Real-time Reconstruction of Comminuted Mandibular Fractures Using 3D Printing.

Background: Comminuted fractures of the jaws are complex injuries requiring special attention. In the past, treatment included closed reduction using maxillomandibular fixation. With advancements in technology and fixation systems, open reduction became a prevalent option. These fractures are difficult to reconstruct during the primary treatment phase, thus resulting in higher complication rates. The introduction of three-dimensional (3D) planning and printing brought about superior outcomes, yet these focus on secondary reconstruction due to the need for outsourcing planning and titanium printing. Methods: In this report, we describe real-time in-house 3D planning and printing using computer-assisted design software and a 3D-fused deposition printer for virtual reduction of the comminuted fractures and printing of the reconstructed mandible. Results: Following virtual 3D reduction, the newly created mandibles were 3D printed. The model was then used to preband a reconstruction plate, which in turn was used as a template during surgery for reducing the segments. The process of virtual reduction and printing should take a couple of hours at most. The results of five cases showed good alignment and proper function. Conclusion: Three-dimensional technology can be applied in the everyday primary care treatment protocol of comminuted fractures as an in-house tool which greatly improves both functional and aesthetic outcomes.

Regeneration of injured articular cartilage using the recombinant human amelogenin protein.

Aims: Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model. Methods: A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 µg/µl recombinant human amelogenin protein (rHAM+) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 µg/µl rHAM+ using immunohistochemistry and immunofluorescence. Results: A total of 12 weeks after treatment, 0.5 µg/µl rHAM+ brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment. Conclusion: We found that 0.5 µg/µl rHAM+ induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment.

Enterococci in Diabetic Foot Infections: Prevalence, Clinical Characteristics, and Outcomes.

Background: Diabetic foot infections (DFIs) are frequently polymicrobial, yet the relevance of each isolated pathogen, remains ill-defined. Specifically, the prevalence and pathogenicity of enterococcal DFIs and the impact of targeted antienterococcal treatment remain elusive. Methods: We collected demographic, clinical, and outcome-related data on patients admitted with DFIs to the Hadassah Medical Center diabetic foot unit between 2014 and 2019. The primary outcome was a composite of in-hospital death or major amputation. Secondary outcomes included any amputation, major amputation, length of stay (LOS), and 1-year major amputation or mortality rate. Results: Enterococci were isolated in 35% of 537 eligible DFI case patients, who were notable for a higher prevalence of peripheral vascular disease, increased levels of C-reactive protein, and higher Wagner scores. Infection in enterococci-positive individuals was mostly polymicrobial (96.8% vs 61.0% in non-enterococci-infected patients; P < .001). Enterococci-infected patients were more likely to undergo amputation (72.3% vs 50.1%; P < .001) and had longer hospital stays (median LOS, 22.5 vs 17 days; P < .001), but the primary end point of major amputation or in-hospital death did not differ between groups (25.5% vs 21.0%; P = .26). Appropriate antienterococcal antibiotics were used in 78.1% of enterococci-infected patients and, compared with results in untreated patients, were associated with a trend toward a lower rate of major amputations (20.4% vs 34.1%; P = .06) but longer hospitalization (median LOS, 24 vs 18 days; P = .07). Conclusions: Enterococci are common in DFIs and associated with higher rates of amputation and longer hospitalization. A reduction in major amputation rates with appropriate enterococci treatment is suggested retrospectively, meriting validation by future prospective studies.

Acute diabetic foot in post kidney transplantation patients receiving chronic immunosuppression-clinical presentation and outcomes.

AIMS: Data regarding diabetic foot ulcers in patients after solid organ transplantation, particularly kidney transplantation, are limited. Chronic immunosuppression may be associated with impaired wound healing and a higher risk of amputations. In this study, we characterised the clinical presentation and outcomes of patients after kidney transplantation admitted to the diabetic foot unit, compared to non-kidney-transplant patients. MATERIALS AND METHODS: Data on the baseline characteristics, clinical presentation, and outcomes of all patients admitted to the diabetic foot unit of a large tertiary centre between the years 2014 and 2019 were collected. The most recent admission of each patient was considered. Primary outcomes were major amputations and 1 year mortality rate. RESULTS: During the study period, 537 patients were hospitalised, 18 of them were receiving immunosuppressive therapy due to kidney transplantation. Baseline characteristics of the patients were broadly similar, except that smoking was reported by 22.0% of the non-transplant patients and by none of the post-transplant patients (p = 0.01). Post-transplant patients tended to be younger (59.4 ± 11.1 vs. 65.3 ± 12.2; p = 0.07), were more likely to have type-1 diabetes (16.7% vs. 5.2%; p = 0.07) and had lower glucose levels upon admission (9.4 ± 4.3 vs. 12.0 ± 6.4 mmol/L; p = 0.07). Overall, 30% of the patients underwent major amputation, in-patient mortality rate was 9.3%, and 1 year mortality rate was 27.2%. Rates were similar in the post-transplant versus the non-post-transplant patients (p = 0.83, 1.00, 0.59, respectively). CONCLUSIONS: Post-transplant patients did not incur worse outcomes in spite of immunosuppressive therapy. Limb salvage efforts should be pursued in these patients similar to the overall population.

Treatment of diabetic foot ulcers in a frail population with severe co-morbidities using at-home photobiomodulation laser therapy: a double-blind, randomized, sham-controlled pilot clinical study.

PURPOSE: To evaluate the safety and efficacy of an at-home photobiomodulation (PBM) device for the treatment of diabetic foot ulcers (DFUs) in a frail population with severe comorbidities. METHODS: Prospective, randomized, double-blind, sham-controlled pilot study. Patients (age = 63 ± 11 years, male:female 13:7) with insulin-dependent diabetes type 2, neuropathy, peripheral artery disease, significant co-morbidities, and large osteomyelitis-associated DFUs (University of Texas grade ≥ III) were randomized to receive active (n = 10) or sham (n = 10) at-home daily PBM treatments (pulsed near-infrared 808 nm Ga-Al-As laser, 250 mW, 8.8 J/cm2) for up to 12 weeks in addition to standard care. The primary outcome was the %wound size reduction. The secondary was adverse events. RESULTS: With the numbers available, PBM-treated group had significantly greater %reduction compared to sham (area [cm2], baseline vs endpoint: PBM 10[20.3] cm2 vs 0.2[2.4] cm2; sham, 7.9 [12.0] cm2 vs 4.6 [13.8] cm2, p = 0.018 by Mann-Whitney U test). Wound closure > 90% occurred in 7 of 10 PBM-treated patients but in only 1 of 10 sham patients (p = 0.006). No adverse device effects were observed. CONCLUSIONS: Photobiomodulation at home, in addition to standard care, may be effective for the treatment of severe DFUs in frail patients with co-morbidities and is particularly relevant at these times of social distancing. Our preliminary results justify the conduction of a larger clinical trial. CLINICALTRIALS: gov: NCT01493895.

Predictors and outcomes of diabetic foot ulcer infection with ESBL-producing bacteria in a large tertiary center.

OBJECTIVES: The aim of this study was to describe the predictors and outcomes of infection with extended-spectrum beta-lactamase (ESBL)-producing bacteria in patients with an acute diabetic foot infection (DFI). METHODS: The records of patients admitted with acute DFI to a large tertiary hospital during the years 2014-2018 were reviewed. Demographic, clinical, and laboratory data were collected, as well as outcomes regarding amputations and mortality. Only cultures obtained during the first 2 weeks following admission were considered. RESULTS: Cultures were available for 493 patients; 121 (24.5%) included bacteria suspected of being ESBL producers. Patients infected with ESBL-producing bacteria were older, more likely to have peripheral vascular disease (PVD), and had higher SINBAD and Wagner scores upon admission. They were also more likely to have been hospitalized in the recent 6 months. Major amputations were more prevalent in patients with versus without an ESBL-producing bacterial infection (30.6% vs 19.4%; P = 0.010), yet overall amputations and mortality rates were similar. CONCLUSIONS: ESBL-producing bacteria are common pathogens in DFI, more prevalent in older patients with PVD, advanced ulcers, and recent hospitalization. They are associated with higher rates of major amputation. These considerations may support the choice of empirical antibiotic therapy in patients admitted with an acute DFI.

[HOSPITALIZATIONS DUE TO ACUTE DIABETIC FOOT: ANNUAL TRENDS AND PREDICTORS OF MORBIDITY AND MORTALITY - 5-YEARS EXPERIENCE OF A MULTIDISCIPLINARY UNIT].

INTRODUCTION: Since 2012, patients presenting to our hospital with an acute diabetic foot are hospitalized in a dedicated unit. This study describes patients' characteristics and trends in amputations, procedures and mortality during the years 2014-2018. METHODS: We retrospectively reviewed the electronic medical records of 694 patients admitted to the unit during the study period. We collected demographic, clinical and laboratory data, procedures and outcomes. Annual trends were studied as well as predictors to any or major amputation and to mortality within 1 year following discharge. RESULTS: The mean age was 63.8±12.7 years and 75.4% of the patients were male. There was a high prevalence of neuropathy, peripheral artery disease and ischemic heart disease (55.3%, 66.1% and 44.2% respectively). Previous hospitalization was noted for 62.0% of the patients and 38.3% had undergone a previous amputation. The majority of the patients had chronic kidney disease and 19.0% were dialysis patients. During hospitalization, 54.3% of the patients underwent any amputation, 25.2% had a major amputation and 6.2% died. The mortality rate within 1 year of discharge was 24.5%. There were no changes in patient demographics, characteristics or outcomes during the study years, although an increase in the proportion of patients who had undergone previous amputation, and of current smokers in recent years was noted. Moreover, in recent years more vascular procedures and surgical procedures in the operating room were performed. Older age, recent hospitalization, previous amputation, neuropathy, ischemic heart disease, peripheral vascular disease, chronic renal insufficiency, elevated inflammatory markers, a progressive ulcer, and a midfoot or hindfoot (vs. forefoot) ulcer were all associated with major amputations. CONCLUSIONS: During the study period, patients' characteristics remained generally stable as did amputation and mortality rates. The high 1-year mortality rate of this population is indicative of these patients' significant morbidity.

Angiogenic potential of mesenchymal stem cells derived from patients with diabetes seeded on decellularized micro fragments.

Mesenchymal stem cells (MSCs) are a potential source of angiogenic factors which may promote wound healing in poorly vascularized diabetic foot ulcers. We demonstrate that MSCs of patients with diabetic foot ulcers seeded on decellularized micro-fragments transcribe and secrete angiogenic factors in amounts comparable to MSCs derived from healthy individuals.

Regeneration of grade 3 ankle sprain, using the recombinant human amelogenin protein (rHAM+ ) in a rat model.

Lateral ligament tears, also known as high-grade ankle sprains, are common, debilitating, and usually heal slowly. Ten to thirty percent of patients continue to suffer from chronic pain and ankle instability even after 3 to 9 months. Previously, we showed that the recombinant human amelogenin (rHAM+ ) induced regeneration of fully transected rat medial collateral ligament, a common proof-of-concept model. Our aim was to evaluate whether rHAM+ can regenerate torn ankle calcaneofibular ligament (CFL), an important component of the lateral ankle stabilizers. Right CFLs of Sabra rats were transected and treated with 0, 0.5, or 1 µg/µL rHAM+ dissolved in propylene glycol alginate (PGA). Results were compared with the normal group, without surgery. Healing was evaluated 12 weeks after treatment by mechanical testing (ratio between the right and left, untransected ligaments of the same rat), and histology including immunohistochemical staining of collagen I and S100. The mechanical properties, structure, and composition of transected ligaments treated with 0.5 µg/µL rHAM+ (experimental) were similar to untransected ligaments. PGA (control) treated ligaments were much weaker, lax, and unorganized compared with untransected ligaments. Treatment with 1 µg/µL rHAM+ was not as efficient as 0.5 µg/µL rHAM+ . Normal arrangement of collagen I fibers and of proprioceptive nerve endings, parallel to the direction of the force, was detected in ligaments treated with 0.5 µg/µL rHAM+ , and scattered arrangement, resembling scar tissue, in control ligaments. In conclusion, we showed that rHAM+ induced significant mechanical and structural regeneration of torn rat CFLs, which might be translated into treatment for grades 2 and 3 ankle sprain injuries.

Serum NT/CT SIRT1 ratio reflects early osteoarthritis and chondrosenescence.

OBJECTIVE: Previous work has established that the deacetylase sirtuin-1 (SIRT1) is cleaved by cathepsin B in chondrocytes subjected to proinflammatory stress, yielding a stable but inactive N-terminal (NT) polypeptide (75SIRT1) and a C-terminal (CT) fragment. The present work examined if chondrocyte-derived NT-SIRT1 is detected in serum and may serve as an investigative and exploratory biomarker of osteoarthritis (OA). METHODS: We developed a novel ELISA assay to measure the ratio of NT to CT of SIRT1 in the serum of human individuals and mice subjected to post-traumatic OA (PTOA) or age-dependent OA (ADOA). We additionally monitored NT/CT SIRT1 in mice subject to ADOA/PTOA followed by senolytic clearance. Human chondrosenescent and non-senescent chondrocytes were exposed to cytokines and analysed for apoptosis and NT/CT SIRT1 ratio in conditioned medium. RESULTS: Wild-type mice with PTOA or ADOA of moderate severity exhibited increased serum NT/CT SIRT1 ratio. In contrast, this ratio remained low in cartilage-specific Sirt1 knockout mice despite similar or increased PTOA and ADOA severity. Local clearance of senescent chondrocytes from old mice with post-traumatic injury resulted in a lower NT/CT ratio and reduced OA severity. While primary chondrocytes exhibited NT/CT ratio increased in conditioned media after prolonged cytokine stimulation, this increase was not evident in cytokine-stimulated chondrosenescent cells. Finally, serum NT/CT ratio was elevated in humans with early-stage OA. CONCLUSIONS: Increased levels of serum NT/CT SIRT1 ratio correlated with moderate OA in both mice and humans, stemming at least in part from non-senescent chondrocyte apoptosis, possibly a result of prolonged inflammatory insult.