Nanomedicines modulate the tumor immune microenvironment for cancer therapy.

INTRODUCTION: In recent years, the evolution of immunotherapy as a means to trigger a robust antitumor immune response has revolutionized cancer treatment. Despite its potential, the effectiveness of cancer immunotherapy is hindered by low response rates and significant systemic side effects. Nanotechnology emerges as a promising frontier in shaping the future of cancer immunotherapy. AREAS COVERED: This review elucidates the pivotal role of nanomedicine in reshaping the immune tumor microenvironment and explores innovative strategies pursued by diverse research groups to enhance the therapeutic efficacy of cancer immunotherapy. It discusses the hurdles encountered in cancer immunotherapy and the application of nanomedicine for small molecule immune modulators and nucleic acid therapeutics. It also highlights the advancements in DNA and mRNA vaccines facilitated by nanotechnology and outlines future trajectories in this evolving field. EXPERT OPINION: Collectively, the integration of nanomedicine into cancer immunotherapy stands as a promising avenue to tackle the intricacies of the immune tumor microenvironment. Innovations such as immune checkpoint inhibitors and cancer vaccines have shown promise. Future developments will likely optimize nanoparticle design through artificial intelligence and create biocompatible, multifunctional nanoparticles, promising more effective, personalized, and durable cancer treatments, potentially transforming the field in the foreseeable future.

Silk vista baby flow diversion beyond the circle of Willis: A single-center experience with long-term outcomes.

INTRODUCTION: There is a lack of evidence of flow diversion (FD) safety for aneurysms treatment beyond the circle of Willis. Therefore, we provide a single-center real-world experience with the Silk Vista Baby (SVB). METHODS: A single-center database was retrospectively reviewed for aneurysms treated with SVB flow diverters. Demographic information, clinical presentation, radiographic characteristics, procedural complications, and outcomes were assessed. RESULTS: About 57 patients (66.7% female, mean age 54.3 ± 13.2) encompassing 57 aneurysms were included. Overall, 40.4% were ruptured: 68.4% saccular, 17.5% blister, 8.7% fusiform, and 5.3% dissecting. The majority were in the anterior circulation (68.4%), and in 48.2% of cases, the distal vessel diameter was inferior to 2 mm. The symptomatic ischemic rate was 5.2%, with one case due to in-stent thrombosis (1.8%). There were no hemorrhagic complications. Complication rates did not differ between ruptured and unruptured lesions (p = 0.356). There were no cases of delayed aneurysm rupture, and overall mortality was 1.8%. The median follow-up time was 18 ± 12 months. In-stent stenosis rate was 10.5% (6/57), all of which were asymptomatic. At the last follow-up, 70.2% of cases had an adequate occlusion (OKM C and D), and 96.5% had an mRS of 0-2. CONCLUSION: In our series, SVB was shown to be a safe device in the treatment of not only distal anterior circulation aneurysms but also in the management of complex posterior fossa and ruptured blister aneurysms. Multicenter studies are needed to confirm and generalize these results.

Resiquimod-loaded cationic liposomes cure mice with peritoneal carcinomatosis and induce specific anti-tumor immunity.

Peritoneal carcinomatosis (PC) is characterized by a high recurrence rate and mortality following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), primarily due to incomplete cancer elimination. To enhance the standard of care for PC, we developed two cationic liposomal formulations aimed at localizing a toll-like receptor agonist, resiquimod (R848), in the peritoneal cavity to activate the immune system locally to specifically eradicate residual tumor cells. These formulations effectively extended R848 retention in the peritoneum by >10-fold, resulting in up to a 2-fold increase in interferon α (IFN-α) induction in the peritoneal fluid, without increasing the plasma levels. In a CT26 colon cancer model with peritoneal metastases, these liposomal R848 formulations, when combined with oxaliplatin (OXA)-an agent used in HIPEC that induces immunogenic cell death-increased tumor infiltration of effector immune cells, including DCs, CD4, and CD8 T cells. This led to the complete elimination of PC in 60-70% of the mice, while the control mice reached humane endpoints by 30 days. The cured mice developed specific antitumor immunity, as re-challenging them with the same tumor cells did not result in tumor establishment. However, inoculation with a different tumor line led to tumor development. Additionally, exposing CT26 tumor antigens to the splenocytes isolated from the cured mice induced the expansion of CD4 and CD8 T cells and the release of IFN-γ, demonstrating long-term immune memory to the specific tumor. The anti-tumor efficacy of these liposomal R848 formulations was mediated via CD8 T cells with different levels of involvement of CD4 and B cells, and the combination with an anti-PD-1 antibody achieved a cure rate of 90%.

Intranasal delivery of low-dose anti-CD124 antibody enhances treatment of chronic rhinosinusitis with nasal polyps.

Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice. αCD124 was mixed with Nano-P or Dendri-P and then intranasally delivered for the treatment of severe CRSwNP in mice. Micro-CT and pathological changes in nasal turbinates showed that these two nano-formulations achieved ∼50 % and ∼40 % reductions in nasal polypoid lesions and eosinophil count, respectively. Both nano-formulations provided enhanced efficacy in suppressing nasal and systemic Immunoglobulin E (IgE) and nasal type 2 inflammatory biomarkers, such as interleukin 13 (IL-13) and IL-25. These effects were superior to those in the protamine formulation group and subcutaneous (s.c.) αCD124 given at a 12.5-fold higher dose. Intranasal delivery of protamine, Nano-P, or Dendri-P did not induce any measurable toxicities in mice.

Systemic delivery of proteins using novel peptides via the sublingual route.

Therapeutic proteins often require needle-based injections, which compromise medication adherence especially for those with chronic diseases. Sublingual administration provides a simple and non-invasive alternative. Herein, two novel peptides (lipid-conjugated protamine and a protamine dimer) were synthesized to enable sublingual delivery of proteins through simple physical mixing with the payloads. It was found that the novel peptides promoted intracellular delivery of proteins via increased pore formation on the cell surface. Results from in vitro models of cell spheroids and human sublingual tissue substitute indicated that the novel peptides enhanced protein penetration through multiple cell layers compared to protamine. The novel peptides were mixed with insulin or semaglutide and sublingually delivered to mice for blood glucose (BG) control. The effects of these sublingual formulations were comparable to the subcutaneous preparations and superior to protamine. In addition to peptide drugs, the novel peptides were shown to enable sublingual absorption of larger proteins with molecular weights from 22 to 150 kDa in mice, including human recombinant growth hormone (rhGH), bovine serum albumin (BSA) and Immunoglobulin G (IgG). The novel peptides given sublingually did not induce any measurable toxicities in mice.

Collaborative Recall and the Construction of Collective Memory Organization: The Impact of Group Structure.

Collaborative recall synchronizes downstream individual retrieval processes, giving rise to collective organization. However, little is known about whether particular stimulus features (e.g., semantic relatedness) are necessary for constructing collective organization and how group dynamics (e.g., reconfiguration) moderates it. We leveraged novel quantitative measures and a rich dataset reported in recent articles to address, (a) whether collective organization emerges even for semantically unrelated material and (b) how group reconfiguration-changing partners from one recall to the next-influences collective organization. Participants studied unrelated words and completed three consecutive recalls in one of three conditions: Always recalling individually (III), collaborating with the same partners twice before recalling alone (CCI), or collaborating with different group members during two initial recalls, before recalling alone (CRI). Collective organization increased significantly following any collaboration (CCI or CRI), relative to "groups" who never collaborated (III). Interestingly, collaborating repeatedly with the same partners (CCI) did not increase collective organization compared to reconfigured groups, irrespective of the reference group structure (from Recall 1 or 2). Individuals, however, did tend to base their final individual retrieval on the most recent group recall. We discuss how the fundamental processes that underlie dynamic social interactions align the cognitive processes of many, laying the foundation for other collective phenomena, including shared biases, attitudes, and beliefs.

Deep learning-based cerebral aneurysm segmentation and morphological analysis with three-dimensional rotational angiography.

BACKGROUND: The morphological assessment of cerebral aneurysms based on cerebral angiography is an essential step when planning strategy and device selection in endovascular treatment, but manual evaluation by human raters only has moderate interrater/intrarater reliability. METHODS: We collected data for 889 cerebral angiograms from consecutive patients with suspected cerebral aneurysms at our institution from January 2017 to October 2021. The automatic morphological analysis model was developed on the derivation cohort dataset consisting of 388 scans with 437 aneurysms, and the performance of the model was tested on the validation cohort dataset consisting of 96 scans with 124 aneurysms. Five clinically important parameters were automatically calculated by the model: aneurysm volume, maximum aneurysm size, neck size, aneurysm height, and aspect ratio. RESULTS: On the validation cohort dataset the average aneurysm size was 7.9±4.6 mm. The proposed model displayed high segmentation accuracy with a mean Dice similarity index of 0.87 (median 0.93). All the morphological parameters were significantly correlated with the reference standard (all P<0.0001; Pearson correlation analysis). The difference in the maximum aneurysm size between the model prediction and reference standard was 0.5±0.7 mm (mean±SD). The difference in neck size between the model prediction and reference standard was 0.8±1.7 mm (mean±SD). CONCLUSION: The automatic aneurysm analysis model based on angiography data exhibited high accuracy for evaluating the morphological characteristics of cerebral aneurysms.

Assessing the Immune Regulatory Role of Metabolites In Vitro.

One method of immune evasion that cancer cells employ is the secretion of immune regulatory metabolites into the tumor microenvironment (TME). These metabolites can promote immunosuppressive cell subsets, while inhibiting key tumor-killing subsets, such as T cells. Thus, the identification of these metabolites may help develop methods for improving cell-based therapy. However, after identifying a potential immune regulatory metabolite, it is crucial to assess the impacts of the metabolite on T cell immunobiology. In this chapter, we describe an in vitro method of testing and analyzing the influence of a specific metabolite on T cell proliferation and function.

Clinically relevant T cell expansion media activate distinct metabolic programs uncoupled from cellular function.

Ex vivo expansion conditions used to generate T cells for immunotherapy are thought to adopt metabolic phenotypes that impede therapeutic efficacy in vivo. The comparison of five different culture media used for clinical T cell expansion revealed unique optima based on different output variables, including proliferation, differentiation, function, activation, and mitochondrial phenotypes. The extent of proliferation and function depended on the culture media rather than stimulation conditions. Moreover, the expanded T cell end products adapted their metabolism when switched to a different media formulation, as shown by glucose and glutamine uptake and patterns of glucose isotope labeling. However, adoption of these metabolic phenotypes was uncoupled to T cell function. Expanded T cell products cultured in ascites from ovarian cancer patients displayed suppressed mitochondrial activity and function irrespective of the ex vivo expansion media. Thus, ex vivo T cell expansion media have profound impacts on metabolism and function.

Understanding Characteristics of Acute Brain Injury in Adult Extracorporeal Membrane Oxygenation: An Autopsy Study.

OBJECTIVES: Current studies lack information on characteristics of acute brain injury in patients with extracorporeal membrane oxygenation. We sought to characterize the types, timing, and risk factors of acute brain injury in extracorporeal membrane oxygenation. DESIGN: Retrospective analysis. SETTING: We reviewed the extracorporeal membrane oxygenation patients who had undergone brain autopsy with gross and microscopic examinations from January 2009 to December 2018 from a single tertiary center. PATIENTS: Twenty-five patients (median age 53 yr) had postmortem brain autopsy. INTERVENTIONS: Description and analysis of neuropathologic findings. MEASUREMENT AND MAIN RESULTS: Of 25, 22 had venoarterial extracorporeal membrane oxygenation (88%) (nine cardiac arrest; 13 cardiogenic shock) and three had venovenous extracorporeal membrane oxygenation cannulation (12%). The median extracorporeal membrane oxygenation support time was 96 hours (interquartile range, 26-181 hr). The most common acute brain injury was hypoxic-ischemic brain injury (44%), followed by intracranial hemorrhage (24%), and ischemic infarct (16%). Subarachnoid hemorrhage (20%) was the most common type of intracranial hemorrhage, followed by intracerebral hemorrhage (8%), and subdural hemorrhage (4%). Only eight patients (32%) were without acute brain injury after extracorporeal membrane oxygenation. The most common involved location for hypoxic-ischemic brain injury was cerebral cortices (82%) and cerebellum (55%). The pattern of ischemic infarct was territorial in cerebral cortices. The risk factors for acute brain injury included hypertension history (11 vs 1; p = 0.01), preextracorporeal membrane oxygenation antiplatelet use (7 vs 0; p = 0.03), and a higher day 1 lactate level (10.0 vs 5.1; p = 0.02). Patients with hypoxic-ischemic brain injury had more hypertension (8 vs 4; p = 0.047), a higher day 1 lactate level (12.6 vs 5.8; p = 0.02), and a lower pH level (7.09 vs 7.24; p = 0.027). Extracorporeal membrane oxygenation duration, cannulation methods, hemoglobin level, coma, renal impairment, and hepatic impairment were not associated with acute brain injury. CONCLUSIONS: In the population who underwent postmortem neuropathologic evaluation, 68% of extracorporeal membrane oxygenation nonsurvivors developed acute brain injury. Hypoxic-ischemic brain injury was the most common type of injury suggesting that patients sustained acute brain injury as a consequence of cardiogenic shock and cardiac arrest. Further research with a systematic neurologic monitoring is necessary to define the timing of acute brain injury in patients with extracorporeal membrane oxygenation.

Hyponatremia and hypercalcemia: a study of a large cohort of patients with lung cancer.

BACKGROUND: Hyponatremia and hypercalcemia are reported to be associated with poorer prognosis in lung cancer. Our study assessed the incidence of hyponatremia and hypercalcemia in a recent large cohort of patients diagnosed with lung cancer in an academic institution and correlated incidence with patient and tumour parameters. METHODS: All patients presented at our regional lung cancer multidisciplinary team meeting between January 2011 and December 2016 were included. The incidence of hyponatremia (serum sodium ≤135 mEq/L) and hypercalcemia (serum calcium >2.62 mmol/L), including severity (mild, moderate or severe) was evaluated and stratified by tumour subtype and stage, and correlated with patient parameters. RESULTS: A total of 624 patients (mean age, 67.4 years; 59.3% male) diagnosed with tissue-proven lung cancer were included. Hyponatremia and hypercalcemia were present in 31.6% (n=197) and 7.1% (n=44) at time of diagnosis. Hyponatremia occurred most commonly in patients with small cell lung carcinoma (SCLC) (n=42; 41.2%; P=0.001). Hypercalcemia occurred most commonly in patients with non-small cell lung carcinoma (NSCLC) squamous subtype (n=27; 12.2%; P=0.003). The incidence of hyponatremia and hypercalcemia were significantly higher in the advanced stages (P<0.041), except in SCLC where no difference in hypercalcemia incidence across the stages was observed (P=0.573). The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score was positively correlated with severity of hyponatremia at the early stage of NSCLC (Spearman correlation coefficient =0.325; P=0.003). CONCLUSIONS: Hyponatremia is a common association in lung cancer, especially in SCLC. Hypercalcemia is an uncommon but significant association in the NSCLC squamous subtype. Hyponatremia might contribute to poorer ECOG-PS scores at the early stage of NSCLC.

Age-related differences in orienting attention to sound object representations.

We examined the effect of age on listeners' ability to orient attention to an item in auditory short-term memory (ASTM) using high-density electroencephalography, while participants completed a delayed match-to-sample task. During the retention interval, an uninformative or an informative visual retro-cue guided attention to an item in ASTM. Informative cues speeded response times, but only for young adults. In young adults, informative retro-cues generated greater event-related potential amplitude between 450 and 650 ms at parietal sites, and an increased sustained potential over the left central scalp region, thought to index the deployment of attention and maintenance of the cued item in ASTM, respectively. Both modulations were reduced in older adults. Alpha and low beta oscillatory power suppression was greater when the retro-cue was informative than uninformative, especially in young adults. Our results point toward an age-related decline in orienting attention to the cued item in ASTM. Older adults may be dividing their attention between all items in working memory rather than selectively focusing attention on a single cued item.

Impact of Smoking Cessation Counseling Prior to Total Joint Arthroplasty.

Perioperative smoking has been linked to surgical complications including poor wound healing, infection, myocardial infarction, prolonged length of stay, need for mechanical ventilation, and death. This study evaluated the effectiveness of preoperative counseling on smoking cessation for patients undergoing elective total joint arthroplasty. Thirty smokers with hip or knee osteoarthritis seeking hip or knee replacement surgery were enrolled prospectively. Interventions included counseling, referrals to smoking cessation programs including the California Smokers' Helpline and the Fontana Tobacco Treatment Program, nicotine replacement therapy (NRT), or instructing patients quit through the "cold turkey" method of abstinence. Patients were scheduled for surgery if they demonstrated abstinence from smoking, confirmed via expired carbon monoxide (CO) breath testing. Short- and long-term smoking cessation rates were evaluated. Thirty patients were enrolled; 21 patients (70%) passed the CO test, whereas 9 patients (30%) failed or did not follow up with a CO test. Thirteen of 21 patients (62%) quit using the "cold turkey" method, 5 of 21 patients (24%) quit using NRT, and 3 of 21 patients (14%) quit using outpatient treatment programs. Eighteen of 21 patients (86%) who quit smoking underwent surgery, and 14 patients had surgery within 6 months of smoking abstinence. Nine of the 14 patients (64%) remained smoke-free 6 months postoperatively confirmed through telephone questionnaire. These results suggest that elective surgery offers a strong incentive for patients to quit smoking, and surgeons can play a role offering a teachable moment and motivating this potentially life-altering behavioral change. [Orthopedics. 2017; 40(2):e323-e328.].

Can Preoperative Patient-reported Outcome Measures Be Used to Predict Meaningful Improvement in Function After TKA?

BACKGROUND: Despite the overall effectiveness of total knee arthroplasty (TKA), a subset of patients do not experience expected improvements in pain, physical function, and quality of life as documented by patient-reported outcome measures (PROMs), which assess a patient's physical and emotional health and pain. It is therefore important to develop preoperative tools capable of identifying patients unlikely to improve by a clinically important margin after surgery. QUESTIONS/PURPOSES: The purpose of this study was to determine if an association exists between preoperative PROM scores and patients' likelihood of experiencing a clinically meaningful change in function 1 year after TKA. METHODS: A retrospective study design was used to evaluate preoperative and 1-year postoperative Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-12 version 2 (SF12v2) scores from 562 patients who underwent primary unilateral TKA. This cohort represented 75% of the 750 patients who underwent surgery during that time period; a total of 188 others (25%) either did not complete PROM scores at the designated times or were lost to follow-up. Minimum clinically important differences (MCIDs) were calculated for each PROM using a distribution-based method and were used to define meaningful clinical improvement. MCID values for KOOS and SF12v2 physical component summary (PCS) scores were calculated to be 10 and 5, respectively. A receiver operating characteristic analysis was used to determine threshold values for preoperative KOOS and SF12v2 PCS scores and their respective predictive abilities. Threshold values defined the point after which the likelihood of clinically meaningful improvement began to diminish. Multivariate regression was used to control for the effect of preoperative mental and emotional health, patient attributes quantified by SF12v2 mental component summary (MCS) scores, on patients' likelihood of experiencing meaningful improvement in function after surgery. RESULTS: Threshold values for preoperative KOOS and SF12v2 PCS scores were a maximum of 58 (area under the curve [AUC], 0.76; p < 0.001) and 34 (AUC, 0.65; p < 0.001), respectively. Patients scoring above these thresholds, indicating better preoperative function, were less likely to experience a clinically meaningful improvement in function after TKA. When accounting for mental and emotional health with a multivariate analysis, the predictive ability of both KOOS and SF12v2 PCS threshold values improved (AUCs increased to 0.80 and 0.71, respectively). Better preoperative mental and emotional health, as reflected by a higher MCS score, resulted in higher threshold values for KOOS and SF12v2 PCS. CONCLUSIONS: We identified preoperative PROM threshold values that are associated with clinically meaningful improvements in functional outcome after TKA. Patients with preoperative KOOS or SF12v2 PCS scores above the defined threshold values have a diminishing probability of experiencing clinically meaningful improvement after TKA. Patients with worse baseline mental and emotional health (as defined by SF12v2 MCS score) have a lower probability of experiencing clinically important levels of functional improvement after surgery. The results of this study are directly applicable to patient-centered informed decision-making tools and may be used to facilitate discussions with patients regarding the expected benefit after TKA. LEVEL OF EVIDENCE: Level III, prognostic study.

The Importance of Risk Adjustment in Reporting Total Joint Arthroplasty Outcomes.

BACKGROUND: This study describes and tests a risk adjustment model developed for the California Joint Replacement Registry to report predictors of complication rates. METHODS: Complication rates were analyzed for 9960 patients enrolled in the California Joint Replacement Registry at 22 medical centers. Multivariable logistic risk models were created to analyze risks of postoperative complications. RESULTS: Age and American Society of Anesthesiologists class were the strongest predictors of complication rates (P < .0001). Congestive heart failure and peripheral vascular disease were also statistically significant predictors of complications. Three hospitals were found to have statistically significantly worse than expected complication rates, and one was found to have a better than expected complication rate after case mix risk adjustment. CONCLUSION: Adequate risk adjustment is a key element in objective comparison of surgeons, hospitals, and devices using total joint arthroplasty registry data.

John Charnley Award: Preoperative Patient-reported Outcome Measures Predict Clinically Meaningful Improvement in Function After THA.

BACKGROUND: Despite the overall effectiveness of total hip arthroplasty (THA), a subset of patients remain dissatisfied with their results because of persistent pain or functional limitations. It is therefore important to develop predictive tools capable of identifying patients at risk for poor outcomes before surgery. QUESTIONS/PURPOSES: The purpose of this study was to use preoperative patient-reported outcome measure (PROM) scores to predict which patients undergoing THA are most likely to experience a clinically meaningful change in functional outcome 1 year after surgery. METHODS: A retrospective cohort study design was used to evaluate preoperative and 1-year postoperative SF-12 version 2 (SF12v2) and Hip Disability and Osteoarthritis Outcome Score (HOOS) scores from 537 selected patients who underwent primary unilateral THA. Minimum clinically important differences (MCIDs) were calculated using a distribution-based method. A receiver operating characteristic analysis was used to calculate threshold values, defined as the levels at which substantial changes occurred, and their predictive ability. MCID values for HOOS and SF12v2 physical component summary (PCS) scores were calculated to be 9.1 and 4.6, respectively. We analyzed the effect of SF12v2 mental component summary (MCS) scores, which measure mental and emotional health, on SF12v2 PCS and HOOS threshold values. RESULTS: Threshold values for preoperative HOOS and PCS scores were a maximum of 51.0 (area under the curve [AUC], 0.74; p < 0.001) and 32.5 (AUC, 0.62; p < 0.001), respectively. As preoperative mental and emotional health improved, which was reflected by a higher MCS score, HOOS and PCS threshold values also increased. When preoperative mental and emotional health were taken into account, both HOOS and PCS threshold values' predictive ability improved (AUCs increased to 0.77 and 0.69, respectively). CONCLUSIONS: We identified PROM threshold values that predict clinically meaningful improvements in functional outcome after THA. Patients with a higher level of preoperative function, as suggested by HOOS or PCS scores above the defined threshold values, are less likely to obtain meaningful improvement after THA. Lower preoperative mental and emotional health decreases the likelihood of achieving a clinically meaningful improvement in function after THA. The results of this study may be used to facilitate discussion between physicians and patients regarding the expected benefit after THA and to support the development of patient-based informed decision-making tools. For example, despite significant disease, patients with high preoperative function, as measured by PROM scores, may choose to delay surgery given the low likelihood of experiencing a meaningful improvement postoperatively. Similarly, patients with notably low MCS scores might best be counseled to address mental health issues before embarking on surgery. LEVEL OF EVIDENCE: Level III, prognostic study.

Quantifying the Burden of Revision Total Joint Arthroplasty for Periprosthetic Infection.

Periprosthetic joint infection (PJI) represents substantial clinical and economic burdens. This study evaluated patient and procedure characteristics and resource utilization associated with revision arthroplasty for PJI. The Nationwide Inpatient Sample (Q4 2005-2010) was analyzed for 235,857 revision THA (RTHA) and 301,718 revision TKA (RTKA) procedures. PJI was the most common indication for RTKA, and the third most common reason for RTHA. PJI was most commonly associated with major severity of illness (SOI) in RTHA, and with moderate SOI in RTKA. RTHA and RTKA for PJI had the longest length of stay. Costs were higher for RTHA/RTKA for PJI than for any other diagnosis except periprosthetic fracture. Epidemiologic differences exist in the rank, severity and populations for RTHA and RTKA for PJI.

Higher Preoperative Patient Activation Associated With Better Patient-reported Outcomes After Total Joint Arthroplasty.

BACKGROUND: Despite widely reported success associated with hip and knee replacements, some patients remain dissatisfied with their outcomes. Patient activation, an individual's propensity to engage in adaptive health behaviors, has been measured as a potentially important factor contributing to health outcomes, cost, and patient experience of care. However, to our knowledge, it has not been studied in patients undergoing total joint arthroplasties (TJAs). QUESTIONS/PURPOSES: We wanted to determine whether patients with higher activation scores would experience (1) greater resolution of pain and improved activity, (2) greater improvements in postoperative physical and mental health, and (3) greater patient satisfaction after primary THA or TKA. METHODS: We approached 174 patients and enrolled 135 who were undergoing primary THA or TKA at one of two hospitals between January 2013 and May 2014. Patient Activation Measure (PAM) scores were obtained preoperatively and patient-reported outcomes were assessed and completed for 125 patients pre- and postoperatively at the 6- or 12-month visit. We assessed pain and activity with the Hip Disability and Osteoarthritis Outcome Score (HOOS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and University of California Los Angeles (UCLA) activity scores. We measured physical and mental health by calculating SF12v2® scores and measured patient satisfaction with the Hip and Knee Satisfaction Scale (HKSS). Linear regression models were used to test the association between baseline PAM and postoperative patient-reported outcomes. RESULTS: Overall, patients with a higher baseline PAM score experienced better pain relief using the HOOS/KOOS pain scores (R2=0.311, p=0.048) and symptoms using the HOOS/KOOS symptom scores (R2=0.272, p=0.021). In addition, higher PAM scores were associated with better postoperative mental health using the SF12v2® (R2=0.057, p<0.001), but were not associated with higher physical health (R2=0.176, p=0.173). Finally, higher PAM scores were associated with having greater postoperative satisfaction after surgery using the HKSS questionnaire (R2=0.048, p=0.023). CONCLUSIONS: Higher preoperative patient activation was associated with better pain relief, decreased symptoms, improved mental health, and greater satisfaction after TJA. Future efforts should be aimed at studying if improving patient activation before surgery results in better patient-reported outcomes after elective THA or TKA. LEVEL OF EVIDENCE: Level II, prognostic study.

Impact of socioeconomic factors on informed decision making and treatment choice in patients with hip and knee OA.

It is unclear how socioeconomic (SES) status influences the effectiveness of shared decision making (SDM) tools. The purpose of this study was to assess the impact of SES on the utility of SDM tools among patients with hip and knee osteoarthritis (OA). We performed a secondary analysis of data from a randomized controlled trial of 123 patients with hip or knee OA. Higher education and higher income were independently associated with higher knowledge survey scores. Patients with private insurance were 2.7 times more likely than patients with Medicare to arrive at a decision after the initial office visit. Higher education was associated with lower odds of choosing surgery, even after adjusting for knowledge. Patient knowledge of their medical condition and treatment options varies with SES.

Comparative Epidemiology of Revision Arthroplasty: Failed THA Poses Greater Clinical and Economic Burdens Than Failed TKA.

BACKGROUND: Revision THA and TKA are growing and important clinical and economic challenges. Healthcare systems tend to combine revision joint replacement procedures into a single service line, and differences between revision THA and revision TKA remain incompletely characterized. These differences carry implications for guiding care and resource allocation. We therefore evaluated epidemiologic trends associated with revision THAs and TKAs. QUESTIONS/PURPOSES: We sought to determine differences in (1) the number of patients undergoing revision TKA and THA and respective demographic trends; (2) differences in the indications for and types of revision TKA and THA; (3) differences in patient severity of illness scoring between THA and TKA; and (4) differences in resource utilization (including cost and length of stay [LOS]) between revision THA and TKA. METHODS: The Nationwide Inpatient Sample (NIS) was used to evaluate 235,857 revision THAs and 301,718 revision TKAs between October 1, 2005 and December 31, 2010. Patient characteristics, procedure information, and resource utilization were compared across revision THAs and TKAs. A revision burden (ratio of number of revisions to total number of revision and primary surgeries) was calculated for hip and knee procedures. Severity of illness scoring and cost calculations were derived from the NIS. As our study was principally descriptive, statistical analyses generally were not performed; however, owing to the large sample size available to us through this NIS analysis, even small observed differences presented are likely to be highly statistically significant. RESULTS: Revision TKAs increased by 39% (revision burden, 9.1%-9.6%) and THAs increased by 23% (revision burden, 15.4%-14.6%). Revision THAs were performed more often in older patients compared with revision TKAs. Periprosthetic joint infection (25%) and mechanical loosening (19%) were the most common reasons for revision TKA compared with dislocation (22%) and mechanical loosening (20%) for revision THA. Full (all-component) revision was more common in revision THAs (43%) than in TKAs (37%). Patients who underwent revision THA generally were sicker (> 50% major severity of illness score) than patients who underwent revision TKA (65% moderate severity of illness score). Mean LOS was longer for revision THAs than for TKAs. Mean hospitalization costs were slightly higher for revision THA (USD 24,697 +/- USD 40,489 [SD]) than revision TKA (USD 23,130 +/- USD 36,643 [SD]). Periprosthetic joint infection and periprosthetic fracture were associated with the greatest LOS and costs for revision THAs and TKAs. CONCLUSIONS: These data could prove important for healthcare systems to appropriately allocate resources to hip and knee procedures: the revision burden for THA is 52% greater than for TKA, but revision TKAs are increasing at a faster rate. Likewise, the treating clinician should understand that while both revision THAs and TKAs bear significant clinical and economic costs, patients undergoing revision THA tend to be older, sicker, and have greater costs of care.