Off-clamp vs on-clamp robot-assisted partial nephrectomy: a systematic review and meta-analysis.

OBJECTIVE: To compare intra- and postoperative outcomes between off-clamp and on-clamp robot-assisted partial nephrectomy (RAPN), using data from randomised controlled trials (RCTs) or covariate-matched studies (propensity score-matched or matched-pair analysis). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature review was conducted on PubMed, EMBASE, Scopus and CENTRAL for relevant studies comparing off-clamp to on-clamp RAPN. Primary outcomes were estimated blood loss, postoperative percentage decrease in estimated glomerular filtration rate (eGFR), and margin positive rate. Secondary outcomes were operative time, postoperative eGFR, length of stay, all postoperative complications, major complications, and need for transfusion. Random-effects meta-analyses were performed to generate mean differences (MDs) or odds ratios (ORs). RESULTS: A total of 10 studies (2307 patients) were shortlisted for analysis. There was no significant difference in estimated operative blood loss between off-clamp and on-clamp RAPN (MD 21.9 mL, 95% confidence interval [CI] -0.9 to 44.7 mL; P = 0.06, I2 = 58%). Off-clamp RAPN yielded a smaller postoperative eGFR deterioration (MD 3.10%, 95% CI 1.05-5.16%; P = 0.008, I2 = 13%) and lower odds of margin positivity (OR 0.62, 95% CI 0.40-0.94; P = 0.03, I2 = 0%). No significant differences were found for all secondary outcomes. CONCLUSIONS: Off-clamp and on-clamp RAPN are similarly effective approaches for selected renal masses. Within the classic trifecta of PN outcomes, off-clamp RAPN yields similar rates of perioperative complications and may possibly offer better preservation of renal function and reduced margin-positive rates.

The CCJR® Charles A. Engh, Sr, MD. Excellence in Hip Research Award: The Evolution of Revision Hip Arthroplasty and Impact on the Trainee's Experience.

BACKGROUND: Advances in total hip arthroplasty (THA) have resulted in evolving revision indications and intraoperative techniques, which can influence the exposure of trainees to complex cases. We report 3 decades of revision experience from a tertiary referral center that trains fellows, comparing the reasons for revision and the complexity of revisions over time. METHODS: We retrospectively reviewed all revision THAs performed at our institution from 1990 to 2022. Revision diagnoses, components revised, types of revision implants used, and exposure techniques were collected. A "complex" revision was defined as a case that involved an extended trochanteric osteotomy, triflange and cup-cage construct, or acetabular augment. RESULTS: A total of 3,556 THA revisions were identified (108 revisions/year). Aseptic loosening was the most common indication in 1990 to 1999 (45 per year), but decreased to 28.3/year in 2010 to 2019. From 1990 to 1999 and 2010 to 2019, fracture increased from 3.1 to 7.3 per year, infection from 2.9/year to 16.9/year, and metallosis from 0.1 to 13.2 per year. Both component revision were common from 1990 to 1994 (42.6 per year), while polyethylene exchange was most common in 2010 to 2019 (43.3 per year). A decrease was observed in "complex" cases over time: 14.8 extended trochanteric osteotomies/year in 2000 to 2004 compared to 5.4 per year in 2018 to 2022, 4.5 triflange and cup-cage constructs/year in 2004 to 2007 compared to 0.8 per year in 2018 to 2022, and 4 acetabular augments per year in 2009 to 2012 compared to 1 per year in 2018 to 2022. CONCLUSIONS: Indications for revision have changed over the decades, while the number of "complex" revisions has gradually decreased, presumably due to advances in implants and materials. If this trend extends to other training institutions, the next generation of arthroplasty surgeons will have less exposure to complex revisions during their training.

Prevalence of temporomandibular disorders and their associated factors in Confucian heritage cultures: A systematic review and meta-analysis.

BACKGROUND: Temporomandibular disorders (TMDs) may be an 'idiom' of psychological distress in Confucian heritage cultures (CHCs). OBJECTIVES: This systematic review/meta-analysis estimated the prevalence of TMDs in CHCs and compared the differences in TMD occurrence between time periods and age groups. Additionally, the associated biopsychosocial risk factors were also examined. METHODS: The study protocol was developed a priori following the PRISMA guidelines and Joanna Briggs Institute systematic review methodology (CRD42021245526). Electronic searches of seven databases were conducted from January 2002 to Dec 2021. Reference lists of identified studies were hand-searched for additional articles. Study selection, quality assessment, and data extraction were done. Meta-analysis was performed using the RevMan 5.4 software. RESULTS: Forty-eight articles were included in the systematic review. Overall prevalences were: TMDs-15% (95% CI: 15-16%); TMD pain-8% (95% CI: 7-9%); TMJ sounds-24% (95% CI: 21-27%); and TMJ locking-7% (95% CI: 1-13%). While TMD prevalence appeared to have declined from 2002 to 2011 to 2012-2021, the occurrence of TMD pain, TMJ sounds, and locking increased marginally or remained constant. TMD prevalence in children/adolescents was 18% (95% CI: 14-22%) and 17% (95% CI: 16-18%) among adults. Significant associations between TMDs and bruxism/psychological distress/education levels were specified by 73%/90%/88% of the relevant studies. CONCLUSIONS: TMDs are prevalent in CHCs and a slight increase in TMD pain (2%) and TMJ sounds (8%) were discerned over the past two decades. TMDs are related to a myriad of biopsychosocial variables, particularly psychological distress, and these factors must be addressed within the cultural context of patients.

Patient-reported functional outcomes and oncological control after primary focal cryotherapy for clinically significant prostate cancer: A Phase II mandatory biopsy-monitored study.

INTRODUCTION: We report herein the impact of focal therapy (FT) on multi-domain functional outcomes in a Phase II prospective clinical trial (NCT04138914) in focal cryotherapy for clinically significant prostate cancer (csPCa). METHODS: The primary outcome was the detection of a ≥5 point deterioration in any of the four main expanded prostate index composite (EPIC) functional domains. Pretreatment multiparametric magnetic resonance imaging (mpMRI) and transperineal targeted and systematic saturation biopsy were used to select patients with prostate-specific antigen (PSA)≤20 ng/mL, Gleason grade group (GG) ≤4, mpMRI lesion volume ≤ 3 mL (for a single lesion) or ≤1.5 mL (where two lesions were present). Focal cryotherapy was performed with a minimum 5 mm margin around each target lesion. EPIC scores were obtained at baseline and posttreatment at 1, 3, 6, and 12 months. Mandatory repeat mpMRI and prostate biopsy were performed at 12 months to determine the infield and outfield recurrence. RESULTS: Twenty-eight patients were recruited. The mean age was 68 years, with PSA of 7.3 ng/mL and PSA density of 0.19 ng/mL2 . No Clavien-Dindo ≥3 complications occurred. Transient worsening of EPIC urinary (mean diff 16.0, p < 0.001, 95% confidence interval [CI]: 8.8-23.6) and sexual function scores (mean diff 11.0, p:0.005, 95% CI: 4.0-17.7) were observed at 1-month posttreatment, with recovery by Month 3. A subgroup who had ablation extending to the neurovascular bundle had a trend to delayed recovery of sexual function to Month 6. At 12-month repeat mpMRI and biopsy, 22 patients (78.6%) had no detectable csPCa. Of the six patients (21.4%) who had csPCa recurrences, four were GG2, one GG3, and one GG4. Four patients underwent repeat FT, one underwent radical prostatectomy, while the remaining one patient with low-volume GG2 cancer opted for active surveillance. CONCLUSION: FT using cryotherapy was associated with a transient deterioration of urinary and sexual function with resolution at 3 months posttreatment and with reasonable early efficacy in well-selected csPCa patients.

Intensive sampling of the umbra and penumbra improves clinically significant prostate cancer detection and reduces risk of grade group upgrading at radical prostatectomy.

PURPOSE: Our objective is to evaluate the clinically significant prostate cancer detection rate of overlapping and perilesional systematic biopsy cores and its impact on grade group (GG) concordance at prostatectomy. MATERIALS AND METHODS: Biopsy maps of those undergoing MRI-targeted (TB) and systematic biopsy (SB) were reviewed to reclassify systematic cores. Perilesional (PL) cores were defined as adjacent cores within 10 mm of the target lesion ("penumbra") whilst overlap (OL) cores were defined as cores within the ROI itself ("umbra"). All other cores were designated as distant cores (DC). The incremental csPCa detection rate (GG ≥ 2) and the rate of GG upgrading on prostatectomy as OL, PL and DC sequentially added to TB were determined. RESULTS: Out of the 398 patients included, the median number of OL and PL cores was 5 (IQR 4-7) and 5 (IQR 3-6) respectively. OL cores detected more csPCa than PL cores (31 vs 16%, p < 0.001). OL and PL cores improved the csPCa detection rate of TB from 34 to 39% (p < 0.001) and 37% (p = 0.001) respectively. TB+OL+PL had greater csPCa detection compared to just TB+OL (41 vs 39%, p = 0.016) and TB+PL (41 vs 37%, p < 0.001). Of the 104 patients who underwent prostatectomy, GG upgrading rate for TB+OL+PL was lower compared to TB (21 vs 36%, p < 0.001) and was not significantly different compared to TB+OL+PL+DC (21 vs 19%, p = 0.500). CONCLUSION: A biopsy strategy incorporating both intensive sampling of the umbra and penumbra improved csPCa detection and reduced risk of GG upgrading at prostatectomy.

A reduction in hospital length of stay reduces costs for colorectal surgery: an economic evaluation of the National Surgical Quality Improvement Program in Singapore.

PURPOSE: In 2017, the National Surgical Quality Improvement Program (NSQIP) was introduced in the Department of Colorectal Surgery at Singapore General Hospital as a pilot quality improvement initiative. This study aimed to examine the cost-effectiveness of NSQIP by evaluating its effects on surgical outcomes, length of stay (LOS), and costs. METHODS: We retrospectively reviewed patients undergoing colorectal surgery (2017-2020). Patients were divided into two cohorts: pre-NSQIP (2017-2018) and post-NSQIP (2019-2020). Outcomes evaluated were 30-day postoperative complications, LOS, and costs. Total cost-savings from NSQIP intervention's impact on LOS were estimated using a decision model with a one-way sensitivity analysis. Multivariate logistic regression was performed to identify factors for prolonged LOS. RESULTS: 1905 patients underwent colorectal surgery, with 996 in the pre-NSQIP cohort and 909 in the post-NSQIP cohort. A significant reduction in overall postoperative complications of 4.7% was observed in the post-NSQIP cohort (36.5% vs. 31.8%, p = 0.029). Patients in the post-NSQIP cohort had a shorter median LOS (8.0 vs. 6.0 days, p < 0.001). The implementation of NSQIP resulted in an 8.5% decrease in prolonged LOS > 6 days (p < 0.001), saving S$0.31 million on LOS. Total costs per case were reduced by 20.8% following NSQIP (S$39,539.05 vs. S$31,311.93, p < 0.001). CONCLUSION: Implementing NSQIP has significantly reduced overall postoperative complications, LOS, and costs and achieved cost savings following colorectal surgery.

Outpatient Total Knee Arthroplasty From a Stand-Alone Surgery Center: Safe as the Hospital?

BACKGROUND: Literature suggests that outpatient arthroplasty may result in low rates of complications and readmissions. There is, however, a dearth of information on the relative safety of total knee arthroplasty (TKA) performed at stand-alone ambulatory surgery centers (ASCs) versus hospital outpatient (HOP) settings. We aimed to compare safety profiles and 90-day adverse events of these 2 cohorts. METHODS: Prospectively collected data were reviewed on all patients who underwent outpatient TKA from 2015 to 2022. The ASC and HOP groups were compared, and differences in demographics, complications, reoperations, revisions, readmissions, and emergency department (ED) visits within 90 days of surgery were analyzed. There were 4 surgeons who performed 4,307 TKAs during the study period, including 740 outpatient cases (ASC = 157; HOP = 583). The ASC patients were younger than HOP patients (ASC = 61 versus HOP = 65; P < .001). Body mass index and sex did not differ significantly between groups. RESULTS: Within 90 days, 44 (6%) complications occurred. No differences were observed between groups in rates of 90-day complications (ASC = 9 of 157, 5.7% versus HOP = 35 of 583, 6.0%; P = .899), reoperations (ASC = 2 of 157, 1.3% versus HOP = 3 of 583, 0.5%; P = .303), revisions (ASC = 0 of 157 versus HOP = 3 of 583, 0.5%; P = 1), readmissions (ASC = 3 of 157, 1.9% versus HOP = 8 of 583, 1.4%; P = .625), and ED visits (ASC = 1 of 157, 0.6% versus HOP = 3 of 583, 0.5%; P = .853). CONCLUSION: These results suggest that in appropriately selected patients, outpatient TKA can be safely performed in both ASC and HOP settings with similar low rates of 90-day complications, reoperations, revisions, readmissions, and ED visits.

Early Practice All-Cause Complications for Fellowship-Trained Anterior Hip Surgeons Are Not Increased When Compared to "Gold Standard" Experienced Posterior Approach Surgeons.

BACKGROUND: Increased complication rates have been reported during the learning curve for direct anterior approach (DAA) total hip arthroplasty (THA). However, emerging literature suggests that complications associated with the learning curve may be substantially reduced with fellowship training. METHODS: Our institutional database was queried to identify 2 groups: (1) 600 THAs comprised of the first 300 consecutive cases performed by 2 DAA fellowship-trained surgeons; and (2) 600 posterolateral approach (PA) THAs, including the most recent 300 primary cases performed by 2 experienced PA surgeons. All-cause complications, revision rates, reoperations, operative times, and transfusion rates were evaluated. RESULTS: Comparing DAA and PA cases, there were no significant differences in rates of all-cause complications (DAA = 18, 3.0% versus PA = 23, 3.8%; P = .43), periprosthetic fractures (DAA = 5, 0.8% versus PA = 10, 1.7%; P = .19), wound complications (DAA = 7, 1.2% versus PA = 2, 0.3%; P = .09), dislocations (DAA = 2, 0.3% versus PA = 8, 1.3%, P = .06), or revisions (DAA = 2, 0.3% versus PL = 5, 0.8%; P = .45) at 120 days postoperatively. There were 4 patients who required reoperation for wound complications, all within the DAA group (DAA = 4, 0.67% versus PA = 0; P = .045). Operative times were shorter in the DAA group (DAA <1.5 hours = 93% versus PA <1.5 hours = 86%; P < .01). No blood transfusions were given in either group. CONCLUSION: In this retrospective study, DAA THAs performed by fellowship-trained surgeons early in practice were not associated with higher complication rates compared to THAs performed by experienced PA surgeons. These results suggest that fellowship training may allow DAA surgeons to complete their learning curve period with complication rates similar to experienced PA surgeons.

Motor Nerve Palsy After Direct Anterior Versus Posterior Total Hip Arthroplasty: Incidence, Risk Factors, and Recovery.

BACKGROUND: There is limited literature on motor nerve palsy in modern total hip arthroplasty (THA). The purpose of this study was to establish the incidence of nerve palsy following THA using the direct anterior (DA) and postero-lateral (PL) approaches, identify risk factors, and describe the extent of recovery. METHODS: Using our institutional database, we examined 10,047 primary THAs performed between 2009 and 2021 using the DA (6,592; 65.6%) or PL (3,455; 34.4%) approach. Postoperative femoral (FNP) and sciatic/peroneal nerve palsies (PNP) were identified. Incidence and time to recovery was calculated, and association between surgical and patient risk factors and nerve palsy were evaluated using Chi-square tests. RESULTS: The overall rate of nerve palsy was 0.34% (34/10,047) and was lower with the DA approach (0.24%) than the PL approach (0.52%), P = .02. The rate of FNPs in the DA group (0.20%) was 4.3 times more than the rate of PNPs (0.05%), while in the PL group the rate of PNPs (0.46%) was 8 times more than that of FNPs (0.06%). Higher rates of nerve palsy were observed with women, shorter patients, and nonosteoarthritis preoperative diagnoses. Full recovery of motor strength occurred in 60% of cases with FNP and 58% of cases with PNP. CONCLUSION: Nerve palsy is rare after contemporary THA through the PL and DA approaches. The PL approach was associated with a higher rate of PNP, whereas the DA approach was associated with a higher rate of FNP. Femoral and sciatic/peroneal palsies had similar rates of complete recovery.

Incorporating artificial intelligence in urology: Supervised machine learning algorithms demonstrate comparative advantage over nomograms in predicting biochemical recurrence after prostatectomy.

OBJECTIVE: After radical prostatectomy (RP), one-third of patients will experience biochemical recurrence (BCR), which is associated with subsequent metastasis and cancer-specific mortality. We employed machine learning (ML) algorithms to predict BCR after RP, and compare them with traditional regression models and nomograms. METHODS: Utilizing a prospective Uro-oncology registry, 18 clinicopathological parameters of 1130 consecutive patients who underwent RP (2009-2018) were recorded, yielding over 20,000 data points for analysis. The data set was split into a 70:30 ratio for training and validation. Three ML models: Naïve Bayes (NB), random forest (RF), and support vector machine (SVM) were studied, and compared with traditional regression models and nomograms (Kattan, CAPSURE, John Hopkins [JHH]) to predict BCR at 1, 3, and 5 years. RESULTS: Over a median follow-up of 70.0 months, 176 (15.6%) developed BCR, at a median time of 16.0 months (interquartile range [IQR]: 11.0-26.0). Multivariate analyses demonstrated strongest association of BCR with prostate-specific antigen (PSA) (p: 0.015), positive surgical margins (p < 0.001), extraprostatic extension (p: 0.002), seminal vesicle invasion (p: 0.004), and grade group (p < 0.001). The 3 ML models demonstrated good prediction of BCR at 1, 3, and 5 years, with the area under curves (AUC) of NB at 0.894, 0.876, and 0.894, RF at 0.846, 0.875, and 0.888, and SVM at 0.835, 0.850, and 0.855, respectively. All models demonstrated (1) robust accuracy (>0.82), (2) good calibration with minimal overfitting, (3) longitudinal consistency across the three time points, and (4) inter-model validity. The ML models were comparable to traditional regression analyses (AUC: 0.797, 0.848, and 0.862) and outperformed the three nomograms: Kattan (AUC: 0.815, 0.798, and 0.799), JHH (AUC: 0.820, 0.757, and 0.750) and CAPSURE nomograms (AUC: 0.706, 0.720, and 0.749) (p < 0.001). CONCLUSION: Supervised ML algorithms can deliver accurate performances and outperform nomograms in predicting BCR after RP. This may facilitate tailored care provisions by identifying high-risk patients who will benefit from multimodal therapy.

Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors.

Drug-induced liver injury (DILI) is the leading cause of acute liver failure and a major concern in drug development. Altered bile acid homeostasis via inhibition of the bile salt export pump (BSEP) is one mechanism of DILI. Dasatinib, pazopanib, and sorafenib are tyrosine kinase inhibitors (TKIs) that competitively inhibit BSEP and increase serum biomarkers for hepatotoxicity in ∼25-50% of patients. However, the mechanism(s) of hepatotoxicity beyond competitive inhibition of BSEP are poorly understood. This study examined mechanisms of TKI-mediated hepatotoxicity associated with altered bile acid homeostasis. Dasatinib, pazopanib, and sorafenib showed bile acid-dependent toxicity at clinically relevant concentrations, based on the C-DILI assay using sandwich-cultured human hepatocytes (SCHH). Among several bile acid-relevant genes, cytochrome P450 (CYP) 7A1 mRNA was specifically upregulated by 6.2- to 7.8-fold (dasatinib) and 5.7- to 9.3-fold (pazopanib), compared with control, within 8 hours. This was consistent with increased total bile acid concentrations in culture medium up to 2.3-fold, and in SCHH up to 1.4-fold, compared with control, within 24 hours. Additionally, protein abundance of sodium taurocholate co-transporting polypeptide (NTCP) was increased up to 2.0-fold by these three TKIs. The increase in NTCP protein abundance correlated with increased function; dasatinib and pazopanib increased hepatocyte uptake clearance (CLuptake) of taurocholic acid, a probe bile acid substrate, up to 1.4-fold. In conclusion, upregulation of CYP7A1 and NTCP in SCHH constitute novel mechanisms of TKI-associated hepatotoxicity. SIGNIFICANCE STATEMENT: Understanding the mechanisms of hepatotoxicity associated with tyrosine kinase inhibitors (TKIs) is fundamental to development of effective and safe intervention therapies for various cancers. Data generated in sandwich-cultured human hepatocytes, an in vitro model of drug-induced hepatotoxicity, revealed that TKIs upregulate bile acid synthesis and alter bile acid uptake and excretion. These findings provide novel insights into additional mechanisms of bile acid-mediated drug-induced liver injury, an adverse effect that limits the use and effectiveness of TKI treatment in some cancer patients.

AAHKS Best Podium Presentation Research Award: Femoral Perforation During Direct Anterior Approach Total Hip Arthroplasty: Incidence, Cohort Characteristics, and Management.

BACKGROUND: Cortical perforation during femoral preparation is a recognized complication of total hip arthroplasty (THA) but the incidence, patient characteristics, management, and outcome have not been described for the direct anterior approach (DAA). METHODS: A database query of all primary and conversion DAA THAs performed by a single surgeon from 2009 to 2021 was used to identify hips that sustained a recognized intraoperative femoral perforation. Radiographs were used to assess stem subsidence, Dorr femur type, and Canal Flare Index. RESULTS: Among 3,973 THAs, 16 patients (0.4%) sustained perforations during broaching including 8 males and 8 females with a mean age at surgery of 65.6 (range 41-81) years and a mean body mass index of 31.0 (range 19.0-44.4). Two hips were converted to longer primary cementless stems to bypass the perforation. For the remaining 14, the broach was redirected and the same primary stem was implanted. Limited weight-bearing (6 patients) or protected weight-bearing as tolerated with a walker/cane (10 patients) was advised postoperatively. At a mean follow-up of 18.7 (range 4-105) months, all stems were stable with no fractures, subsidence, or revisions. Factors associated with perforation included difficulty with exposure (body mass index >40 or a contracture), measurable osteoporosis (Canal Flare Index <3.0), and abnormal proximal femoral anatomy due to prior trauma, retained hardware, or Perthes disease. CONCLUSION: In this case series, isolated perforation of an otherwise intact femur during DAA was successfully managed with redirection of the broach, implantation of a primary stem that achieved axial/rotational stability, and protected weight-bearing. LEVEL OF EVIDENCE: IV, Case Series.

Factors Associated With the Incidence and Timing of Total Knee Arthroplasty Infection.

BACKGROUND: Periprosthetic joint infection (PJI) following total knee arthroplasty remains a challenging clinical problem. This study examined variables related to the incidence and timing of PJI. METHODS: We retrospectively reviewed 8462 primary total knee arthroplasties performed at our institution between 2006 and 2018 for PJI. The mean follow-up is 3.7 years. Eighty-seven variables including patient-reported diagnoses, demographics, and medications were collected. Time to infection, bacterial organism, success of infection treatment, and variables associated with infection are reported. RESULTS: PJI occurred in 105 (1.24%) cases. The incidence of infection in the first year was 0.72% and represented 58% of all infections. Multivariate Cox regression revealed males (hazard ratio [HR] = 2.85, 95% confidence interval [CI], 1.69-4.79) and patients with major depression or anxiety (HR = 2.11, 95% CI, 1.21-3.67) were more likely to develop an infection in the first year. After the first year, patients with a history of cellulitis (HR = 3.97, 95% CI, 1.91-8.27) and those taking antiepileptic medications (HR = 3.61, 95% CI, 1.73-7.52) were more likely to develop an infection. Culture-negative infections were more common after one year than before (23% vs 8%, P = .04). Debridement, antibiotics, and implant retention was used in 79% (48/61) of infections in the first year and 55% (24/44) after one year with success rates of 51% and 70%, respectively (P = .16). CONCLUSION: The majority of infections occur during the first year after surgery. Importantly, patient variables associated with infection are different among infections that occur before and after one year. A multicenter study with a much larger number of infections may allow analysis of more time intervals after surgery.

Does Approach Influence the Dislocation Rate Following Head and Liner Exchange in Revision Hip Arthroplasty?

BACKGROUND: Revision total hip arthroplasty with modular component exchange can limit morbidity by retaining well-fixed components but dislocation has been a relatively frequent postoperative complication. This study evaluated the effect of surgical approach on dislocation rate in a modern revision cohort. METHODS: From 2010 to 2020, 248 aseptic head and liner exchanges were performed at a single institution. The mean patient age at revision was 64.9 ± 10.4 years and 50% (123/248) were performed among males. Indications for revision included 140 (56%) for polyethylene wear, 68 (27%) for failed metal-on-metal components, and 40 (16%) for instability. The mean follow-up after revision was 2.3 years. RESULTS: Thirty (12%) hips dislocated at a mean of 0.6 years (range 0.01-4.6) postoperatively. The dislocation rate by revision approach was 17% (9/54) for the direct anterior, 6% (5/80) for the direct lateral, and 14% (16/114) for the posterolateral approach (P = .13). Hips revised by the direct anterior approach that dislocated were more abducted (51 ± 8 vs 45 ± 8, P = .05) and more anteverted (26 ± 9 vs 20 ± 7, P = .04) than non-dislocators. Among all 248 hips, cups with more than 48° of abduction were 2.6 times more likely to dislocate (P = .01). Head diameter, neck length, patient age, and gender were not associated with dislocation (P ≥ .20). CONCLUSION: Dislocation remains a common complication after head and liner exchange regardless of approach. Cup position is associated with postoperative instability and must be critically evaluated during preoperative planning.

Direct Anterior Approach for Primary Total Hip Arthroplasty Lowers the Risk of Dislocation Compared to the Posterior Approach: A Single Institution Experience.

BACKGROUND: One purported benefit of the direct anterior approach (DAA) for total hip arthroplasty (THA) is a lower rate of postoperative dislocation. METHODS: An institutional database was used to identify 8840 primary THAs performed from 2003 to 2020 including 5065 (57%) performed using the DAA and 3775 (43%) performed via the posterior approach (PA). Direction and mechanism of dislocation were determined from chart review. Outcomes were compared using Kaplan-Meier survivorship with dislocation as the endpoint and a Cox multivariate regression was used to investigate factors associated with dislocation. The mean follow-up was 1.7 ± 2.0 years for the DAA and 3.1 ± 3.3 years for the PA. RESULTS: The 0.5% (26/5065) incidence of dislocation among DAA hips was significantly less than the 3.3% (126/3775) among PA cases (P < .001). The majority of dislocations were posterior (DAA 57%, PA 79%) and occurred during activities of daily living (DAA 82%, PA 77%). Five-year survivorship was significantly higher for the DAA group compared to the PA group (99.1% vs 95.4%, P < .001). Dislocation risk was 4.9 times higher for the PA compared to the DAA (hazard ratio = 4.9, 95% confidence interval = 3.2-7.5, P < .001). Increasing head diameter reduced the risk (hazard ratio = 0.70, 95% confidence interval = 0.57-0.86, P < .001). The 0.2% incidence (10/5065) of revision for instability among the DAA group was significantly lower than the 1.1% (43/3775) rate for the PA group (P < .001). CONCLUSION: Compared to primary THAs performed with the PA, DAA cases had a lower risk of dislocation, higher survivorship with dislocation as an endpoint, and a lower risk of revision for instability in this single institution cohort.

Identification of Key Amino Acids that Impact Organic Solute Transporter α/ß (OSTα/ß).

Organic solute transporter α/ß (OSTα/ß) is a bidirectional bile acid transporter localized on the basolateral membrane of hepatic, intestinal, and renal epithelial cells. OSTα/ß plays a critical role in intestinal bile acid reabsorption and is upregulated in hepatic diseases characterized by elevated bile acids, whereas genetic variants in SLC51A/B have been associated with clinical cholestasis. OSTα/ß also transports and is inhibited by commonly used medications. However, there is currently no high-resolution structure of OSTα/ß, and structure-function data for OSTα, the proposed substrate-binding subunit, are lacking. The present study addressed this knowledge gap and identified amino acids in OSTα that are important for bile acid transport. This was accomplished using computational modeling and site-directed mutagenesis of the OSTα subunit to generate OSTα/ß mutant cell lines. Out of the 10 OSTα/ß mutants investigated, four (S228K, T229S, Q269E, Q269K) exhibited decreased [3H]-taurocholate (TCA) uptake (ratio of geometric means relative to OSTα/ß wild type (WT) of 0.76, 0.75, 0.79, and 0.13, respectively). Three OSTα/ß mutants (S228K, Q269K, E305A) had reduced [3H]-TCA efflux % (ratio of geometric means relative to OSTα/ß WT of 0.86, 0.65, and 0.79, respectively). Additionally, several OSTα/ß mutants demonstrated altered expression and cellular localization when compared with OSTα/ß WT. In summary, we identified OSTα residues (Ser228, Thr229, Gln269, Glu305) in predicted transmembrane domains that affect expression of OSTα/ß and may influence OSTα/ß-mediated bile acid transport. These data advance our understanding of OSTα/ß structure/function and can inform future studies designed to gain further insight into OSTα/ß structure or to identify additional OSTα/ß substrates and inhibitors. SIGNIFICANCE STATEMENT: OSTα/ß is a clinically important transporter involved in enterohepatic bile acid recycling with currently no high-resolution protein structure and limited structure-function data. This study identified four OSTα amino acids (Ser228, Thr229, Gln269, Glu305) that affect expression of OSTα/ß and may influence OSTα/ß-mediated bile acid transport. These data can be utilized to inform future investigation of OSTα/ß structure and refine molecular modeling approaches to facilitate the identification of substrates and/or inhibitors of OSTα/ß.

Defining prostate cancer size and treatment margin for focal therapy: does intralesional heterogeneity impact the performance of multiparametric MRI?

OBJECTIVES: To evaluate the impact of intralesional heterogeneity on the performance of multiparametric magnetic resonance imaging (mpMRI) in determining cancer extent and treatment margins for focal therapy (FT) of prostate cancer. PATIENTS AND METHODS: We identified men who underwent primary radical prostatectomy for organ- confined prostate cancer over a 3-year period. Cancer foci on whole-mount histology were marked out, coding low-grade (LG; Gleason 3) and high-grade (HG; Gleason 4-5) components separately. Measurements of entire tumours were grouped according to intralesional proportion of HG cancer: 0%, <50% and ≥50%; the readings were corrected for specimen shrinkage and correlated with matching lesions on mpMRI. Separate measurements were also taken of HG cancer components only, and correlated against entire lesions on mpMRI. Size discrepancies were used to derive the optimal tumour size and treatment margins for FT. RESULTS: There were 122 MRI-detected cancer lesions in 70 men. The mean linear specimen shrinkage was 8.4%. The overall correlation between histology and MRI dimensions was r = 0.79 (P < 0.001). Size correlation was superior for tumours with high burden (≥50%) compared to low burden (<50%) of HG cancer (r = 0.84 vs r = 0.63; P = 0.007). Size underestimation by mpMRI was more likely for larger tumours (51% for >12 mm vs 26% for ≤12 mm) and those containing HG cancer (44%, vs 20% for LG only). Size discrepancy analysis suggests an optimal tumour size of ≤12 mm and treatment margins of 5-6 mm for FT. For tumours ≤12 mm in diameter, applying 5- and 6-mm treatment margins would achieve 98.6% and 100% complete tumour ablation, respectively. For tumours of all sizes, using the same margins would ablate >95% of the HG cancer components. CONCLUSIONS: Multiparametric MRI performance in estimating prostate cancer size, and consequently the treatment margin for FT, is impacted by tumour size and the intralesional heterogeneity of cancer grades.

Periprosthetic Femur Fracture Risk: Influenced by Stem Choice, Not Surgical Approach.

BACKGROUND: Periprosthetic femur fracture (PFF) remains a common reason for failure after total hip arthroplasty (THA). For over 10 years, our institution has performed both anterior approach (AA) and posterolateral (PL) approaches for primary THA with multiple stem designs. The aim of this study is to determine the 90-day relative risk of PFF with regard to approach and stem design. METHODS: A retrospective review of our institutional database was performed on all patients undergoing primary THA from 2007 to 2018 using AA or PL approaches. Five surgeons performing 6309 THAs (AA = 4510; PL = 1799) using single-wedge taper (n = 2417) or fit-and-fill (n = 3892) stems were included. PFF occurring within 90 days of the index procedure were analyzed. Differences in PFF rates, fracture location, stem type, and treatment method were assessed. Comparisons were made using a Cox regression analysis. RESULTS: The 90-day revision rate for fracture was 0.3%. Clinically significant fractures requiring cerclage cabling, stem change, revision, or open reduction internal fixation occurred in 0.9% of patients (intraoperative = 37, 0.6%; postoperative = 17, 0.3%). Cox regression found PFF risk was significant for female patients (P = .008), patients older than age 65 (P < .01), single-wedge taper stems (P = .05), and for cases with collarless stems (P = .04). Among PFF cases that required surgical intervention, risk factors were female sex, age older than 65, and body mass index under 25 (P < .05). Collarless stems were 2.6 times more likely to result in PFF than collared stems (P = .04). Single-wedge taper stems were 2.3 times more likely to result in PFF than fit-and-fill stems (P = .05). Approach was not found to be an independent risk factor for PFF (P = .85). CONCLUSION: Our single-center experience demonstrates the risk of periprosthetic fracture within 90 days of surgery is significantly lower with collared stems and fit-and-fill stem designs. Female sex, age over 65, and body mass index below 25 nearly double the PFF risk. Surgical approach did not influence fracture rates.

Alignment in Medial Fixed-Bearing Unicompartmental Knee Arthroplasty: The Limb Has a Leg Up on the Component.

BACKGROUND: To assess how implant alignment affects unicompartmental knee arthroplasty (UKA) outcome, we compared tibial component alignment of well-functioning UKAs against 2 groups of failed UKAs, revised for progression of lateral compartment arthritis ("Progression") and aseptic loosening ("Loosening"). METHODS: We identified 37 revisions for Progression and 61 revisions for Loosening from our prospective institutional database of 3351 medial fixed-bearing UKAs performed since 2000. Revision cohorts were matched on age, gender, body mass index, and postoperative range of motion with "Successful" unrevised UKAs with minimum 10-year follow-up and Knee Society Score ≥70. Tibial component coronal (TCA) and sagittal (TSA) plane alignment was measured on postoperative radiographs. Limb alignment was quantified by hip-knee-ankle (HKA) angle on long-leg radiographs. In addition to directly comparing groups, a multivariate logistic regression examined how limb and component alignments were associated with UKA revision. RESULTS: In the Progression group, component alignment was similar to the matched successes (TCA 3.6° ± 3.5° varus vs 5.1° ± 3.5° varus, P = .07; TSA 8.4° ± 4.4° vs 8.8° ± 3.6°, P = .67), whereas HKA angle was significantly more valgus (0.3° ± 3.6° valgus vs 4.4° ± 2.6° varus, P < .001). Loosening group component alignment was also similar to the matched successes (TCA 6.1° ± 3.7° varus vs 5.9° ± 3.1° varus, P = .72; TSA 8.4° ± 4.6° vs 8.1° ± 3.9°, P = .68), and HKA was significantly more varus (6.1° ± 3.1° varus vs 4.0° ± 2.7° varus, P < .001). Using a multivariate logistic regression, HKA angle was the most significant factor associated with revision (P < .001). CONCLUSION: In this population of revised UKAs and long-term successes, limb alignment was a more important determinant of outcome than tibial component alignment. LEVEL OF EVIDENCE: Level III case-control study.

Multiparametric MRI-ultrasonography software fusion prostate biopsy: initial results using a stereotactic robotic-assisted transperineal prostate biopsy platform comparing systematic vs targeted biopsy.

OBJECTIVE: To compare the detection rates of prostate cancer between systematic biopsy and targeted biopsy using a stereotactic robot-assisted transperineal prostate platform. MATERIALS AND METHODS: We identified consecutive patients with suspicious lesion(s) on multiparametric magnetic resonance imaging (mpMRI), who underwent both systematic and MRI-transrectal ultrasonography (US) fusion targeted biopsy using our proprietary transperineal robot-assisted prostate biopsy platform between January 2015 and January 2019 at our institution, for retrospective analysis. Comparative analysis was performed between systematic and targeted biopsy using McNemar's test, and the cohort was further stratified by prior biopsy status and Prostate Imaging Reporting and Data System (PI-RADS) v2.0 score. International Society of Urological Pathology (ISUP) grade group (GG) ≥2 cancers (previously known as Gleason grade ≥7) were considered to be clinically significant. RESULTS: A total of 500 patients were included in our final analysis, of whom 67 (13%) were patients with low-risk cancer on active surveillance. Of the 433 patients without prior diagnosis of cancer, 288 (67%) were biopsy-naïve. A total of 248 (57%) were diagnosed with prostate cancer, with 199 (46%) having clinically significant prostate cancer (ISUP GG ≥2). There were no statistically significant differences in the overall prostate cancer and clinically significant prostate cancer detection rate between systematic and targeted biopsy (51% vs 49% and 40% vs 38% respectively; P = 0.306 and P = 0.609). Of the 248 prostate cancers detected, 75% (187/248) were detected on both systematic and targeted biopsy, 14% (35/248) were detected on systematic biopsy alone and 11% (26/248) were detected on targeted biopsy alone. Of the 199 clinically significant cancers detected, 69% (138/199) were detected on both systematic and targeted biopsy, 17% (33/199) on systematic biopsy alone and 14% (28/199) on targeted biopsy alone. There were no statistically significant differences in the detection rate between systematic and targeted biopsy for both overall and clinically significant prostate cancer, even when the cohort was stratified by prior biopsy status and PI-RADS score. Targeted biopsy has greater sampling efficiency compared to systematic biopsy for both overall and clinically significant prostate cancer (23.2% vs 9.8%, P < 0.001 and 14.8% vs 5.6%, P < 0.001). CONCLUSIONS: Using our robot-assisted transperineal prostate platform, combined MRI-US targeted biopsy with concurrent systematic prostate systematic biopsy probably represents the optimal method for the detection of clinically significant prostate cancer.