Clinical outcomes of patellofemoral arthroplasty: robotic assistance produces superior short and mid-term outcomes.

INTRODUCTION: Patellofemoral arthroplasty (PFA) has been shown to provide symptomatic improvement for isolated patellofemoral osteoarthritis (PFOA). The efficacy of robotic-assisted PFA and the most suitable PFA implant design, however, remain ongoing matters of debate. This study sought to compare clinical outcomes between patients who underwent robotic-assisted versus conventional PFAs with inlay and onlay prosthetic designs. METHODS: A single-center retrospective review found 237 knees (211 patients) which underwent PFA between 2011 and 2021. One hundred eighty-four knees were included in the final analysis after cases were excluded for having indications other than osteoarthritis or having less than one year of follow-up. There were 90 conventional PFAs and 94 robotic-assisted PFAs performed. Inlay components were implanted in 89 knees and onlay components were implanted in 95 knees. Propensity score matching was utilized to address demographic differences between groups. RESULTS: Overall, there was a revision-free survivorship rate of 89.7% with an average time to follow-up of 4.6 years (range 1.2 to 11.1). Twenty-nine knees (15.8%) required various non-conversion procedures. The conventional matched cohort exhibited a higher all-cause revision rate, accounting for revision PFAs and conversions to TKA, (18.8 vs. 6.4%, p = 0.014) and a shorter mean time to revision than the robotic-assisted cohort (3.1 vs. 5.8 years, p = 0.026). A Kaplan-Meier survivorship curve showed differences between the conventional and robotics cohorts (p = 0.041). All revisions following robotic-assisted PFA were caused by progression of osteoarthritis, whereas conventional PFAs also required revision due to aseptic loosening and patellar maltracking. The rate of infection resulting in irrigation and debridement was higher for conventional cases (4.3 vs. 0%, p = 0.041). No significant differences in clinical outcomes between the inlay and onlay prosthetic design matched cohorts were identified. CONCLUSION: PFA is an effective treatment for addressing advanced patellofemoral arthritis. Robotic-assisted surgery may lead to improved clinical outcomes. LEVEL OF EVIDENCE: III.

"Stuck in the middle": the missing lumbosacral link in total hip arthroplasty.

INTRODUCTION: Spinopelvic mobility drives functional acetabular position, influencing dislocation risk after total hip arthroplasty (THA). Patients have been described as "stuck sitting" or "stuck standing" based on pelvic tilt (PT). We hypothesised that some patients are "stuck in the middle," meaning their PT changes minimally from sitting to standing - increasing their risk of dislocation. METHODS: We reviewed 195 patients with standing and sitting whole body radiographs prior to THA. Standing anterior pelvic plane tilt (APPT) and standing and sitting sacral slope (SS) were measured and used to calculate sitting APPT. Normal standing and sitting were defined as APPT >-10° and <-20°, respectively. Spinal stiffness was classified as <10° change in sacral slope between sitting and standing. Patients were categorised as: (A) able to fully sit and stand; (B) "stuck sitting" - able to fully sit; unable to fully stand; (C) "stuck standing" - able to fully stand; unable to fully sit; or (D) "stuck in the middle" - unable to sit or stand fully. RESULTS: 84 patients could sit and stand normally (A), 22 patients were stuck sitting (B), 76 patients were stuck standing (C), and 13 patients were stuck in the middle (D). While 111 patients (56.9%) were considered stuck, only 58 patients (29.7%) met criteria for spinal stiffness. DISCUSSION: We identified a subset of patients with stiff spines and abnormal PT in both sitting and standing, including 37.1% of patients who would be classified as "stuck sitting" based only on standing radiographs. Placing acetabular components in less than anatomic anteversion in these patients may increase posterior dislocation risk.

The Influence of Tourniquet and Adductor Canal Block Use on Pain and Opioid Consumption after Total Knee Arthroplasty.

Reducing pain and opioid consumption after total knee arthroplasty (TKA) is an important perioperative consideration. Though commonly used, the combined influence of tourniquets and adductor canal blocks (ACBs) on pain and opioid consumption is unknown. This study evaluated inpatient opioid consumption and pain between patients with TKA based on tourniquet and/or ACB use. Pain and opioid consumption were highest when a tourniquet, but no ACB was used, and lowest when an ACB, but no tourniquet was used - though absolute differences in pain scores were not clinically significant. Tourniquet and ACB use should be considered as part of TKA opioid-sparing protocols.

Hospital Teaching Status and Patient-Reported Outcomes Following Primary Total Hip Arthroplasty: An American Joint Replacement Registry Study.

INTRODUCTION: Previous studies have shown lower morbidity and mortality rates after total hip arthroplasty (THA) at academic teaching hospitals. This study sought to determine the relationship between hospital teaching status and patient-reported outcome measures following primary THA. METHODS: Using American Joint Replacement Registry data from 2012 to 2020, 4,447 primary, elective THAs with both preoperative and one year postoperative Hip disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS, JR) scores were analyzed. The main exposure variable was hospital teaching status, with three cohorts, as follows: major teaching hospitals, minor teaching hospitals, and non-teaching hospitals. Mean preoperative and one year postoperative HOOS, JR scores were compared. RESULTS: Preoperative HOOS, JR scores (nonteaching: 49.69 ± 14.42 versus major teaching: 47.68 ± 15.10 versus minor teaching: 42.46 ± 19.19, P < .001) were significantly higher at non-teaching hospitals than major and minor teaching hospitals, and these differences persisted at one year postoperatively (87.40 ± 15.14 versus 83.87 ± 16.68 versus 80.37 ± 19.27, P < .001). Both preoperative and postoperative differences in HOOS, JR scores were less than the minimum clinically important difference (MCID) at both time points. In multivariate regressions, non-teaching and minor teaching hospitals had similar odds of MCID achievement in HOOS, JR scores compared to major teaching hospitals. CONCLUSION: Using the HOOS, JR score as a validated outcome measure, undergoing primary THA at an academic teaching hospital did not correlate with higher postoperative HOOS, JR scores or greater chances of MCID achievement in HOOS, JR scores compared to non-teaching hospitals. Further work is required to determine the most important factors that may lead to improvement in patient-reported outcomes following THA.

Crohn's Disease Increases In-Hospital Lengths of Stay, Medical Complications, and Costs of Care following Primary Total Knee Arthroplasty.

The literature has shown an increase in prevalence of Crohn's disease (CD) within the United States alongside a concomitant rise in primary total knee arthroplasty (TKA) procedures. As such, with these parallel increases, orthopaedic surgeons will invariably encounter CD patients requiring TKA. Limited studies exist evaluating the impact of this disease on patients undergoing the procedure; therefore, this study endeavors to determine whether CD patients undergoing primary TKA have higher rates of (1) in-hospital lengths of stay (LOS), (2) medical complications, and (3) episode of care (EOC) costs. To accomplish this, a nationwide database was queried from January 1, 2005 to March 31, 2014 to identify patients undergoing TKA. The study group, patients with CD, was randomly matched to the controls, patients without CD, in a 1:5 ratio after accounting for age, sex, and medical comorbidities associated with CD. Patients consuming corticosteroids were excluded, as they are at risk of higher rates of adverse events following TKA. This query ultimately yielded a total of 96,213 patients, with 16,037 in the study cohort and 80,176 in the control one. The study compared in-hospital (LOS), 90-day medical complications, and day of surgery and total global 90-day EOC costs between CD and non-CD patients undergoing primary TKA. The results found CD patients undergoing primary TKA had significantly longer in-hospital LOS (4- vs. 3 days, p < 0.0001) compared with non-CD patients. CD patients were also found to have significantly higher incidence and odds of 90-day medical complications (25.31 vs. 10.75; odds ratio: 2.05, p < 0.0001) compared with their counterparts. Furthermore, CD patients were found to have significantly higher 90-day EOC costs ($15,401.63 vs. 14,241.15, p < 0.0001) compared with controls. This study demonstrated that, after adjusting for age, sex, and medical comorbidities, patients with CD have prolonged in-hospital LOS, increased medical complications, and higher EOC costs following primary TKA. Therefore, it establishes the importance for orthopaedists to adequately counsel CD patients of the potential complications and outcomes following their procedure.

Mast cells impair melanoma cell homing and metastasis by inhibiting HMGA1 secretion.

Metastatic disease is the major cause of death from cancer. From the primary tumour, cells remotely prepare the environment of the future metastatic sites by secreted factors and extracellular vesicles. During this process, known as pre-metastatic niche formation, immune cells play a crucial role. Mast cells are haematopoietic bone marrow-derived innate immune cells whose function in lung immune response to invading tumours remains to be defined. We found reduced melanoma lung metastasis in mast cell-deficient mouse models (Wsh and MCTP5-Cre-RDTR), supporting a pro-metastatic role for mast cells in vivo. However, due to evidence pointing to their antitumorigenic role, we studied the impact of mast cells in melanoma cell function in vitro. Surprisingly, in vitro co-culture of bone-marrow-derived mast cells with melanoma cells showed that they have an intrinsic anti-metastatic activity. Mass spectrometry analysis of melanoma-mast cell co-cultures secretome showed that HMGA1 secretion by melanoma cells was significantly impaired. Consistently, HMGA1 knockdown in B16-F10 cells reduced their metastatic capacity in vivo. Importantly, analysis of HMGA1 expression in human melanoma tumours showed that metastatic tumours with high HMGA1 expression are associated with reduced overall and disease-free survival. Moreover, we show that HMGA1 is reduced in the nuclei and enriched in the cytoplasm of melanoma metastatic lesions when compared to primary tumours. These data suggest that high HMGA1 expression and secretion from melanoma cells promote metastatic behaviour. Targeting HMGA1 expression intrinsically or extrinsically by mast cells actions reduce melanoma metastasis. Our results pave the way to the use of HMGA1 as anti-metastatic target in melanoma as previously suggested in other cancer types.

Duration of antibiotics for penetrating spine trauma: a systematic review.

Penetrating trauma to the spine with resultant spinal and paraspinal infection represents a potentially devastating injury for which there is little consensus regarding management. The duration, route and type of antibiotics required to prevent infections such as epidural abscess, vertebral osteomyelitis, and discitis is remain controversial. Several studies support standard prophylactic antimicrobial treatment for 48 hours following penetrating spinal trauma while others demonstrate that extended therapy for one week or greater is necessary to reduce risk of infection. However, there is no established protocol or consensus for management. Our systematic review aims to determine the ideal duration of antibiotics following penetrating spine trauma. Three databases (PubMed, SCOPUS, and Ovid) were queried using the following keywords: penetrating spine trauma, spine infection, spine trauma antibiotics. Nine articles were found to meet the inclusion criteria for this systematic review. The majority of studies included in final analysis discussed penetrating spinal trauma in the form of gunshot wounds. 459 patients were included in total across all studies and 21 patients developed spinal or paraspinal infection (4.58%). Five studies demonstrated an infection rate below 5% with antibiotic therapy for 5 days or longer while 2 more recent studies demonstrated a similar infection rate in their cohort with only 48 hours of antimicrobial prophylaxis. Our systematic review finds a low rate of paraspinal and spinal infections following penetrating spine trauma. As all studies included are retrospective in nature, no definitive recommendations can be made regarding duration of therapy. Forty-eight hours of antimicrobial prophylaxis may be sufficient for most patients except for those with trans-colonic injuries as these are associated with a greater contamination and risk for spinal infection.

Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.

Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis.

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP+ exosomes. Moreover, uptake of CEMIP+ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.

Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.

The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Exo-S, 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.