Browsing by Author "Dilley, Julian E."
Now showing 1 - 10 of 15
Results Per Page
Sort Options
Item The AAHKS Clinical Research Award: Extended Oral Antibiotics Prevent Periprosthetic Joint Infection in High-Risk Cases: 3855 Patients With 1-Year Follow-Up(Elsevier, 2021) Kheir, Michael M.; Dilley, Julian E.; Ziemba-Davis, Mary; Meneghini, R. Michael; Orthopaedic Surgery, School of MedicineBackground: Surgical and host factors predispose patients to periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). While surgical factors are modifiable, host factors can be challenging, and there are limited data demonstrating that preoperative patient optimization decreases risk of PJI. The goal of this study was to evaluate whether extended oral antibiotic prophylaxis reduces the one-year infection rate in high-risk patients. Methods: A total of 3855 consecutive primary THAs and TKAs performed between 2011 and 2019 at a suburban academic hospital with modern perioperative and infection-prevention protocols were retrospectively reviewed. Beginning in January 2015, a 7-day oral antibiotic prophylaxis protocol was implemented after discharge for patients at high risk for PJI. The percentage of high-risk patients diagnosed with PJI within 1 year was compared between groups that did and did not receive extended antibiotic prophylaxis. Univariate and logistic regression analyses were performed, with P ≤ .05 denoting statistical significance. Results: Overall 1-year infection rates were 2.26% and 0.85% after THA and TKA, respectively. High-risk patients with extended antibiotic prophylaxis had a significantly lower rate of PJI than high-risk patients without extended antibiotic prophylaxis (0.89% vs 2.64%, respectively; P < .001). There was no difference in the infection rate between high-risk patients who received antibiotics and low-risk patients (0.89% vs 1.29%, respectively; P = .348) with numbers available. Conclusion: Extended postoperative oral antibiotic prophylaxis for 7 days led to a statistically significant and clinically meaningful reduction in 1-year infection rates of patients at high risk for infection. In fact, the PJI rate in high-risk patients who received antibiotics was less than the rate seen in low-risk patients. Thus, extended oral antibiotic prophylaxis may be a simple measure to effectively counteract poor host factors. Moreover, the findings of this study may mitigate the incentive to select healthier patients in outcome-based reimbursement models. Further study with a multicenter randomized control trial is needed to further validate this protocol.Item Age- and sex-dependent role of osteocytic pannexin1 on bone and muscle mass and strength(Nature Research, 2019-09-25) Aguilar-Perez, Alexandra; Pacheco-Costa, Rafael; Atkinson, Emily G.; Deosthale, Padmini; Davis, Hannah M.; Essex, Alyson L.; Dilley, Julian E.; Gomez, Leland; Rupert, Joseph E.; Zimmers, Teresa A.; Thompson, Roger J.; Allen, Matthew R.; Plotkin, Lilian I.; Anatomy and Cell Biology, School of MedicinePannexins (Panxs), glycoproteins that oligomerize to form hemichannels on the cell membrane, are topologically similar to connexins, but do not form cell-to-cell gap junction channels. There are 3 members of the family, 1-3, with Panx1 being the most abundant. All Panxs are expressed in bone, but their role in bone cell biology is not completely understood. We now report that osteocytic Panx1 deletion (Panx1Δot) alters bone mass and strength in female mice. Bone mineral density after reaching skeletal maturity is higher in female Panx1Δot mice than in control Panx1fl/fl mice. Further, osteocytic Panx1 deletion partially prevented aging effects on cortical bone structure and mechanical properties. Young 4-month-old female Panx1Δot mice exhibited increased lean body mass, even though pannexin levels in skeletal muscle were not affected; whereas no difference in lean body mass was detected in male mice. Furthermore, female Panx1-deficient mice exhibited increased muscle mass without changes in strength, whereas Panx1Δot males showed unchanged muscle mass and decreased in vivo maximum plantarflexion torque, indicating reduced muscle strength. Our results suggest that osteocytic Panx1 deletion increases bone mass in young and old female mice and muscle mass in young female mice, but has deleterious effects on muscle strength only in males.Item Alcohol Drinking and Blood Alcohol Concentration Revisited(Wiley, 2017) Dilley, Julian E.; Nicholson, Emily; Fischer, Stephen M.; Zimmer, Robin; Froehlich, Janice C.; Medicine, School of MedicineBackground It is widely assumed that the amount of alcohol in the blood reflects the amount of alcohol consumed. However, several factors in addition to amount of alcohol consumed can influence blood alcohol concentration (BAC). This study examines the effect of alcohol dose, concentration, and volume on BAC in rats with a high-alcohol-drinking (HAD) phenotype. Methods Study 1 examined the relationship between the amount of alcohol consumed and BAC. Alcohol-naïve, male, HAD rats (N = 7) were given access to alcohol for 2 h/d for 9 consecutive days with food and water ad libitum. Alcohol intake and BAC were measured at 30, 60, and 90 minutes after onset of access. Study 2 examined the effects of altering alcohol dose, concentration, and volume on BAC (as measured by area under the curve). Alcohol-naïve, male, HAD rats (N = 39) were infused, via an intragastric cannulus, with 1.16, 2.44, or 3.38 g alcohol/kg body weight (BW), produced by varying alcohol volume while holding concentration constant or by holding volume constant while varying concentration. Other rats were infused with 10, 15, or 20% v/v alcohol solutions while holding dose constant. Results BAC was more strongly correlated with the ratio of alcohol intake (g/kg BW) to total fluid intake (mls) (R = 0.85 to 0.97, p < 0.05 to p < 0.001) than it was with the amount of alcohol consumed (g/kg BW) (R = 0.70 to 0.81, p < 0.05). No effect of alcohol dose was seen during the first hour following the onset of an alcohol infusion regardless of whether dose was achieved by altering alcohol volume or concentration. After 1 hour, higher alcohol doses were predictive of greater BACs. Conclusions The fact that a 3-fold difference in alcohol dose did not result in significant differences in BACs during the first 30 minutes after ingestion of alcohol has potentially important implications for interpretation of studies that measure alcohol-sensitive end points during this time.Item CAMKK2 is Upregulated in Primary Human Osteoarthritis and its Inhibition Protects Against Chondrocyte Apoptosis(Elsevier, 2023) Dilley, Julian E.; Seetharam, Abhijit; Ding, Xinchun; Bello, Margaret A.; Shutter, Jennifer; Burr, David B.; Natoli, Roman M.; McKinley, Todd O.; Sankar, Uma; Anatomy, Cell Biology and Physiology, School of MedicineObjective: To investigate the role of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) in human osteoarthritis. Materials and methods: Paired osteochondral plugs and articular chondrocytes were isolated from the relatively healthier (intact) and damaged portions of human femoral heads collected from patients undergoing total hip arthroplasty for primary osteoarthritis (OA). Cartilage from femoral plugs were either flash frozen for gene expression analysis or histology and immunohistochemistry. Chondrocyte apoptosis in the presence or absence of CAMKK2 inhibition was measured using flow cytometry. CAMKK2 overexpression and knockdown in articular chondrocytes were achieved via Lentivirus- and siRNA-mediated approaches respectively, and their effect on pro-apoptotic and cartilage catabolic mechanisms was assessed by immunoblotting. Results: CAMKK2 mRNA and protein levels were elevated in articular chondrocytes from human OA cartilage compared to paired healthier intact samples. This increase was associated with elevated catabolic marker matrix metalloproteinase 13 (MMP-13), and diminished anabolic markers aggrecan (ACAN) and type II collagen (COL2A1) levels. OA chondrocytes displayed enhanced apoptosis, which was suppressed following pharmacological inhibition of CAMKK2. Levels of MMP13, pSTAT3, and the pro-apoptotic marker BAX became elevated when CAMKK2, but not its kinase-defective mutant was overexpressed, whereas knockdown of the kinase decreased the levels of these proteins. Conclusions: CAMKK2 is upregulated in human OA cartilage and is associated with elevated levels of pro-apoptotic and catabolic proteins. Inhibition or knockdown of CAMKK2 led to decreased chondrocyte apoptosis and catabolic protein levels, whereas its overexpression elevated them. CAMKK2 may be a therapeutic target to prevent or mitigate human OA.Item Co-Administration of Low-Dose Naltrexone and Bupropion Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats(Wiley, 2018) Nicholson, Emily R.; Dilley, Julian E.; Froehlich, Janice C.; Medicine, School of MedicineBackground This study examined whether combining naltrexone (NTX) with bupropion (BUP) is more effective in reducing alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake than either drug alone. Methods Alcohol-experienced, adult, male, P rats were fed NTX alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 20.0 mg/kg BW, NTX (10.0 mg/kg BW) + BUP (10.0 mg/kg BW), or vehicle (VEH) at 1 hour prior to onset of a daily 2-hour alcohol access period for 5 consecutive days. Results When administered alone, neither NTX (10.0 mg/kg BW) nor BUP, in either of 2 doses (10.0 mg/kg BW or 20.0 mg/kg BW), reduced voluntary alcohol intake in P rats. However, NTX combined with BUP (10.0 mg/kg NTX + 10.0 mg/kg BUP) and given as a single medication significantly reduced alcohol consumption throughout prolonged treatment. Conclusions Combining low doses of NTX and BUP, each of which is ineffective when given alone, increases the efficacy of the medication. Low drug doses circumvent the problem of negative side effects that can occur with higher doses of either drug. A reduction in side effects can facilitate patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake. The results, together with those from our prior studies, demonstrate the strength of a combinatorial pharmacotherapeutic approach to the treatment of alcohol use disorder.Item Combining varenicline (Chantix) with naltrexone decreases alcohol drinking more effectively than does either drug alone in a rodent model of alcoholism(Wiley, 2016-09) Froehlich, Janice C.; Fischer, Stephen M.; Dilley, Julian E.; Nicholson, Emily; Smith, Teal; Filosa, Nick; Rademacher, Logan; Cellular and Integrative Physiology, School of MedicineBackground This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. Methods Alcohol experienced P rats that had been drinking alcohol (15% v/v) for 2 hrs/day for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0 or 2.0 mg/kg BW), NTX alone (10.0, 15.0 or 20.0 mg/kg BW) or VAR + NTX in one of four dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days and the effects on alcohol intake were assessed. Results When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. Conclusions Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side-effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.Item Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism(Wiley, 2016-09) Froehlich, Janice C.; Fischer, Stephen M.; Dilley, Julian E.; Nicholson, Emily; Smith, Teal; Filosa, Nick; Rademacher, Logan; Department of Medicine, IU School of MedicineBackground This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. Methods Alcohol-experienced P rats that had been drinking alcohol (15% v/v) for 2 h/d for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0, or 2.0 mg/kg body weight [BW]), NTX alone (10.0, 15.0, or 20.0 mg/kg BW), or VAR + NTX in 1 of 4 dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days, and the effects on alcohol intake were assessed. Results When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. Conclusions Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.Item Effect of Tobacco Use on Radiolucent Lines in Modern Cementless Total Knee Arthroplasty Tibial Components(Elsevier, 2023-01-14) Patel, Sohum K.; Dilley, Julian E.; Carlone, Andrew; Deckard, Evan R.; Meneghini, R. Michael; Sonn, Kevin A.; Orthopaedic Surgery, School of MedicineBackground: The link between tobacco consumption and wound complications following total knee arthroplasty (TKA) is well established. However, the effect of tobacco use on biologic fixation in cementless TKA remains unknown. This study evaluated the influence of tobacco use on the presence of radiolucent lines of tibial components in cementless TKA. Methods: A total of 293 consecutive cementless TKAs of 2 contemporary designs were retrospectively reviewed. Tibial radiolucent lines and component alignment were measured using an established measurement protocol. Patients with any history of tobacco use or active tobacco use (tobacco users) were compared to those with no history of tobacco use (tobacco nonusers). No significant differences which influenced outcomes were detected between the tobacco user and tobacco nonuser groups (P ≥ .071). Results: Radiolucent lines decreased from 1-month to latest follow-up (mean 2.5 years) in all 10 radiographic zones regardless of tobacco use (P ≤ .084). However, evaluating intrapatient change in radiolucent line width, the tobacco nonuser group had more radiolucent lines resolve by the latest follow-up in nearly all radiographic zones, although most differences did not reach statistical significance, except for anteroposterior zone 1 (-31% vs -19%, P = .022). No tibial components were revised for aseptic loosening. Conclusions: Results from this study suggest that any tobacco use prior to cementless TKA has the potential to hinder biologic fixation of tibial components. While no tibial components were revised for aseptic loosening, follow-up was relatively short at 2.5 years and therefore warrants further study to discern the effect of persistent radiolucent lines on long-term fixation.Item Hyaluronic acid as an adjunct to microfracture in the treatment of osteochondral lesions of the talus: a systematic review of randomized controlled trials(BMC, 2022-04-02) Dilley, Julian E.; Everhart, Joshua S.; Klitzman, Robert G.; Orthopaedic Surgery, School of MedicineBackground: Osteochondral lesions of the talus (OLT) are common after ankle trauma. Studies have shown that bioactive substances, such as hyaluronic acid (HA), alone, or in combination, with surgical treatment could improve cartilage regeneration and repair, but the effect of HA on patient reported outcomes is unclear. Methods: Literature searches were performed across four databases (PubMed, SPORTDiscus, Scopus, and The Cochrane Library) for randomized controlled trials in which at least one treatment arm involved use of HA as an adjunct to microfracture to treat patients with OLT. Primary outcomes included the American Orthopaedic Foot and Ankle Society scores (AOFAS), and the Visual Analog Scale (VAS) for pain. The level of evidence and methodological quality were evaluated using the Modified Coleman Methodology Score (MCMS). Results: Three randomized studies were eligible for review with a total of 132 patients (35, 40, 57 patients, respectively) and follow-up ranged from 10.5 to 25 months. Utilization of HA at the time of microfracture resulted in greater improvement in AOFAS scores compared to microfracture alone. The pooled effect size was moderate (Standardized Mean Difference [SMD] 0.45, 95% Confidence Interval [CI] 0.06, 0.84; P = .02) and between-study heterogeneity was low (I-squared = 0%). Utilization of HA during microfracture also led to greater improvement in VAS-pain scores compared to microfracture alone. The pooled effect size was very large (SMD -3.86, 95% CI -4.75, - 2.97; P < .001) and heterogeneity was moderate (I-squared = 69%). Conclusion: Hyaluronic acid injection as an adjunct to arthroscopic MF in OLT provides clinically important improvements in function and pain at short-term follow-up compared to MF alone. Future longer-term follow-up studies are warranted to investigate the durability of MF with HA for treatment of OLT.Item Osteocytic miR21 deficiency improves bone strength independent of sex despite having sex divergent effects on osteocyte viability and bone turnover(Wiley, 2019) Davis, Hannah M.; Deosthale, Padmini J.; Pacheco-Costa, Rafael; Essex, Alyson L.; Atkinson, Emily G.; Aref, Mohammad W.; Dilley, Julian E.; Bellido, Teresita; Ivan, Mircea; Allen, Matthew; Plotkin, Lilian I.; Anatomy and Cell Biology, School of MedicineOsteocytes play a critical role in mediating cell–cell communication and regulating bone homeostasis, and osteocyte apoptosis is associated with increased bone resorption. miR21, an oncogenic microRNA, regulates bone metabolism by acting directly on osteoblasts and osteoclasts, but its role in osteocytes is not clear. Here, we show that osteocytic miR21 deletion has sex‐divergent effects in bone. In females, miR21 deletion reduces osteocyte viability, but suppresses bone turnover. Conversely, in males, miR21 deletion increases osteocyte viability, but stimulates bone turnover and enhances bone structure. Further, miR21 deletion differentially alters osteocyte cytokine production in the two sexes. Interestingly, despite these changes, miR21 deletion increases bone mechanical properties in both sexes, albeit to a greater extent in males. Collectively, our findings suggest that miR21 exerts both sex‐divergent and sex‐equivalent roles in osteocytes, regulating osteocyte viability and altering bone metabolism through paracrine actions on osteoblasts and osteoclasts differentially in males vs females, whereas, influencing bone mechanical properties independent of sex.