Posterior-stabilized versus mid-level constraint polyethylene components in total knee arthroplasty.

Aims: Mid-level constraint designs for total knee arthroplasty (TKA) are intended to reduce coronal plane laxity. Our aims were to compare kinematics and ligament forces of the Zimmer Biomet Persona posterior-stabilized (PS) and mid-level designs in the coronal, sagittal, and axial planes under loads simulating clinical exams of the knee in a cadaver model. Methods: We performed TKA on eight cadaveric knees and loaded them using a robotic manipulator. We tested both PS and mid-level designs under loads simulating clinical exams via applied varus and valgus moments, internal-external (IE) rotation moments, and anteroposterior forces at 0°, 30°, and 90° of flexion. We measured the resulting tibiofemoral angulations and translations. We also quantified the forces carried by the medial and lateral collateral ligaments (MCL/LCL) via serial sectioning of these structures and use of the principle of superposition. Results: Mid-level inserts reduced varus angulations compared to PS inserts by a median of 0.4°, 0.9°, and 1.5° at 0°, 30°, and 90° of flexion, respectively, and reduced valgus angulations by a median of 0.3°, 1.0°, and 1.2° (p ≤ 0.027 for all comparisons). Mid-level inserts reduced net IE rotations by a median of 5.6°, 14.7°, and 17.5° at 0°, 30°, and 90°, respectively (p = 0.012). Mid-level inserts reduced anterior tibial translation only at 90° of flexion by a median of 3.0 millimetres (p = 0.036). With an applied varus moment, the mid-level insert decreased LCL force compared to the PS insert at all three flexion angles that were tested (p ≤ 0.036). In contrast, with a valgus moment the mid-level insert did not reduce MCL force. With an applied internal rotation moment, the mid-level insert decreased LCL force at 30° and 90° by a median of 25.7 N and 31.7 N, respectively (p = 0.017 and p = 0.012). With an external rotation moment, the mid-level insert decreased MCL force at 30° and 90° by a median of 45.7 N and 20.0 N, respectively (p ≤ 0.017 for all comparisons). With an applied anterior load, MCL and LCL forces showed no differences between the two inserts at 30° and 90° of flexion. Conclusion: The mid-level insert used in this study decreased coronal and axial plane laxities compared to the PS insert, but its stabilizing benefit in the sagittal plane was limited. Both mid-level and PS inserts depended on the MCL to resist anterior loads during a simulated clinical exam of anterior laxity.

Prophylactic cable prevents tapered titanium stem subsidence with 2 cm of stem-cortical engagement in a cadaveric model.

Aims: When performing revision total hip arthroplasty using diaphyseal-engaging titanium tapered stems (TTS), the recommended 3 to 4 cm of stem-cortical diaphyseal contact may not be available. In challenging cases such as these with only 2 cm of contact, can sufficient axial stability be achieved and what is the benefit of a prophylactic cable? This study sought to determine, first, whether a prophylactic cable allows for sufficient axial stability when the contact length is 2 cm, and second, if differing TTS taper angles (2° vs 3.5°) impact these results. Methods: A biomechanical matched-pair cadaveric study was designed using six matched pairs of human fresh cadaveric femora prepared so that 2 cm of diaphyseal bone engaged with 2° (right femora) or 3.5° (left femora) TTS. Before impaction, three matched pairs received a single 100 lb-tensioned prophylactic beaded cable; the remaining three matched pairs received no cable adjuncts. Specimens underwent stepwise axial loading to 2600 N or until failure, defined as stem subsidence > 5 mm. Results: All specimens without cable adjuncts (6/6 femora) failed during axial testing, while all specimens with a prophylactic cable (6/6) successfully resisted axial load, regardless of taper angle. In total, four of the failed specimens experienced proximal longitudinal fractures, three of which occurred with the higher 3.5° TTS. One fracture occurred in a 3.5° TTS with a prophylactic cable yet passed axial testing, subsiding < 5 mm. Among specimens with a prophylactic cable, the 3.5° TTS resulted in lower mean subsidence (0.5 mm (SD 0.8)) compared with the 2° TTS (2.4 mm (SD 1.8)). Conclusion: A single prophylactic beaded cable dramatically improved initial axial stability when stem-cortex contact length was 2 cm. All implants failed secondary to fracture or subsidence > 5 mm when a prophylactic cable was not used. A higher taper angle appears to decrease the magnitude of subsidence but increased the fracture risk. The fracture risk was mitigated by the use of a prophylactic cable.

Early Femoral Insufficiency Fractures After Primary Total Knee Arthroplasty.

Background: Periprosthetic femur fracture following total knee arthroplasty (TKA) is a devastating complication. Although trauma-related periprosthetic femur fractures have been well studied, early atraumatic insufficiency periprosthetic fractures (IPFs) are gaining attention. We present the largest IPF series to date to better understand and prevent this complication. Methods: A retrospective study of all patients who underwent a revision surgery for periprosthetic fracture within 6 months of primary TKA between 2007 and 2020 was performed. Patient demographics, preoperative radiographs, implant details, and fracture radiographs were reviewed. Alignment measurements and fracture characteristics were assessed. Results: Sixteen patients met criteria (rate 0.05%), and 11 had posterior-stabilized TKAs. The mean age was 79 years, mean body mass index was 31 kg/m2, and 94% (15/16) were female. Seven (47%) patients had a confirmed history of osteoporosis. IPF occurred on average 4 weeks (range, 4 days-13 weeks) after the index TKA. Overall, 12 of 16 (73%) had preoperative valgus deformities, and 11 patients (10 valgus, 1 varus) had preoperative deformities >10 degrees. A characteristic radiographic appearance of femoral condylar impaction and collapse was noted in 12 of 16 cases (75%); 11 of these 12 fractures (92%) involved the unloaded compartment based on preoperative varus/valgus deformity. Conclusions: Patients who developed IPFs were most commonly elderly, obese women with osteoporosis and severe preoperative valgus deformities. The apparent mechanism of failure was overloading of previously unloaded osteopenic femoral condyle. In high-risk patients, the use of a cruciate-retaining femoral component or a femoral stem for a posterior-stabilized femur may be considered to help avoid this catastrophic complication.

Prophylaxis for Venous Thromboembolic Events in Elective Total Hip and Total Knee Arthroplasty.

Venous thromboembolism (VTE) is a serious complication after major orthopaedic operations, such as a total hip (THA) and knee (TKA) arthroplasty. Therefore, perioperative VTE prophylaxis is recommended; a multitude of modern options are available, including both pharmacologic (aspirin, unfractionated and lowmolecular- weight heparin, vitamin K antagonists, and novel oral anticoagulants) and/or mechanical interventions (early mobilization, graduated compression stockings, intermittent pneumatic compression devices, and venous foot pumps). However, because of the abundance of these possibilities, it is crucial to understand the benefits and drawbacks of each VTE prophylaxis option to ensure that the optimal treatment plan is developed for each patient. The American College of Chest Physicians (AACP) and the American Academy of Orthopaedic Surgeons (AAOS) have both published individual guidelines on VTE prophylaxis regimens, alongside numerous studies evaluating the efficacy and outcomes of the different prophylaxis modalities. The purpose of this review is to provide a summary of the evidence on VTE prophylaxis after elective total hip and knee arthroplasty based on current guidelines and highlight the major concerns and potential complications.

Do Antibiotic-Loaded Calcium Sulfate Beads Improve Outcomes After Debridement, Antibiotics, and Implant Retention? A Matched Cohort Study.

BACKGROUND: Dissolvable antibiotic-loaded calcium sulfate beads are used as an intraoperative adjunct during debridement with antibiotics and implant retention (DAIR) for periprosthetic joint infections (PJI) to reduce the historically higher failure rates than one- or two-stage exchange. This study evaluated clinical outcomes after DAIRs performed with and without these antibiotic beads. The primary outcome was post-DAIR failure secondary to recurrent PJI at 2 years. The secondary outcome was early failure secondary to recurrent PJI within 90 days. MATERIAL AND METHODS: DAIRs performed for acute or acute hematogenous PJI at a single institution were retrospectively identified between 2013 and 2018. All DAIRs with adjunctive antibiotic beads (cases) were then exactly matched to a cohort of DAIRs without beads (controls) based on Charlson Comorbidity Index. The McNemar's test and Wilcoxon signed-rank test were used to evaluate differences in outcomes and patient characteristics. RESULTS: Twenty DAIR cases (with antibiotic beads) were matched with 20 DAIR controls. There was no difference in age, sex, body mass index, joint, erythrocyte sedimentation rate, C-reactive protein, microbiology profile, antibiotic-resistance profile, or intraoperative lavage adjuncts between groups. There were no statistically significant differences between cases and controls for either overall infection-related failure at 2 years (P = .21) or early infection-related failure at 90 days (P = 1.00). CONCLUSION: Adjunctive dissolvable antibiotic-loaded calcium sulfate beads did not reduce the incidence of recurrent PJIs at 2 years or 90 days postoperatively after DAIR. Given the added cost of these antibiotic dissolvable beads without clinical benefits, we cannot recommend their use as an adjunct treatment during DAIRs.

Extended Trochanteric Osteotomy Closure Performed Before or After Canal Preparation and Stem Impaction Does Not Affect Axial Stability.

BACKGROUND: An extended trochanteric osteotomy (ETO) safely addresses femoral component removal during challenging revision total hip arthroplasty. However, no prior study has evaluated whether a difference in axial stability exists between ETO closure performed before (reconstitution) or after (scaffolding) canal preparation and stem impaction. We hypothesized that given the absence of clinical reports of outcome differences despite the wide use of both practices, no significant difference in the initial axial stability would exist between the 2 fixation techniques. METHODS: ETOs were performed and repaired using the reconstitution technique for the 6 right-sided femora and the scaffolding technique for the six left-sided femora. The 195-mm long, 3.5°-tapered splined titanium monobloc stems were impacted into 6 matched pairs of human fresh cadaveric femora. Three beaded cables were placed in a standardized fashion on each specimen, 1 for prophylaxis against osteotomy propagation during reaming/impaction and 2 to close the ETO. Stepwise axial loading was performed to 2600 N or until failure, which was defined as subsidence >5 mm or femoral/cable fracture. RESULTS: All specimens successfully resisted axial testing, with no stem in either ETO repair group subsiding >2 mm. The mean subsidence for the reconstitution group was 0.9 ± 0.4 mm, compared to 1.2 ± 0.5 mm for the scaffolding group (P = .2). CONCLUSION: In this cadaveric model with satisfactory proximal bone stock, no difference existed between the reconstitution and scaffolding ETO repair techniques, and both provide sufficient immediate axial stability in a simulated revision total hip arthroplasty setting under physiologic loads.

Highly cross-linked polyethylene in primary total knee arthroplasty is associated with a lower rate of revision for aseptic loosening: a meta-analysis of 962,467 cases.

BACKGROUND: The evolution in total knee arthroplasty (TKA) includes the highly cross-linked polyethylene (HXLPE) which has been reported as an effective manner to reduce the wear of the polyethylene and the osteolysis. The purpose of the present study is to synthesize the results of comparative studies between HXLPE and conventional polyethylenes and determine their effect in primary TKA. METHODS: The US National Library of Medicine (PubMed/MEDLINE) and the Cochrane Database of Systematic Reviews were queried for publications utilizing the following keywords: "cross-linked", "polyethylene", "HXLPE", "conventional", "total knee arthroplasty", "TKA", "total knee replacement" and "TKR" combined with Boolean operators AND and OR. RESULTS: Ten studies met the inclusion criteria and were included in the present meta-analysis with 962,467 patients. No significant difference was found regarding the revision rate for any reason between the patients who received HXLPE and those with conventional liner (OR 0.67; 95% CI 0.39-1.18; I2: 97.7%). In addition, there was no difference regarding the radiolucent lines between the two types of liners (OR 0.54; 95% CI 0.20-1.49; I2: 69.4%). However, with data coming from seven studies enrolling a total of 411,543 patients, it was demonstrated that patients who received HXLPE were less likely to be revised due to aseptic loosening compared to the patients with conventional liners (OR 0.35; 95% CI 0.31-0.39; I2: 0.0%). CONCLUSION: The present meta-analysis showed that regarding the overall revision rate and radiographic outcomes there was no significant difference between the two types of liners. On the other hand, the significantly less revision rate due to loosening supports the routine continued use of HXLPE in primary TKA.

High variability and lack of standardization in the evaluation of return to sport after ACL reconstruction: a systematic review.

PURPOSE: Return to sport (RTS) after ACL reconstruction (ACLR) has been recognized as an important outcome, which is associated with success of the surgery. This study aimed to assess the methods used to determine return to sport after ACLR in the published literature, report on variability of methods and evaluate their strength in establishing accurate RTS data. METHODS: Electronic databases (PubMed, Cochrane Library and Embase) were searched via a defined search strategy with no limits, to identify relevant studies from January 2008 to December 2020 for inclusion in the review. Defined eligibility criteria included studies specifically measuring and reporting on return to sport after ACLR with a clear methodology. Each included study was assessed for the definition of successful RTS, successful return to pre-injury level of sport and for methods used to determine RTS. RESULTS: One hundred and seventy-one studies were included. Of the included studies, six studies (4%) were level of evidence 1 and seventy-two studies (42%) were level of evidence 4. Forty-one studies (24%) reported on return to a specific sport and 130 studies (76%) reported on return to multiple sports or general sport. Sixteen studies (9%) reported on RTS in the pediatric population, 36 (21%) in the adult population and 119 (70%) reported on a mixed-aged population. The most commonly used definition of successful RTS was return to the same sport (44 of 125 studies, 35%). The most common method used to determine RTS was a non-validated study-specific questionnaire (73 studies, 43%), which was administered in various ways to the patients. Time of RTS assessment was variable and ranged between 6 months and 27 years post-surgery. CONCLUSION: This review demonstrates high variability in defining, evaluating and reporting RTS following ACLR. The findings of this study reveal low reliability and unproven validity of methods used to evaluate RTS and highlight the challenges in interpreting and using RTS data reported in literature. LEVEL OF EVIDENCE: IV.

Monobloc Dual Mobility With a Minimum 5-Year Follow-Up: A Safe and Effective Solution in Primary Total Hip Arthroplasty.

BACKGROUND: Instability constitutes over 20% of revisions after total hip arthroplasty (THA). Dual mobility (DM) designs were introduced as a solution to this problem. However, the few publications that have reported promising results for monobloc DM constructs have been limited by sample size or length of follow-up. The purpose of this study is to evaluate mid-term outcomes (minimum 5-year follow-up) of a single-surgeon series utilizing a monobloc DM acetabular component in patients with high risk for dislocation. METHODS: This is a single-surgeon consecutive series of 207 primary THAs implanted with a monobloc DM component in patients who were considered at high risk for dislocation. Patient demographics and case-specific data were collected retrospectively. All patients had a minimum of 5-year follow-up. The Mann-Whitney U test was used to assess continuous variables, whereas categorical variables were analyzed using the chi-square test. Survival probability was calculated using the Kaplan-Meier method. RESULTS: Radiographic analysis did not reveal acetabular radiolucency in any patients, and there were no revisions for aseptic loosening. In addition, there were no dislocations. Seven of 205 patients (3.4%) were revised, 5 on the femoral side due to periprosthetic fracture and the remaining two for infection. Survivorship of the acetabular component from revision was 99%. The mean Veteran RAND (VR-12) physical score improved from 7 (standard deviation [SD]: 13.7) preoperatively to 9.5 (SD: 17.6) at the final follow-up. Similarly, the hip disability osteoarthritis score improved from 8 (SD: 17.9) preoperatively to 21.2 (SD: 37). CONCLUSION: Monobloc DM components reliably prevent dislocation after primary THA in high-risk patients. At mid-term follow-up, this DM monobloc component demonstrates excellent implant survivorship, radiographic fixation, and improved functional outcomes.

Use of elevated liners in primary total hip arthroplasty: a systematic review of the literature.

PURPOSE: Instability remains one of the most frequent complications requiring revision surgery after primary total hip arthroplasty (THA). Elevated liners are often utilized to reduce the risk of dislocation; however, the literature is inconclusive, with no systematic reviews summarizing the data. Thus, this systematic review aimed to establish a consensus for the efficacy of elevated liners in primary THA by determining rates of overall revision and revision specifically for recurrent dislocation. MATERIALS AND METHODS: This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized-controlled trials and observational studies reporting on the use of elevated liners in primary total hip arthroplasty were identified through May 2020. A random effects model meta-analysis was conducted, and the I2 statistic was used to assess for heterogeneity. RESULTS: Eight studies met inclusion criteria, and overall, 26,507 patients undergoing primary THA with use of an elevated liner were included. In aggregate, the most common cause of revision was recurrent hip dislocation (1.3%, N = 82/6,267) followed by joint infection (1.2%, N = 45/3,772) and acetabular loosening (0.3%, N = 10/3,772). Notably, elevated liners were associated with a lower risk of revision for recurrent dislocation compared to neutral liners (HR: 0.74; 95% CI: 0.55-1.00; p = 0.048). CONCLUSION: This review found that after primary THA with the use of elevated liners, hip dislocation and prosthetic joint infection continued to be the most frequent reasons for revision surgery. However, elevated liners had a lower risk of revision for recurrent dislocation compared to neutral liners.

Relatively Low Rate of Heterotopic Ossification Following Primary Total Knee Arthroplasty: A Systematic Review and Meta-analysis.

BACKGROUND: Heterotopic ossification (HO) is abnormal growth of ectopic bone and negatively affects the outcomes after total knee arthroplasty (TKA). This systematic review and meta-analysis were performed to characterize the prevalence and severity of HO after primary TKA. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Patient demographics, publication year, and HO prevalence after a primary TKA were recorded. A meta-analysis was performed to determine the overall prevalence of HO formation, and a subanalysis compared the studies published in different timeframes to determine whether a temporal effect exists for HO prevalence. RESULTS: Two thousand nine hundred eighty-eight patients underwent primary TKA across the included studies. Fourteen percent of patients (9% to 20%; I2: 93.68%) developed HO postoperatively during a mean follow-up of 40.1 months (11 to 108 months). HO rates seemed to decrease in studies published in more recent years, with a pooled HO prevalence of 5% (0% to 13%; I2: 92.26%) among studies published in the past 15 years compared with 18% (12% to 25%; I2: 92.49%) among studies published before then. CONCLUSION: Although studies reported a relatively low overall rate of HO after a primary TKA, the absence of a single, standardized classification system precludes the comparisons of HO severity between studies. Overall, HO prevalence seems to have decreased over time, likely reflecting the changes in perioperative medication protocols.

How Does Contact Length Impact Titanium Tapered Splined Stem Stability: A Biomechanical Matched Pair Cadaveric Study.

BACKGROUND: Titanium tapered stems (TTS) achieve fixation in the femoral diaphysis and are commonly used in revision total hip arthroplasty. The initial stability of a TTS is critical, but the minimum contact length needed and impact of implant-specific taper angles on axial stability are unknown. This biomechanical study was performed to better guide operative decision-making by addressing these clinical questions. METHODS: Two TTS with varying conical taper angles (2° spline taper vs 3.5° spline taper) were implanted in 9 right and left matched fresh human femora. The proximal femur was removed, and the remaining femoral diaphysis was prepared to allow for either a 2 cm (n = 6), 3 cm (n = 6), or 4 cm (n = 6) cortical contact length with each implanted stem. Stepwise axial load was then applied to a maximum of 2600N or until the femur fractured. Failure was defined as either subsidence >5 mm or femur fracture. RESULTS: All 6 femora with 2 cm of stem-cortical contact length failed axial testing, a significantly higher failure rate (P < .02) than the 4 out of 6 femora and all 6 femora that passed testing at 3 cm and 4 cm, respectively, which were not statistically different from each other (P = .12). Taper angle did not influence success rates, as each matched pair either succeeded or failed at the tested contact length. CONCLUSION: 4 cm of cortical contact length with a TTS demonstrates reliable initial axial stability, while 2 cm is insufficient regardless of taper angle. For 3 cm of cortical contact, successful initial fixation can be achieved in most cases with both taper angle designs.

Total knee arthroplasty in dialysis patients: Is it safe? A systematic review of the literature.

PURPOSE: This systematic review characterizes the safety and efficacy of total knee arthroplasty (TKA) in end stage renal disease (ESRD) patients due to the unique challenges they face. RESULTS: The cumulative complication rate for 3684 patients on dialysis for ESRD after primary TKA was 25%(N = 925/3702), with incidence rates of 2.5%(N = 92/3702) for periprosthetic joint infection, 3.7%(N = 71/1895) for reoperations, and 2.5%(N = 90/3578) for mortality. CONCLUSION: Patients on dialysis for ESRD face significant mortality rates after primary TKA, in addition to other major complications. Careful counseling regarding risks and benefits should be provided prior to TKA in this population.

Heterotopic Ossification Negatively Influences Range of Motion After Revision Total Knee Arthroplasty.

BACKGROUND: The incidence of heterotopic ossification (HO) after total knee arthroplasty (TKA) varies and is of unclear clinical significance. This study aimed to identify the incidence of HO in patients undergoing revision TKA for either stiffness or aseptic loosening/instability and determine if the presence of HO is associated with inferior absolute range of motion (ROM) and ROM gains. METHODS: Eighty-seven patients were prospectively enrolled and separated into 2 cohorts to evaluate ROM after revision TKA (2017-2019). Group 1 (N = 40) patients were revised for stiffness, while group 2 (N = 47) patients were revised for either aseptic loosening or instability. Goniometer-measured ROM values were obtained preoperatively and at 6 weeks, 6 months, and 1 year postoperatively. Statistical analysis included a Fisher's exact test to assess for an association between preoperative HO and final ROM at 1 year after revision TKA. RESULTS: HO was identified on preoperative radiographs in 17 patients (20%). There was a significantly higher rate of preoperative HO in patients revised for stiffness compared to patients revised for instability or loosening (30% vs 11%; P = .03). Five cases of HO qualitatively identified as most clinically severe were associated with lower ROM at each time point compared to the remainder of HO cases in this study cohort (P < .02). CONCLUSION: The presence of HO is greater in patients undergoing revision TKA for stiffness. Additionally, HO severity appears to have a major effect on preoperative and postoperative ROM trajectory. This information should help guide patient expectations and highlight the need for a comprehensive, standardized classification system for HO.

Time interval affects physical activity scores: a comparison of the Marx Activity Rating Scale and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale.

PURPOSE: The Marx Activity Rating Scale (Marx Scale) is a commonly used activity-related patient-reported outcome which evaluates the highest activity level within the last year, whereas the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) assesses highest activity level within the last month. This study aims to determine whether the different timeframes used for the common items of Marx Scale and HSS Pedi-FABS affect scores, and if so, to determine whether age or injury status affect this difference. METHODS: The Marx Scale and four analogous items on the HSS Pedi-FABS were administered in random order to patients being evaluated for knee injuries and in addition to healthy controls to enroll an uninjured comparison group. Responses to each question were scored from 0 to 4 for a maximum overall score of 16. Paired and independent-sample t tests were used to determine mean differences between groups. RESULTS: The final cohort included 88 participants of which 47% were children (ages 10-17) and 51% had a knee injury. All participants except for healthy adults scored significantly lower on the HSS Pedi-FABS than the Marx Scale (p < 0.05). On the HSS Pedi-FABS activity scale, healthy participants scored significantly higher than injured participants (p < 0.01), but there were no significant differences based on age. Conversely, on the Marx Scale, children scored higher than adults (p ≤ 0.001), but there were no significant differences based on injury. CONCLUSION: Physical activity level differs when evaluated with the Marx Scale or the analogue part of HSS Pedi-FABS with timeframe being the only difference between the two. The lower scores on the HSS Pedi-FABS are likely due to seasonal changes in activity which do not affect the Marx Scale. HSS Pedi-FABS analyzes a shorter window and it is more likely to capture changes in physical activity due to a recent injury than the Marx Scale which is better suited for assessing general physical activity level unaffected by seasonality or recent injury. Understating the differences between these physical activity scales can better guide clinicians when using them and interpreting scores. LEVEL OF EVIDENCE: II.

Dual regulation of decorin by androgen and Hedgehog signaling during prostate morphogenesis.

BACKGROUND: Prostate ductal branching morphogenesis involves a complex spatiotemporal regulation of cellular proliferation and remodeling of the extracellular matrix (ECM) around the developing ducts. Decorin (Dcn) is a small leucine-rich proteoglycan known to sequester several growth factors and to act as a tumor suppressor in prostate cancer. RESULTS: Dcn expression in the developing prostate paralleled branching morphogenesis and was dynamically regulated by androgen and Hedgehog (Hh) signaling. DCN colocalized with collagen in the periductal stroma and acellular interstitium. Exogenous DCN decreased epithelial proliferation in ex vivo organ cultures of developing prostate, whereas genetic ablation of Dcn resulted in increased epithelial proliferation in the developing prostate. CONCLUSIONS: Dcn expression and localization in the developing prostate is consistent with a primary role in organizing collagen around the developing ducts. Regulation of Dcn expression appears to be complex, involving both androgen and Hh signaling. The growth inhibitory effect of Dcn suggests a unique linkage between a structural proteoglycan and epithelial growth regulation. This may serve to coordinate two elements of the morphogenetic process: ductal growth and organization of the collagen matrix around the nascent duct. Developmental Dynamics 247:679-685, 2018. © 2018 Wiley Periodicals, Inc.

Retrograde double-labeling demonstrates convergent afferent innervation of the prostate and bladder.

BACKGROUND: Prostatic inflammation is a common histologic finding in men with lower urinary tract symptoms (LUTS). It has been postulated that prostatic inflammation could sensitize afferent neurons innervating the bladder and thereby produce changes in voiding behavior. In support of this, we demonstrate an anatomic basis for pelvic cross-talk involving the prostate and bladder. METHODS: Retrograde labeling was performed by an application of a neuro-tracer Fast Blue (FB) to one side of either the anterior prostate (AP), dorsal lateral prostate (DLP)/ventral prostate (VP), bladder, or seminal vesicle (SV). RESULTS: Examination of dorsal root ganglion (DRG) neuron labeling revealed shared afferent innervation of the prostate and bladder at spinal segments of T13, L1, L2, L6, and S1. Dual labeling was performed by an application of FB and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyaine perchlorate (DiI) to the AP and bladder, respectively. We observed double-labeled DRG neurons at T13, L1, L2, L6, and S1--a finding that proves convergent innervation of prostate and bladder. CONCLUSIONS: Our observations demonstrate the potential for neural cross-talk between the prostate and bladder and support a postulated mechanism that prostatic inflammation may induce hyper-sensitization of bladder afferents and produce irritative LUTS.