Outpatient total hip and knee arthroplasty - Patient expectations versus experience.

Aims & objectives: With modern advancements in surgical techniques and rapid recovery protocols, incidence of outpatient total joint arthroplasty (TJA) is increasing. Previous literature has historically focused on cost, safety, and clinical outcomes, with few studies investigating patient expectations and experiences. The aim of this study was to survey preoperative patient expectations related to outpatient TJA surgery compared with perioperative perceptions and experience. Materials & methods: Prospective study of patients undergoing outpatient total hip or knee arthroplasty at a single Tertiary Academic center. Preoperative and postoperative surveys were administered during routine clinic visits. Results: One hundred and six patients completed preoperative surveys; 79 completed postoperative surveys and were included in the final data analysis. Fifty (63.3 %) patients reported being aware of outpatient TJA prior to undergoing the procedure. There was no difference between preoperative anticipated pain control and postoperative perceived pain control (6.64 vs. 6.88, p = 0.77). Most postoperative patients (N = 56, 70.9 %) rated outpatient surgery as "much better" or "better" than expected. Most postoperative patients (N = 68, 86 %) would opt to have outpatient surgery again. Fifty-two (65.8 %) of postoperative patients believed outpatient surgery sped up their postoperative rehabilitation. Conclusion: For most patients, the outpatient surgical experience met or exceeded expectations. Nearly 90 % of patients would prefer to have outpatient surgery in the future, further supporting the continued migration of elective arthroplasty away from inpatient sites of care.

The histone chaperone SPT2 regulates chromatin structure and function in Metazoa.

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.

FAM111A regulates replication origin activation and cell fitness.

FAM111A is a replisome-associated protein and dominant mutations within its trypsin-like peptidase domain are linked to severe human developmental syndrome, the Kenny-Caffey syndrome. However, FAM111A functions remain unclear. Here, we show that FAM111A facilitates efficient activation of DNA replication origins. Upon hydroxyurea treatment, FAM111A-depleted cells exhibit reduced single-stranded DNA formation and a better survival rate. Unrestrained expression of FAM111A WT and patient mutants causes accumulation of DNA damage and cell death, only when the peptidase domain remains intact. Unrestrained expression of FAM111A WT also causes increased single-stranded DNA formation that relies on S phase entry, FAM111A peptidase activity but not its binding to proliferating cell nuclear antigen. Altogether, these data unveil how FAM111A promotes DNA replication under normal conditions and becomes harmful in a disease context.

Radiographic parameters of pelvic and proximal femoral morphology do not predict outcomes for direct anterior total hip arthroplasty.

BACKGROUND: Radiographic predictors of outcomes associated with direct anterior approach (DAA) total hip arthroplasty (THA) are largely unknown. Anecdotally, some surgeons limit surgery to patients with low body mass index (BMI) or "favorable" bony morphology. Objective data on the impact of these factors is limited. We sought to determine radiographic and demographic predictors of outcomes after DAA arthroplasty. METHODS: A consecutive series of patients undergoing unilateral, elective DAA THA, who had linked pre- and post-operative patient reported outcome scores, from January 1, 2017 to March 30, 2019 were included. Radiographic measurements, including proxies for pelvic overhang, femoral canal access, acetabular morphologic changes, and markers of disease severity, were performed on calibrated radiographs. Intra-observer consistency was also evaluated. Outcome measures included disease specific and general health patient-reported outcomes scores, while surgical difficulty was approximated by estimated blood loss and surgical time. Multivariate analyses were performed to determine statistically significant correlations. RESULTS: 168 patients were included. Overall, patients experienced significant improvement in outcome scores (mean ∆ HOOS-JR 39.4, PROMIS-physical 12.3). There were two reoperations (1.2%), for recurrent dislocation. Female sex (p = 0.015) and increasing age (p == 0.019) were associated with shorter surgical times. No statistically significant correlations were found between the radiographic parameters and outcome measures. Intraclass correlation coefficients of the radiographic measurements were overall strong (0.73-1.0). CONCLUSION: We demonstrated consistent results in this series of patients despite variation in bony morphology. Our findings suggest that DAA THA can be safely performed on a broader patient population.

Intussusception Allograft Prosthetic Composites in Total Hip Arthroplasty: A Salvage Operation for Extensive Femoral Bone Loss.

BACKGROUND: Allograft prosthetic composites (APCs) have been used to perform revision total hip arthroplasty (THA) for massive femoral bone loss or deformity. Intussusception, or "telescoping", APC techniques have been proposed to enhance the contact area of this interface and provide superior mechanical fixation over conventional methods. The purpose of this study is to present to our knowledge, the largest series of telescoping APC THAs, along with surgical technique details and midterm (average 5-10 years) clinical results. METHODS: Between 1994 and 2015, 46 revision THAs performed with proximal femoral telescoping APCs were retrospectively reviewed at a single institution. Overall survival, reoperation-free survival, and construct survival rates were calculated via Kaplan-Meier methods. In addition, radiographic analyses were performed to evaluate for component loosening, union at the APC-host interface, and resorption of the allograft. RESULTS: At 10 years, the overall patient survival was 58%, reoperation-free survival was 76%, and construct survival was 95%. Reoperation was performed in 20% (n = 9) and only 2 constructs required resection. Radiographic analyses performed at latest follow-up revealed no instances of radiographic femoral stem loosening, an 86% union rate at the APC-host site, 23% with signs of some allograft resorption, and a 54% trochanteric union. The mean postoperative Harris hip score was 71 points (range, 46-100). CONCLUSION: Telescoping APCs are technically demanding, but provide reliable mechanical fixation for the reconstructing of large proximal femoral bone deficits in revision THA with excellent construct survivorship, acceptable reoperation rates, and good clinical outcomes. LEVEL OF EVIDENCE: IV.

Lessons Learned From the Comprehensive Care for Joint Replacement Model at an Academic Tertiary Center: The Good, the Bad, and the Ugly.

BACKGROUND: Our institution participated in the Comprehensive Care for Joint Replacement (CJR) model from 2016 to 2020. Here we review lessons learned from a total joint arthroplasty (TJA) care redesign at a tertiary academic center amid changing: (1) CJR rules; (2) inpatient only rules; and (3) outpatient trends. METHODS: Quality, financial, and patient demographic data from the years prior to and during participation in CJR were obtained from institutional and Medicare reconciled CJR performance data. RESULTS: Despite an increase in true outpatients and new challenges that arose from changing inpatient-only rules, there was significant improvement in quality metrics: decreased length of stay (3.48-1.52 days, P < .001), increased home discharge rate (70.2-85.5%, P < .001), decreased readmission rate (17.7%-5.1%, P < .001), decreased complication rate (6.5%-2.0%, P < .001), and the Centers for Medicare and Medicaid Services (CMS) Composite Quality Score increased from 4.4 to 17.6. Over the five year period, CMS saved an estimated $8.3 million on 1,486 CJR cases, $7.5 million on 1,351 non-CJR cases, and $600,000 from the voluntary classification of 371 short-stay inpatients as outpatient-a total savings of $16.4 million. Despite major physician time and effort leading to marked improvements in efficiency, quality, and large cost savings for CMS, CJR participation resulted in a net penalty of $304,456 to our institution, leading to zero physician gainsharing opportunities. CONCLUSION: The benefits of CJR were tempered by malalignment of incentives among payer, hospital, and physician as well as a lack of transparency. Future payment models should be refined based on the successes and challenges of CJR.

Surgical Management of Tibial Bone Loss in Revision Total Knee Arthroplasty: Clinical Outcomes and Radiographic Analysis of Tantalum Cones, Titanium Cones and Titanium Sleeves.

Background: The use of metaphyseal cones and sleeves has improved the ability to manage tibial bone loss in revision total knee arthroplasty (TKA). The purpose of this study was to compare the outcomes of three systems used for tibial metaphyseal reconstruction in revision TKA. Methods: We performed a retrospective review of a consecutive series of 723 revision TKAs, including 145 (20%) knee revisions using tibial cones or sleeves. We compared porous tantalum (TM) cones, titanium (Ti) cones and titanium sleeves. The mean follow-up was 2.5 years. Results: The rate of revision for any reason was similar among all groups. Revision-free survival rates were similar among all systems studied at a mean follow-up of 2.5 years (TM cones 93%, Ti cones 94%, titanium sleeves 89%). Ti cones had a lower complication rate (6%) compared to TM cones (24%) and sleeves (29%). TM cones (15%) and titanium sleeves (13%) had higher reoperation rates (for any cause) than Ti cones (2%). Radiographic loosening was higher for sleeves (11%) than TM and Ti cones (2%). Conclusion: Metaphyseal reconstruction for tibial bone loss in revision TKA using tantalum cones, titanium cones and titanium sleeves showed successful and comparable early clinical outcomes at a mean follow-up of 2.5 years with higher rates of radiographic loosening for titanium sleeves. Level of Evidence: III.

The Role of MTBP as a Replication Origin Firing Factor.

The initiation step of replication at replication origins determines when and where in the genome replication machines, replisomes, are generated. Tight control of replication initiation helps facilitate the two main tasks of genome replication, to duplicate the genome accurately and exactly once each cell division cycle. The regulation of replication initiation must ensure that initiation occurs during the S phase specifically, that no origin fires more than once per cell cycle, that enough origins fire to avoid non-replicated gaps, and that the right origins fire at the right time but only in favorable circumstances. Despite its importance for genetic homeostasis only the main molecular processes of eukaryotic replication initiation and its cellular regulation are understood. The MTBP protein (Mdm2-binding protein) is so far the last core replication initiation factor identified in metazoan cells. MTBP is the orthologue of yeast Sld7. It is essential for origin firing, the maturation of pre-replicative complexes (pre-RCs) into replisomes, and is emerging as a regulation focus targeted by kinases and by regulated degradation. We present recent insight into the structure and cellular function of the MTBP protein in light of recent structural and biochemical studies revealing critical molecular details of the eukaryotic origin firing reaction. How the roles of MTBP in replication and other cellular processes are mutually connected and are related to MTBP's contribution to tumorigenesis remains largely unclear.

Refining the domain architecture model of the replication origin firing factor Treslin/TICRR.

Faithful genome duplication requires appropriately controlled replication origin firing. The metazoan origin firing regulation hub Treslin/TICRR and its yeast orthologue Sld3 share the Sld3-Treslin domain and the adjacent TopBP1/Dpb11 interaction domain. We report a revised domain architecture model of Treslin/TICRR. Protein sequence analyses uncovered a conserved Ku70-homologous ß-barrel fold in the Treslin/TICRR middle domain (M domain) and in Sld3. Thus, the Sld3-homologous Treslin/TICRR core comprises its three central domains, M domain, Sld3-Treslin domain, and TopBP1/Dpb11 interaction domain, flanked by non-conserved terminal domains, the CIT (conserved in Treslins) and the C terminus. The CIT includes a von Willebrand factor type A domain. Unexpectedly, MTBP, Treslin/TICRR, and Ku70/80 share the same N-terminal domain architecture, von Willebrand factor type A and Ku70-like ß-barrels, suggesting a common ancestry. Binding experiments using mutants and the Sld3-Sld7 dimer structure suggest that the Treslin/Sld3 and MTBP/Sld7 ß-barrels engage in homotypic interactions, reminiscent of Ku70-Ku80 dimerization. Cells expressing Treslin/TICRR domain mutants indicate that all Sld3-core domains and the non-conserved terminal domains fulfil important functions during origin firing in human cells. Thus, metazoa-specific and widely conserved molecular processes cooperate during metazoan origin firing.

Citrullination Was Introduced into Animals by Horizontal Gene Transfer from Cyanobacteria.

Protein posttranslational modifications add great sophistication to biological systems. Citrullination, a key regulatory mechanism in human physiology and pathophysiology, is enigmatic from an evolutionary perspective. Although the citrullinating enzymes peptidylarginine deiminases (PADIs) are ubiquitous across vertebrates, they are absent from yeast, worms, and flies. Based on this distribution PADIs were proposed to have been horizontally transferred, but this has been contested. Here, we map the evolutionary trajectory of PADIs into the animal lineage. We present strong phylogenetic support for a clade encompassing animal and cyanobacterial PADIs that excludes fungal and other bacterial homologs. The animal and cyanobacterial PADI proteins share functionally relevant primary and tertiary synapomorphic sequences that are distinct from a second PADI type present in fungi and actinobacteria. Molecular clock calculations and sequence divergence analyses using the fossil record estimate the last common ancestor of the cyanobacterial and animal PADIs to be less than 1 billion years old. Additionally, under an assumption of vertical descent, PADI sequence change during this evolutionary time frame is anachronistically low, even when compared with products of likely endosymbiont gene transfer, mitochondrial proteins, and some of the most highly conserved sequences in life. The consilience of evidence indicates that PADIs were introduced from cyanobacteria into animals by horizontal gene transfer (HGT). The ancestral cyanobacterial PADI is enzymatically active and can citrullinate eukaryotic proteins, suggesting that the PADI HGT event introduced a new catalytic capability into the regulatory repertoire of animals. This study reveals the unusual evolution of a pleiotropic protein modification.

OAF: a new member of the BRICHOS family.

Summary: The 10 known BRICHOS domain-containing proteins in humans have been linked to an unusually long list of pathologies, including cancer, obesity and two amyloid-like diseases. BRICHOS domains themselves have been described as intramolecular chaperones that act to prevent amyloid-like aggregation of their proteins' mature polypeptides. Using structural comparison of coevolution-based AlphaFold models and sequence conservation, we identified the Out at First (OAF) protein as a new member of the BRICHOS family in humans. OAF is an experimentally uncharacterized protein that has been proposed as a candidate biomarker for clinical management of coronavirus disease 2019 infections. Our analysis revealed how structural comparison of AlphaFold models can discover remote homology relationships and lead to a better understanding of BRICHOS domain molecular mechanism. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

PERCC1, a new member of the Yap/TAZ/FAM181 transcriptional co-regulator family.

Motivation: Disrupted PERCC1 gene expression causes an intractable congenital diarrhoea in infants. However, this gene's molecular mechanism is unknown and no homologous proteins have been reported. Results: Our detailed evolutionary analysis of PERCC1 sequence reveals it to be a previously unappreciated member of the YAP/TAZ/FAM181 family of homologous transcriptional regulators. Like YAP and TAZ, PERCC1 likely interacts with DNA via binding to TEA/ATTS domain transcription factors (TEADs) using its conserved interface-2 and -3 sequences. We compare the expression patterns of PERCC1 with those of YAP, TAZ, TEADs. Our report provides the identification and first in-depth bioinformatic analysis of a YAP/TAZ homologue, and a likely new regulator of the YAP/TAZ-TEAD transcriptional complex. Availability and implementation: The data underlying this article are available in UniProt Database. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Extending the Horizon of Homology Detection with Coevolution-based Structure Prediction.

Traditional sequence analysis algorithms fail to identify distant homologies when they lie beyond a detection horizon. In this review, we discuss how co-evolution-based contact and distance prediction methods are pushing back this homology detection horizon, thereby yielding new functional insights and experimentally testable hypotheses. Based on correlated substitutions, these methods divine three-dimensional constraints among amino acids in protein sequences that were previously devoid of all annotated domains and repeats. The new algorithms discern hidden structure in an otherwise featureless sequence landscape. Their revelatory impact promises to be as profound as the use, by archaeologists, of ground-penetrating radar to discern long-hidden, subterranean structures. As examples of this, we describe how triplicated structures reflecting longin domains in MON1A-like proteins, or UVR-like repeats in DISC1, emerge from their predicted contact and distance maps. These methods also help to resolve structures that do not conform to a "beads-on-a-string" model of protein domains. In one such example, we describe CFAP298 whose ubiquitin-like domain was previously challenging to perceive owing to a large sequence insertion within it. More generally, the new algorithms permit an easier appreciation of domain families and folds whose evolution involved structural insertion or rearrangement. As we exemplify with α1-antitrypsin, coevolution-based predicted contacts may also yield insights into protein dynamics and conformational change. This new combination of structure prediction (using innovative co-evolution based methods) and homology inference (using more traditional sequence analysis approaches) shows great promise for bringing into view a sea of evolutionary relationships that had hitherto lain far beyond the horizon of homology detection.

Attitudes of Medical Students Towards Psychiatry in Venezuela: a 6-Year Longitudinal Study.

OBJECTIVE: The authors evaluated changes in attitude towards psychiatry of medical students in one medical school in Venezuela. METHODS: Balon's modified questionnaire was administered to first and sixth-year medical students to analyze their attitude towards psychiatry. The answers were compared with McNemar's test. RESULTS: The students' negative perception of psychiatry increased by the end of medical school with 45% of sixth-year students reportedly feeling uncomfortable when working with patients with psychiatric illness compared to only 8.3% of first-year medical students. Interest in specializing in psychiatry decreased from 2.6% in first-year medical students to 0% in sixth-year medical students (p=0.001). CONCLUSION: Different factors may lead to the loss of interest in psychiatry of medical students in Venezuela, such as little time spent with patients, being in contact only with patients with psychosis, stigma about psychiatry among medical doctors and friends, feeling more comfortable with other specialties, and other specialties having a higher perceived status and being better paid.

Spontaneous thrombosis of a vein of Galen malformation associated with acute sinusitis: a case report.

The vein of Galen malformation is caused by an abnormal shunting between choroidal arteries and the median prosencephalic vein during embryological development, leading to increased blood flow to the deep cerebral veins, intracranial damage, and systemic repercussions. Idiopathic spontaneous thrombosis of a vein of Galen malformation is rare, and its association with acute sinusitis has not been reported in the literature. We present the case of a girl with a postnatal diagnosis of a vein of Galen malformation at the age of 16 months, with secondary pulmonary hypertension that was adequately controlled with spironolactone. At 3 years old, while expecting elective endovascular treatment, the patient developed spontaneous thrombosis of the vein of Galen malformation, concomitant to an acute sinusitis episode, with complete resolution of the vascular malformation and secondary pulmonary hypertension. The patient continued with normal neurological development over a 5-year follow-up. We discuss the main pathophysiologic mechanisms that can explain spontaneous thrombosis of VOGMs and the patient's outcome. Awareness of different mechanisms that can lead to spontaneous thrombosis can help in the decision-making process and prompt targeted approaches to individual patients with a vein of Galen malformation.

A hybrid implementation-effectiveness randomized trial of CYP2D6-guided postoperative pain management.

PURPOSE: Cytochrome P450 2D6 (CYP2D6) genotype-guided opioid prescribing is limited. The purpose of this type 2 hybrid implementation-effectiveness trial was to evaluate the feasibility of clinically implementing CYP2D6-guided postsurgical pain management and determine that such an approach did not worsen pain control. METHODS: Adults undergoing total joint arthroplasty were randomized 2:1 to genotype-guided or usual pain management. For participants in the genotype-guided arm with a CYP2D6 poor (PM), intermediate (IM), or ultrarapid (UM) metabolizer phenotype, recommendations were to avoid hydrocodone, tramadol, codeine, and oxycodone. The primary endpoints were feasibility metrics and opioid use; pain intensity was a secondary endpoint. Effectiveness outcomes were collected 2 weeks postsurgery. RESULTS: Of 282 patients approached, 260 (92%) agreed to participate. In the genotype-guided arm, 20% had a high-risk (IM/PM/UM) phenotype, of whom 72% received an alternative opioid versus 0% of usual care participants (p < 0.001). In an exploratory analysis, there was less opioid consumption (200 [104-280] vs. 230 [133-350] morphine milligram equivalents; p = 0.047) and similar pain intensity (2.6 ± 0.8 vs. 2.5 ± 0.7; p = 0.638) in the genotype-guided vs. usual care arm, respectively. CONCLUSION: Implementing CYP2D6 to guide postoperative pain management is feasible and may lead to lower opioid use without compromising pain control.

Hip arthroscopy for lateral cam morphology: how important are the vessels?

The purpose of this narrative review is to identify the anatomy and relevant blood supply to the femoral head as it pertains to hip arthroscopy and lateral cam morphology. The primary blood supply to the femoral head is the lateral ascending superior retinacular vessels, which are terminal branches of the medial femoral circumflex artery. These vessels penetrate the femoral head at the posterolateral head-neck junction. Surgeons performing posterolateral femoral osteoplasty must respect this vasculature to avoid iatrogenic avascular necrosis (AVN). Avoidance of excessive traction, avoidance of distal posterolateral capsulotomy and avoidance of disruption of the superior retinacular vessels should keep the risk for AVN low. Hip extension, internal rotation and distraction are useful in hip arthroscopy to better visualize lateral/posterolateral cam morphology to facilitate an accurate comprehensive cam correction and avoid vascular disruption.

Cerebrospinal fluid closing pressure-guided tap test for the diagnosis of idiopathic normal pressure hydrocephalus: A descriptive cross-sectional study.

BACKGROUND: Tap test improves symptoms of idiopathic normal pressure hydrocephalus (iNPH); hence, it is widely used as a diagnostic procedure. However, it has a low sensitivity and there is no consensus on the parameters that should be used nor the volume to be extracted. We propose draining cerebrospinal fluid (CSF) during tap test until a closing pressure of 0 cm H2O is reached as a standard practice. We use this method with all our patients at our clinic. METHODS: This is a descriptive cross-sectional study where all patients with presumptive diagnosis of iNPH from January 2014 to December 2019 were included in the study. We used a univariate descriptive analysis and stratified analysis to compare the opening pressure and the volume of CSF extracted during the lumbar puncture, between patients in whom a diagnosis of iNPH was confirmed and those in which it was discarded. RESULTS: A total of 92 patients were included in the study. The mean age at the time of presentation was 79.4 years and 63 patients were male. The diagnosis of iNPH was confirmed in 73.9% patients. The mean opening pressure was 14.4 cm H2O mean volume of CSF extracted was 43.4 mL. CONCLUSION: CSF extraction guided by a closing pressure of 0 cm H2O instead of tap test with a fixed volume of CSF alone may be an effective method of optimizing iNPH symptomatic improvement and diagnosis.

Fam151b, the mouse homologue of C.elegans menorin gene, is essential for retinal function.

Fam151b is a mammalian homologue of the C. elegans menorin gene, which is involved in neuronal branching. The International Mouse Phenotyping Consortium (IMPC) aims to knock out every gene in the mouse and comprehensively phenotype the mutant animals. This project identified Fam151b homozygous knock-out mice as having retinal degeneration. We show they have no photoreceptor function from eye opening, as demonstrated by a lack of electroretinograph (ERG) response. Histological analysis shows that during development of the eye the correct number of cells are produced and that the layers of the retina differentiate normally. However, after eye opening at P14, Fam151b mutant eyes exhibit signs of retinal stress and rapidly lose photoreceptor cells. We have mutated the second mammalian menorin homologue, Fam151a, and homozygous mutant mice have no discernible phenotype. Sequence analysis indicates that the FAM151 proteins are members of the PLC-like phosphodiesterase superfamily. However, the substrates and function of the proteins remains unknown.

Hexa-Longin domain scaffolds for inter-Rab signalling.

SUMMARY: CPLANE is a protein complex required for assembly and maintenance of primary cilia. It contains several proteins, such as INTU, FUZ, WDPCP, JBTS17 and RSG1 (REM2- and RAB-like small GTPase 1), whose genes are mutated in ciliopathies. Using two contrasting evolutionary analyses, coevolution-based contact prediction and sequence conservation, we first identified the INTU/FUZ heterodimer as a novel member of homologous HerMon (Hermansky-Pudlak syndrome and MON1-CCZ1) complexes. Subsequently, we identified homologous Longin domains that are triplicated in each of these six proteins (MON1A, CCZ1, HPS1, HPS4, INTU and FUZ). HerMon complexes are known to be Rab effectors and Rab GEFs (Guanine nucleotide Exchange Factors) that regulate vesicular trafficking. Consequently, INTU/FUZ, their homologous complex, is likely to act as a GEF during activation of Rab GTPases involved in ciliogenesis. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.