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.

Examining racial disparities in utilization rate and perioperative outcomes following knee and hip arthroplasty.

BACKGROUND: Previous arthroplasty utilization research predominantly examined Black and White populations within the US. This is the first known study to examine utilization and complications in poorly studied minority racial groups such as Asians and Native Hawaiian/Pacific-Islanders (NHPI) as compared to Whites. RESULTS: Data from 3304 primary total hip and knee arthroplasty patients (2011 to 2019) were retrospectively collected, involving 1789 Asians (52.2%), 1164 Whites (34%) and 320 Native Hawaiians/Pacific Islanders (NHPI) (9.3%). The 2012 arthroplasty utilization rates for Asian, White, and NHPI increased by 32.5%, 11.2%, and 86.5%, respectively, by 2019. Compared to Asians, Whites more often underwent hip arthroplasty compared to knee arthroplasty (odds ratio (OR) 1.755; p < 0.001). Compared to Asians, Whites and NHPI more often received total knee compared to unicompartmental knee arthroplasty (White: OR 1.499; NHPI: OR 2.013; p < 0.001). White patients had longer hospitalizations (2.66 days) compared to Asians (2.19 days) (p = 0.005) following bilateral procedures. Medicare was the most common insurance for Asians (66.2%) and Whites (54.2%) while private insurance was most common for NHPI (49.4%). Compared to Asians, economic status was higher for Whites (White OR 0.695; p < 0.001) but lower for NHPI (OR 1.456; p < 0.001). After controlling for bilateral procedures, NHPI had a lower risk of transfusion compared to Asians (OR 0.478; p < 0.001) and Whites had increased risk of wound or systemic complications compared to Asians (OR 2.086; p = 0.045). CONCLUSIONS: Despite NHPI demonstrating a significantly poorer health profile and lower socioeconomic status, contrary to previous literature involving minority racial groups, no significant overall differences in arthroplasty utilization rates or perioperative complications could be demonstrated amongst the racial groups examined.

The influence of mental health on early outcomes following total hip arthroplasty.

BACKGROUND: Poor mental health is difficult to recognize and as a result, its association with recovery from total joint arthroplasty is difficult to assess. The purpose of this study was to investigate the relationship between overall mental health scores and outcomes in the early postoperative period following unilateral total hip arthroplasty (THA). METHODS: This is a retrospective review of prospectively collected data involving 142 patients who underwent primary unilateral THA. Independent variables included patient demographics and preoperative Patient-Reported Outcomes Measurement Information System (PROMIS), Global Physical Health (GPH) and Global Mental Health (GMH) and Hip Disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS JR) scores as well as diagnoses of depression or anxiety. Dependent variables included length of stay (LOS), disposition at discharge, narcotic consumption until discharge, 6-week postoperative GPH, GMH and HOOS JR scores and magnitude of change compared to preoperative scores. Preoperative GMH and postoperative outcomes were compared using Pearson correlation coefficient, independent t-tests, Pearson's Chi-Square test, and univariate logistic regression. RESULTS: Patients with preoperative GMH scores below the 25% quartile were less likely to be discharged home and resulted in lower GPH, GMH and HOOS JR scores at 6-week follow-up compared to patients with preoperative GMH scores in the top 25% quartile. However, patients with low preoperative GMH scores demonstrated a greater magnitude of improvement in both the GPH and GMH scores compared to patients in the top 25% quartile. There was no difference in opioid consumption or LOS between either groups. When comparing patients with and without depression/anxiety, no difference was seen in any of the outcomes measured. CONCLUSION: Unilateral THA offers significant improvements in both physical and mental function to patients with hip osteoarthritis and poor mental health, though overall scores remain lower than in those with better mental health.

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.

Themes in neuronavigation research: A machine learning topic analysis.

Objective: To understand trends in neuronavigation we employed machine learning methods to perform a broad literature review which would be impractical by manual inspection. Methods: PubMed was queried for articles with "Neuronavigation" in any field from inception-2020. Articles were designated neuronavigation-focused (NF) if "Neuronavigation" was a major MeSH. The latent dirichlet allocation topic modeling technique was used to identify themes of NF research. Results: There were 3896 articles of which 1727 (44%) were designated as NF. Between 1999-2009 and 2010-2020, the number of NF publications experienced 80% growth. Between 2009-2014 and 2015-2020, there was a 0.3% decline. Eleven themes covered 1367 (86%) NF articles. "Resection of Eloquent Lesions" comprised the highest number of articles (243), followed by "Accuracy and Registration" (242), "Patient Outcomes" (156), "Stimulation and Mapping" (126), "Planning and Visualization" (123), "Intraoperative Tools" (104), "Placement of Ventricular Catheters" (86), "Spine Surgery" (85), "New Systems" (80), "Guided Biopsies" (61), and "Surgical Approach" (61). All topics except for "Planning and Visualization", "Intraoperative Tools", and "New Systems" exhibited a monotonic positive trend. When analyzing subcategories, there were a greater number of clinical assessments or usage of existing neuronavigation systems (77%) rather than modification or development of new apparatuses (18%). Conclusion: NF research appears to focus on the clinical assessment of neuronavigation and to a lesser extent on the development of new systems. Although neuronavigation has made significant strides, NF research output appears to have plateaued in the last decade.

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.

Improved hip symmetry with an adjustable fluoroscopic grid during total hip arthroplasty.

BACKGROUND: The use of intraoperative fluoroscopy (IF) is common with direct anterior total hip arthroplasty (THA), however image distortion in IF may limit its usefulness. The supplementation of IF with an adjustable grid (AG) may provide consistently better accuracy in component placement. Therefore, the purpose of this study was to compare the accuracy, consistency, and surgical efficiency between IF only and AG supplementation. METHODS: 2 cohorts were retrospectively evaluated, including 573 IF only patients and 211 AG patients having undergone unilateral THA between 2011 and 2018. Post-THA radiographic assessment was performed to evaluate the accuracy of component placement, with target placements for global hip offset (GHO) and leg-length differences (LLD) <10 mm and acetabular cup abduction of 45° (±10°). Accuracy and surgical efficiency were evaluated between groups and over time. RESULTS: The AG group had a significant greater percentage of components placed within the target zone compared to IF only for GHO (99.5%, 92.7%, p < 0.001), LLD (99.1%, 96.5%, p = 0.039) and abduction (99.5%, 96.3%, p = 0.009), with no difference in fluoroscopic time (p = 0.973). Over time, accuracy was significantly different in IF group for GHO (p = 0.008) and abduction (p = 0.002) and trended toward significance for LLD (p = 0.055). There were no significant differences over time for the AG group. CONCLUSIONS: The addition of an AG to IF significantly increased the accuracy of component placement during direct anterior THA. These results were consistent over 2 years of use and did not decrease surgical efficiency.

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.

Component placement accuracy of two digital intraoperative fluoroscopy supplementation systems in direct anterior total hip arthroplasty.

INTRODUCTION: Intraoperative fluoroscopy (IF) may increase accuracy of component placement when performing direct anterior approach total hip arthroplasty (THA), however, unguided IF continues to produce inconsistent results. Supplementation of IF, with a digital grid (Grid) system or digital overlay (Overlay), may increase component placement accuracy. The purpose of this study was to compare component placement accuracy following THA when IF was supplemented with the Grid or Overlay technique. MATERIALS AND METHODS: Acetabular abduction and anteversion, with leg length discrepancy (LLD) and global hip offset (GHO) were retrospectively evaluated for unilateral and bilateral THA patients from 6-week post-operative radiographs. Target component placement were GHO and LLD < 10 mm, abduction 45° ± 10° and anteversion 15° ± 10° for Overlay and 17° ± 10° for Grid. Differences between the Overlay and Grid were determined by univariate analyses. RESULTS: The Overlay and Grid groups included 178 patients (217 hips) and 262 patients (317 hips), respectively. Target placement with the Overlay and Grid was achieved for GHO in 98.3% and 95.7% of cases (p = 0.108), LLD in 100% and 98.4% of cases (p = 0.121), cup abduction in 98.2% and 97.4% of cases (p = 0.384), and cup anteversion in 97.7% and 71.1% of cases (p < 0.001), respectively. Surgical time was significantly longer in Overlay compared to Grid (Unilateral 77.5 ± 14.1 min and 68.8 ± 12.2; p < 0.001; Bilateral 184.6 ± 27.0 min and 165.5 ± 23.1; p < 0.001, respectively). CONCLUSION: Although no difference was found between the Grid and the Overlay cohorts for LLD, GHO or abduction angle, the Overlay resulted in greater accuracy for acetabular component anteversion angle, with only a slight decrease in surgical efficiency.

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.

Stepping toward outpatient total hip arthroplasty with a rapid discharge protocol.

With total hip arthroplasty no longer an inpatient only procedure, this study retrospectively evaluated the percentage of same day, outpatient (<24 h) and inpatient (>24 h) discharges between 543 standard discharge (SDP) and 372 rapid discharge (RDP) patients. Outpatient discharges increased from 31.9% with SDP to 87.4% with RDP (p < 0.001) and 16.4% achieving same day discharge. Patients not achieving outpatient discharge were more commonly older (odds ratio (OR):1.052, p = 0.003), female (OR:2.715, p = 0.003) and a higher comorbidity classification (OR:2.751, p = 0.002). The 12.6% of patients failing to achieve outpatient discharge suggests that careful patient selection may be necessary to obtain 100% success.

Perioperative strategies to reduce transfusion rates in one-stage bilateral total hip arthroplasty via direct anterior approach.

Despite several blood management strategies available, blood transfusion rates following total hip arthroplasty remain high. Therefore, this study evaluated transfusion rates following bilateral hip arthroplasty via direct anterior approach using a multimodal blood loss management approach for 213 consecutive patients. All patients received standard surgical and post-operative procedures, with allogenic transfusion performed if hemoglobin was less than 8.0 g/dL with persistent clinical symptoms. Thirty-two patients (15%) required transfusion, with those patients significantly older and had lower pre-operative hemoglobin compared to non-transfusion patients. This transfusion rate was much lower than previous literature and could be an appropriate, multimodal blood loss management strategy.

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.