Fluorescently Tagged Verticillium dahliae to Understand the Infection Process on Cotton (Gossypium hirsutum) and Weed Plant Species.

Verticillium wilt is a soil-borne disease caused by distinct vegetative compatibility groups (VCG) of the fungus Verticillium dahliae. Defoliating (VCG 1A) and non-defoliating (VCG 2A) pathotypes of V. dahliae have contributed to yield losses of cotton production in Australia. To study the virulence and the infection process of V. dahliae on cotton, two isolates, one representing each VCG, have been transformed with fluorescent protein genes. The transformants maintained their ability to infect the host, and both strains were observed to move through the plant vasculature to induce wilt symptoms. Furthermore, virulence testing suggests that the cotton V. dahliae strains can endophytically colonise common weed plant species found in the Australian landscape, and that is contrasted by their ability to infect and colonise native tobacco plants. The fluorescently labelled strains of V. dahliae not only allowed us to gain a thorough understanding of the infection process but also provided a method to rapidly identify recovered isolates from host colonisation studies.

A Polyphasic Approach including Whole Genome Sequencing Reveals Paecilomyces paravariotii sp. nov. as a Cryptic Sister Species to P. variotii.

Whole genome sequencing is rapidly increasing phylogenetic resolution across many groups of fungi. To improve sequencing coverage in the genus Paecilomyces (Eurotiales), we report nine new Paecilomyces genomes representing five different species. Phylogenetic comparison between these genomes and those reported previously showed that Paecilomyces paravariotii is a distinct species from its close relative P. variotii. The independence of P. paravariotii is supported by analysis of overall gene identify (via BLAST), differences in secondary metabolism and an inability to form ascomata when paired with a fertile P. variotii strain of opposite mating type. Furthermore, whole genome sequencing resolves the P. formosus clade into three separate species, one of which lacked a valid name that is now provided.

Association Between Initial Prescription Size and Likelihood of Opioid Refill After Total Knee and Hip Arthroplasty.

BACKGROUND: The present study was designed to test the hypothesis that there was no association between initial opioid prescription size and the likelihood of refill after elective primary total knee (TKA) and hip arthroplasty (THA). METHODS: We retrospectively analyzed large national datasets of commercial and Medicare insurance claims to identify a weighted cohort of 120,889 primary total joint arthroplasties (76,900 TKA and 43,989 THA) comprised of opioid-naive patients aged 18 to 75 years who had surgery between January 2015 and November 2019. The primary outcome was refill of any prescription opioid medication within 30 days after discharge, and the primary predictor variable was the total amount of opioid filled in the initial discharge prescription measured in oral morphine equivalents (OMEs). Logistic regressions were used to estimate the likelihood of refill, given a particular prescription size while adjusting for multiple patient factors, including age, sex, comorbidities, and year of surgery. RESULTS: The 30-day refill rate was 59.6% following TKA and 26.1% for THA. Adjusted odds of refill decreased by 2% for every 75 OME (10 tablets of 5 mg oxycodone) increase to the initial prescription size among the THA cohort (adjusted odds ratio [OR] = 0.98; 95% CI 0.97-0.99), and decreased by 3% for the TKA cohort (aOR = 0.97; 95% CI 0.97-0.98). CONCLUSION: These nationally representative data demonstrated that larger initial opioid prescription size was associated with small but clinically insignificant decreases in 30-day refill after total joint arthroplasty. This finding should allay concerns about efforts to decrease postsurgical opioid prescribing.

A Natural Fungal Gene Drive Enacts Killing via DNA Disruption.

Fungal spore killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to isolate, our understanding of the mechanisms underlying spore killers are limited. In particular, how these loci kill other spores within the fungal ascus is largely unknown. Here, we overcome these experimental barriers by developing model systems in 2 evolutionary distant organisms, Escherichia coli (bacterium) and Saccharomyces cerevisiae (yeast), similar to previous approaches taken to examine the wtf spore killers. Using these systems, we show that the Podospora anserina spore killer protein SPOK1 enacts killing through targeting DNA. IMPORTANCE Natural gene drives have shaped the genomes of many eukaryotes and recently have been considered for applications to control undesirable species. In fungi, these loci are called spore killers. Despite their importance in evolutionary processes and possible applications, our understanding of how they enact killing is limited. We show that the spore killer protein Spok1, which has homologues throughout the fungal tree of life, acts via DNA disruption. Spok1 is only the second spore killer locus in which the cellular target of killing has been identified and is the first known to target DNA. We also show that the DNA disrupting activity of Spok1 is functional in both bacteria and yeast suggesting a highly conserved mode of action.

Biopharmaceutical nanoclusters: Towards the self-delivery of protein and peptide therapeutics.

Protein and peptide biopharmaceuticals have had a major impact on the treatment of a number of diseases. There is a growing interest in overcoming some of the challenges associated with biopharmaceuticals, such as rapid degradation in physiological fluid, using nanocarrier delivery systems. Biopharmaceutical nanoclusters (BNCs) where the therapeutic protein or peptide is clustered together to form the main constituent of the nanocarrier system have the potential to mimic the benefits of more established nanocarriers (e.g., liposomal and polymeric systems) whilst eliminating the issue of low drug loading and potential side effects from additives. These benefits would include enhanced stability, improved absorption, and increased biopharmaceutical activity. However, the successful development of BNCs is challenged by the physicochemical complexity of the protein and peptide constituents as well as the dynamics of clustering. Here, we present and discuss common methodologies for the synthesis of therapeutic protein and peptide nanoclusters, as well as review the current status of this emerging field.

Discovery of sterically-hindered phenol compounds with potent cytoprotective activities against ox-LDL-induced retinal pigment epithelial cell death as a potential pharmacotherapy.

Late-stage dry age-related macular degeneration (AMD) or geographic atrophy (GA) is an irreversible blinding condition characterized by degeneration of retinal pigment epithelium (RPE) and the associated photoreceptors. Clinical and genetic evidence supports a role for dysfunctional lipid processing and accumulation of harmful oxidized lipids in the pathogenesis of GA. Using an oxidized low-density lipoprotein (ox-LDL)-induced RPE death assay, we screened and identified sterically-hindered phenol compounds with potent protective activities for RPE. The phenol-containing PPARγ agonist, troglitazone, protected against ox-LDL-induced RPE cell death, whereas other more potent PPARγ agonists did not protect RPE cells. Knockdown of PPARγ did not affect the protective activity of troglitazone in RPE, confirming the protective function is not due to the thiazolidine (TZD) group of troglitazone. Prototypical hindered phenol trolox and its analogs potently protected against ox-LDL-induced RPE cell death whereas potent antioxidants without the phenol group failed to protect RPE. Hindered phenols preserved lysosomal integrity against ox-LDL-induced damage and FITC-labeled trolox was localized to the lysosomes in RPE cells. Analogs of trolox inhibited reactive oxygen species (ROS) formation induced by ox-LDL uptake in a dose-dependent fashion and were effective at sub-micromolar concentrations. Treatment with trolox analog 2,2,5,7,8-pentamethyl-6-chromanol (PMC) significantly induced the expression of the lysosomal protein NPC-1 and reduced intracellular cholesterol level upon ox-LDL uptake. Our data indicate that the lysosomal-localized hindered phenols are uniquely potent in protecting the RPE against the toxic effects of ox-LDL, and may represent a novel pharmacotherapy to preserve the vision in patients with GA.

New persistent opioid use after surgery in patients with a history of remote opioid use.

BACKGROUND: Postoperative pain management is particularly challenging in patients using opioids preoperatively, but previous studies have not stratified patients not using opioids at the time of surgery according to history of opioid use. This study was designed to test the hypothesis that history of opioid use among patients not reporting opioid use at the time of surgery was independently associated with new persistent opioid use after surgery. METHODS: Using prospective perioperative data from the Analgesic Outcomes Study, we assessed outcomes of patients 18 years of age or older who underwent elective surgery between December 2015 and January 2019 and were not using opioids at the time of surgery. Patient self-reported outcome measures were collected on the day of surgery and at 2 weeks, 1 month, and 3 months postoperatively. The primary outcome was new persistent opioid use, defined as continued opioid use 3 months after surgery. The primary explanatory variable was history of opioid use, which was categorized as no history of opioid use, history of non-continuous opioid use, or history of continuous opioid use (defined as daily or almost every day for 3 months or longer). Other covariates included demographics, validated measures (pain, mood), surgery type and approach, comorbidities, and use of tobacco, alcohol, cannabis, and benzodiazepines. Backward stepwise logistic regression models were used to determine patient factors associated with new persistent opioid use and refill after surgery. RESULTS: A total of 1,249 patients not taking opioids preoperatively were included in the study cohort for new persistent opioid use. A total of 54 (4.3%) patients had continued use 3 months after surgery. New persistent opioid use after surgery was independently associated with non-continuous opioid use history (adjusted odds ratio 2.9, [95% confidence interval, 1.21 to 6.94]), continuous opioid use history (adjusted odds ratio 5.0, [95% confidence interval, 1.48 to 16.76]), and moderate to high alcohol use (adjusted odds ratio 2.5, [95% confidence interval, 1.24 to 4.93]). Similarly, opioid prescription refill at 1 month after surgery was independently associated with history of non-continuous opioid use (adjusted odds ratio 1.6, [95% confidence interval, 1.12 to 2.24]), history of continuous opioid use (adjusted odds ratio 2.2, [95% confidence interval, 1.15 to 4.06]), and moderate to high alcohol use (adjusted odds ratio 1.7, [95% confidence interval, 1.18 to 2.48]). CONCLUSION: Among patients not using opioids preoperatively, a history of opioid use was independently associated with new persistent opioid use after surgery, especially those with a history of continuous opioid use.

Reasons for Preoperative Opioid Use Are Associated with Persistent Use following Surgery Among Patients Undergoing Total Knee and Hip Arthroplasty.

OBJECTIVE: Most studies on preoperative opioid use only describe whether or not patients use opioids without characterizing reasons for use. Knowing why patients use opioids can help inform perioperative opioid management. The objective of this study was to explore pain specific reasons for preoperative opioid use prior to total hip and knee arthroplasty (THA and TKA) and their association with persistent use. METHODS: This is a prospective study of 197 patients undergoing THA (n = 99) or TKA (n = 98) enrolled in the Analgesic Outcomes Study between December 2015 and November 2018. All participants reported preoperative opioid use. RESULTS: Reasons for preoperative opioid use were categorized as surgical site pain only (81 [41.1%]); pain in other body areas only (22 [11.2%]); and combined pain (94 [47.7%]). Compared to patients taking opioids for surgical site pain, those with combined reasons for use had 1.24 (P = .40) and 2.28 (P = .16) greater odds of persistent use at 3 and 6 months postoperatively, adjusting for relevant covariates. CONCLUSIONS: This study provides novel insights into the heterogeneity of reasons for presurgical opioid use in patients undergoing a THA or TKA. One key take away is that not all preoperative opioid use is the same and many patients are taking opioids preoperatively for more than just pain at the surgical site. Combined reasons for use was associated with long-term use, suggesting nonsurgical pain, in part, drives persistent opioid use after surgery. Future directions in perioperative care should focus on pain and non-pain reasons for presurgical opioid use to create tailored postoperative opioid weaning plans.

Two peptides targeting endothelial receptors are internalized into murine brain endothelial cells.

The blood-brain barrier (BBB) is one of the main obstacles for therapies targeting brain diseases. Most macromolecules fail to pass the tight BBB, formed by brain endothelial cells interlinked by tight junctions. A wide range of small, lipid-soluble molecules can enter the brain parenchyma via diffusion, whereas macromolecules have to transcytose via vesicular transport. Vesicular transport can thus be utilized as a strategy to deliver brain therapies. By conjugating BBB targeting antibodies and peptides to therapeutic molecules or nanoparticles, it is possible to increase uptake into the brain. Previously, the synthetic peptide GYR and a peptide derived from melanotransferrin (MTfp) have been suggested as candidates for mediating transcytosis in brain endothelial cells (BECs). Here we study uptake, intracellular trafficking, and translocation of these two peptides in BECs. The peptides were synthesized, and binding studies to purified endocytic receptors were performed using surface plasmon resonance. Furthermore, the peptides were conjugated to a fluorophore allowing for live-cell imaging studies of their uptake into murine brain endothelial cells. Both peptides bound to low-density lipoprotein receptor-related protein 1 (LRP-1) and the human transferrin receptor, while lower affinity was observed against the murine transferrin receptor. The MTfp showed a higher binding affinity to all receptors when compared to the GYR peptide. The peptides were internalized by the bEnd.3 mouse endothelial cells within 30 min of incubation and frequently co-localized with endo-lysosomal vesicles. Moreover, our in vitro Transwell translocation experiments confirmed that GYR was able to cross the murine barrier and indicated the successful translocation of MTfp. Thus, despite binding to endocytic receptors with different affinities, both peptides are able to transcytose across the murine BECs.

Patient Factors Associated With Opioid Consumption in the Month Following Major Surgery.

OBJECTIVE: The aim of this study was to determine preoperative patient characteristics associated with postoperative outpatient opioid use and assess the frequency of postoperative opioid overprescribing. SUMMARY BACKGROUND DATA: Although characteristics associated with inpatient opioid use have been described, data regarding patient factors associated with opioid use after discharge are lacking. This hampers the development of individualized approaches to postoperative prescribing. METHODS: We included opioid-naïve patients undergoing hysterectomy, thoracic surgery, and total knee and hip arthroplasty in a single-center prospective observational cohort study. Preoperative phenotyping included self-report measures to assess pain severity, fibromyalgia survey criteria score, pain catastrophizing, depression, anxiety, functional status, fatigue, and sleep disturbance. Our primary outcome measure was self-reported total opioid use in oral morphine equivalents. We constructed multivariable linear-regression models predicting opioids consumed in the first month following surgery. RESULTS: We enrolled 1181 patients; 1001 had complete primary outcome data and 913 had complete phenotype data. Younger age, non-white race, lack of a college degree, higher anxiety, greater sleep disturbance, heavy alcohol use, current tobacco use, and larger initial opioid prescription size were significantly associated with increased opioid consumption. Median total oral morphine equivalents prescribed was 600 mg (equivalent to one hundred twenty 5-mg hydrocodone pills), whereas median opioid consumption was 188 mg (38 pills). CONCLUSIONS: In this prospective cohort of opioid-naïve patients undergoing major surgery, we found a number of characteristics associated with greater opioid use in the first month after surgery. Future studies should address the use of non-opioid medications and behavioral therapies in the perioperative period for these higher risk patients.

Ultrasound-mediated delivery enhances therapeutic efficacy of MMP sensitive liposomes.

To improve therapeutic efficacy of nanocarrier drug delivery systems, it is essential to improve their uptake and penetration in tumour tissue, enhance cellular uptake and ensure efficient drug release at the tumour site. Here we introduce a tumour targeting drug delivery system based on the ultrasound-mediated delivery of enzyme sensitive liposomes. These enzyme sensitive liposomes are coated with cleavable poly(ethylene glycol) (PEG) which will be cleaved by two members of the enzyme matrix metalloproteinase family (MMP-2 and MMP-9). Cleavage of the PEG coat can increase cellular uptake and will destabilize the liposomal membrane which can result in accelerated drug release. The main aim of the work was to study the effect of focused ultrasound and microbubbles on the delivery and therapeutic efficacy of the MMP sensitive liposome. The performance of the MMP sensitive liposome was compared to a non-MMP sensitive version and Doxil-like liposomes. In vitro, the cellular uptake and cytotoxicity of the liposomes were studied, while in vivo the effect of ultrasound and microbubbles on the tumour accumulation, biodistribution, microdistribution, and therapeutic efficacy were investigated. For all tested liposomes, ultrasound and microbubble treatment resulted in an improved tumour accumulation, increased extravasation, and increased penetration of the liposomes from blood vessels into the extracellular matrix. Surprisingly, penetration depth was independent of the ultrasound intensity used. Ultrasound-mediated delivery of free doxorubicin and the Doxil-like and MMP sensitive liposome resulted in a significant reduction in tumour volume 28 days post the first treatment and increased median survival. The MMP sensitive liposome showed better therapeutic efficacy than the non-MMP sensitive version indicating that cleaving the PEG-layer is important. However, the Doxil-like liposome outcompeted the MMP and non-MMP sensitive liposome, both with and without the use of ultrasound and microbubbles.

Post-operative urinary retention after lower extremity arthroplasty and the peri-operative role of selective alpha-1 adrenergic blocking agents in adult male patients: a propensity-matched retrospective cohort study.

PURPOSE: The purpose of this study was to determine whether male patients taking pre-operative selective alpha-1 adrenergic blocking agents have a lower likelihood of developing post-operative urinary retention (POUR) and a shorter length of hospitalization following lower extremity arthroplasty. METHODS: A retrospective cohort study was conducted of patients who underwent primary or revision total hip or knee arthroplasty, or unicompartmental knee arthroplasty at an academic institution from January 2002 to May 2014. A cohort of male patients aged 35 and older who were taking a selective alpha-1 blocker prior to surgery (N = 229) were compared with a control group (N = 330) not taking one of these medications. Propensity score-matched logistic regression was performed to isolate the effect of taking a selective alpha-1 blocker on POUR. RESULTS: When evaluating for the outcome of POUR while controlling for age, hypertension, benign prostatic hyperplasia, urinary tract infections, type of anaesthesia, and procedure, those patients taking an alpha-1 blocker had a 12.1% decreased relative risk (95% CI 3.4 to 20.8%; p = 0.007) of developing POUR compared with patients not taking these medications. Mean length of stay was 3.8 days (95% CI 3.6 to 4.1) in the cohort taking selective alpha-1 blockers compared with 4.7 days (95% CI 4.4 to 4.9) for the control cohort. CONCLUSIONS: After controlling for known risk factors for the development of POUR, the use of selective alpha-1 blockers pre-operatively reduces the risk of developing urinary retention after lower extremity arthroplasty and is associated with a 1-day decreased length of stay.

Angiogenic and Arthritogenic Properties of the Soluble Form of CD13.

Aminopeptidase N/CD13 is expressed by fibroblast-like synoviocytes (FLS) and monocytes (MNs) in inflamed human synovial tissue (ST). This study examined the role of soluble CD13 (sCD13) in angiogenesis, MN migration, phosphorylation of signaling molecules, and induction of arthritis. The contribution of sCD13 was examined in angiogenesis and MN migration using sCD13 and CD13-depleted rheumatoid arthritis (RA) synovial fluids (SFs). An enzymatically inactive mutant CD13 and intact wild-type (WT) CD13 were used to determine whether its enzymatic activity contributes to the arthritis-related functions. CD13-induced phosphorylation of signaling molecules was determined by Western blotting. The effect of sCD13 on cytokine secretion from RA ST and RA FLS was evaluated. sCD13 was injected into C57BL/6 mouse knees to assess its arthritogenicity. sCD13 induced angiogenesis and was a potent chemoattractant for MNs and U937 cells. Inhibitors of Erk1/2, Src, NF-κB, Jnk, and pertussis toxin, a G protein-coupled receptor inhibitor, decreased sCD13-stimulated chemotaxis. CD13-depleted RA SF induced significantly less MN migration than sham-depleted SF, and addition of mutant or WT CD13 to CD13-depleted RA SF equally restored MN migration. sCD13 and recombinant WT or mutant CD13 had similar effects on signaling molecule phosphorylation, indicating that the enzymatic activity of CD13 had no role in these functions. CD13 increased the expression of proinflammatory cytokines by RA FLS, and a CD13 neutralizing Ab inhibited cytokine secretion from RA ST organ culture. Mouse knee joints injected with CD13 exhibited increased circumference and proinflammatory mediator expression. These data support the concept that sCD13 plays a pivotal role in RA and acute inflammatory arthritis.

The AAHKS Clinical Research Award: Prophylactic Tamsulosin Does Not Reduce the Risk of Urinary Retention Following Lower Extremity Arthroplasty: A Double-Blinded Randomized Controlled Trial.

BACKGROUND: Postoperative urinary retention (POUR) is common. Selective alpha-1 adrenergic antagonists, such as tamsulosin, are effective for treating urinary retention. The purpose of this study is to determine whether perioperative prophylactic tamsulosin reduces the incidence of POUR following total hip and knee arthroplasty. METHODS: Male patients 35 years of age and older undergoing primary total hip or knee arthroplasty at a single center from 2015 to 2018 were eligible for inclusion. Patients were randomized to receive tamsulosin 0.4 mg or placebo daily for 5 days preoperatively, the morning of surgery, and the first postoperative day. The incidence of POUR was determined during the postoperative hospitalization. RESULTS: A total of 176 patients were enrolled in the study. Two patients were withdrawn prior to randomization. The remaining 174 were randomized to tamsulosin (n = 87) or placebo (n = 87). After an additional 43 patients were withdrawn prior to surgery, 131 patients completed the study (tamsulosin, n = 64; placebo, n = 67). A total of 42 patients (32.1%) developed POUR, with 18 cases (28.1%) in the tamsulosin group and 24 cases (35.8%) in the placebo group (P = .345), resulting in an odds ratio of 0.701 and a risk difference of 7.69%. CONCLUSION: Prophylactic tamsulosin did not reduce the incidence of POUR after hip and knee arthroplasty compared to placebo. The odds ratio indicates an approximately 30% decreased odds of developing POUR in the tamsulosin group, albeit not statistically significant. Tamsulosin does not appear to be effective as a prophylactic measure for reducing POUR in male hip and knee arthroplasty patients.

Multifarious Biologic Loaded Liposomes that Stimulate the Mammalian Target of Rapamycin Signaling Pathway Show Retina Neuroprotection after Retina Damage.

A common event in optic neuropathies is the loss of axons and death of retinal ganglion cells (RGCs) resulting in irreversible blindness. Mammalian target of rapamycin (mTOR) signaling pathway agonists have been shown to foster axon regeneration and RGC survival in animal models of optic nerve damage. However, many challenges remain in developing therapies that exploit cell growth and tissue remodeling including (i) activating/inhibiting cell pathways synergistically, (ii) avoiding tumorigenesis, and (iii) ensuring appropriate physiological tissue function. These challenges are further exacerbated by the need to overcome ocular physiological barriers and clearance mechanisms. Here we present liposomes loaded with multiple mTOR pathway stimulating biologics designed to enhance neuroprotection after retina damage. Liposomes were loaded with ciliary neurotrophic factor, insulin-like growth factor 1, a lipopeptide N-fragment osteopontin mimic, and lipopeptide phosphatase tension homologue inhibitors for either the ATP domain or the c-terminal tail. In a mouse model of N-methyl-d-aspartic acid induced RGC death, a single intravitreal administration of liposomes reduced both RGC death and loss of retina electrophysiological function. Furthermore, combining liposomes with transplantation of induced pluripotent stem cell derived RGCs led to an improved electrophysiological outcome in mice. The results presented here show that liposomes carrying multiple signaling pathway modulators can facilitate neuroprotection and transplant electrophysiological outcome.

Association Between the 2011 Fibromyalgia Survey Criteria and Multisite Pain Sensitivity in Knee Osteoarthritis.

OBJECTIVES: The present study evaluated the relationship between the 2011 American College of Rheumatology fibromyalgia (FM) survey criteria and quantitative sensory testing (QST). MATERIALS AND METHODS: Patients with knee osteoarthritis scheduled to undergo knee arthroplasty completed the FM survey criteria and self-report measures assessing clinical symptoms. Patients also underwent a battery of QST procedures at the surgical knee and remote body sites, including pressure algometry, conditioned pain modulation, and temporal summation. All assessments were completed before surgery. FM survey criteria were used to calculate a continuous FM score indicating FM severity. RESULTS: A total of 129 patients were analyzed. Of these, 52.7% were female, 93.8% were Caucasian, and 3.8% met the FM survey criteria for FM classification. Mean age for females (63.6 y) and males (64.7 y) was similar. Females and males differed significantly in nearly every outcome, including FM severity, clinical pain, anxiety, depression, and pressure pain sensitivity. In females, FM scores significantly correlated with pressure pain sensitivity, but not conditioned pain modulation or temporal summation, such that increased sensitivity was associated with greater FM severity at all body sites examined. In addition, as FM scores increased, the association between pain sensitivity at the surgical knee and pain sensitivity at remote body sites also increased. No relationship between FM score and QST was observed in males. DISCUSSION: We demonstrated an association between diffuse hyperalgesia as measured by QST and FM severity in females with knee osteoarthritis. These results suggest that the FM survey criteria may represent a marker of pain centralization in females with potential utility in clinical decision making.

Changes in Anxiety and Depression Are Mediated by Changes in Pain Severity in Patients Undergoing Lower-Extremity Total Joint Arthroplasty.

BACKGROUND: Depression and anxiety are common comorbidities in chronic pain including osteoarthritis patients undergoing total joint arthroplasty (TJA). What is not clear is whether psychiatric comorbidity precedes the manifestation of painful states or represents a reaction to living with chronic pain and associated functional impairment. The objective of this research was to explore whether decreases in depressive and anxiety symptoms after lower-extremity TJA could be due to postsurgical reductions in pain. METHODS: We conducted a secondary analysis of data from 1448 TJA patients enrolled in the Analgesics Outcome Study. Patients completed measures of pain intensity, functional status, and depressive and anxiety symptoms preoperatively and at 3 and 6 months postoperatively. Data were analyzed using a structural equation modeling approach. RESULTS: We found that improvement in pain and physical function from baseline to 6 months postoperatively was associated with improvement in depression and anxiety symptoms. We also found that a change in overall body pain at 3 months after surgery significantly mediated changes in both the depression and anxiety scores at 6 months after surgery even when controlling for age, sex, baseline body pain, education, opioid use, and type of surgery. CONCLUSIONS: Presurgical affective symptoms not only have an effect on change in postsurgical pain, whereby lower preoperative scores on depression and anxiety were associated with lower postsurgical pain, but also postsurgical decreases in pain were associated with lower levels of depression and anxiety after surgery. Taking these points into consideration may prove useful in working toward better outcomes for TJA.

Post-operative medical and surgical complications after primary total joint arthroplasty in solid organ transplant recipients: a case series.

PURPOSE: In a series of solid organ transplant (SOT) recipients who underwent a subsequent primary total joint arthroplasty (TJA) procedure, this study aimed to determine: (1) 90-day morbidity and mortality after primary total knee or hip arthroplasty (TKA and THA), (2) overall post-operative infection rates, and (3) how complication and infection rates compared across primary TJA procedure and type of transplant organ. METHODS: The University of Michigan Health System database was retrospectively searched using current procedural terminology codes for any primary TKA or THA performed at the institution in years 2000-2012 in a patient who previously received a successful SOT at any hospital. RESULTS: The search yielded 44 arthroplasties performed in 29 SOT recipients (average age 54.8 years, average follow-up about 30 months for both groups). No deaths were reported, but 13/27 (48.1%) THA patients and 2/6 (33.3%) TKA patients experienced a total of 29 complications within 90 days of surgery. One patient (3.7%) [1/27 patients, 1/37 joints] underwent revision hip arthroplasty to correct limb length. One THA patient and two TKA patients developed infection requiring revision surgery (3.7% and 33%, respectively). Type of transplant did not affect complication rates (P=0.65), and infection was more common after TKA (P=0.01). CONCLUSIONS: A series of SOT recipients demonstrated increased rates of infection and other complications following TJA. Surgical and medical teams should work closely to optimize this population for TJA surgery and minimize peri-operative complications. LEVEL OF EVIDENCE & STUDY DESIGN: Level IV, Prognostic Case-Series.

No Difference in Dislocation Seen in Anterior Vs Posterior Approach Total Hip Arthroplasty.

BACKGROUND: The direct anterior approach (DAA) for total hip arthroplasty (THA) has rapidly become popular, but there is little consensus regarding the risks and benefits of this approach in comparison with a modern posterior approach (PA). METHODS: A total of 2147 patients who underwent DAA THA were propensity score matched with patients undergoing PA THA on the basis of age, gender, body mass index, and American Society of Anesthesia classification using data from a state joint replacement registry. Mean age of the matched cohort was 64.8 years, mean body mass index was 29.1 kg/m(2), and 53% were female. Multilevel logistic regression models using generalized estimating equations to control for grouping at the hospital level were used to identify differences in various outcomes. RESULTS: There was no difference in the dislocation rate between patients undergoing DAA (0.84%) and PA (0.79%) THA. Trends indicating a slightly longer length of stay with the PA and a slightly greater risk of fracture, increased blood loss, and hematoma with the DAA are consistent with previous studies. CONCLUSION: On the basis of short-term outcome and complication data, neither approach has a compelling advantage over each other, including no difference in the dislocation risk.