A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals.

Urinary tract infection is among the most common infections worldwide, typically studied in animals and cell lines with limited uropathogenic strains. Here, we assessed diverse bacterial species in a human urothelial microtissue model exhibiting full stratification, differentiation, innate epithelial responses, and urine tolerance. Several uropathogens invaded intracellularly, but also commensal Escherichia coli, suggesting that invasion is a shared survival strategy, not solely a virulence hallmark. The E. coli adhesin FimH was required for intracellular bacterial community formation, but not for invasion. Other shared lifestyles included filamentation (Gram-negatives), chaining (Gram-positives), and hijacking of exfoliating cells, while biofilm-like aggregates were formed mainly with Pseudomonas and Proteus. Urothelial cells expelled invasive bacteria in Rab-/LC3-decorated structures, while highly cytotoxic/invasive uropathogens, but not commensals, disrupted host barrier function and strongly induced exfoliation and cytokine production. Overall, this work highlights diverse species-/strain-specific infection strategies and corresponding host responses in a human urothelial microenvironment, providing insights at the microtissue, cell, and molecular level.

Three Doses of Platelet-Rich Plasma Therapy Are More Effective Than One Dose of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis.

PURPOSE: To compare the efficacy of a single dose of platelet-rich plasma (PRP) with multiple doses of PRP therapy in the treatment of knee osteoarthritis (KOA). METHODS: The PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, and Cochrane Library databases were searched from database inception to May 2022; in addition, the gray literature and bibliographic references were searched. Only randomized controlled trials comparing the effect of a single dose versus multiple doses of PRP for KOA were included. Literature retrieval and data extraction were conducted by 3 independent reviewers. The inclusion and exclusion criteria were based on type of study, research subjects, intervention, outcome, language, and availability of data. Pooled analyses of visual analog scale (VAS) scores, Western Ontario and McMaster Universities Arthritis Index scores, and adverse events were conducted. RESULTS: Seven studies (all randomized controlled trials) of high methodologic quality involving 575 patients were included. The ages of the patients included in this study ranged from 20 to 80 years, and the sex ratio was balanced. Triple-dose PRP therapy resulted in significantly better VAS scores compared with single-dose PRP therapy at 12 months (P < .0001), with no significant change in VAS scores between double-dose PRP and single-dose PRP at 12 months. Regarding adverse events, double-dose (P = .28) and triple-dose (P = .24) therapy showed no significant differences in safety from single-dose therapy. CONCLUSIONS: Although there is a paucity of large high-quality Level I studies, current best evidence suggests that 3 doses of PRP for KOA are more effective than 1 dose of PRP at providing pain relief up to 1 year after administration. LEVEL OF EVIDENCE: Level II, systematic review of Level II studies.

Both Medialization and Anteromedialization Tibial Tubercle Osteotomies are Effective Surgical Management for Skeletally Mature Patients with Patellofemoral Instability when Combined with Medial Patellofemoral Ligament Reconstruction.

The study aimed to compare the midterm outcomes of medialization and anteromedialization tibial tubercle osteotomies when used in the management of recurrent patellofemoral instability. The hypothesis is that both techniques would result in significant improvement for patellofemoral instability, but anteromedialization would result in a lower incidence of early osteoarthritis. In the cohort study, all skeletally mature patients aged 18 years old or younger who underwent tibial tubercle osteotomy for recurrent patellofemoral instability within a 10-year period in a single institution were included. All patients underwent either medialization or anteromedialization tibial tubercle osteotomy. The preoperative and postoperative outcomes of the tibial tubercle osteotomies were compared. All patients included in the study had a minimum of 5-year follow-up duration before the conclusion of the study. There was no statistically significant difference in the rates of preoperative and postoperative patellofemoral dislocation when either technique was employed (p = 0.999). Additionally, both the preoperative and postoperative Kujala scores were similar (p = 0.166 and p = 0.554, respectively). The knees did not have a statistically significant difference in their patellar tilt angles and tibial tubercle-trochlear groove distances preoperatively or postoperatively when either technique was used (p = 0.165 and 0.149, respectively). There was also no incidence of osteoarthritis identified in either of the groups (p = 0.999). Both anteriorization and anteromedialization tibial tubercle osteotomies were effective surgical management for patellofemoral instability when combined with medial patellofemoral ligament reconstruction. There were no significant differences in clinical, functional, and radiological outcomes when either medialization or anteromedialization tibial tubercle osteotomy was performed.

Comparing the efficacy of dual Platelet-Rich Plasma (PRP) and Hyaluronic Acid (HA) therapy with PRP-alone therapy in the treatment of knee osteoarthritis: a systematic review and meta-analysis.

PURPOSE: This study aims to compare the efficacy of a dual therapy of Platelet-Rich Plasma (PRP) and Hyaluronic Acid (HA) compared with PRP-alone therapy in the treatment of knee osteoarthritis (KOA). METHODS: PubMed, Embase, CINAHL, SCOPUS, Cochrane Library, grey literature and bibliographic references were searched from inception to January 2021. Only randomized controlled trials (RCTs) and retrospective cohort studies comparing the effect of PRP and HA versus PRP-alone therapy for KOA were included. Literature retrieval and data extraction were conducted by three independent reviewers. Pooled analysis of Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), International Knee Documentation Committee (IKDC) scores and adverse events were conducted. RESULTS: Ten studies (7 RCTs, 3 cohort studies) involving 983 patients were covered. Dual PRP and HA therapy resulted in significant reduction in VAS compared to PRP-alone therapy at 4-6 weeks (P < 0.00001) and 12 months (P < 0.00001). Dual therapy resulted in better WOMAC score improvement at 3 (P = 0.02), 6 (P = 0.05) and 12 months (P < 0.0001) compared to PRP-alone therapy. The IKDC score for dual therapy was also higher at 6 months compared to PRP-alone therapy (P = 0.007). Regarding adverse events, dual therapy was generally safer than PRP-alone therapy (P = 0.02). CONCLUSION: While there is a paucity of large high-quality Level I studies, current best evidence suggests that dual therapy with PRP and HA for KOA may be effective at providing pain relief and improvement in function up to 1 year following administration. LEVEL OF EVIDENCE: II.