Amyloid-like Assembly Activates a Phosphatase in the Developing Drosophila Embryo.

Prion-like proteins can assume distinct conformational and physical states in the same cell. Sequence analysis suggests that prion-like proteins are prevalent in various species; however, it remains unclear what functional space they occupy in multicellular organisms. Here, we report the identification of a prion-like protein, Herzog (CG5830), through a multimodal screen in Drosophila melanogaster. Herzog functions as a membrane-associated phosphatase and controls embryonic patterning, likely being involved in TGF-ß/BMP and FGF/EGF signaling pathways. Remarkably, monomeric Herzog is enzymatically inactive and becomes active upon amyloid-like assembly. The prion-like domain of Herzog is necessary for both its assembly and membrane targeting. Removal of the prion-like domain impairs activity, while restoring assembly on the membrane using a heterologous prion-like domain and membrane-targeting motif can restore phosphatase activity. This study provides an example of a prion-like domain that allows an enzyme to gain essential functionality via amyloid-like assembly to control animal development.

Regulators of rDNA array morphology in fission yeast.

Nucleolar morphology is a well-established indicator of ribosome biogenesis activity that has served as the foundation of many screens investigating ribosome production. Missing from this field of study is a broad-scale investigation of the regulation of ribosomal DNA morphology, despite the essential role of rRNA gene transcription in modulating ribosome output. We hypothesized that the morphology of rDNA arrays reflects ribosome biogenesis activity. We established GapR-GFP, a prokaryotic DNA-binding protein that recognizes transcriptionally-induced overtwisted DNA, as a live visual fluorescent marker for quantitative analysis of rDNA organization in Schizosaccharomyces pombe. We found that the morphology-which we refer to as spatial organization-of the rDNA arrays is dynamic throughout the cell cycle, under glucose starvation, RNA pol I inhibition, and TOR activation. Screening the haploid S. pombe Bioneer deletion collection for spatial organization phenotypes revealed large ribosomal protein (RPL) gene deletions that alter rDNA organization. Further work revealed RPL gene deletion mutants with altered rDNA organization also demonstrate resistance to the TOR inhibitor Torin1. A genetic analysis of signaling pathways essential for this resistance phenotype implicated many factors including a conserved MAPK, Pmk1, previously linked to extracellular stress responses. We propose RPL gene deletion triggers altered rDNA morphology due to compensatory changes in ribosome biogenesis via multiple signaling pathways, and we further suggest compensatory responses may contribute to human diseases such as ribosomopathies. Altogether, GapR-GFP is a powerful tool for live visual reporting on rDNA morphology under myriad conditions.

Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube.

Signaling pathways regulate the patterns of Hox gene expression that underlie their functions in the specification of axial identity. Little is known about the properties of cis-regulatory elements and underlying transcriptional mechanisms that integrate graded signaling inputs to coordinately control Hox expression. Here, we optimized a single molecule fluorescent in situ hybridization (smFISH) technique with probes spanning introns to evaluate how three shared retinoic acid response element (RARE)-dependent enhancers in the Hoxb cluster regulate patterns of nascent transcription in vivo at the level of single cells in wild-type and mutant embryos. We predominately detect nascent transcription of only a single Hoxb gene in each cell, with no evidence for simultaneous co-transcriptional coupling of all or specific subsets of genes. Single and/or compound RARE mutations indicate that each enhancer differentially impacts global and local patterns of nascent transcription, suggesting that selectivity and competitive interactions between these enhancers is important to robustly maintain the proper levels and patterns of nascent Hoxb transcription. This implies that rapid and dynamic regulatory interactions potentiate transcription of genes through combined inputs from these enhancers in coordinating the retinoic acid response.

Notch signalling drives synovial fibroblast identity and arthritis pathology.

The synovium is a mesenchymal tissue composed mainly of fibroblasts, with a lining and sublining that surround the joints. In rheumatoid arthritis the synovial tissue undergoes marked hyperplasia, becomes inflamed and invasive, and destroys the joint1,2. It has recently been shown that a subset of fibroblasts in the sublining undergoes a major expansion in rheumatoid arthritis that is linked to disease activity3-5; however, the molecular mechanism by which these fibroblasts differentiate and expand is unknown. Here we identify a critical role for NOTCH3 signalling in the differentiation of perivascular and sublining fibroblasts that express CD90 (encoded by THY1). Using single-cell RNA sequencing and synovial tissue organoids, we found that NOTCH3 signalling drives both transcriptional and spatial gradients-emanating from vascular endothelial cells outwards-in fibroblasts. In active rheumatoid arthritis, NOTCH3 and Notch target genes are markedly upregulated in synovial fibroblasts. In mice, the genetic deletion of Notch3 or the blockade of NOTCH3 signalling attenuates inflammation and prevents joint damage in inflammatory arthritis. Our results indicate that synovial fibroblasts exhibit a positional identity that is regulated by endothelium-derived Notch signalling, and that this stromal crosstalk pathway underlies inflammation and pathology in inflammatory arthritis.

Quantifying Nucleation In Vivo Reveals the Physical Basis of Prion-like Phase Behavior.

Protein self-assemblies modulate protein activities over biological timescales that can exceed the lifetimes of the proteins or even the cells that harbor them. We hypothesized that these timescales relate to kinetic barriers inherent to the nucleation of ordered phases. To investigate nucleation barriers in living cells, we developed distributed amphifluoric FRET (DAmFRET). DAmFRET exploits a photoconvertible fluorophore, heterogeneous expression, and large cell numbers to quantify via flow cytometry the extent of a protein's self-assembly as a function of cellular concentration. We show that kinetic barriers limit the nucleation of ordered self-assemblies and that the persistence of the barriers with respect to concentration relates to structure. Supersaturation resulting from sequence-encoded nucleation barriers gave rise to prion behavior and enabled a prion-forming protein, Sup35 PrD, to partition into dynamic intracellular condensates or to form toxic aggregates. Our results suggest that nucleation barriers govern cytoplasmic inheritance, subcellular organization, and proteotoxicity.

rRNA transcription is integral to phase separation and maintenance of nucleolar structure.

Transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus is necessary for ribosome biogenesis, which is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis results in tissue specific disorders termed ribosomopathies in association with alterations in nucleolar structure. However, how rRNA transcription and ribosome biogenesis regulate nucleolar structure during normal development and in the pathogenesis of disease remains poorly understood. Here we show that homozygous null mutations in Pol I subunits required for rRNA transcription and ribosome biogenesis lead to preimplantation lethality. Moreover, we discovered that Polr1a-/-, Polr1b-/-, Polr1c-/- and Polr1d-/- mutants exhibit defects in the structure of their nucleoli, as evidenced by a decrease in number of nucleolar precursor bodies and a concomitant increase in nucleolar volume, which results in a single condensed nucleolus. Pharmacological inhibition of Pol I in preimplantation and midgestation embryos, as well as in hiPSCs, similarly results in a single condensed nucleolus or fragmented nucleoli. We find that when Pol I function and rRNA transcription is inhibited, the viscosity of the granular compartment of the nucleolus increases, which disrupts its phase separation properties, leading to a single condensed nucleolus. However, if a cell progresses through mitosis, the absence of rRNA transcription prevents reassembly of the nucleolus and manifests as fragmented nucleoli. Taken together, our data suggests that Pol I function and rRNA transcription are required for maintaining nucleolar structure and integrity during development and in the pathogenesis of disease.

Wnt and TGFß coordinate growth and patterning to regulate size-dependent behaviour.

Differential coordination of growth and patterning across metazoans gives rise to a diversity of sizes and shapes at tissue, organ and organismal levels. Although tissue size and tissue function can be interdependent1-5, mechanisms that coordinate size and function remain poorly understood. Planarians are regenerative flatworms that bidirectionally scale their adult body size6,7 and reproduce asexually, via transverse fission, in a size-dependent manner8-10. This model offers a robust context to address the gap in knowledge that underlies the link between size and function. Here, by generating an optimized planarian fission protocol in Schmidtea mediterranea, we show that progeny number and the frequency of fission initiation are correlated with parent size. Fission progeny size is fixed by previously unidentified mechanically vulnerable planes spaced at an absolute distance along the anterior-posterior axis. An RNA interference screen of genes for anterior-posterior patterning uncovered components of the TGFß and Wnt signalling pathways as regulators of the frequency of fission initiation rather than the position of fission planes. Finally, inhibition of Wnt and TGFß signalling during growth altered the patterning of mechanosensory neurons-a neural subpopulation that is distributed in accordance with worm size and modulates fission behaviour. Our study identifies a role for TGFß and Wnt in regulating size-dependent behaviour, and uncovers an interdependence between patterning, growth and neurological function.

Genome-wide quantification of contributions to sexual fitness identifies genes required for spore viability and health in fission yeast.

Numerous genes required for sexual reproduction remain to be identified even in simple model species like Schizosaccharomyces pombe. To address this, we developed an assay in S. pombe that couples transposon mutagenesis with high-throughput sequencing (TN-seq) to quantitatively measure the fitness contribution of nonessential genes across the genome to sexual reproduction. This approach identified 532 genes that contribute to sex, including more than 200 that were not previously annotated to be involved in the process, of which more than 150 have orthologs in vertebrates. Among our verified hits was an uncharacterized gene, ifs1 (important for sex), that is required for spore viability. In two other hits, plb1 and alg9, we observed a novel mutant phenotype of poor spore health wherein viable spores are produced, but the spores exhibit low fitness and are rapidly outcompeted by wild type. Finally, we fortuitously discovered that a gene previously thought to be essential, sdg1 (social distancing gene), is instead required for growth at low cell densities and can be rescued by conditioned medium. Our assay will be valuable in further studies of sexual reproduction in S. pombe and identifies multiple candidate genes that could contribute to sexual reproduction in other eukaryotes, including humans.

S. pombe wtf drivers use dual transcriptional regulation and selective protein exclusion from spores to cause meiotic drive.

Meiotic drivers bias gametogenesis to ensure their transmission into more than half the offspring of a heterozygote. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility. wtf drivers encode both a Wtfpoison protein and a Wtfantidote protein using alternative transcriptional start sites. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4poison, but only the spores that inherit wtf4 receive a dose of Wtf4antidote sufficient for survival. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4poison transcript. This transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. We propose that these features contribute to the evolutionary success of the wtf drivers.

Enzymatic modules of the SAGA chromatin-modifying complex play distinct roles in Drosophila gene expression and development.

The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex is a transcriptional coactivator that contains four different modules of subunits. The intact SAGA complex has been well characterized for its function in transcription regulation and development. However, little is known about the roles of individual modules within SAGA and whether they have any SAGA-independent functions. Here we demonstrate that the two enzymatic modules of Drosophila SAGA are differently required in oogenesis. Loss of the histone acetyltransferase (HAT) activity blocks oogenesis, while loss of the H2B deubiquitinase (DUB) activity does not. However, the DUB module regulates a subset of genes in early embryogenesis, and loss of the DUB subunits causes defects in embryogenesis. ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) analysis revealed that both the DUB and HAT modules bind most SAGA target genes even though many of these targets do not require the DUB module for expression. Furthermore, we found that the DUB module can bind to chromatin and regulate transcription independently of the HAT module. Our results suggest that the DUB module has functions within SAGA and independent functions.

Predictors of Reoperation and Survival Experience (Minimum 1 Year) for Primary Versus Conversion Total Hip Arthroplasty in Young Patients.

BACKGROUND: Total hip arthroplasty (THA), including primary and conversion procedures, is commonly used for many types of joint disease in patients aged below 65 years, though few studies have evaluated THA outcomes in young patients (≤ 40 years old). This study examined a large cohort of patients who underwent THA at a young (≤ 40 years old) age to identify predictors of reoperation and compare survivorship between primary and conversion THAs. METHODS: A retrospective study was conducted on 497 patients who underwent 612 primary and conversion THAs at 40 years old or younger between 1990 and 2020. Medical records were reviewed to collect patient/surgical data. A multivariable logistic regression model identified independent predictors of reoperation, and Kaplan-Meier analysis with log-rank tests was used to compare survival curves by THA type. RESULTS: The median age at surgery (interquartile range) was 31 years (25 to 36). The median follow-up time was 6.6 years (range, 3.8 to 10.5). Conversion THAs had an increased rate of both revisions (12.3 versus 5.6%, P = 0.02) and nonrevision reoperations (8.9 versus 3.2%, P = 0.03) compared to primary THAs. A ceramic-on-ceramic articulation (odds ratio: 5.17; P = 0.03) and a higher estimated blood loss (odds ratio: 1.0007; P = 0.03) were independent predictors of reoperation for primary and conversion THA, respectively. Conversion THAs had a lower 15-year survival (77.8 versus 90.8%, P = 0.009) compared to primary THAs. CONCLUSIONS: Patients ≤ 40 years old who underwent primary and conversion THAs demonstrated an impressive 15-year survival comparable to that of older populations (74 to 93%), while conversion procedures had a higher reoperation rate. Although primary THA may be more ideal, there are promising outcomes for patients who need THA at a younger age than typically implemented, especially for those who are very young (≤ 30 years old).

Reverse Fragility Index: Comparing Revision Rates Between Direct Anterior and Other Approaches in Total Hip Arthroplasty. A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Despite increasing adoption of the direct anterior (DA) approach in total hip arthroplasty (THA), uncertainty persists regarding its outcomes beyond the 1-year mark in comparison to other approaches. We used the reverse fragility index (RFI) to evaluate the robustness of reported findings in the literature. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) comparing implant revision rates between DA and other approaches in THA, defined as all those different from DA. Our primary outcome was the RFI, which gauges the number of events needed for a nonsignificant result to become significant, in the revision rate between DA and other approaches. We also calculated the reverse fragility quotient by dividing the RFI by each study's sample size. Median values and interquartile ranges (IQRs) were displayed. RESULTS: A total of 10 RCTs with a total of 971 patients were included. The median RFI was 5 (IQR, 4 to 5), indicating the study's results would be statistically significant if the outcomes of 5 patients in 1 treatment arm were reversed. The median reverse fragility quotient was 0.049 (IQR, 0.04 to 0.057), indicating that a change of outcome in 4.9% of patients would render the revision rate significant. The median number of patients lost to follow-up was 4 (IQR, 0 to 7). Of the 10 RCTs, 6 had more patients lost to follow-up than their respective RFI values. CONCLUSIONS: Notable fragility was evidenced in most studies comparing DA to other approaches for THA. Surgeons should not solely rely on the P value to determine clinical significance and instead use multiple metrics. LEVEL OF EVIDENCE: II.

Predictors of reoperation and survival experience for primary total knee arthroplasty in young patients with degenerative and inflammatory arthritis.

INTRODUCTION: While total knee arthroplasty (TKA) is typically implemented in patients > 65 years old, young patients may need to undergo TKA for pain relief and functional improvement. Current data are limited by older cohorts and short-term survival rates. This study aimed to examine a large sample size of patients with degenerative and inflammatory conditions who underwent primary TKA at a young (≤ 40) age to identify predictors of reoperation, as well 15-year survivorship. MATERIALS AND METHODS: A retrospective study was performed on 77 patients (92 surgeries) who underwent primary TKA at ≤ 40 years old, between January 1990 and January 2020. Patient charts were reviewed and a multivariable logistic regression model identified independent predictors of reoperation. Kaplan-Meier analysis was employed to build survival curves and log-rank tests analyzed survival between groups. RESULTS: Of the 77 patients, the median age at the time of surgery was 35.7 years (IQR: 31.2-38.7) and median follow-up time was 6.88 years. Twenty-one (22.8%) primary TKAs underwent 24 reoperations, most commonly due to stiffness (n = 9, 32.1%) and infection (n = 13, 46.4%) more significantly in the OA group (p = 0.049). There were no independent predictors of reoperation in multivariable analysis, and 15-year revision-free survivorship after TKA did not differ by indication (77.3% for OA/PTOA vs. 96.7% for autoimmune, p = 0.09) or between ≤ 30 and 31-40 year age groups (94.7% vs. 83.6%, p = 0.55). CONCLUSIONS: In this cohort of patients ≤ 40 years old, revision-free survival was comparable to that reported in the literature for older TKA patients with osteoarthritis/autoimmune conditions (81-94% at 15-years). Though nearly a quarter of TKAs required reoperation and causes of secondary surgery differed between degenerative and inflammatory arthritis patients, there were no significant predictors of increased reoperation rate. Very young patients ≤ 30 years old did not have an increased risk of revision compared to those aged 31-40 years.

Patterns and Persistence of Perioperative Plasma and Cerebrospinal Fluid Neuroinflammatory Protein Biomarkers After Elective Orthopedic Surgery Using SOMAscan.

BACKGROUND: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. METHODS: SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes ( P < .05; absolute value of the fold change [|FC|] > 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels ( P < .05; |FC| > 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.

Dramatically diverse Schizosaccharomyces pombe wtf meiotic drivers all display high gamete-killing efficiency.

Meiotic drivers are selfish alleles that can force their transmission into more than 50% of the viable gametes made by heterozygotes. Meiotic drivers are known to cause infertility in a diverse range of eukaryotes and are predicted to affect the evolution of genome structure and meiosis. The wtf gene family of Schizosaccharomyces pombe includes both meiotic drivers and drive suppressors and thus offers a tractable model organism to study drive systems. Currently, only a handful of wtf genes have been functionally characterized and those genes only partially reflect the diversity of the wtf gene family. In this work, we functionally test 22 additional wtf genes for meiotic drive phenotypes. We identify eight new drivers that share between 30-90% amino acid identity with previously characterized drivers. Despite the vast divergence between these genes, they generally drive into >85% of gametes when heterozygous. We also identify three wtf genes that suppress other wtf drivers, including two that also act as autonomous drivers. Additionally, we find that wtf genes do not underlie a weak (64% allele transmission) meiotic driver on chromosome 1. Finally, we find that some Wtf proteins have expression or localization patterns that are distinct from the poison and antidote proteins encoded by drivers and suppressors, suggesting some wtf genes may have non-meiotic drive functions. Overall, this work expands our understanding of the wtf gene family and the burden selfish driver genes impose on S. pombe.

Driving integrative structural modeling with serial capture affinity purification.

Streamlined characterization of protein complexes remains a challenge for the study of protein interaction networks. Here we describe serial capture affinity purification (SCAP), in which two separate proteins are tagged with either the HaloTag or the SNAP-tag, permitting a multistep affinity enrichment of specific protein complexes. The multifunctional capabilities of this protein-tagging system also permit in vivo validation of interactions using acceptor photobleaching Förster resonance energy transfer and fluorescence cross-correlation spectroscopy quantitative imaging. By coupling SCAP to cross-linking mass spectrometry, an integrative structural model of the complex of interest can be generated. We demonstrate this approach using the Spindlin1 and SPINDOC protein complex, culminating in a structural model with two SPINDOC molecules docked on one SPIN1 molecule. In this model, SPINDOC interacts with the SPIN1 interface previously shown to bind a lysine and arginine methylated sequence of histone H3. Our approach combines serial affinity purification, live cell imaging, and cross-linking mass spectrometry to build integrative structural models of protein complexes.

Are There More Radiolucent Lines in Patients Who Underwent Total Knee Arthroplasty With or Without a Tourniquet During Cementation at 5 to 8 Years After Surgery?

BACKGROUND: This study investigated the presence and progression of radiolucent lines (RLLs) after cemented total knee arthroplasty (TKA) with or without tourniquet use. METHODS: There were 369 consecutive primary cemented TKAs with 5 to 8 years of follow-up. A tourniquet was used during component cementation in patients who underwent surgery from January 3, 2006, to March 31, 2010. No tourniquet was used from August 14, 2009, to October 14, 2014. There were 192 patients in the tourniquet group (TQ) and 177 patients in the no tourniquet group (NQ). Patient demographics, reoperations, and complications were recorded. RLLs were identified on anteroposterior, lateral, and skyline x-rays at 1, 2, and 5 to 8 years postoperatively using the modern knee society radiographic evaluation system. Demographics, reoperations, complications, and RLLs were compared. Age, sex, and body mass index were similar between groups. Mean tourniquet time in TQ was 11 minutes (range, 8 to 25). RESULTS: The presence of RLLs differed between groups, with 65% of TQ knees having RLLs under any part of the prostheses versus 46% of NQ knees (P < .001). The progression of RLL >2 mm occurred in 26.0% of knees in TQ and 16.7% of knees in NQ (P = .028). There were 13 TKAs that underwent subsequent revision surgery. There was no statistically or clinically significant difference in revision rate between groups (7 revisions in TQ, 6 in NQ, P = .66). CONCLUSION: Less RLLs were identified in NQ versus TQ. There were no statistically or clinically significant differences in revision rates between the NQ and TQ groups at 5 to 8 years.

Patient-Specific Safe Zones for Acetabular Component Positioning in Total Hip Arthroplasty: Mathematically Accounting for Spinopelvic Biomechanics.

BACKGROUND: Despite a growing understanding of spinopelvic biomechanics in total hip arthroplasty (THA), there is no validated approach for executing patient-specific acetabular component positioning. The purpose of this study was to (1) validate quantitative, patient-specific acetabular "safe zone" component positioning from spinopelvic parameters and (2) characterize differences between quantitative patient-specific acetabular targets and qualitative hip-spine classification targets. METHODS: From 2,457 consecutive primary THA patients, 22 (0.88%) underwent revision for instability. Spinopelvic parameters were measured prior to index THA. Acetabular position was measured following index and revision arthroplasty. Using a mathematical proof, we developed an open-source tool translating a surgeon-selected, preoperative standing acetabular target to a patient-specific safe zone intraoperative acetabular target. Difference between the patient-specific safe zone and the actual component position was compared before and after revision. Hip-spine classification targets were compared to patient-specific safe zone targets. RESULTS: Of the 22 who underwent revision, none dislocated at follow-up (4.6 [range, 1 to 6.9]). Patient-specific safe zone targets differed from prerevision acetabular component position by 9.1 ± 4.2° inclination/13.3 ± 6.7° version; after revision, the mean difference was 3.2 ± 3.0° inclination/5.3 ± 2.7° version. Differences between patient-specific safe zones and the median and extremes of recommended hip-spine classification targets were 2.2 ± 1.9° inclination/5.6 ± 3.7° version and 3.0 ± 2.3° inclination/7.9 ± 3.5° version, respectively. CONCLUSION: A mathematically derived, patient-specific approach accommodating spinopelvic biomechanics for acetabular component positioning was validated by approximating revised, now-stable hips within 5° version and 3° inclination. These patient-specific safe zones augment the hip-spine classification with prescriptive quantitative targets for nuanced preoperative planning.

The Association of Sacro-Femoro-Pubic Angle and Postoperative Dislocation Following Total Hip Arthroplasty.

BACKGROUND: Spino-pelvic orientation may affect dislocation risk following total hip arthroplasty (THA). It can be measured on lateral lumbo-pelvic radiographs. The sacro-femoro-pubic (SFP) angle, measured on an antero-posterior (AP) pelvis radiograph, is a reliable proxy for pelvic tilt, a measurement of spino-pelvic orientation measured on a lateral lumbo-pelvic radiograph. The purpose of this study was to investigate the relationship between SFP angle and dislocation following THA. METHODS: An Institutional Review Board-approved retrospective case-control study was conducted at a single academic center. We matched 71 dislocators (cases) to 71 nondislocators (controls) following THA performed by 1 of 10 surgeons between September 2001 and December 2010. Two authors (readers) independently calculated SFP angle from single preoperative AP pelvis radiographs. Readers were blinded to cases and controls. Conditional logistic regressions were used to identify factors differentiating cases and controls. RESULTS: The data did not show a clinically relevant or statistically significant difference in SFP angles after adjusting for gender, American Society of Anesthesiologists classification, prosthetic head size, age at time of THA, measurement laterality, and surgeon. CONCLUSION: We did not find an association between preoperative SFP angle and dislocation following THA in our cohort. Based on our data, SFP angle as measured on a single AP pelvis radiograph should not be used to assess dislocation risk prior to THA.