Monoblock tapered stems in management of UCS B2 and B3 periprosthetic fractures in revision total hip arthroplasty.

Aims: United Classification System (UCS) B2 and B3 periprosthetic fractures in total hip arthroplasties (THAs) have been commonly managed with modular tapered stems. No study has evaluated the use of monoblock fluted tapered titanium stems for this indication. This study aimed to evaluate the effects of a monoblock stems on implant survivorship, postoperative outcomes, radiological outcomes, and osseointegration following treatment of THA UCS B2 and B3 periprosthetic fractures. Methods: A retrospective review was conducted of all patients who underwent revision THA (rTHA) for periprosthetic UCS B2 and B3 periprosthetic fracture who received a single design monoblock fluted tapered titanium stem at two large, tertiary care, academic hospitals. A total of 72 patients met inclusion and exclusion criteria (68 UCS B2, and four UCS B3 fractures). Primary outcomes of interest were radiological stem subsidence (> 5 mm), radiological osseointegration, and fracture union. Sub-analysis was also done for 46 patients with minimum one-year follow-up. Results: For the total cohort, stem osseointegration, fracture union, and stem subsidence were 98.6%, 98.6%, and 6.9%, respectively, at latest follow-up (mean follow-up 27.0 months (SD 22.4)). For patients with minimum one-year of follow-up, stem osseointegration, fracture union, and stem subsidence were 97.8%, 97.8%, and 6.5%, respectively. Conclusion: Monoblock fluted stems can be an acceptable modality for the management of UCS B2 periprosthetic fractures in rTHAs due to high rates of stem osseointegration and survival, and the low rates of stem subsidence, and revision. Further research on the use of this stem for UCS B3 periprosthetic fractures is warranted to determine if the same conclusion can be made for this fracture pattern.

Posteromedial Accessory Incision for Posterior Capsular Release and Retractor Placement in a Total Ankle Replacement.

The standard approach for performing a total ankle replacement (TAR) is the anterior approach as this offers good direct visualization of the tibiotalar joint. Irrespective of implant system used, most commonly, bone cuts are made in the anterior to posterior direction and may potentially injure the posterior neurovascular structures and tendons running close to the ankle joint. Careful consideration must be taken to ensure these structures are protected. We introduce a new intraoperative technique of protection for the posteromedial soft tissues and neurovascular structures and include the early results of 60 consecutive patients where the described technique was employed. There were no technique-related complications, or evidence of injury to the PTT, FHL, flexor digitorum longus (FDL), or neurovascular bundles.

Comparison of Cruciate-Sacrificing vs Posterior-Stabilized Total Knee Replacement Using a Contemporary Total Knee System.

BACKGROUND: The use of highly conforming polyethylene tibial inserts in cruciate-retaining total knee arthroplasty (TKA) often requires posterior cruciate ligament (PCL) release/sacrifice for balancing (CS TKA). The CS TKA relies on the posterior capsule, collateral ligaments, and articular conformity without a cam or post to achieve stability. Using prospectively collected data we compared clinical outcomes of CS TKA to posterior-stabilized (PS) TKA utilizing a contemporary TKA system. METHODS: Sixty-nine consecutive CS TKAs were compared to 45 consecutive PS TKAs at 2-year minimum follow-up. CS knees were balanced with the PCL released. Preoperative/postoperative range of motion (ROM), Knee Society Scores (KSS), stair function, and squatting ROM were analyzed. RESULTS: At minimum 2-year follow up, CS and PS TKA demonstrated significant improvement in ROM (P < .001), KSS (Pain, P < .001; Function, P < .001), and KSS stair function (P < .001), with no revisions. There was no difference in preoperative to postoperative improvements for passive knee ROM (10° (0°-20°) vs 13° (5°-25°); P = .16), KSS Pain (34 (21-42) vs 38 (24-46); P = .22), KSS Function (35 (30-50) vs 35 (18-50); P = .34), and KSS stair function (10 (10-20) vs 10 (0-20); P = .37) for CS and PS TKA, respectively. CS TKA had higher squatting ROM (P = .02) at minimum 2-year follow-up compared to PS TKA. CONCLUSION: Both PS and CS TKA provided significant improvement in clinical outcomes, with no differences in passive ROM, KSS, or stair function postoperatively. Our data support that with proper articular conformity and balancing, cruciate-retaining TKA in a PCL-deficient knee (CS TKA) is appropriate. This may be design specific and further prospective randomized studies are needed to corroborate these findings.

Viscoelastic and failure properties of two configurations of triple-folded hamstring tendons used for anterior cruciate ligament (ACL) reconstruction.

BACKGROUND: Hamstring autografts are commonly used for anterior cruciate ligament (ACL) reconstruction. Different folding techniques exist in tripling the semitendinosus. Few anatomical studies exist in evaluating their viscoelastic properties. The purpose of this study was to characterize and compare the viscoelastic and failure properties of two hamstring graft configurations, the "Z" construct and "2" construct. METHODS: Ten matched pairs of fresh-frozen cadaveric semitendinosus hamstring grafts were used to create the "2" configuration or "Z" configuration. The biomechanical testing consisted of four phases: preconditioning, where graft dimensions (mm) were measured; stress relaxation, where load, displacement and time data were collected and equilibrium relaxation (%) was calculated; dynamic creep, where the total construct elongation was calculated; and ramp-to-failure, where maximum failure load was recorded. RESULTS: The "2" configuration demonstrated recorded forces (N) significantly greater at each time point when compared to the "Z" configuration during stress relaxation (p = 0.003). The "2" configuration exhibited significantly less construct elongation (mm) during dynamic creep at 10 cycles (p = 0.008) and 2000 cycles (p = 0.0001). The maximum measured load at failure was significantly greater in the "2" configuration constructs than "Z" configuration (p = 0.013). Moreover, the axial loads at 2, 3 and 4 mm of displacement were, on average, greater in the "2" configuration than "Z" configuration (p = 0.152; p = 0.080; p = 0.012), respectively. CONCLUSION: The results of this study provide support for folding techniques for tripled grafts to provide higher viscoelastic and failure properties for techniques with less suture interfaces. Future studies can potentially evaluate the clinical significance of these findings.

Short term methylphenidate treatment does not increase myocardial injury in the ischemic rat heart.

Methylphenidate is commonly used for the treatment of attention deficit hyperactivity disorder. The cardiovascular safety of methylphenidate has been a subject of debate with some studies indicating that methylphenidate increases the likelihood of experiencing a myocardial infarction. However, it is unknown whether methylphenidate worsens the extent of injury during an ischemic insult. The purpose of this study was to determine whether short term exposure to methylphenidate increases the extent of myocardial injury during an ischemic insult. Male and female rats received methylphenidate (5 mg/kg/day) or saline for 10 days by oral gavage. Hearts were subjected to 20 min of ischemia and 2 h of reperfusion on a Langendorff isolated heart apparatus on day 11. Cardiac contractile function was monitored via an intraventricular balloon and myocardial injury was assessed by triphenyltetrazolium chloride staining. Methylphenidate significantly increased locomotor activity in male and female rats, confirming absorption of this psychostimulant into the central nervous system. Male hearts had significantly larger infarcts than female hearts, but methylphenidate had no impact on infarct size or postischemic recovery of contractile function in hearts of either sex. These data indicate that methylphenidate does not increase the extent of injury induced by an ischemic insult.

Biomechanical Investigation of an Integrated 2-Screw Cephalomedullary Nail Versus a Sliding Hip Screw in Unstable Intertrochanteric Fractures.

OBJECTIVE: To compare the efficacy of 2 intertrochanteric (IT) fracture fixation devices in conferring mechanical stability to unstable IT femur fractures. METHODS: Nine pairs of cadaveric female femurs with a groupwise average bone quality indicative of osteopenia were used. An unstable IT fracture without calcar support (OTA/AO 31-A2) was created and stabilized with either a sliding hip screw and side plate (SHS) or a cephalomedullary nail using an integrated dual-screw fixation [InterTAN (ITN)]. Constructs were evaluated under stepwise and increasing cyclic loading up to 50,000 cycles (1500 N) or by failure in a test model that may best simulate hip joint contact forces at heel strike. Number of cycles to failure, failure load, and femoral head rotation about the screw axis were compared between groups. RESULTS: The average number of cycles in the ITN group was greater compared with that in the SHS group (48,383 vs. 31,403 cycles, P = 0.046). Similarly, the average maximum load survived by the ITN group was greater than that of the SHS group (1456 vs. 1113 N, P = 0.046). The number of constructs that survived up to the maximum applied load of 1500 N was greater in the ITN group (8/9, 89%) when compared with that of the SHS constructs (3/9, 33%) (P = 0.049). Finally, the ITN group conferred greater rotational control of the femoral head compared with the SHS constructs (1.5 vs. 5.5 degrees, P = 0.018), and reduced the amount of varus collapse (11.1 vs. 31.1 degrees, P = 0.038). CONCLUSIONS: The integrated dual-screw construct appeared to confer significantly greater fracture stability compared with a sliding hip screw and side plate using a worst-case model that simulates heel strike during gait. Study data provide biomechanical evidence that the ITN device may provide more stability and rotational resistance than a sliding hip screw in the elderly female patient population with an unstable IT fracture and compromised bone quality.

Biomechanical Comparison of 3 Inferiorly Directed Versus 3 Superiorly Directed Locking Screws on Stability in a 3-Part Proximal Humerus Fracture Model.

OBJECTIVE: To quantify the stability of 3 points of inferiorly directed versus 3 points of superiorly directed locking screw fixation compared with the full contingent of 6 points of locked screw fixation in the treatment of a 3-part proximal humerus fracture. METHODS: A standardized 3-part fracture was created in 10 matched pairs (experimental groups) and 10 nonmatched humeri (control group). Osteosynthesis was performed using 3 locking screws in the superior hemisphere of the humeral head (suspension), 3 locking screws in the inferior hemisphere (buttress), or the full complement of 6 locking screws (control). Specimens were tested in varus cantilever bending (7.5 Nm) to 10,000 cycles or failure. Construct survival (%) and the cycles to failure were compared. RESULTS: Seven of 10 controls survived the 10,000-cycle runout (70%: 8193 average cycles to failure). No experimental constructs survived the 10,000-cycle runout. Suspension and buttress screw groups failed an average of 331 and 516 cycles, respectively (P = 1.00). The average number of cycles to failure and the number of humeri surviving the 10,000-cycle runout were greater in the control group than in the experimental groups (P ≤ 0.006). CONCLUSION: Data support the use of a full contingent of 6 points of locking screw fixation over 3 superior or 3 inferior points of fixation in the treatment of a 3-part proximal humerus fracture with a locking construct. No biomechanical advantage to the 3 buttress or 3 suspension screws used in isolation was observed.

Sensitivity and Specificity of Skyline and Carpal Shoot-Through Fluoroscopic Views of Volar Plate Fixation of the Distal Radius: A Cadaveric Investigation of Dorsal Cortex Screw Penetration.

BACKGROUND: Volar plate fixation of distal radius fractures can result in soft tissue injuries. Abnormal contour of the dorsal cortex of the distal radius provides difficulties in discerning screw penetration on standard radiographs. The skyline and carpal shoot-through views are additional views to improve dorsal cortex visibility. We report on the sensitivity and specificity of determining screw protrusion with these views. METHODS: Seven fresh frozen cadavers were instrumented with a distal radius volar locking plate. Initial screw length was determined by depth gauge measurement. A dorsal dissection of the wrist was performed to detect screw penetration. Protruding screws were documented and replaced with screws of the appropriate length and deemed as baseline. Screws were then sequentially lengthened by 2 and 4 mm. Skyline and carpal shoot-through views were obtained at baseline, 2 mm, and 4 mm. The images were randomized and compiled into an untimed survey asking orthopedic surgeons to determine whether screws were penetrating through the dorsal cortex. RESULTS: Based on depth gauge measurements, 4 out of 44 (9.1%) volar plate locking screws penetrated the dorsal cortex, as confirmed with dorsal dissection. Sensitivities for the skyline and carpal shoot-through views were 75% and 86% ( P ≤ .001), respectively, for 2-mm protrusions, and 76% and 89% ( P ≤ .001), respectively, for 4-mm screw protrusions. Specificities were 85% and 84% for the skyline and shoot-through views, respectively. CONCLUSIONS: We believe that the carpal shoot-through view has utility and can be implemented to augment standard intraoperative views, and may decrease the incidence of screw protrusion resulting in soft tissue injuries.

Radiographic evaluation of acute distal radius fracture stability: A comparative cadaveric study between a thermo-formable bracing system and traditional fiberglass casting.

BACKGROUND: Distal radius fractures are common musculoskeletal injuries and many can be treated non-operatively with cast immobilization. A thermo-formable brace has been developed for management of such fractures, but no data exist regarding its comparative stabilizing efficacy to fiberglass casting. METHODS: A worst-case distal radius fracture was created in 6 cadaveric forearms. A radiolucent loading fixture was created to apply cantilever bending/compression loads ranging from 4.5N to 66.7N across the simulated fracture in the: (1) non-stabilized, (2) braced; and (3) casted forearms, each forearm serving as its own control. Fracture fragment translations and rotations were measured radiographically using orthogonal radiographs and a 2D-3D, CT-based transformation methodology. FINDINGS: Under 4.5N of load in the non-stabilized condition, average sagittal plane rotation and 3D center of mass translation of the fracture fragment were 12.3° and 5.3mm, respectively. At the 4.5N load step, fragment rotation with the brace (avg. 0.0°) and cast (0.1°) reduced sagittal plane rotation compared to the non-stabilized forearm (P<0.001). There were no significant differences in measured sagittal plane fracture fragment rotations or 3D fragment translations between the brace or cast at any of the four load steps (4.5N, 22.2N, 44.5N, and 66.7N, P≥0.138). INTERPRETATION: In this in vitro radiographic study utilizing 6 cadaveric forearms with simulated severe-case, unstable and comminuted distal radius fractures, the thermo-formable brace stabilized the fracture in a manner that was not radiographically or biomechanically different from traditional fiberglass casting. Study results support the use of the thermo-formable brace clinically.

Comparison of 3 Methods for Maintaining Inter-Fragmentary Compression After Fracture Reduction and Fixation.

OBJECTIVES: It is recommended that the intra-articular component of a supracondylar distal femoral fracture be stabilized by a lag screw to create interfragmental compression. Generally, it is thought that lag screw fixation should precede any positional screw or locking screw application. This study compared 3 methods of maintaining interfragmentary compression after fracture reduction with a reduction clamp. METHODS: Intra-articular vertical split fractures were created in synthetic femora. A force transducer was interposed between the medial and lateral condyles and 20 lbs of compression was applied to the fracture with a reduction clamp. 3.5-mm cortical lag screws (group 1), 3.5-mm cortical position screws (group 2), and 5.4-mm distal locking screws through a distal femur locking plate (group 3) were placed across the fracture (n = 4/group). After screw placement, the clamp was removed and the amount of residual interfragmentary compression was recorded. After 2 minutes, a final steady-state force was measured and compared across groups. RESULTS: Locking screws placed through the plate (group 3) maintained 27% of the initial force applied by the clamp (P = 0.043), whereas positional screws (group 2) maintained 90% of the initial force applied by the clamp (P = 0.431). The steady-state compression force measured with lag screws (group 1) increased by 240% (P = 0.030) relative to the initial clamp force. The steady-state force in the lag screw group was significantly greater than groups 1 and 2 (P = 0.012). CONCLUSIONS: When reducing intra-articular fractures and applying interfragmentary compression with reduction clamps, additional lag screws increase the amount of compression across the fracture interface. Compressing a fracture with reduction clamps and relying on locking screws to maintain the compression result in a loss of interfragmentary compression and should be avoided. This study lends biomechanical support that lag screws placed outside of the plate before locking screws for fracture fixation help maintain optimal interfragmentary compression.

Nuclear targeting is required for hepatoma-derived growth factor-stimulated mitogenesis in vascular smooth muscle cells.

We recently identified hepatoma-derived growth factor (HDGF) as a nuclear targeted vascular smooth muscle cell (VSM) mitogen that is expressed in developing vascular lesions. In the present study, VSM in culture express endogenous HDGF only in the nucleus and target a green fluorescent protein (GFP)-HDGF fusion to the nucleus. To define the features of the HDGF molecule that are essential for nuclear localization and mitogenic function, deletion and site-directed mutagenesis were performed. Deletion analysis identified the carboxyl-terminal half of HDGF to be responsible for nuclear targeting in VSM. Overexpression of tagged HDGF proteins with point mutations in the putative bipartite nuclear localization sequence in the carboxyl terminus demonstrated that single Lys --> Asn mutations randomized HDGF expression to both the nucleus and cytoplasm similar to the empty vector. Importantly, the Lys --> Asn mutation of all three lysines blocked nuclear entry. Point mutation of a p34(cdc2) kinase consensus motif within the nuclear localization sequence had no effect on nuclear targeting. Moreover, nuclear entry was essential for the HDGF mitogenic effect, as transfection with the triple Lys --> Asn mutant HA-HDGF significantly attenuated bromodeoxyuridine uptake when compared with transfection with wild type HA-HDGF. We conclude that HDGF contains a true bipartite nuclear localization sequence with all three lysines necessary for nuclear targeting. Nuclear targeting of HDGF is required for HDGF stimulation of DNA replication in VSM.

Angiotensin II regulates phosphorylation of translation elongation factor-2 in cardiac myocytes.

Increased protein synthesis is the cardinal feature of cardiac hypertrophy. We have studied angiotensin II (ANG II)-dependent regulation of eukaryotic elongation factor-2 (eEF-2), an essential component of protein translation required for polypeptide elongation, in rat neonatal cardiac myocytes. eEF2 is fully active in its dephosphorylated state and is inhibited following phosphorylation by eEF2 kinase. ANG II treatment (10(-10) - 10(-7) M) for 30 min produced an AT(1) receptor-specific and concentration- and time-dependent reduction in the phosphorylation of eEF-2. Protein phosphatase 2A (PP2A) inhibitors okadaic acid and fostriecin, but not the PP2B inhibitor FK506, attenuated ANG II-dependent dephosphorylation of eEF-2. ANG II activated mitogen-activated protein kinase, (MAPK) within 10 min of treatment, and blockade of MAPK activation with PD-98059 (1--20 nM) inhibited eEF-2 dephosphorylation. The effect of ANG II on eEF-2 dephosphorylation was also blocked by LY-29004 (1-20 nM), suggesting a role for phosphoinositide 3-kinase, but the mammalian target rapamycin inhibitor rapamycin (10--100 nM) had no effect. Together these results suggest that the ANG II-dependent increase in protein synthesis includes activation of eEF-2 via dephosphorylation by PP2A by a process that involves both PI3K and MAPK.

Protein phosphatase inhibitors arrest cell cycle and reduce branching morphogenesis in fetal rat lung cultures.

Protein phosphatase 2A (PP2A) is a key signal transduction intermediate in the regulation of cellular proliferation and differentiation in vitro. However, the role of PP2A in the context of a developing organ is unknown. To explore the role of PP2A in the regulation of lung development, we studied the effect of PP2A inhibition on new airway branching, induction of apoptosis, DNA synthesis, and expression of epithelial marker genes in whole organ explant cultures of embryonic (E14) rat lung. Microdissected lung primordia were cultured in medium containing one of either two PP2A inhibitors, okadaic acid (OA, 0-9 nM) or cantharidin (Can, 0-3,600 nM), or with the PP2B inhibitor deltamethrin (Del, 0-10 microM) as a control for a PP2A-specific effect for 48 h. PP2A inhibition with OA and Can significantly inhibited airway branching and overall lung growth. PP2B inhibition with Del did not affect lung growth or new airway development. Histologically, both PP2A- and PP2B-inhibited explants were similar to controls. Increased apoptosis was not the mechanism of decreased lung growth and new airway branching inasmuch as OA-treated explant sections subjected to the terminal deoxynucleotidyltransferase dUTP nick end labeling reaction demonstrated a decrease in apoptosis. However, PP2A inhibition with OA increased DNA content and 5-bromo-2'-deoxyuridine uptake that correlated with a G(2)/M cell cycle arrest. PP2A inhibition also resulted in altered differentiation of the respiratory epithelium as evidenced by decreased mRNA levels of the early epithelial marker surfactant protein C. These findings suggest that inhibition of protein phosphatases with OA and Can halted mesenchymal cell cycle progression and reduced branching morphogenesis in fetal rat lung explant culture.

Developmental expression of protein phosphatase 2A in the kidney.

Although a number of growth and transcription factors are known to regulate renal growth and development, the signal transduction molecules necessary to mediate these developmental signals are relatively unknown. Therefore, the activity and mRNA and protein expression of the signal transduction molecule protein phosphatase 2A (PP2A) were examined during rat kidney development. Northern analysis of total kidney RNA or Western analysis of kidney protein homogenates from embryonic day 15 to 90-d-old adults demonstrated developmental regulation of the catalytic, major 55-kD B regulatory subunit and A structural subunit with the highest levels of expression in late embryonic and newborn kidneys. Similarly, okadaic acid-inhibitable phosphatase enzyme activity was highest in the embryonic and newborn kidney. To map cell-specific expression of PP2A in the developing kidney, in situ hybridization with a catalytic subunit digoxigenin-labeled cRNA was performed on embryonic day 20 and newborn kidneys. PP2A was found predominately in the nephrogenic cortex and particularly in the developing glomeruli and non-brush border tubules in the embryonic day 20 and newborn kidneys. Similarly, immunocytochemistry with a specific PP2A catalytic subunit polyclonal anti-peptide antibody demonstrated catalytic subunit protein particularly concentrated in the podocytes of glomeruli in the newborn kidney. In the adult kidney, PP2A protein was no longer detectable except in the nuclei of distal tubular cells. Therefore, the developmental regulation of PP2A activity and protein during kidney development and its mapping to the nephrogenic cortex, developing glomeruli, and tubules suggests a role for PP2A in the regulation of nephron growth and differentiation.