Trends in revision hip and knee arthroplasty observations after implementation of a regional joint replacement registry.

BACKGROUND: National joint replacement registries outside North America have been effective in reducing revision risk. However, there is little information on the role of smaller regional registries similar to those found in Canada or the United States. We sought to understand trends in total hip (THA) and knee (TKA) arthroplasty revision patterns after implementation of a regional registry. METHODS: We reviewed our regional joint replacement registry containing all 30 252 cases of primary and revision THA and TKA performed between Jan. 1, 2005, and Dec. 31, 2013. Each revision case was stratified into early (< 2 yr), mid (2-10 yr) or late (> 10 yr), and we determined the primary reason for revision. RESULTS: The early revision rate for TKA dropped from 3.0% in 2005 to 1.3% in 2011 (R(2) = 0.84, p = 0.003). Similarly, the early revision rate for THA dropped from 4.2% to 2.1% (R(2) = 0.78, p = 0.008). Despite primary TKA and THA volumes increasing by 35.5% and 39.5%, respectively, there was no concomitant rise in revision volumes. The leading reasons for TKA revision were infection, instability, aseptic loosening and stiffness. The leading reasons for THA revision were infection, instability, aseptic loosening and periprosthetic fracture. There were no discernible trends over time in reasons for early, mid-term or late revision for either TKA or THA. CONCLUSION: After implementation of a regional joint replacement registry we observed a significant reduction in early revision rates. Further work investigating the mechanism by which registry reporting reduces early revision risk is warranted.

CONTEXTE: Ailleurs qu'en Amérique du Nord, les registres nationaux des remplacements articulaires ont été efficaces pour réduire le risque de révision. Cependant, il y a peu d'information sur le rôle des plus petits registres régionaux comme ceux qu'on trouve au Canada et aux États-Unis. Nous avons donc cherché à comprendre les tendances en matière de révision des arthroplasties totales de la hanche (ATH) et du genou (ATG) après la création d'un registre régional. MÉTHODES: Nous avons passé en revue notre registre régional des remplacements articulaires, qui contient les 30 252 ATH et ATG primaires et de révision effectuées entre le 1er janvier 2005 et le 31 décembre 2013. Chaque cas de révision a été classé précoce (< 2 ans), moyen (de 2 à 10 ans) ou tardif (> 10 ans), et nous avons déterminé la raison principale de la révision. RÉSULTATS: Le taux de révision précoce pour l'ATG a diminué de 3,0 % en 2005 à 1,3 % en 2011 (R2 = 0,84, p = 0,003). De même, le taux de révision précoce pour l'ATH a diminué de 4,2 % à 2,1 % (R2 = 0,78, p = 0,008). Malgré une augmentation des nombres d'ATG et d'ATH primaires de 35,5 % et de 39,5 %, respectivement, il n'y a pas eu de hausse concomitante du nombre de révisions. Les principaux motifs de révision de l'ATG étaient l'infection, l'instabilité, le descellement aseptique et la raideur. Les principaux motifs de révision de l'ATH étaient l'infection, l'instabilité, le descellement aseptique et les fractures périprothétiques. Aucune tendance n'a été décelée au fil du temps dans les motifs de révision précoce, moyenne et tardive pour l'une ou l'autre des interventions. CONCLUSION: Nous avons observé une baisse significative des taux de révision précoce après la mise en œuvre d'un registre régional des remplacements articulaires. Il serait pertinent d'étudier plus en profondeur le mécanisme par lequel le signalement dans un registre réduit le risque de révision précoce.

Ileal Interposition for Ureteral Reconstruction Following Treatment for Abdominopelvic Malignancy: Complications and Outcomes From a Comprehensive Cancer Center.

OBJECTIVE: To characterize the outcomes of ileal interposition for the management of ureteral obstruction from tumor and ureteral stricture following treatment for abdominopelvic malignancy. MATERIALS AND METHODS: A retrospective database analysis was performed for all cases of ileal interposition performed by 5 surgeons from January 2013 to December 2020. Patients were ≥18 years of age and included if undergoing ileal interposition in either the primary setting of a surgical procedure for tumor extirpation or in the delayed setting. RESULTS: In total, 23 patients who underwent repair of 27 ureteral units were included. The mean age was 60.2 years. Median follow-up was 21.6 months. The most common primary diagnoses were urothelial (35%), colorectal (31%), and cervical (22%) cancer. The etiologies of ureteral obstruction were malignant in 48% and ureteral stricture in 52%. Types of repairs included unilateral interposition in 13 patients, bilateral interposition in 1 patient, interposition to an ileal conduit in 3 patients, and interposition with cystoplasty in 6 patients. There was a statistically significant difference between the mean preoperative (Creatinine 1.05 mg/dL, Estimated Glomerular Filtration Rate 77 ml/min/1.73 m2) renal function and postoperative (Creatinine 1.26 mg/dL, Estimated Glomerular Filtration Rate 67 mL/min/1.73 m2) renal function at the most recent follow-up (P = .024). Eight minor (grade 1-2) and 6 major (grade ≥3) complications developed for a minor and major complication rate of 35% and 26%, respectively. CONCLUSION: Ileal interposition is successfully utilized as a reconstructive technique at the time of enbloc resection involving the ureter and to address ureteral stricture in the delayed setting.

Role of CBFs as integrators of chloroplast redox, phytochrome and plant hormone signaling during cold acclimation.

Cold acclimation of winter cereals and other winter hardy species is a prerequisite to increase subsequent freezing tolerance. Low temperatures upregulate the expression of C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB1) which in turn induce the expression of COLD-REGULATED (COR) genes. We summarize evidence which indicates that the integration of these interactions is responsible for the dwarf phenotype and enhanced photosynthetic performance associated with cold-acclimated and CBF-overexpressing plants. Plants overexpressing CBFs but grown at warm temperatures mimic the cold-tolerant, dwarf, compact phenotype; increased photosynthetic performance; and biomass accumulation typically associated with cold-acclimated plants. In this review, we propose a model whereby the cold acclimation signal is perceived by plants through an integration of low temperature and changes in light intensity, as well as changes in light quality. Such integration leads to the activation of the CBF-regulon and subsequent upregulation of COR gene and GA 2-oxidase (GA2ox) expression which results in a dwarf phenotype coupled with increased freezing tolerance and enhanced photosynthetic performance. We conclude that, due to their photoautotrophic nature, plants do not rely on a single low temperature sensor, but integrate changes in light intensity, light quality, and membrane viscosity in order to establish the cold-acclimated state. CBFs appear to act as master regulators of these interconnecting sensing/signaling pathways.

Cold acclimation and BnCBF17-over-expression enhance photosynthetic performance and energy conversion efficiency during long-term growth of Brassica napus under elevated CO2 conditions.

The effects of cold acclimation and long-term elevated CO(2) on photosynthetic performance of wild-type (WT) and BnCBF17-over-expressing line of Brassica napus cv. Westar (BnCBF17-OE) grown at either 20/16 °C (non-acclimated) or 5/5 °C (cold acclimated) and at either ambient (380 µmol C mol(-1)) or elevated (700 µmol C mol(-1)) CO(2) were studied. Compared with non-acclimated WT, the BnCBF17-OE grown at 20 °C mimicked the effects of cold acclimation on WT B. napus with respect to compact dwarf phenotype and increased rates of light-saturated CO(2) assimilation and photosynthetic electron transport. This was associated with enhanced energy conversion efficiency into biomass as assessed by decreased excitation pressure coupled to decreased dependence on non-photochemical energy dissipation for a given irradiance. Growth at elevated CO(2) decreased the light and CO(2)-saturated rates of photosynthesis by 30 % for non-acclimated WT relative to growth at ambient CO(2). This was associated with inhibition in electron transport rates (20 %), decrease in amount of rbcL (35 %) and cytosolic FBPase (70 %) and increased excitation pressure and non-photochemical quenching in elevated versus ambient CO(2)-grown non-acclimated WT. In contrast, light and CO(2)-saturated rates of photosynthesis, electron transport, excitation pressure, non-photochemical quenching and levels of rbcL, cytosolic FBPase and Lhcb1 were insensitive to growth under elevated CO(2) in BnCBF17-OE and cold-acclimated WT. Thus, BnCBF17-over-expression and cold acclimation maintain enhanced energy conversion efficiency and reduced sensitivity to feedback-limited photosynthesis during long-term growth of B. napus under elevated CO(2). Our results indicated that CBFs transcription factors regulate not only freezing tolerance but also has major whole plant effects.

Urethrocutaneous fistula repair following hypospadias surgery using the PATIO technique for small fistulae: A single centre experience.

INTRODUCTION: Urethrocutaneous fistula (UCF) development following primary hypospadias repair is a common complication with high rates of recurrence despite attempts at repair. A novel technique for the management of these fistulae, the PATIO (preserve the tract and turn it inside out) repair, has been described and has shown encouraging outcomes in previous reports. OBJECTIVE: The aim of this study was to evaluate fistula repair outcomes in patients undergoing the PATIO technique compared with standard repair. STUDY DESIGN: A retrospective chart-based review was performed for pediatric patients undergoing UCF repair from January 2005 to July 2018. Data including: age, follow-up, meatal location, meatal stenosis, number of fistulae and repairs, UCF location, complications, and outcomes was obtained. Cases were categorized into PATIO repair, standard repair, and PATIO repair following prior standard repair. Surgical outcome with respect to freedom from fistula recurrence was determined. RESULTS: In total, 586 patients underwent hypospadias surgery with 44 patients developing 52 UCF cases that required repair during the study period for a fistula rate of 8.9%. Mean age at repair was 19 months. Median follow-up time was 28 months. For PATIO repair alone, 21/26 (81%) had success. For standard repair alone, 8/18 (44%) had success and for standard repair followed by PATIO repair, 8/8 (100%) were successful. A statistically significant difference was noted for success when comparing standard repair with PATIO repair (p = 0.023, p < 0.05) and PATIO repair following standard repair (p = 0.010, p < 0.05). There was a statistically non-significant difference between PATIO repair and PATIO repair following standard repair (p = 0.309, p < 0.05). Failure following PATIO repair was found in cases where the procedure was early in implementation and experience was limited. DISCUSSION: UCF repair using the PATIO technique has shown encouraging results in the short-term, with a majority of patients achieving a successful outcome compared with standards techniques. As this procedure continues to be used and experience develops, a larger sample of cases will become available for analysis and longer follow-up will prove necessary in examining the long-term outcomes of this procedure. The outcomes examined have demonstrated consistency with previously reported outcomes in the literature. Limitations include small sample size, short-term follow up, and the retrospective nature of the review. CONCLUSIONS: The findings of this study have provided further support to the use of this technique in conventional UCF repair as a means to decrease the risk of recurrence and provide durable results in the short-term. Ongoing follow up will prove necessary to examine success in the long-term.

Remodeling of the tumor microenvironment through PAK4 inhibition sensitizes tumors to immune checkpoint blockade.

PAK4 inhibition can sensitize tumors to immune checkpoint blockade (ICB) therapy, however, the underlying mechanisms remain unclear. We report that PAK4 inhibition reverses immune cell exclusion by increasing the infiltration of CD8 T cells and CD103+ dendritic cells (DCs), a specific type of DCs that excel at cross-presenting tumor antigens and constitute a source of CXCL10. Interestingly, in melanoma clinical datasets, PAK4 expression levels negatively correlate with the presence of CCL21, the ligand for CCR7 expressed in CD103+ DCs. Furthermore, we extensively characterized the transcriptome of PAK4 knock out (KO) tumors, in vitro and in vivo, and established the importance of PAK4 expression in the regulation of the extracellular matrix, which can facilitate immune cell infiltration. Comparison between PAK4 wild type (WT) and KO anti-PD-1 treated tumors revealed how PAK4 deletion sensitizes tumors to ICB from a transcriptomic perspective. In addition, we validated genetically and pharmacologically that inhibition of PAK4 kinase activity is sufficient to improve anti-tumor efficacy of anti-PD-1 blockade in multiple melanoma mouse models. Therefore, this study provides novel insights into the mechanism of action of PAK4 inhibition and provides the foundation for a new treatment strategy that aims to overcome resistance to PD-1 blockade by combining anti-PD-1 with a small molecule PAK4 kinase inhibitor.

Primary localized amyloidosis causing urethral stricture disease: a mimicker of urothelial carcinoma.

We describe a case of mild lower urinary tract symptoms and microscopic hematuria in a 53-year-old-male with hypertension found to have urethral stricture disease suspicious for urothelial carcinoma. During the investigation, cystoscopy and biopsy demonstrated eosinophilic amyloid proteins consistent with primary localized urethral amyloidosis. No systemic evidence of amyloidosis was demonstrated. Following a trial of conservative management with serial dilatations, the patient elected to proceed with surgical management by anterior urethroplasty using an excision and primary anastomosis technique. The patient has done well with resolution of his symptoms and no further recurrence of urethral amyloid disease at ongoing follow up.

The use of Group 3 LEA proteins as fusion partners in facilitating recombinant expression of recalcitrant proteins in E. coli.

Late embryogenesis abundant (LEA) proteins are intrinsically disordered proteins that accumulate in organisms during the development of dehydration stress tolerance and cold acclimation. Group 3 LEA proteins have been implicated in the prevention of cellular protein denaturation and membrane damage during desiccation and anhydrobiosis. We tested the ability of LEA proteins to facilitate recombinant expression of recalcitrant and intrinsic membrane proteins. Two Brassica napus Group 3 LEA proteins, BN115m and a truncated fragment of BNECP63, were fused to two target proteins identified as recalcitrant to overexpression in soluble form or outside of inclusion bodies. Fusion of a truncated peptide of BNECP63 is sufficient to provide soluble and high levels of recombinant overexpression of BNPsbS (an intrinsic membrane chlorophyll-binding protein of photosystem II light harvesting complex) and a peptide of the Hepatitis C viral polyprotein. Furthermore, fusion of the recombinant target proteins to BNECP63 or BN115 prevented irreversible heat- and freeze-induced precipitation. These experiments not only underscore the exploitation of LEA-type peptides in facilitating protein overexpression and protection, but also provide insights into the mechanism of LEA proteins in cellular protection.

Annotation of androgen dependence to human prostate cancer-associated genes by microarray analysis of mouse prostate.

In silico methods and array technologies have identified genes differentially expressed in prostate cancer. Biological functions of the identified genes are often unclear. Considering the biological significance of androgens in prostate cancer, we profiled the prostate transcripts of congenital androgen-deficient mice with or without androgen replacement in vivo using murine gene expression array. In parallel genes differentially expressed in human prostate cancer were identified by Digital Differential Display and the Serial Analysis of Gene Expression. Androgen dependence of the identified genes was then determined by the steady-state mRNA levels of the murine orthologs in response to androgen treatment. The annotation is supported by the finding that some of the androgen target genes have been reported previously with independent experiments.

Trypan blue to aid visualization of the vitreous during anterior segment surgery.

We describe the usefulness of intracameral injection of trypan blue to highlight vitreous in the anterior chamber. The technique was used in 3 eyes of 3 patients who had vitreous prolapse in the anterior chamber. Trypan blue 0.06% was injected in the anterior chamber under air to visualize and resect the prolapsed vitreous. Trypan blue stained the clear vitreous and improved visualization for a safe and atraumatic vitrectomy. No complications associated with the dye were found.

Oncogenic action of secreted phospholipase A2 in prostate cancer.

Mortality from prostate cancer is associated with progression of tumors to androgen-independent growth and metastasis. Eicosanoid products of both the cyclooxygenase (COX) and lipoxygenase (LOX) pathways are important mediators of the proliferation of prostate cancer cells in culture and regulate tumor vascularization and metastasis in animal models. Pharmacologic agents that block either COX or LOX products effectively reduce the size of prostate cancer xenografts. Phospholipase A(2) (PLA(2)) enzymes regulate the provision of arachidonic acid to both COX- and LOX-derived eicosanoids, and a secreted form of the enzyme (sPLA(2)-IIA) is elevated in prostate cancer tissues. Here, we show by immunohistochemistry, in patients receiving androgen ablation therapy, that sPLA(2)-IIA remains elevated in remaining cancer cells relative to benign glands after treatment. Furthermore, sPLA(2)-IIA expression seen in benign glands is substantially decreased after androgen depletion, whereas cytosolic PLA(2)-alpha (cPLA(2)-alpha) levels are unchanged. sPLA(2)-IIA mRNA expression is detectable and inducible by androgen (0.01-10 nmol/L) in the androgen-sensitive cell line LNCaP, and exogenous addition of sPLA(2)-IIA (1-100 nmol/L), but not an inactive sPLA(2)-IIA mutant (H(48)Q), results in a dose-dependent increase in cell numbers or the fraction of cells in G(2)-M phase, which is inhibited by sPLA(2)-IIA-selective inhibitors. The effect of exogenous sPLA(2)-IIA can also be blocked by inhibition of cPLA(2)-alpha, suggesting a role for cPLA(2)-alpha in mediating sPLA(2)-IIAlpha action. sPLA(2)-IIA inhibitors suppressed basal proliferation in LNCaP cells and in the androgen-independent, sPLA(2)-positive cell line PC3 but not in the sPLA(2)-IIA-negative androgen-independent cell line DU145. Established PC3 xenograft tumors grew more slowly in mice treated with sPLA(2)-IIA inhibitors than those treated with saline only. The PLA(2) enzymes, and sPLA(2)-IIA in particular, thus represent important targets for the treatment of sPLA(2)-IIA-positive androgen-independent prostate cancer.