitivity, and specificity of the overall system were evaluated. A receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) were used to demonstrate the overall performance of the computer vision algorithm. The lunate object detector was 97.0% accurate at identifying the lunate. Accuracy was 98.7% among the sub-group of normal wrist radiographs, and 91.3% among the sub-group of wrist radiographs with perilunate/lunate dislocations. The perilunate/lunate dislocation classifier had a sensitivity (recall) of 93.8%, specificity of 93.3%, and accuracy of 93.4%. The AUC was 0.986. We have developed a proof-of-concept computer vision system for diagnosis of perilunate/lunate dislocations on lateral wrist radiographs. This novel deep learning algorithm has potential to improve clinical sensitivity to ultimately prevent delayed or missed diagnosis of these injuries.

Hyperglycemic Ins2AkitaLdlr⁻/⁻ mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular disease.

Accelerated atherosclerosis is the leading cause of death in type 1 diabetes, but the mechanism of type 1 diabetes-accelerated atherosclerosis is not well understood, in part due to the lack of a good animal model for the long-term studies required. In an attempt to create a model for studying diabetic macrovascular disease, we have generated type 1 diabetic Akita mice lacking the low density lipoprotein receptor (Ins2(Akita)Ldlr⁻/⁻). Ins2(Akita)Ldlr⁻/⁻ mice were severely hyperglycemic with impaired glucose tolerance. Compared with Ldlr⁻/⁻ mice, 20-week-old Ins2(Akita)Ldlr⁻/⁻ mice fed a 0.02% cholesterol AIN76a diet showed increased plasma triglyceride and cholesterol levels, and increased aortic root cross-sectional atherosclerotic lesion area [224% (P < 0.001) in males and 30% (P < 0.05) in females]. Microarray and quantitative PCR analyses of livers from Ins2(Akita)Ldlr⁻/⁻ mice revealed altered expression of lipid homeostatic genes, including sterol-regulatory element binding protein (Srebp)1, liver X receptor (Lxr)α, Abca1, Cyp7b1, Cyp27a1, and Lpl, along with increased expression of pro-inflammatory cytokine genes, including interleukin (Il)1α, Il1ß, Il2, tumor necrosis factor (Tnf)α, and Mcp1. Immunofluorescence staining showed that the expression levels of Mcp1, Tnfα, and Il1ß were also increased in the atherosclerotic lesions and artery walls of Ins2(Akita)Ldlr⁻/⁻ mice. Thus, the Ins2(Akita)Ldlr⁻/⁻ mouse appears to be a promising model for mechanistic studies of type 1 diabetes-accelerated atherosclerosis.

Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet.

RATIONALE: The complications of atherosclerosis are a major cause of death and disability in type 2 diabetes. Defective clearance of apoptotic cells by macrophages (efferocytosis) is thought to lead to increased necrotic core formation and inflammation in atherosclerotic lesions. OBJECTIVE: To determine whether there is defective efferocytosis in a mouse model of obesity and atherosclerosis. METHODS AND RESULTS: We quantified efferocytosis in peritoneal macrophages and in atherosclerotic lesions of obese ob/ob or ob/ob;Ldlr(-/-) mice and littermate controls. Peritoneal macrophages from ob/ob and ob/ob;Ldlr(-/-) mice showed impaired efferocytosis, reflecting defective phosphatidylinositol 3-kinase activation during uptake of apoptotic cells. Membrane lipid composition of ob/ob and ob/ob;Ldlr(-/-) macrophages showed an increased content of saturated fatty acids (FAs) and decreased omega-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) compared to controls. A similar defect in efferocytosis was induced by treating control macrophages with saturated free FA/BSA complexes, whereas the defect in ob/ob macrophages was reversed by treatment with eicosapentaenoic acid/BSA or by feeding ob/ob mice a fish oil diet rich in omega-3 FAs. There was also defective macrophage efferocytosis in atherosclerotic lesions of ob/ob;Ldlr(-/-) mice and this was reversed by a fish oil-rich diet. CONCLUSIONS: The findings suggest that in obesity and type 2 diabetes elevated levels of saturated FAs and/or decreased levels of omega-3 FAs contribute to decreased macrophage efferocytosis. Beneficial effects of fish oil diets in atherosclerotic cardiovascular disease may involve improvements in macrophage function related to reversal of defective efferocytosis and could be particularly important in type 2 diabetes and obesity.

Optimizing Treatment of Hand Infections: Is MRSA Coverage Always Necessary?

Multiple publications have highlighted the prevalence of methicillin resistant Staphylococcus aureus (MRSA) as a cause of hand infections. We hypothesized that these publications have shifted the empiric treatment of hand infections. The aim of this study was to identify the current standard of care, the most common causative bacteria, and factors leading to extended length of stay for hand infection patients at a suburban hospital to improve treatment and establish an optimized care protocol. METHODS: Retrospective cohort analysis was conducted to identify all patients admitted for hand infections over an 8-year period. A comprehensive chart review of each patient's hospital course was completed. RESULTS: A total of 70 patients were included. Maximum white blood cell count ≥ 12 was associated with a significantly longer hospital length of stay (9.1 days versus 5.4 days) compared to WBC values < 12 (P < 0.05). Also, 11 out of 23 (47.8%) underwent two or more incision and drainages (I&D's), compared with patients with maximum WBC < 12. Vancomycin use as an empiric antibiotic was widespread (68 patients, 97.1%), despite only 14 (20%) having MRSA positive cultures. Univariate analysis identified a significant increased likelihood for increased length of stay (P < 0.05) and rise in creatinine (P < 0.05) in patients with an initial vancomycin trough level > 20. CONCLUSIONS: This analysis of hand infection treatment in a suburban hospital demonstrates the incidence of MRSA hand infections may not be universally high across institutions. Each hospital should review its own data to optimize hand infection treatment and its associated costs.

The impact of skin allograft on inpatient outcomes in the treatment of major burns 20-50% total body surface area - A propensity score matched analysis using the nationwide inpatient sample.

BACKGROUND: Human cadaveric skin (allograft) is used in treating major burns both as temporizing wound coverage and a means of testing wound bed viability following burn excision. There is limited information on outcomes, and clinicians disagree on indications for application in intermediate-sized burns. This study aims to improve understanding of allograft use in 20-50% total body surface burns by assessing current utilization and evaluating inpatient outcomes. METHODS: Discharge data from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality assessed 3557 major burn patients (>second degree depth and 20-50% TBSA) undergoing operative treatment. Outcomes were evaluated with propensity score matching. The primary outcome was mortality with secondary outcomes including complications, length of stay, total burn operations, and charges. RESULTS: After matching, 771 allografted patients were paired with 1774 controls. Covariate mean standard differences were all <11% after matching. The average treatment effect (ATE) of allograft on inpatient mortality was an increase of 2.8% (95% CI 0.2-5.3%, p=0.041). Allograft ATEs were all significantly higher for secondary outcomes: composite complication index increased 0.13 (95% CI 0.07-0.20, p<0.001), length of stay 8.4days (95% CI 6.1-1.9 days, p<0.001), total burn operations 1.6 (95% CI 1.4-1.9, p<0.001), and total charges $139,476 [$100,716-178,236, p<0.001). CONCLUSIONS: Allograft use in major burns 20-50% TBSA was associated with a significant increase in inpatient mortality. There was a notable correlation with increased inpatient complications, longer length of stay, more burn operations, and greater total charges. Better studies are needed to justify the use of this costly and limited resource in the intermediate sized major burn population.

Retrospective cohort-based comparison of intraoperative liposomal bupivacaine versus bupivacaine for donor site iliac crest analgesia during alveolar bone grafting.

INTRODUCTION: Bone grafting of alveolar clefts is routinely performed with cancellous bone harvested from the iliac crest. Graft site morbidity is frequently seen, with early postoperative pain being one of the most common complaints. Liposomal bupivacaine (LB) has been demonstrated to provide improvement in postoperative pain for patients undergoing bunionectomy or hemorrhoidectomy, which may translate to patients requiring iliac crest bone graft harvest. METHODS: Thirty-eight patients undergoing iliac crest bone harvest were included in the study. Twenty-one patients underwent open iliac crest bone graft harvest with administration of 0.25% bupivacaine at the hip donor site, while 17 patients received local infiltration of 1.3% liposomal bupivacaine. Patient-reported pain scores, total narcotic use, length of stay, and postoperative steps were monitored. RESULTS: There were no significant differences in age, weight, distribution of clefts, or choice of donor hip between the two groups. There were no significant differences in length of hospitalization stay. However, differences were noted in average postoperative pain scores at five of six time points in the first 24 h, total oral morphine equivalents administered (4.7 ±â€¯5.3 vs. 14.3 ±â€¯12.0), and steps at postoperative days one to three (p < 0.001, for all three days) for patients receiving 1.3% LB versus 0.25% bupivacaine, respectively. CONCLUSION: Reduced pain scores and increased postoperative activity highlight the potential of LB to improve postoperative pain management in children undergoing iliac crest bone harvest for alveolar bone grafting.

Regional Variation and Trends in the Timing of Lower Extremity Reconstruction: A 10-Year Review of the Nationwide Inpatient Sample.

BACKGROUND: The ideal timing of soft-tissue coverage for open lower extremity fractures remains controversial. Using U.S. national data, this study aims to characterize secular trends and regional variation in the timing of soft-tissue coverage. METHODS: Using discharge data from the Nationwide Inpatient Sample (2002 to 2011), the authors identified 888 encounters admitted from the emergency department with isolated open lower extremity fractures treated with pedicled or free tissue transfer. Soft-tissue coverage timing was assessed by patient factors, hospital characteristics, and fracture patterns. Statistical significance and secular trends were analyzed with generalized linear models. RESULTS: The mean day of soft-tissue reconstruction was at 6.64 days. Over the 10-year period, the day of reconstruction increased significantly (from 6.12 days in 2002 to 12.50 days in 2011; coefficient, 0.09; 95 percent CI, 0.05 to 0.12; p < 0.001). Demographic and facility factors did not significantly impact timing. Elixhauser comorbidity scores greater than 2 were associated with later coverage (10.13 days versus 6.29 days; p = 0.001) along with multisite fractures (8.35 days; p = 0.022) and external fixators (8.78 days; p < 0.001). The U.S. Census division showed significant variation in timing ranging from 0.94 days (East North Central) to 9.84 days (Pacific). CONCLUSIONS: A progressive delay in the timing of soft-tissue reconstruction was noted and may be attributed to negative-pressure wound therapy. The timing of soft-tissue coverage varied by region after adjusting for patient and hospital factors. Additional studies are needed to understand the impact of delayed soft-tissue coverage on patient outcomes and health services utilization.

Overcoming the learning curve: a curriculum-based model for teaching zone II flexor tendon repairs.

BACKGROUND: Repairs of zone II flexor tendons have benefited in recent years from modifications involving suture technique and configuration. These advances, however, present new obstacles in resident training. A focused tutorial incorporating a practical, hands-on exercise and standardization of technique may offer an effective low-risk, low-cost strategy for overcoming these challenges. METHODS: Plastic surgery residents (n=14) were asked to perform their preferred zone II flexor tendon repair using a tabletop exercise before and after a focused tutorial. The tutorial reviewed primary literature and presented a standardized technique. Repairs were photographed, tested for load strength, and analyzed to determine effectiveness of this teaching approach. Participants were retested at 6 months to evaluate for persistence of findings. RESULTS: Posttutorial repairs required higher loads to generate a 2-mm gap (p<0.001) and ultimate breakage (p<0.001). Tendon purchase and resident confidence increased significantly. Subgroup analysis demonstrated significant improvements for both junior and senior residents. Retesting at 6 months revealed that gains were maintained over time. CONCLUSIONS: The authors created a practical educational model to teach zone II flexor tendon repair outside of the time- and error-sensitive confines of the operating room. Analysis of resident pretutorial repairs revealed common misconceptions in suture technique, strand count, and purchase. This may in part be attributable to the multitude of suggested repair techniques, difficulty in comparing data across multiple studies, and steep learning curve. Training programs can use this hands-on teaching exercise as part of a hand surgery simulation curriculum.

Human flexor tendon tissue engineering: decellularization of human flexor tendons reduces immunogenicity in vivo.

BACKGROUND: In mutilating hand injuries, tissue engineered tendon grafts may provide a reconstructive solution. We have previously described a method to decellularize cadaveric human flexor tendons while preserving mechanical properties and biocompatibility. The purpose of this study is to evaluate the immunogenicity and strength of these grafts when implanted into an immunocompetent rat model. METHODS: Cadaveric human flexor tendons were divided into two groups. Group 1 was untreated, and Group 2 was decellularized by treatment with sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), and peracetic acid (PAA). Both groups were then analyzed for the presence of major histocompatibility complexes by immunohistochemistry (IHC). Pair-matched tendons from each group were then placed into the dorsal subcutaneous tissue and anchored to the spinal ligaments of Wistar rats for 2 or 4 weeks, and harvested. The infiltration of B-cells and macrophages was determined using IHC. The explants where then subjected to mechanical testing to determine the ultimate tensile stress (UTS) and elastic modulus (EM). Statistical analysis was performed using a paired Student's t-test. RESULTS: The decellularization protocol successfully removed cells and MHC-1 complexes. At 2 weeks after implantation, there was increased infiltration of B-cells in Group 1 (untreated) compared with Group 2 (acellular), both in the capsule and tendon substance. There was improved ultimate tensile stress (UTS, 42.7 ± 8.3 vs. 22.8 ± 7.8 MPa, p<0.05) and EM (830.2 ± 206.7 vs. 421.2 ± 171.3 MPa, p<0.05) in tendons that were decellularized. At 4 weeks, there was continued B-cell infiltration in Group 1 (untreated) compared with Group 2 (acellular). There was no appreciable difference in macrophage infiltration at both time points. At 4 weeks Group 2 (acellular) demonstrated persistently greater UTS (40.5 ± 9.1 vs. 14.6 ± 4.2 MPa, p<0.05) and EM (454.05 ± 101.5 vs. 204.6 ± 91.3 MPa, p<0.05) compared with Group 1 (untreated). CONCLUSIONS: Human flexor tendons that were decellularized with SDS, EDTA, and PAA resulted in removal of cellular antigens and a decreased immune response when placed into Wistar rats. These grafts showed better mechanical properties at 2 and 4 weeks when compared with control tendons. Decellularization is an important step toward the use of tissue engineered flexor tendons in upper extremity reconstruction.

Flexor tendon tissue engineering: acellularization of human flexor tendons with preservation of biomechanical properties and biocompatibility.

OBJECTIVE: Acellular human tendons are a candidate scaffold for tissue engineering flexor tendons of the hand. This study compared acellularization methods and their compatibility with allogeneic human cells. METHOD: Human flexor tendons were pretreated with 0.1% ethylenediaminetetracetic acid (EDTA) for 4 h followed by 24 h treatments of 1% Triton X-100, 1% tri(n-butyl)phosphate, or 0.1% or 1% sodium dodecyl sulfate (SDS) in 0.1% EDTA. Outcomes were assessed histologically by hematoxylin and eosin and SYTO green fluorescent nucleic acid stains and biochemically by a QIAGEN DNeasy kit, Sircol collagen assay, and 1,9 dimethylmethylene blue glycosaminoglycan assay. Mechanical data were collected using a Materials Testing System to pull to failure tendons acellularized with 0.1% SDS. Acellularized tendons were re-seeded in a suspension of human dermal fibroblasts. Attachment of viable cells to acellularized tendon was assessed biochemically by a cell viability assay and histologically by a live/dead stain. Data are reported as mean±standard deviation. RESULT: Compared with the DNA content of fresh tendons (551±212 ng DNA/mg tendon), only SDS treatments significantly decreased DNA content (1% SDS [202.8±37.4 ng DNA/mg dry weight tendon]; 0.1% SDS [189±104 ng DNA/mg tendon]). These findings were confirmed by histology. There was no decrease in glycosaminoglycans or collagen following acellularization with SDS. There was no difference in the ultimate tensile stress (55.3±19.2 [fresh] vs. 51.5±6.9 [0.1% SDS] MPa). Re-seeded tendons demonstrated attachment of viable cells to the tendon surface using a viability assay and histology. CONCLUSION: Human flexor tendons were acellularized with 0.1% SDS in 0.1% EDTA for 24 h with preservation of mechanical properties. Preservation of collagen and glycoaminoglycans and re-seeding with human cells suggest that this scaffold is biocompatible. This will provide a promising scaffold for future human flexor tendon tissue engineering studies to further assess biocompatibility through cell proliferation and in vivo studies.

Three-dimensional-construct bioreactor conditioning in human tendon tissue engineering.

Human tendon tissue engineering attempts to address the shortage of autologous tendon material arising from mutilating injuries and diseases of the hand and forearm. It is important to maximize the tissue-engineered construct's (TEC's) biomechanical properties to ensure that the construct is in its strongest possible state before reimplantation. In this study, we sought to determine the bioreactor treatment parameters that affect these properties. Using small- and large-chamber three-dimensional-construct bioreactors (SCB and LCB, respectively), we applied cyclic axial load to TECs comprising reseeded human flexor and extensor tendons of the hand. First, small-sample pilot studies using the LCB were performed on matched-paired full-length flexor tendons to establish proof of concept. Next, large-sample studies using the SCB were performed on matched-paired extensor tendon segments to determine how reseeding, load duty cycle, load magnitude, conditioning duration, and testing delay affected ultimate tensile stress (UTS) and elastic modulus (EM). We found that compared with reseeded matched-paired controls under dynamic-loading at 1.25 N per TEC for 5 days, (1) acellular TECs had lower UTS (p=0.04) and EM (p<0.01), (2) unloaded TECs had lower UTS (p=0.01) and EM (p=0.02), (3) static-loaded TECs had lower UTS (p=0.01) and EM (p<0.01), (4) TECs conditioned for 3 days had lower UTS (p=0.03) and EM (p=0.04), and (5) TECs conditioned for 8 days had higher UTS (p=0.04) and EM (p=0.01). However, TECs conditioned at higher loads (2.5 N per TEC) and lower loads (0.625 N per TEC) possessed similar UTS (p=0.83 and p=0.89, respectively) and EM (p=0.48 and p=0.89, respectively) as controls stimulated with 1.25 N per TEC. After cycle completion, there is attrition of UTS (p=0.03) and EM (p=0.04) over a 2-day period. Our study showed that the material properties of human allograft TECs can be enhanced by reseeding and dynamic-conditioning. While conditioning duration has a significant effect on material properties, the load magnitude does not. The issue of attrition in biomechanical properties with time following cycle completion must be addressed before bioreactor preconditioning can be successfully introduced as a step in the processing of these constructs for clinical application.

Optimization of human tendon tissue engineering: peracetic acid oxidation for enhanced reseeding of acellularized intrasynovial tendon.

BACKGROUND: Tissue engineering of human flexor tendons combines tendon scaffolds with recipient cells to create complete cell-tendon constructs. Allogenic acellularized human flexor tendon has been shown to be a useful natural scaffold. However, there is difficulty repopulating acellularized tendon with recipient cells, as cell penetration is restricted by a tightly woven tendon matrix. The authors evaluated peracetic acid treatment in optimizing intratendinous cell penetration. METHODS: Cadaveric human flexor tendons were harvested, acellularized, and divided into experimental groups. These groups were treated with peracetic acid in varying concentrations (2%, 5%, and 10%) and for varying time periods (4 and 20 hours) to determine the optimal treatment protocol. Experimental tendons were analyzed for differences in tendon microarchitecture. Additional specimens were reseeded by incubation in a fibroblast cell suspension at 1 × 10(6) cells/ml. This group was then analyzed for reseeding efficacy. A final group underwent biomechanical studies for strength. RESULTS: The optimal treatment protocol comprising peracetic acid at 5% concentration for 4 hours produced increased scaffold porosity, improving cell penetration and migration. Treated scaffolds did not show reduced collagen or glycosaminoglycan content compared with controls (p = 0.37 and p = 0.65, respectively). Treated scaffolds were cytotoxic to neither attached cells nor the surrounding cell suspension. Treated scaffolds also did not show inferior ultimate tensile stress or elastic modulus compared with controls (p = 0.26 and p = 0.28, respectively). CONCLUSIONS: Peracetic acid treatment of acellularized tendon scaffolds increases matrix porosity, leading to greater reseeding. It may prove to be an important step in tissue engineering of human flexor tendon using natural scaffolds.