How do pre-operative intra-articular injections impact periprosthetic joint infection risk following primary total hip arthroplasty? A systematic review and meta-analysis.

INTRODUCTION: Although intra-articular injections (IAIs) serve as the first-line non-surgical management for severe osteoarthritis (OA), recent analyses have suggested they are associated with an increased infection risk following primary total hip arthroplasty (THA). Therefore, our systematic review and meta-analysis explored the relationship between IAIs and periprosthetic joint infection (PJI) following THA reported in the current literature. METHODS: Five online databases were queried for analyses published from January 1st, 2000-May 1st, 2021 reporting on PJI rates between patients undergoing primary THA who did and did not preoperatively receive an IAI. The overall pooled effect of injection status on PJI incidence was determined using Mantel-Haenszel (M-H) models. This was similarly conducted for segregated preoperative intervals: 0-3 months, > 3-6 months, > 6 + months. RESULTS: A total of 11 articles were included in our analysis reporting on 278,782 THAs (IAI: n = 41,138; no IAI: n = 237,644). Patients receiving pre-operative injections had a significantly higher risk of PJI (OR: 1.31, 95% CI 1.07-1.62; p = 0.009). However, this finding was not robust. IAI receipt within 3-months of THA was associated with significantly higher PJI rates (OR: 1.68, 95% CI 1.48-1.90; p < 0.001). However, no significant difference was demonstrated in the > 3-6 month (OR: 1.19, 95% CI 0.94-1.52; p = 0.16) and > 6 + month sub-analyses (OR: 1.20, 95% CI 0.96-1.50; p = 0.11). The results of all sub-analyses remained were robust. DISCUSSION: Our findings suggest that patients requiring THA should wait at least 3-months following IAI to reduce post-operative infection risk. This information can help inform patients considering OA management options, as well as adult reconstruction surgeons during preoperative optimization.

An Anatomic Study of the Proximal Tibial Epiphysis With Relevance to Percutaneous Epiphysiodesis Using Transphyseal Screws (PETS).

BACKGROUND: Percutaneous epiphysiodesis using transphyseal screws (PETS) is a common procedure to correct lower extremity limb-length discrepancies in the pediatric population. A potential complication of this procedure is development of tibial valgus deformity, which may occur secondary to decreased screw purchase in the thinner medial proximal tibial epiphysis. The thickness of the proximal tibial epiphysis has not yet been well quantified, which was the aim of this study. METHODS: Three-dimensional surface scans of 32 cadaveric proximal tibial epiphyses in specimens aged 3 to 17 years old were obtained and computer modeling software was utilized to measure the thickness of the proximal tibial epiphysis at 20 standardized potential screw insertion points according to a generated 5×4 map. RESULTS: When normalized to the total width of the proximal tibial epiphysis, the lateral side is thicker compared with the medial side. The positions with the greatest thickness are located at the midline in the sagittal plane and 33% of the total physeal width away from the medial and lateral edges in the coronal plane (0.265 and 0.261 normalized thickness, respectively). The proximal tibial epiphysis is particularly thin 25% from the medial edge (normalized thickness range: 0.196 to 0.221). Multiple regression analysis revealed a significant relationship between increasing age and female sex with thinner normalized medial and lateral heights. CONCLUSIONS: During PETS, areas for greater screw purchase are located centrally in the sagittal plane and 33% of the total width away from the medial and lateral edges of the proximal tibial epiphysis in the coronal plane. Caution should be taken when inserting screws in the medial 25% of the proximal tibial epiphysis as it is thinner relative to the lateral edge, particularly in females. CLINICAL RELEVANCE: This study provides quantitative, anatomic data on the thickness of the proximal tibial epiphysis, which can direct screw placement during PETS for correcting limb-length discrepancies. These data may help lessen the risk of developing tibial valgus deformity although future clinical studies are necessary to fully evaluate this possibility.

α-Crystallin chaperone mimetic drugs inhibit lens γ-crystallin aggregation: Potential role for cataract prevention.

Γ-Crystallins play a major role in age-related lens transparency. Their destabilization by mutations and physical chemical insults are associated with cataract formation. Therefore, drugs that increase their stability should have anticataract properties. To this end, we screened 2560 Federal Drug Agency-approved drugs and natural compounds for their ability to suppress or worsen H2O2 and/or heat-mediated aggregation of bovine γ-crystallins. The top two drugs, closantel (C), an antihelminthic drug, and gambogic acid (G), a xanthonoid, attenuated thermal-induced protein unfolding and aggregation as shown by turbidimetry fluorescence spectroscopy dynamic light scattering and electron microscopy of human or mouse recombinant crystallins. Furthermore, binding studies using fluorescence inhibition and hydrophobic pocket-binding molecule bis-8-anilino-1-naphthalene sulfonic acid revealed static binding of C and G to hydrophobic sites with medium-to-low affinity. Molecular docking to HγD and other γ-crystallins revealed two binding sites, one in the "NC pocket" (residues 50-150) of HγD and one spanning the "NC tail" (residues 56-61 to 168-174 in the C-terminal domain). Multiple binding sites overlap with those of the protective mini αA-crystallin chaperone MAC peptide. Mechanistic studies using bis-8-anilino-1-naphthalene sulfonic acid as a proxy drug showed that it bound to MAC sites, improved Tm of both H2O2 oxidized and native human gamma D, and suppressed turbidity of oxidized HγD, most likely by trapping exposed hydrophobic sites. The extent to which these drugs act as α-crystallin mimetics and reduce cataract progression remains to be demonstrated. This study provides initial insights into binding properties of C and G to γ-crystallins.

An anatomic and 3D study of the development of the proximal humeral physis.

PURPOSE: During maturation, the ossification centers of the proximal humerus form a characteristic pattern consisting of a metaphyseal peak and corresponding epiphyseal valley. The surface topographies of the metaphyseal peak and epiphyseal valley are not well described and may have variation with age and structural importance to the pathogenesis of proximal humeral epiphysiolysis. METHODS: High-resolution 3-dimensional surface scans of 24 cadaveric proximal humeral epiphyses and metaphyses in specimens aged 3 to 18 years were obtained. Computer modeling software was used to measure the peak height of the metaphysis and maximal depth of the epiphysis relative to a perpendicular line drawn across the proximal humeral physis. RESULTS: The metaphyseal peak had a mean height of 12.7 ± 1.6 mm while the epiphyseal valley had a mean depth of 13.1 ± 2.1 mm, both consistently positioned in the posterolateral quadrant. Both the absolute metaphyseal peak height (R2 = 0.536; p < 0.001) and absolute epiphyseal valley depth (R2 = 0.524; p < 0.001) increase with advancing age. Multiple linear regression analysis demonstrated that normalized metaphyseal peak height + sex (adjusted R2 = 0.408; p < 0.002) correlated more with age than normalized epiphyseal valley depth + sex (adjusted R2 = 0.128; p < 0.091). CONCLUSION: Prominence of the metaphyseal peak and epiphyseal valley both increase with advancing age, with a lower correlation between normalized sizes with age as compared to the absolute sizes, suggesting that these structures stay relatively proportional with growth.

Intra-articular injection receipt within 3 months prior to primary total knee arthroplasty is associated with increased periprosthetic joint infection risk.

PURPOSE: This systematic review and meta-analysis analyzed the influence of pre-operative intra-articular injections (IAI) on periprosthetic joint infection (PJI) rates after primary total knee arthroplasty (TKA). METHODS: Studies published between January 1st, 2000 and May 1st, 2021 evaluating PJI rates among TKA patients with and without IAI were identified from PubMed, Cochrane Library, MEDLINE, EBSCO Host, and Google Scholar. The pooled effect of IAI on PJI risk was calculated utilizing Mantel-Haenszel (M-H) models. Sub-analysis comparisons were conducted based on the interval from IAI to TKA: 0-3 months; > 3-6 months; > 6-12 months. The Methodological Index for Non-Randomized Studies (MINORS) and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool were utilized to evaluate the quality of each included study. RESULTS: The present analysis included 12 studies reporting on 349,605 TKAs (IAI: n = 115,122; No IAI: n = 234,483). Patients receiving an IAI at any point prior to TKA (2850/115,122; 2.48%) had statistically significant increased risk of infection compared to patients not receiving IAIs (4479/234,483; 1.91%; OR: 1.14, 95% CI: 1.08-1.20; p < 0.0001). However, this finding was not demonstrated across sensitivity analyses. Receiving injections within 3 months prior to TKA was associated with increased infection risk (OR: 1.23, 95% CI: 1.14-1.31; p < 0.0001). There were no differences in infection rates when injections were given between > 3 and 6 months (OR: 0.82, 95% CI: 0.47-1.43; p = 0.49) and > 6-12 months prior to TKA (OR: 1.26, 95% CI: 0.89-1.78; p = 0.18). CONCLUSIONS: Based on the current literature, the findings of this analysis suggest that patients receiving IAI should wait at least 3 months before undergoing TKA to mitigate infection risk. Orthopaedic surgeons and patients can utilize this information when undergoing shared decision-making regarding osteoarthritis management options and timing. LEVEL OF EVIDENCE: Level III.

Periprosthetic joint infection rates across primary total hip arthroplasty surgical approaches: a systematic review and meta-analysis of 653,633 procedures.

INTRODUCTION: Evidence demonstrates comparable clinical outcomes across the various surgical approaches to primary total hip arthroplasty (THA). However, high-quality contemporary data regarding periprosthetic joint infection (PJI) risk between direct anterior approach (DAA) and other (THA) approaches is lacking. This systematic review and meta-analysis evaluated PJI rates reported in the literature between the DAA and other approaches. MATERIALS AND METHODS: Five online databases were queried for all studies published from January 1st, 2000 through February 17th, 2021 that reported PJI rates between DAA and other surgical approaches. Studies reporting on primary THAs for osteoarthritis (OA) and that included PJI rates segregated by surgical approach were included. Articles reporting on revision THA, alternative THA etiologies, or minimally invasive techniques were excluded. Mantel-Haenszel (M-H) models were utilized to evaluate the pooled effect of surgical approach on infection rates. Validated risk of bias and methodological quality assessment tools were applied to each study. Multiple sensitivity analyses were conducted to evaluate the robustness of analyses. RESULTS: 28 articles reporting on 653,633 primary THAs were included. No differences were found between DAA cohorts and combined other approaches (OR: 0.95; 95% CI 0.74-1.21; p = 0.67) as well as segregated anterolateral approach cohorts (OR: 0.82, 95% CI 0.64-1.06; p = 0.13). However, DAA patients had a significantly reduced risk of infection compared to those undergoing posterior (OR: 0.66, 95% CI 0.58-0.74; p < 0.0001) and direct lateral (OR: 0.56, 95% CI 0.48-0.65; p < 0.00001) approaches. CONCLUSION: The DAA to primary THA had comparable or lower PJI risk when compared to other contemporary approaches. The results of the most up-to-date evidence available serve to encourage adult reconstruction surgeons who have already adopted the DAA. Additionally, orthopaedic surgeons considering adoption or use of the direct anterior approach for other reasons should not be dissuaded over theoretical concern for a general increase in the risk of PJI. LEVEL OF EVIDENCE: Level III.

An anatomical study defining the safe range of angles in percutaneous iliosacral and transsacral screw fixation.

Percutaneous iliosacral screw fixation and transsacral fixation are challenging procedures requiring extensive knowledge of sacral anatomy to avoid damaging nearby neurovascular structures. Greater knowledge of anatomical screw trajectory and size allowances would be helpful to guide surgical placement. An anatomical study of 40 cadaveric sacra in specimens ages 18-65 was performed. Three-dimensional surface scans were obtained, and computer modeling software was used to simulate a 7.3 mm diameter screw with 1 mm buffer inserted orthogonal to the sacroiliac joint in the pelvic inlet and outlet views. Transsacral screws were also inserted into S1 and S2 vertebrae. For screws orthogonal to the sacroiliac joint, the overall mean screw insertion angle was 4.1° ± 7.5° (range, -18.3° to 22.0°) in the inlet view in the posterior to anterior direction, and 21.7° ± 5.1° (range, 8.2°-36.3°) in the outlet view in the caudal to cranial direction. Before breaching the sacrum, the range of sacral tunnel lengths was between 31.1 and 70.1 mm with a range of diameters between 9.3 and 13.3 mm. Transsacral screws inserted into either the S1 or S2 vertebrae did not breach the sacrum in 40% (16/40) at each level. 30% (12/40) of sacra could not safely accommodate both S1 and S2 transsacral screws. There is an initial screw insertion angle range of -4° to 12° in the inlet view and 16°-27° in the outlet view. There was always adequate size to accept a 7.3 mm or larger screw.