The 2023 Orthopaedic Research Society's International Consensus Meeting on musculoskeletal infection: Summary from the host immunity section.

Musculoskeletal infections (MSKI), which are a major problem in orthopedics, occur when the pathogen eludes or overwhelms the host immune system. While effective vaccines and immunotherapies to prevent and treat MSKI should be possible, fundamental knowledge gaps in our understanding of protective, nonprotective, and pathogenic host immunity are prohibitive. We also lack critical knowledge of how host immunity is affected by the microbiome, implants, prior infection, nutrition, antibiotics, and concomitant therapies, autoimmunity, and other comorbidities. To define our current knowledge of these critical topics, a Host Immunity Section of the 2023 Orthopaedic Research Society MSKI International Consensus Meeting (ICM) proposed 78 questions. Systematic reviews were performed on 15 of these questions, upon which recommendations with level of evidence were voted on by the 72 ICM delegates, and another 12 questions were voted on with a recommendation of "Unknown" without systematic reviews. Two questions were transferred to another ICM Section, and the other 45 were tabled for future consideration due to limitations of available human resources. Here we report the results of the voting with internet access to the questions, recommendations, and rationale from the systematic reviews. Eighteen questions received a consensus vote of ≥90%, while nine recommendations failed to achieve this threshold. Commentary on why consensus was not achieved on these questions and potential ways forward are provided to stimulate specific funding mechanisms and research on these critical MSKI host defense questions.

Evidence of Neutralizing and Non-Neutralizing Anti-Glucosaminidase Antibodies in Patients With S. Aureus Osteomyelitis and Their Association With Clinical Outcome Following Surgery in a Clinical Pilot.

Staphylococcus aureus osteomyelitis remains a very challenging condition; recent clinical studies have shown infection control rates following surgery/antibiotics to be ~60%. Additionally, prior efforts to produce an effective S. aureus vaccine have failed, in part due to lack of knowledge of protective immunity. Previously, we demonstrated that anti-glucosaminidase (Gmd) antibodies are protective in animal models but found that only 6.7% of culture-confirmed S. aureus osteomyelitis patients in the AO Clinical Priority Program (AO-CPP) Registry had basal serum levels (>10 ng/ml) of anti-Gmd at the time of surgery (baseline). We identified a small subset of patients with high levels of anti-Gmd antibodies and adverse outcomes following surgery, not explained by Ig class switching to non-functional isotypes. Here, we aimed to test the hypothesis that clinical cure following surgery is associated with anti-Gmd neutralizing antibodies in serum. Therefore, we first optimized an in vitro assay that quantifies recombinant Gmd lysis of the M. luteus cell wall and used it to demonstrate the 50% neutralizing concentration (NC50) of a humanized anti-Gmd mAb (TPH-101) to be ~15.6 µg/ml. We also demonstrated that human serum deficient in anti-Gmd antibodies can be complemented by TPH-101 to achieve the same dose-dependent Gmd neutralizing activity as purified TPH-101. Finally, we assessed the anti-Gmd physical titer and neutralizing activity in sera from 11 patients in the AO-CPP Registry, who were characterized into four groups post-hoc. Group 1 patients (n=3) had high anti-Gmd physical and neutralizing titers at baseline that decreased with clinical cure of the infection over time. Group 2 patients (n=3) had undetectable anti-Gmd antibodies throughout the study and adverse outcomes. Group 3 (n=3) had high titers +/- neutralizing anti-Gmd at baseline with adverse outcomes. Group 4 (n=2) had low titers of non-neutralizing anti-Gmd at baseline with delayed high titers and adverse outcomes. Collectively, these findings demonstrate that both neutralizing and non-neutralizing anti-Gmd antibodies exist in S. aureus osteomyelitis patients and that screening for these antibodies could have a value for identifying patients in need of passive immunization prior to surgery. Future prospective studies to test the prognostic value of anti-Gmd antibodies to assess the potential of passive immunization with TPH-101 are warranted.

Computational analysis of Lisfranc surgical repairs.

Ligamentous Lisfranc injuries cause debilitating pain and loss of function. Even small diastasis of this normally rigid joint after injury requires surgical treatment, but outcomes remain poor. Existing literature has compared the different surgical procedures using cadaveric models, but no approach has been recommended over others. This study uses a computational biomechanical approach consistent with a cadaveric study to evaluate the different procedures' ability to stabilize the Lisfranc joint without inducing secondary consequences. A validated rigid body model for the cadaver foot with a Lisfranc injury was extended to compare the stability of four different surgical repairs-three open reduction and internal fixation procedures with different hardware (cannulated screws, endobuttons, and screws with a dorsal plate) and primary arthrodesis with screws. Forces calculated from the rigid body model for 50% partial weight bearing provided boundary conditions for a finite element model of the surgical repairs. Comparing the different surgical procedures, the open reduction and internal fixation with screws and primary arthrodesis with screws showed the most stable postoperative Lisfranc joint. However, the use of cannulated screws for fixation showed regions of high stress that may be susceptible to breakage and also resulted in higher contact forces in joints adjacent to the surgery site. Endobuttons and dorsal plates did not restore sufficient stability. Since all procedures showed different points of concern that could impact outcomes, additional surgical approaches could be needed in the future. This study offers a standard protocol for benchmarking the new procedures against those currently used.

Low albumin level is more strongly associated with adverse outcomes and Staphylococcus aureus infection than hemoglobin A1C or smoking tobacco.

Postsurgical deep musculoskeletal infections are a major clinical problem in Orthopaedic Surgery. A serum-based nomogram, which can objectively risk-stratify patients, and aid surgeons in delineating infection risk associated with orthopedic surgical interventions, would be immensely helpful. Here, we constructed a multi-parametric nomogram based on serum anti-Staphylococcus aureus antibody responses, patient characteristics including demographics and standard clinical tests. This nomogram was formally tested in a prospective cohort study comparing 303 hospitalized patients with culture-confirmed S. aureus infection compared with a cohort of 223 healthy screened preoperative patients. Serum anti-S. aureus antibody responses, standard of care clinical tests, and patient demographic data were utilized to perform multivariate logistic regression analysis to quantify the presence of infection and adverse outcome using odds ratios (OR) and to assess predictive ability via area under the ROC curve (AUC). At enrollment, high anti-S. aureus IgG titers were predictive of infection. Remarkably, low serum albumin was found to be significantly associated with infection (OR = 479.963, 95% CI 61.59 - 3740.33, p < 0.0001) and this finding was surprisingly higher than BMI or HbA1c-associations. Combining all risk factors in the nomogram yielded a diagnostic AUC of 0.949 for predicting S. aureus infection. Our results indicate that a serum-based multi-parametric nomogram can be useful in diagnosing S. aureus infections, and importantly, malnourishment is significantly associated with these infections.

Serum antibodies against Staphylococcus aureus can prognose treatment success in patients with bone infections.

Prognosing life-threatening orthopedic infections caused by Staphylococcus aureus remains a major clinical challenge. To address this, we developed a multiplex assay to assess the humoral immune proteome against S. aureus in patients with musculoskeletal infections. We found initial evidence that antibodies against some antigens (autolysins: Amd, Gmd; secreted immunotoxins: CHIPS, SCIN, Hla) were associated with protection, whereas antibodies against the iron-regulated surface determinant (Isd) proteins (IsdA, IsdB, IsdH) were aligned with adverse outcomes. To formally test this, we analyzed antibody levels and 1-year clinical outcomes of 194 patients with confirmed S. aureus bone infections (AO Trauma Clinical Priority Program [CPP] Bone Infection Registry). A staggering 20.6% of the enrolled patients experienced adverse clinical outcomes (arthrodesis, reinfection, amputation, and septic death) after 1-year. At enrollment, anti-S. aureus immunoglobulin G (IgG) levels in patients with adverse outcomes were 1.35-fold lower than those in patients whose infections were successfully controlled (p < 0.0001). Overall, there was a 51%-69% reduction in adverse outcome risk for every 10-fold increase in initial IgG concentration against Gmd, Amd, IsdH, CHIPS, SCIN, and Hla (p < 0.05). Notably, anti-IsdB antibodies remained elevated in patients with adverse outcomes; for every 10-fold change in the ratio of circulating anti-Isd to anti-Atl IgG at enrollment, there was a trending 2.6-fold increased risk (odds ratio = 2.555) of an adverse event (p = 0.105). Moreover, antibody increases over time correlated with adverse outcomes and decreases with positive outcomes. These studies demonstrate the potential of the humoral immune response against S. aureus as a prognostic indicator for assessing treatment success and identifying patients requiring additional interventions.

A Biomechanical Comparison of the Effect of Baseplate Design and Bone Marrow Fat Infiltration on Tibial Baseplate Pullout Strength.

BACKGROUND: Early clinical results of a new total knee arthroplasty (TKA) implant design show promise for improved outcomes and patellofemoral function scores. However, reports of early tibial component-cement interface debonding requiring revision have been published. This study investigated the biomechanical properties of three different tibial baseplates to understand potential causes of failure. METHODS: PFC Sigma (control), Attune (1st generation) and Attune S+ (2nd generation) tibial baseplates were implanted into 4th generation sawbone tibia models using a standardized technique. Three of each baseplate were cemented with and without additional bovine bone marrow fat. All models were tested to failure with measured axial distraction force. Implant type, presence or absence of bovine marrow and load to failure were all recorded and compared. Two-way ANOVA followed by post-hoc pairwise comparisons were used to determine statistical significance, which was set to P < .05. RESULTS: The 2nd generation tibial baseplates required significantly more force to failure. The presence of bovine marrow significantly reduced the pullout force of the implant designs overall. No significant difference was detected between the 1st generation and control baseplates. Failure mode for each model was also noted to be different irrespective of the presence or absence of bone marrow fat. CONCLUSION: The 2nd generation baseplates required significantly more force to failure compared with older designs. The presence of bone marrow during cementation of a tibial base plate significantly decreased axial pullout strength of a tibial baseplate in this laboratory model. All 1st generation baseplates exhibited debonding at the cement-implant interface.

Lack of Humoral Immunity Against Glucosaminidase Is Associated with Postoperative Complications in Staphylococcus aureus Osteomyelitis.

BACKGROUND: Glucosaminidase (Gmd) is known to be a protective antigen in animal models of Staphylococcus aureus osteomyelitis. We compared the endogenous anti-Gmd antibody levels in sera of patients with culture-confirmed S. aureus bone infections to their sera at 1 year after operative treatment of the infection. METHODS: A novel global biospecimen registry of 297 patients with deep-wound culture-confirmed S. aureus osteomyelitis was analyzed to assess relationships between baseline anti-Gmd serum titers (via custom Luminex assay), known host risk factors for infection, and 1-year postoperative clinical outcomes (e.g., infection control, inconclusive, refracture, persistent infection, septic nonunion, amputation, and septic death). RESULTS: All patients had measurable humoral immunity against some S. aureus antigens, but only 20 patients (6.7%; p < 0.0001) had high levels of anti-Gmd antibodies (>10 ng/mL) in serum at baseline. A subset of 194 patients (65.3%) who completed 1 year of follow-up was divided into groups based on anti-Gmd level: low (<1 ng/mL, 54 patients; 27.8%), intermediate (<10 ng/mL, 122 patients; 62.9%), and high (>10 ng/mL, 18 patients; 9.3%), and infection control rates were 40.7%, 50.0%, and 66.7%, respectively. The incidence of adverse outcomes in these groups was 33.3%, 16.4%, and 11.1%, respectively. Assessing anti-Gmd level as a continuous variable showed a 60% reduction in adverse-event odds (p = 0.04) for every tenfold increase in concentration. No differences in patient demographics, body mass index of >40 kg/m, diabetes status, age of ≥70 years, male sex, Charlson Comorbidity Index of >1, or Cierny-Mader host type were observed between groups, and these risk factors were not associated with adverse events. Patients with low anti-Gmd titer demonstrated a significant 2.68-fold increased odds of adverse outcomes (p = 0.008). CONCLUSIONS: Deficiency in circulating anti-Gmd antibodies was associated serious adverse outcomes following operative treatment of S. aureus osteomyelitis. At 1 year, high levels of anti-Gmd antibodies were associated with a nearly 3-fold increase in infection-control odds. Additional prospective studies clarifying Gmd immunization for osteomyelitis are needed. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Evolving concepts in bone infection: redefining "biofilm", "acute vs. chronic osteomyelitis", "the immune proteome" and "local antibiotic therapy".

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone. In contrast, S. aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies (MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

Biomechanical evaluation of the risk of secondary fracture around short versus long cephalomedullary nails.

INTRODUCTION: For proximal femur fractures, long cephalomedullary nails (CMNs) are often selected to avoid a diaphyseal stress riser at the tip of a shorter nail. Secondary peri-implant fracture rates for long and short CMN have not been shown to differ clinically. This study biomechanically compares both CMN in a cadaveric model. METHODS: Ten matched pairs of cadaveric femora with short or long CMN were axially loaded and internally rotated to failure. RESULTS: Resulting fractures involved distal interlocking screws of the short and long CMN. Energy and rotation to failure were significantly greater for short CMN. Torque at failure trended higher for short CMN but not significantly. No statistical difference was detected in stiffness of the short and long CMN. DISCUSSION: A greater risk of secondary fracture is not indicated for short versus long CMN under torsional stress. Short CMN may be suitable in the younger patient.

High Risk of Surgical Glove Perforation From Surgical Rotatory Instruments.

BACKGROUND: Surgical gloves can be damaged during the course of a procedure, which can place the surgeon and patient at risk. Glove perforation may not always be readily apparent, and determining the risk factors for glove perforation can aid the surgeon in deciding when a glove change is advisable. Time of wear and needle sticks have been well studied; however, other mechanisms including mechanical stress from surgical equipment have had limited evaluation to date. QUESTIONS/PURPOSES: We evaluated the risk of glove perforation in gloves that were caught in a surgical rotatory device (such as drills and reamers). The aims of our study were (1) to determine the percentage of undetected microperforations after entanglement on a rotatory tool during orthopaedic procedures, (2) to determine which kinds of rotatory devices most commonly cause such microperforations, and (3) to assess whether time of wear had an effect on the risk of perforation. METHODS: From July 2014 to September 2015, 33 gloves were obtained from all orthopaedic subspecialties at our Level I trauma center if they were caught in a rotatory device greater than one revolution. Time of glove wear and location of the glove that was caught in a rotatory device were recorded. After an evaluation for macroperforations (≥ 5 mm), the gloves were evaluated for microperforations (< 5 mm) via the American Society for Testing and Materials (ASTM) one-liter load test. Time of wear was compared among gloves with macroperforations, microperforations, and no perforations. RESULTS: The 33 gloves obtained came from 33 procedures. Seventeen of 33 (52 %) gloves had perforations. Seven of the 17 perforated gloves had macroperforations while 10 had microperforations. Eleven of 33 entanglements were caught by drills, nine by reamers, eight by K-wires, and the remaining five gloves were caught by various other instruments. Eight of 17 perforations were caused by drills, three by reamers, three by K-wires, and three by various other instruments. The average time of wear was 58 minutes which did not differ with pattern of glove damage. CONCLUSION: Surgical gloves caught in a rotatory power instrument are likely to have been perforated, regardless of the amount of time that they had been worn. Visual inspection appears to be an inadequate test of glove integrity. When a glove becomes entangled in a rotary instrument such as a drill, pin, or reamer, a surgeon should change the gloves regardless of whether he or she believes a perforation is present. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Bone-Prosthesis Junction for Active Tendon Implants: A Biomechanical Comparison of 2 Fixation Techniques.

PURPOSE: To study the biomechanical characteristics (percent stretch, stiffness, and ultimate load) of 2 distal fixation techniques for an active tendon implant used in the reconstruction of flexor tendons. METHODS: We evaluated percent stretch after cyclical loading and at failure, stiffness during load-to-failure, and peak load of 28 bone-prosthesis junctions using cadaveric canine middle phalanges to study 2 fixation techniques: metal cleat and screw versus polyester cords secured with a knot. RESULTS: The knot constructs displayed greater percent stretch during and following cyclical loading between 2 N and 50 N and at peak load. The screw construct showed greater stiffness from 50 N to 150 N during load-to-failure. Both fixation techniques failed at a mean peak load greater than 340 N. CONCLUSIONS: Both fixation techniques for active tendon implants withstood loads seen with passive and active motion in the immediate postoperative period. Knot constructs displayed significant stretch during cyclical and load-to-failure testing, which would need to be compensated for during surgery. The screw constructs showed greater stiffness than the constructs secured with the surgeon's knot, but failure created an intra-articular fracture. CLINICAL RELEVANCE: The results may aid the surgeon in choosing which fixation technique to use, during tensioning of cords, and in permitting active motion following surgery.

Biomechanical Performance of Lateral Versus Dual Locking Plates for Calcaneal Fractures.

Given the high rates of wound complications with a standard lateral extensile incision, small dual incision techniques might result in less soft tissue destruction. The goal of the present study was to compare the biomechanical performance between a single locking plate and a dual locking plating system for an intra-articular calcaneal fracture model. A Sanders IIB type joint depression calcaneal fracture was created in 10 paired, fresh-frozen, cadaveric calcanei (age 47 ± 12, range 35 to 78 years). The calcanei of each pair were randomly assigned for fixation using either a lateral locking reconstruction plate or lateral and medial locking reconstruction plates. The specimens were axially loaded in cyclic fashion for 1000 cycles, followed by load to failure. The relative fragment movement was monitored optically in both the sagittal and the coronal planes. The amount of overall construct displacement increased with cycling, although no difference was found between the plating techniques. For fragment movement during cycling, the lateral joint fragment migrated anteroinferiorly along the fracture line relative to the tuberosity fragment for dual plated specimens by a small, but statistically significant, amount. This same translation was smaller for lateral plated specimens but was not found to be significant. During load to failure testing, no statistically significant differences were found for construct stiffness. A tendency was seen toward more interfragmentary motion in the sagittal plane (lateral joint fragment movement relative to the fracture line), with less movement overall in the coronal plane (anterior fragment translation and twist) for dual plating, although the difference from the lateral plate was not statistically significant. The present study demonstrated that for this calcaneal fracture model, the dual plating technique experienced a small amount of fragment translation during cycling that was significantly different statistically from that with lateral plating but was not clinically relevant. During the load to failure, the dual plating technique was comparable to the lateral plate. Thus, dual plating could be a viable biomechanical option for fracture reduction if avoidance of a large extensile lateral approach associated with lateral plating is warranted.

Hip contact stress and femoral neck retroversion: a biomechanical study to evaluate implication of femoroacetabular impingement.

The current literature on femoroacetabular impingement (FAI) is focused on acetabular orientation and femoral head asphericity, with little emphasis on the effect of version of the femoral neck. A biomechanical model was developed to determine the causative effect, if any, of femoral retroversion on hip contact stress and, if present, delineate the type of FAI with femoral neck retroversion. Five pairs of cadaveric hips (n = 10) were tested by loading the hip in 90° of flexion and measured the peak joint pressure and the location of the peak joint pressure. The experiment was repeated after performing a subtrochanteric osteotomy and retroverting the proximal femur by 10°. Ten hips were successfully tested, with one hip excluded due to an outlier value for peak joint pressure. Retroversion of the proximal femur significantly increased the magnitude of mean peak joint pressure. With retroversion, the location of the peak joint pressure was shifted posteroinferiorly in all cases. In conclusion, femoral neck retroversion increases peak joint pressure in the flexed position and may act as a cause of femoroacetabular impingement. The location of peak joint pressure suggests a pincer-type impingement with retroversion. The version of femoral neck should be assessed as a possible causative factor in patients with FAI, especially those with pincer-type impingement.

Proximal tendon-prosthesis junction for active tendon implants of the hand: a biomechanical comparison of 2 techniques.

PURPOSE: To study the biomechanical characteristics (percent stretch, stiffness, and ultimate load) of 2 tendon-prosthesis techniques used to connect the proximal tendon stump to silicone active tendon implants used in reconstruction of flexor tendons. METHODS: We evaluated percent stretch following cyclic loading and at failure, stiffness during load to failure, and ultimate load of 16 tendon-prosthesis junctions using cadaveric canine flexor digitorum profundus tendons to re-create 2 junction techniques: the tendon loop (TL) and the polyester weave (PW). RESULTS: The TL junction showed greater percent stretch at a static load of 2 N, following 500 cycles of loading between 2 N and 50 N, and at peak load. The PW junction displayed greater stiffness from 50 to 150 N during load to failure. Both junctions failed at a mean ultimate load greater than 220 N. CONCLUSIONS: The described proximal junction techniques for active tendon implants were strong enough to resist early active motion in the immediate postoperative period without significant elongation. The PW technique displayed greater stiffness and ultimate load compared with the TL. CLINICAL RELEVANCE: Data on tendon-prosthesis characteristics of these 2 methods may aid the surgeon in choosing which junction technique to use, during surgical tensioning decisions, and in considering activity protocols after surgery. These data may also serve as a baseline for further investigations regarding active tendon implants.

Reattachment of flexor digitorum profundus avulsion: biomechanical performance of 3 techniques.

PURPOSE: To investigate whether inclusion of the volar plate in repair of flexor digitorum profundus avulsions increases the strength of the repair and resists gapping. METHODS: Cadaveric fingers (n = 18) were divided into 3 equal groups. The first technique involved 2 micro-suture anchors only (A). The second used only volar plate repair (VP). The third group was a hybrid, combining a micro-suture anchor with volar plate augmentation (AVP). Specimens were loaded cyclically to simulate passive motion rehabilitation before being loaded to failure. Clinical failure was defined as 3 mm of gapping, and physical failure as the highest load associated with hardware failure, suture breakage, anchor pullout, or volar plate avulsion. RESULTS: Gapping throughout cycling was significantly greater for the A group than VP and AVP with no difference detected between VP and AVP groups. Gapping exceeded 3 mm during cycling of 3 A specimens, but in none of the VP or AVP specimens. Load at clinical and physical failure for A was significantly lower than for VP and AVP, whereas no difference was detected between VP and AVP. CONCLUSIONS: In this cadaveric model, incorporating the volar plate conferred a significant advantage in strength, increasing the mean load to physical failure by approximately 100 N. CLINICAL RELEVANCE: According to previous biomechanical studies, current reconstructive strategies for flexor digitorum profundus zone I avulsions are not strong enough to withstand active motion rehabilitation. We demonstrated the potential use of volar plate augmentation and the prospective advantageous increase in strength in this cadaveric model. In vivo performance and effects on digital motion are not known.

Unicortical PEEK inset locking fixation for metacarpal fractures: a biomechanical study.

PURPOSE: There are numerous constructs employed in the treatment of metacarpal fractures with varying degrees of success. While plate fixation commonly involves dorsal application of a bicortical non-locking plate, there has been recent exploration of other fixation options including unicortical locked plating. The purpose of this study was to evaluate the biomechanical integrity of a polyetheretherketone (PEEK) inset locking plate and, in doing so, compare it to standard plate fixation (utilizing a clinically proven bicortical non-locking titanium plate) in a simulated porcine metacarpal fracture model. METHODS: Reproducible mid-shaft fractures were created in porcine second metacarpals. The fractured specimens were reduced and plated with either a bicortical non-locking plate or a unicortical locking plate with a PEEK locking design. Constructs were then loaded to failure in the same fashion as performed to create the fracture. Peak load was measured as the apex on the load-to-failure deflection curve. Stiffness was calculated as the linear slope on the load-to-failure deflection curve. Data were analyzed via Student's t test. RESULTS: Unicortical locking constructs failed at 344 ± 119 N, while bicortical non-locking constructs were found to fail at 277 ± 101 N (p = 0.19). The unicortical locking constructs demonstrated a stiffness of 80 ± 36 N/mm compared with the bicortical non-locking constructs (69 ± 36 N/mm) although again the difference was not found to be statistically different (p = 0.49). CONCLUSION: Based on this study, a locked plating construct using a polymer mechanism provides an interesting new locking fixation method for small bone fractures and with our limited number of specimens tested, provided at least a similar strength and rigidity profile in comparison with bicortical fixation in the treatment of metacarpal fractures.

Proximal humeral fracture fixation: a biomechanical comparison of two constructs.

BACKGROUND: Different options exist for stabilizing proximal humeral fractures. This study compared the mechanical stability of 2 common proximal humeral fixation plates in bending and torsion. METHODS: Tests were conducted on 40 synthetic and 10 matched pairs of cadaveric humeri (evenly fixed with DePuy S3 proximal humeral plating system [DePuy Orthopaedics, Warsaw, IN, USA] and Synthes proximal humerus locking compression plate [Synthes, Paoli, PA, USA]). Half of the humeri were tested by cantilevered bending in flexion, extension, varus, and valgus for 100 cycles of ±5 mm of displacement at 1 mm/s before loading to failure in varus. The other half were tested in torsion for 100 cycles of ±8° of rotational displacement at 1°/s before loading to failure in external rotation. RESULTS: Peak cyclic loads for synthetic constructs were higher for DePuy plates than Synthes plates in varus and valgus (P < .0001), but a difference was not detected in extension (P > .40) or flexion (P = .0675). Peak cyclic loads for cadaveric constructs showed a significant difference in extension and flexion (Synthes > DePuy, P < .0001) and in varus (DePuy > Synthes, P < .05) but not in valgus (P > .10). Bending stiffness during varus failure testing was higher for DePuy plates than Synthes plates (P < .0001) for synthetic constructs. Regarding torsion of synthetic and cadaveric constructs, DePuy plates experienced higher peak cyclic torques over all cycles in both directions (P < .0001). For synthetic constructs, DePuy plates showed higher torsional stiffness in external failure than Synthes plates (P < .0001). CONCLUSIONS: The DePuy plate was stiffer than the Synthes plate with varus and valgus bending, as well as in torsion. The Synthes plate tended to be stiffer in flexion and extension.

Effect of pressure applied during casting on temperatures beneath casts.

BACKGROUND: Burns and pressure sores are common injuries during cast application. Various factors such as water temperature, padding, and cast material layers may play a role in these injuries; however, the effect of cast molding on temperatures and pressures has not been investigated. This raises the following questions, does the application of molding during cast application: (1) alter skin level temperatures in a variety of cast materials? and (2) risk inducing either thermal injury or pressure necrosis? METHODS: An upper extremity model was created to measure pressure and temperature underneath casting materials. Cast padding, water bath temperature, and cast thickness were standardized. A 3-point mold was simulated using 3 casting materials-Fiberglass only, Plaster Only splint, and Plaster splint overwrapped with Fiberglass-while pressure and temperature were recorded. RESULTS: : Pressure application led to a statistically significant (P<0.0001) increase in temperature at the sites where the mold was applied although absolute temperature did not reach the theoretical burn threshold of 49 to 50°C for the casting materials studied. With pressure applied, the Plaster/Fiberglass combination reached an average peak temperature of 47.9°C, which was maintained for up to 6 minutes. Neither Fiberglass nor Plaster Only reached peak temperatures of this magnitude (average of 42.7 and 43.6°C, respectively). Peak (369 mm Hg) and highest residual (21 mm Hg) pressures were below harmful levels. CONCLUSIONS: Pressure application during casting is a risk factor for burn injuries. Care should be taken when molding a plaster splint overwrapped in fiberglass by waiting until the plaster has fully cooled. CLINICAL RELEVANCE: Combined with other known risk factors, the pressure from molding a cast could increase the likelihood of causing cutaneous burns.

Biomechanical evaluation of a locking and nonlocking reconstruction plate in an osteoporotic calcaneal fracture model.

BACKGROUND: This study evaluated the effects of locking vs nonlocking configuration on the biomechanical performance of a calcaneal reconstruction plate in an osteoporotic cadaveric model. MATERIALS AND METHODS: A Saunders II B type calcaneal fracture was created in ten matched pair of cadaveric calcanei. Each pair was fixed with the Ascension calcaneal reconstruction plate using either locking or nonlocking screws in the same hole pattern. Specimens were axially loaded for 1000 cycles through the talus followed by load to failure. Statistical comparisons were made between the locking and nonlocking constructs on the displacements during cyclic loading as well as construct stiffness and load achieved at selected fragment displacements. RESULTS: No significant difference was detected between the locking and nonlocking constructs in displacement during cyclic loading (p > 0.2) for the numbers available. Similarly no significant difference was found in stiffness of the constructs between the groups: 445.7 ± 148.8 (N/mm ± SD) for the locking plate and 395.2 ± 127.7 for the nonlocking plate (p > 0.14). The load achieved at 2 mm displacement of the posterior fragment for the two groups were not different: locking plate at 744.6 ± 237.2 N and nonlocking plate at 739.3 ± 269.7 N (p > 0.99). CONCLUSION: This study did not reveal a mechanical advantage to locking technology for calcaneal fractures with the selected plate and fracture model. CLINICAL RELEVANCE: While locking plate technology has shown mechanical advantages for fracture management in other osteoporotic models, in our fracture model and plating construct, this was not found. It is still unclear which fixation technique is most beneficial in these calcaneal fractures.

Increased diversity of libraries from libraries: chemoinformatic analysis of bis-diazacyclic libraries.

Combinatorial libraries continue to play a key role in drug discovery. To increase structural diversity, several experimental methods have been developed. However, limited efforts have been performed so far to quantify the diversity of the broadly used diversity-oriented synthetic libraries. Herein, we report a comprehensive characterization of 15 bis-diazacyclic combinatorial libraries obtained through libraries from libraries, which is a diversity-oriented synthetic approach. Using MACCS keys, radial and different pharmacophoric fingerprints as well as six molecular properties, it was demonstrated the increased structural and property diversity of the libraries from libraries over the individual libraries. Comparison of the libraries to existing drugs, NCI diversity, and the Molecular Libraries Small Molecule Repository revealed the structural uniqueness of the combinatorial libraries (mean similarity <0.5 for any fingerprint representation). In particular, bis-cyclic thiourea libraries were the most structurally dissimilar to drugs retaining drug-like character in property space. This study represents the first comprehensive quantification of the diversity of libraries from libraries providing a solid quantitative approach to compare and contrast the diversity of diversity-oriented synthetic libraries with existing drugs or any other compound collection.