The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.     

Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model

Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work we have investigated in an LPS-based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1β. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds.     

Disparities Among Leading Publishers of Arthroplasty Research

BackgroundDespite the importance of diversity in advancing scientific progress, diversity among leading authors in arthroplasty has not been examined. This study aimed to identify, characterize, and assess disparities among leading authors in arthroplasty literature from 2002 to 2019.MethodsArticles published between 2002 and 2019 from 12 academic journals that publish orthopedic and arthroplasty research were extracted from PubMed. Original articles containing keywords related to arthroplasty were analyzed. Author gender was assigned using the Genderize algorithm. Gender and characterization of the top 100 male and female authors utilized available information on academic profiles.ResultsFrom the 14,692 articles that met inclusion criteria, the genders of 23,626 unique authors were identified. Women were less likely than men to publish 5 years after beginning their publishing careers (adjusted odds ratio 0.51, 95% confidence interval 0.45-0.57, P < .001). Of the top 100 authors, 96 were men, while only 4 were women. Orthopedic surgeons made up 93 of 100 top authors, of which 92 were men and 1 was a woman. Among the top 10 publishing female and male authors, 10 of 10 men were orthopedic surgeons, only 2 of 10 women were physicians, and only one was an attending orthopedic surgeon.ConclusionWhile the majority of authors with high arthroplasty publication volume were orthopedic surgeons, there were significant gender disparities among the leading researchers. We should continue working to increase gender representation and supporting the research careers of women in arthroplasty.     

Trends of Prosthetic Joint Infection Organisms and Recurrence for a Single High-Volume Arthroplasty Surgeon Over 20 Years

BackgroundProsthetic joint infection (PJI) is a morbid complication following total joint arthroplasty (TJA). PJI diagnosis and treatment has changed over time, and patient co-management with a high-volume musculoskeletal infectious disease (MSK ID) specialist has been implemented at our institution in the last decade.MethodsWe retrospectively evaluated all consecutive TJA patients treated for PJI between 1995 and 2018 by a single high-volume revision TJA surgeon. Microbial identities, antibiotic resistance, prior PJI, and MSK ID consultation were investigated.ResultsIn total, 261 PJI patients (median age 66 years, interquartile range 57-75) were treated. One-year and 5-year reinfection rates were 15.8% (95% confidence interval [CI] 11.6-20.7) and 22.1% (95% CI 17.0-27.7), respectively. Microbial identities and antibiotic resistances did not change significantly over time. Despite seeing more prior PJI patients (53.3% vs 37.6%, P = .012), MSK ID-managed patients had similar infection rates as non-MSK ID-managed patients (hazard ratio [HR] 1.02, 95% CI 0.6-1.75, P = .93). Prior PJI was associated with higher reinfection risk (HR 2.39, 95% CI 1.39-4.12, P = .002) overall and in patients without MSK ID consultation, specifically (HR 2.78, 95% CI 1.37-5.65, P = .005). This risk was somewhat lower and did not reach significance in prior PJI patients with MSK ID consultation (HR 1.97, 95% CI 0.87-4.48, P = .106).ConclusionWe noted minimal differences in microbial/antibiotic resistances for PJI over 20 years in a single institution, suggesting current standards of PJI treatment remain encouragingly valid in most cases. MSK ID involvement was not associated with lower reinfection risk overall; however, in patients with prior PJI, the risk of reinfection appeared to be somewhat lower with MSK ID involvement.Level of EvidenceLevel IV–Case Series.     

Is Preoperative Staphylococcus aureus Screening and Decolonization Effective at Reducing Surgical Site Infection in Patients Undergoing Orthopedic Surgery? A Systematic Review and Meta-Analysis With a Special Focus on Elective Total Joint Arthroplasty

BackgroundStaphylococcus aureus is a major pathogen implicated in orthopedic infections worldwide. Preoperative decolonization has been promoted but different strategies present mixed results. Thus, the goals of this study are to determine (1) whether S aureus screening and/or decolonization is effective at reducing surgical site infection in orthopedic surgery, (2) with a special focus on elective total joint arthroplasty (TJA), and (3) which preoperative S aureus screening/treatment strategy is most cost-effective for TJA.MethodsPubMed, Ovid MEDLINE, and Cochrane databases were searched on January 1, 2020, using a systematic strategy. We included papers with data comparing surgical site infection and periprosthetic joint infection rate in orthopedic surgery and/or elective total hip and knee arthroplasty patients before/after S aureus screening and/or decolonization protocol and papers evaluating the cost-effectiveness of different S aureus screening/treatment strategies.ResultsA total of 1260 papers were screened, and 32 papers were ultimately included. Results showed an increased risk of developing any infection (relative risk [RR] = 1.71 ± 0.16) and S aureus infection (RR = 2.79 ± 0.45) after orthopedic surgery without previous nares and whole-body decolonization. Focusing exclusively on elective TJA, there was an increased risk of developing any infection (RR = 1.70 ± 0.17) and S aureus infection (RR = 2.18 ± 0.41) if no decolonization is performed. All strategies appeared to be cost-effective, although universal decolonization without screening seemed to be the most advantageous.ConclusionPreoperative S aureus screening/decolonization protocol lowered the risk of infection after elective orthopedic and TJA surgeries. However, further studies are needed to determine optimal clinical and cost-effective methodologies.     

Feasibility and delivery of patient-reported outcomes in clinical practice among racially diverse bladder and prostate cancer patients

ObjectiveTo assess the feasibility of enrollment and collecting patient-reported outcome (PRO) data as part of routine clinical urologic care for bladder and prostate cancer patients and examine overall patterns and racial variations in PRO use and symptom reports over time.Subjects/Patients and MethodsWe recruited 76 patients (n = 29 Black and n = 47 White) with prostate or bladder cancer at a single, comprehensive cancer center. The majority of prostate cancer patients had intermediate risk (57%) disease and underwent either radiation or prostatectomy. Over half (58%) of bladder cancer patients had muscle invasive disease and underwent cystectomy.Patients were asked to complete PRO symptom surveys using their preferred mode [web- or phone-based interactive voice response (IVR)]. Symptom summary reports were shared with providers during visits. Surveys were completed at 3 time points and assessed urinary, sexual, gastrointestinal, anxiety/depression, and sleep symptoms. Feasibility of enrollment and survey completion were calculated, and linear mixed effects models estimated differences in outcomes by race and time.ResultsSixty three percent of study participants completed all PRO measures at all 3 time points. Black patients were more likely to select IVR as their survey mode (40% vs. 13%, P < 0.05), and less likely to complete all surveys (55% vs. 74%, P = 0.13). Patients using IVR were also less likely to complete all surveys (41% vs. 69%, P = 0.046).ConclusionsReported preferences for survey mode and completion rates differ by race, which may influence survey completion rates and highlight potential obstacles for equitable implementation of PROs into clinical care.     

Urinary testosterone as a marker of risk of recurrence in operable breast cancer

Summary We investigated the role of urinary testosterone levels as a marker of risk of recurrent disease in 113 operable breast cancer patients (70 premenopausal, 43 postmenopausal). Twenty-four-hour urine collections for testosterone measurement were obtained before surgical treatment, between 20–40 days thereafter, and then every 6 months for 5 years. The cutoff values to separate high testosterone (A+) from normal testosterone (A–) were 8.0µg/24h in premenopause and 4.9µg/24h in postmenopause. Urinary testosterone levels were considered high when they exceeded the cutoff value in at least 2 of the first 3 measurements (pretreatment, post-treatment, 6 months) of each patient. According to the aforementioned criterion, 33 patients (29.2%) had high testosterone levels, which were associated to axillary node involvement in 16 patients. Thirteen of the latter relapsed during the 5-year follow-up period (5/7 in premenopause, 8/9 in postmenopause). Relapse-free survival (RFS) curves were drawn only for node-positive patients owning to the small number of recurrences observed in the node-negative group. In premenopausal node-positive patients, RFS was significantly different for patients presenting high and normal urinary testosterone levels (77% vs 28%, respectively; logrank test, p< 0.006). In postmenopausal node-positive patients, RFS was also different between the two groups (54% vs 11% in high and normal excretors, respectively) but the difference was not statistically significant. The present findings suggest that urinary testosterone is a prognostic indicator of early breast cancer recurrence in node-positive patients.     

Kinetic versus thermodynamic factors in calcium renal lithiasis

Calcium renal lithiasis formation depends on the balance between thermodynamic (supersaturation) and kinetic (inhibitors, nucleants)factors. In this paper, the importance of both groups was evaluated using(a) the complete urine analysis data obtained from 32 healthy volunteers and 141 active stone-formers, and (b) a comprehensive computer model to calculate the supersaturation values of calcium oxalate monohydrate,hydroxyapatite and brushite in each urine sample. The results of this evaluation were used to assess the possible effectiveness of a given pharmacological treatment. This revised version was published online in August 2006 with corrections to the Cover Date.