Group A Streptococcus induces lysosomal dysfunction in THP-1 macrophages.

The human-specific bacterial pathogen group A Streptococcus (GAS) is a significant cause of morbidity and mortality. Macrophages are important to control GAS infection, but previous data indicate that GAS can persist in macrophages. In this study, we detail the molecular mechanisms by which GAS survives in THP-1 macrophages. Our fluorescence microscopy studies demonstrate that GAS is readily phagocytosed by macrophages, but persists within phagolysosomes. These phagolysosomes are not acidified, which is in agreement with our findings that GAS cannot survive in low pH environments. We find that the secreted pore-forming toxin Streptolysin O (SLO) perforates the phagolysosomal membrane, allowing leakage of not only protons but also large proteins including the lysosomal protease cathepsin B. Additionally, GAS recruits CD63/LAMP-3, which may contribute to lysosomal permeabilization, especially in the absence of SLO. Thus, although GAS does not inhibit fusion of the lysosome with the phagosome, it has multiple mechanisms to prevent proper phagolysosome function, allowing for persistence of the bacteria within the macrophage. This has important implications for not only the initial response but also the overall functionality of the macrophages, which may lead to the resulting pathologies in GAS infection. Our data suggest that therapies aimed at improving macrophage function may positively impact patient outcomes in GAS infection.

Influence of obesity and intra-operative imaging guidance technology on acetabular cup positioning in total hip arthroplasty.

BACKGROUND: Accuracy of acetabular cup positioning during total hip arthroplasty (THA) can be improved with intra-operative imaging but may be influenced by body mass index (BMI). This study assessed the influence of BMI (kg/m2) on cup accuracy when using intra-operative fluoroscopy (IF) alone or supplemented with a commercial product. METHODS: This retrospective review included four consecutive cohorts of patients having undergone anterior approach THA with IF alone (2011-2015), IF and Overlay (2015-2016) (Radlink Inc., Los Angeles, CA), IF and Grid (2017-2018) (HipGrid Drone™, OrthoGrid Systems Inc., Salt Lake City, UT) and IF and Digital (2018-2020) (OrthoGrid Phantom®, OrthoGrid Systems, Inc., Salt Lake City, UT). Component placement accuracy was measured on 6-week post-operative weight bearing radiographs and compared between four BMI patient groups (BMI ≤ 25, 25 < BMI ≤ 30, 30 < BMI ≤ 35, and 35 < BMI). Total fluoroscopy times were also recorded directly from the fluoroscopy unit. RESULTS: Abduction angle significantly increased as BMI increased (p = 0.003) with IF alone but no difference was present in groups with guidance technology. Anteversion was significantly different between BMI groups for IF alone (p = 0.028) and Grid (p = 0.027) but was not different in Overlay (p = 0.107) or Digital (p = 0.210). Fluoroscopy time was significantly different between BMI categories for IF alone (p = 0.005) and Grid (p = 0.018) but was not different in Overlay (p = 0.444) or Digital (p = 0.170). CONCLUSION: Morbid obesity (BMI > 35) increases risk for malpositioning of acetabular cups and increases surgical time with IF alone or the Grid. Additional IF guidance technology (Overlay or Digital) increased cup positioning accuracy without decreasing surgical efficiency.

Preoperative Educational Classes in Elderly Patients May Not be Necessary Prior to Elective Joint Arthroplasty.

Preoperative arthroplasty classes decrease complications and readmissions, however, in-person classes are inconvenient for elderly patients with mobility limitations. This retrospective review included 232 patients (305 joints) with in-person preoperative educational classes (IPC) and 155 patients (192 joints) with telephone preoperative educational classes (TC). Compared to IPC, TC patients had a shorter length of stay (P<.009), but a greater percentage made at least one postoperative clinic call (22.8% vs 40%; P<.001). No differences were noted in complications, but emergency room visits significantly decreased for total knee TC patients (P=.039). The increase in clinic calls may be addressed through focused changes to the preoperative telephone dialogue, providing a safe and efficient alternative to IPCs.

A smaller femoral stem is needed for asian females.

BACKGROUND: Current femoral implants are manufactured based on Western anatomical structures and may be too large for smaller physiques, such as those of Asian females. This study reviewed the femoral stem size distribution used in a high-volume total hip arthroplasty (THA) practice and evaluated malalignment in patients receiving a size one implant. MATERIALS AND METHODS: A consecutive cohort of female patients self-reported as Asian (257 patients, 331 hips) or Caucasian (158 patients and 190 hips) were retrospectively evaluated. A single femoral stem type was used in all cases, performed by a single surgeon. Global hip offset (GHO) and leg length difference (LLD) were measured before and 6 weeks following THA. Differences between races were evaluated through Mann-Whitney U tests and chi-squared tests for continuous and categorical variables, respectively. RESULTS: The proportion of size one implants was higher amongst Asian patients (20.5%) than Caucasian patients (2.6%) (p < 0.001). A LLD greater than 6 mm was noted in 24.6% of size one patients and 11.4% of all other sizes (p = 0.010). Varus malalignment occurred in 47.9% of size one patients and 22.1% of all other sizes (p < 0.001). No fractures occurred in size one patients, and nine fractures (one intraoperative and eight post-operative) occurred in all other sizes (p = 0.258). CONCLUSION: The high proportion of size one stems required in Asian females and the higher incidence of LLD > 6 mm and varus malalignment suggest a distinct need for smaller femoral implants, especially for Asian females.

Reducing transfusion in hip arthroplasty: tranexemic acid diminishes influence of anesthesia administered.

BACKGROUND: The risk of transfusion following total hip arthroplasty (THA) continues to be problematic. The best choice of anesthesia (spinal vs general) and impact of tranexamic acid (TXA) use in reducing transfusions following surgery remain unclear. Therefore, the purpose of this study was to compare rates of blood transfusion following THA via the anterior approach using three different anesthesia protocols with and without TXA. MATERIALS AND METHODS: This retrospective review included 1399 patients (1659 hips), receiving spinal anesthesia (SA) without (248 patients) and with TXA (77 patients), general anesthesia (GA) without (151 patients) and with TXA (171) and general anesthesia with paravertebral block (GA-PVB) and TXA (748 patients). All procedures were performed by a single surgeon. Chi-Squared tests and logistic regression were performed to evaluate the rate and risks of transfusion between groups. RESULTS: Without TXA, transfusion rate with GA (24.5%) was higher than SA (13.4%) (p = 0.004). With TXA, there was no difference in transfusion rates between GA (4.6%), SA (3.9%) or GA-PVB (4.0%). The multivariable regression revealed bilateral (Odds Ratio (OR): 6.473; p < 0.001), female (OR: 2.046; p = 0.004), age (OR: 1.028; p = 0.012) and pre-operative anemia (OR: 2.604; p < 0.001) as increasing the risk of transfusion while use of TXA (OR: 0.168; p < 0.001) significantly reduced transfusion risk. CONCLUSION: The use of TXA during THA via the anterior approach removed the influence of anesthesia type regarding risk of transfusion. The use of TXA may reverse presumed disadvantages of GA alone, potentially facilitating rapid discharge following surgery.

Varus malalignment of short femoral stem not associated with post-hip arthroplasty fracture.

INTRODUCTION: Periprosthetic femoral fractures are an increasingly common post-operative complication of total hip arthroplasty (THA). Though varus malalignment is known to increase fracture risk in standard-length femoral stems, varus malalignment is not as well studied in short stems. Therefore, the purpose of this study was to determine if varus malalignment contributes to early periprosthetic fracture risk in a cementless taper-wedged, short femoral stem. MATERIALS AND METHODS: This retrospective review included 366 consecutive patients (441 THAs) having undergone THA via anterior approach by a single surgeon between July 2014 and December 2016. All patients received the same short, cementless femoral stem. Femoral component angle was measured on 6-week post-THA weight-bearing radiographs, with malalignment defined as a femoral component angle exceeding 0° ± 3°. Periprosthetic femoral fracture and aseptic loosening occurring within 2 years post-THA were recorded. RESULTS: The final data analysis included 426 hips with a mean follow-up time of 32.9 ± 10.2 months. Varus and neutral alignment occurred in 84 (19.6%) and 342 (79.9%) of stems, respectively. Three (0.7%) periprosthetic femoral fractures occurred within 2 years, all occurring in patients with neutrally aligned femoral stems. One (0.2%) stem failed due to aseptic loosening and was malaligned. CONCLUSION: Despite nearly 20% of stems placed in varus alignment, three of the four early complications occurred in a neutrally aligned stem. Based on these results, forceful intraoperative realignment of a short femoral stem with good initial fixation may present an unnecessary increased risk of intraoperative fracture.

Does femoral stem choice influence fracture type or incidence for direct anterior approach total hip arthroplasty?

INTRODUCTION: Despite similar fracture rates, the incidence of intraoperative and post-operative fractures between standard (ST) length and short (SH) femoral stems remains unclear. Therefore, this study compared the incidence of intraoperative and early postoperative fractures between three ST and a single tapered-wedge SH femoral stem. MATERIALS AND METHODS: Data were retrospectively collected on 1113 patients (1306 hips) having undergone total hip arthroplasty, via the anterior approach on a fracture table, between 2014 and 2019. One surgeon completed all ST procedures (314 hips), using one of three implants without discretion. One surgeon completed all SH procedures (992 hips), using one implant design. Differences between ST and SH groups were evaluated by independent t tests (continuous variables) and Chi-square tests (categorical variables). RESULTS: Patients in the SH group were significantly older (p < 0.001) and had a lower body mass index (p = 0.001) compared to the ST group. The total number of fractures was 12 (3.8%) and 14 (1.4%) in the ST and SH groups, respectively. The 12 ST fractures occurred intraoperatively, compared to two (0.2%) in the SH group. The remaining seven (0.7%) SH fractures occurred post-operatively. There was no difference in fracture rate between the three ST designs (p = 0.882). Interestingly, five (0.5%) insufficiency fractures were diagnosed in the SH group. CONCLUSION: The risk of intraoperative and post-operative fractures following anterior total hip arthroplasty may be biased toward ST and SH implants, respectively. These results, along with the presence of five insufficient fractures, identify potential fracture risks and mechanisms for specific implant designs.

Does age increase perioperative complications for single-stage bilateral total hip arthroplasty?

The potential of post-operative complication may exclude elderly patients from undergoing single-staged bilateral total hip arthroplasty (SSBTHA). This study retrospective compared perioperative complications between SSBTHA patients <70 (N = 157) and ≥70 (N = 56) years of age. Patients ≥70 had significantly lower body mass index (p = 0.029) and had a higher ASA classification (p = 0.041) compared to patients <70. No differences in post-operative complications or transfusion rates were found between age groups. However, patients ≥70 were less likely to be discharged home. While SSBTHA can safely be performed in patients ≥70, the risk of transfusion may suggest pre-operative hemoglobin screenings, especially for patients ≥70.

Comparison of Component Placement Accuracy Using Two Intraoperative Fluoroscopic Grid Technologies During Direct Anterior Total Hip Arthroplasty.

BACKGROUND: Intraoperative fluoroscopy is beneficial when performing total hip arthroplasty (THA) via the direct anterior approach; however, image distortion may influence component placement. A manual gridding system (MGS) and a digital gridding system (DGS) are commercially available, aimed at visually representing or correcting image distortion. Therefore, the purpose of this study is to compare component placement accuracy following direct anterior approach THA when intraoperative fluoroscopy was supplemented with MGS or DGS. METHODS: A retrospective evaluation of acetabular cup abduction (ABD), leg length discrepancy (LLD) and global hip offset difference (GHO) was completed for consecutive patients from 6 week post-THA weight-bearing radiographs. The predefined target LLD and GHO was <10 mm and ABD target was 45° ± 10°. Differences between MGS and DGS were determined by independent t-tests. RESULTS: The MGS (250 patients, 315 hips) and DGS (183 patients, 218 hips) achieved targeted ABD in 98.7% and 96.8% of cases, respectively, and ABD was significantly lower in the MGS group (45.14 ± 4.03° and 47.01 ± 4.39°, respectively) (P < .001). Compared to MGS, the DGS group averaged significantly higher GHO (3.64 ± 2.44 and 4.45 ± 2.73 mm, respectively, P = .002) but was not significantly different regarding LLD (2.92 ± 2.55 and 3.19 ± 2.46 mm, respectively, P = .275). No significant group difference was noted for percentage within the targeted LLD and GHO; however, 93.5% of DGS and 97.6% of MGS achieved all three (P = .031). CONCLUSION: The use of both the MGS and DGS resulted in consistent component placement within the predefined target zone. Although the MGS appeared to be slightly more consistent, these differences are unlikely to be clinically significant.

Clinical and molecular sub-classification of hepatocellular carcinoma relative to alpha-fetoprotein level in an Asia-Pacific island cohort.

Aim: Increased serum alpha-fetoprotein (AFP) levels are associated with specific molecular sub-classes of hepatocellular carcinoma (HCC), supporting AFP as a predictive or therapeutic biomarker for precision treatment of this disease. Considering recent efforts to validate HCC molecular classification systems across different populations, we applied existing signature-based classification templates to Hawaii cohorts and examined whether associations between HCC molecular sub-class, AFP levels, and clinical features found elsewhere can also be found in Hawaii, a region with a unique demographic and risk factor profile for HCC. Methods: Whole-genome expression profiling was performed on HCC tumors collected from 40 patients following partial hepatectomy. Tumors underwent transcriptome-based categorization into 3 molecular sub-classes (S1, S2, and S3). Patient groups based on molecular sub-class and AFP level were then compared with regards to clinical features and survival. Differences associated with AFP level and other clinical parameters were also examined at the gene signature level by gene set enrichment analysis. Results: Statistically confident (false discovery rate < 0.05) sub-classifications were made in 98% (39/40) of tumors. Patient sub-groups differed significantly with regards to serum AFP level, with significantly lower levels in the S3 sub-group as compared to S1 (P = 0.048) and S2 (P = 0.010). Serum AFP > 400 ng/mL predicted significant tumor enrichment for genes corresponding to MYC target activation, high cell proliferation, poor clinical prognosis, and the S2 sub-class. AFP > 400 ng/mL and non-S3 tumor classification were found to be significant predictors of overall survival. Conclusion: Distinct sub-classes of HCC associated with different molecular features and survival outcomes can be detected with statistical confidence in a Pacific Island cohort. Molecular classification signatures and other predictive markers for HCC that are valid for all patient populations are needed to support multi-center efforts to develop targeted therapies for HCC.