Why are patients still in hospital after fast-track,unilateral unicompartmental knee arthroplasty

Background and purpose — Previous studies have investigated risk factors related to prolonged length of stay following total knee arthroplasty (TKA), but little is known about specific factors resulting in continued hospitalization within the 1st postoperative days after unicompartmental knee arthroplasty (UKA). We investigated what specific factors prevent patients from being discharged on the day of surgery (DOS) and the first postoperative day (POD-1) following primary UKA in a fast-track setting.Patients and methods — We prospectively collected data on 100 consecutive and unselected medial UKA patients operated from December 2017 to May 2019. All patients were operated in a standardized fast-track setup with functional discharge criteria continuously evaluated from DOS and until discharge.Results — Median length of stay for the entire cohort was 1 day. 22% and 78% of all patients were discharged on DOS and POD-1, respectively. Lack of mobilization and pain separately delayed discharge in respectively 78% and 24% of patients on DOS. The main reasons for lack of mobilization were motor blockade (37%) and logistical factors (26%). For patients placed 1st or 2nd on the operating list, we estimate that the same-day discharge rate would increase to 55% and 40% respectively, assuming that pain and mobilization were successfully managed.Interpretation — One-fifth of unselected UKA patients operated in a standardized fast-track setup were discharged on DOS. Pain and lack of mobilization were the major reasons for continued hospitalization within the initial postoperative 24–48 hours. Strategies aimed at decreasing length of stay after UKA should strive to improve analgesia and postoperative mobilization.

The number of unicompartmental knee arthroplasties (UKAs) performed in patients suffering from osteoarthritis has steadily increased. UKA has the potential benefit of not only improving patient-reported outcomes, but also to reduce morbidity, complications, and cost (Liddle et al. 2014, Beard et al. 2019). In the United Kingdom, 9% of all primary knee arthroplasties performed in 2018 were UKAs while this number is as high as 20% in Denmark (Danish Knee Arthroplasty Register 2019, National Joint Registry for England 2019).UKA is effective and safe when performed in a fast-track setting and outpatient UKA in selected patients has been shown to be feasible and safe (Munk et al. 2012, Cross and Berger 2014, Bovonratwet et al. 2017, Kort et al. 2017). However, the number of patients actually being discharged on DOS that were scheduled for outpatient surgery differs between studies and ranges from 37% to 100% (Gondusky et al. 2014, Bradley et al. 2017, Jenkins et al. 2019, Rytter et al. 2019).Studies have shown an association between increased length of stay (LOS) and an increase in both complication and readmission rates (Otero et al. 2016). In order to reduce LOS and increase patient satisfaction, a focus on successfully managing well-defined discharge criteria in a multimodal approach is imperative (Husted et al. 2008, Cross and Berger 2014). In addition, decreased LOS and outpatient procedures are associated with financial benefits, which have further fueled interest in decreasing LOS and ensuring DOS discharged following UKA (Bradley et al. 2017). Finally, decreased LOS is also shown to increase patient satisfaction levels (Reilly et al. 2005, Richter and Diduch 2017).A study has been conducted to explore reasons for prolonged hospitalization in a fast-track setting following TKA (Husted et al. 2011). However, in spite of a growing number of UKAs performed each year, no study explicitly exploring reasons for prolonged hospitalization beyond DOS following UKA in a fast-track setting has been published at present.Therefore, we investigated reasons for continued hospitalization beyond DOS following UKA in a fast-track setting.     

Does cup position differ between trabecular metal and titanium cups? A radiographic propensity score matched study of 300 hips

Background and purpose — The use of trabecular metal cups in primary total hip arthroplasty (THA) is increasing, despite the survival of Continuum cups being slightly inferior compared with other uncemented cups in registries. This difference is mainly explained by a higher rate of dislocation revisions. Cup malpositioning is a risk factor for dislocation and, being made of a highly porous material, Continuum cups might be more difficult to position. We evaluated whether Continuum cups had worse cup positioning compared with other uncemented cups.Patients and methods — Based on power calculation, 150 Continuum cups from 1 center were propensity score matched with 150 other uncemented cups from 4 centers. All patients had an uncemented stem, femoral head size of 32 mm or 36 mm, and BMI between 19 and 35. All operations were done for primary osteoarthrosis through a posterior approach. Patients were matched using age, sex, and BMI. Cup positioning was measured from anteroposterior pelvic radiograph using the Martell Hip Analysis Suite software.Results — There was no clinically relevant difference in mean inclination angle between the study group and the control group (43° [95% CI 41–44] and 43° [CI 42–45], respectively). The study group had a larger mean anteversion angle compared with the control group, 19° (CI 18–20) and 17° (CI 15–18) respectively.Interpretation — Continuum cups had a greater anteversion compared with the other uncemented cups. However, the median anteversion was acceptable in both groups and this difference does not explain the larger dislocation rate in the Continuum cups observed in earlier studies.

Trabecular metal (TM) has become an increasingly popular implant material in both primary and revision total hip arthroplasty (THA) (Laaksonen et al. 2017, 2018). Its highly porous surface provides good initial stability and improves bone ingrowth (Bobyn et al. 1999, Beckmann et al. 2014). Continuum cups (Zimmer Biomet, Warsaw, IN, USA) with TM surface have showed higher revision rates than other uncemented cups after primary THA in some register studies mainly due to a higher dislocation rate (Laaksonen et al. 2018, Hemmilä et al. 2019).Dislocation is one of the most common postoperative complications leading to revision surgery (AOANJRR 2017, Finnish Arthroplasty Register [FAR] 2017). Risk for recurrent dislocation and periprosthetic joint infection increases after revision surgery and therefore prevention of the first dislocation is vital (Ezquerra et al. 2017). Potential risk factors for dislocation are posterior approach, small femoral head size, fracture as the indication for surgery, female sex, and suboptimal acetabular cup positioning (Hailer et al. 2012, Zijlstra et al. 2017). Optimal cup positioning to avoid dislocation is traditionally defined by Lewinnek safe zones. According to this definition optimal cup inclination angle is 40° ± 10° and optimal anteversion angle is 15° ± 10° (Lewinnek et al. 1978. Slight modifications to optimize the stability have also been presented (Danoff et al. 2016). In particular, lower anteversion has been associated with increased dislocation rate (Seagrave et al. 2017a). We theorized that the higher dislocation rate for Continuum cups compared with other uncemented cups may be caused by suboptimal cup positioning due to difficulties in optimizing the acetabular cup position with this highly porous material.In this observational multicenter cohort study, we analyzed whether there is a difference in acetabular implant positioning while using Continuum acetabular cups compared with other uncemented acetabular cups in primary total hip arthroplasty.     

Slow-decaying presynaptic calcium dynamics gate long-lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse

Action potentials trigger two modes of neurotransmitter release, with a fast synchronous component and a temporally delayed asynchronous release. Asynchronous release contributes to information transfer at synapses, including at the hippocampal mossy fiber (MF) to CA3 pyramidal cell synapse where it controls the timing of postsynaptic CA3 pyramidal neuron firing. Here, we identified and characterized the main determinants of asynchronous release at the MF–CA3 synapse. We found that asynchronous release at MF–CA3 synapses can last on the order of seconds following repetitive MF stimulation. Elevating the stimulation frequency or the external Ca²⁺ concentration increased the rate of asynchronous release, thus, arguing that presynaptic Ca²⁺ dynamics is the major determinant of asynchronous release rate. Direct MF bouton Ca²⁺ imaging revealed slow Ca²⁺ decay kinetics of action potential (AP) burst-evoked Ca²⁺ transients. Finally, we observed that asynchronous release was preferentially mediated by Ca²⁺ influx through P/Q-type voltage-gated Ca²⁺ channels, while the contribution of N-type VGCCs was limited. Overall, our results uncover the determinants of long-lasting asynchronous release from MF terminals and suggest that asynchronous release could influence CA3 pyramidal cell firing up to seconds following termination of granule cell bursting.     

Use of Cyclodextrin as a Novel Agent in the SEC-HPLC Mobile Phase to Mitigate the Interactions of Proteins or Peptide or their Impurities with the Residual Silanols of Commercial SEC-HPLC Columns with Improved Separation and Resolution

Purpose

Accurate quantification of the intact proteins, antibodies or peptides and their impurities without interaction to silanols of HPLC column.

Methods

Hydroxypropyl ß Cyclodextrin (HPCD) is added in the mobile phase at different concentrations. Different commercial SEC-HPLC columns and biologics with a molecular weight ranging from 5.8 kDa to 150kDa were assessed with and without cyclodextrin.

Results

Addition of non-ionic sugars such as Hydroxypropyl ß Cyclodextrin in the mobile phase, resulted improved peak performance such as theoretical plates, peak resolution, peak width, peak height, and improved quantification of aggregates in biologics such as antibodies Humira and Actemra, and peptides such as insulin. There is an increase in peak height, reduced retention time, increased plate and reduced peak width with increasing concentration of cyclodextrin studied.

Discussion

High ionic strength, basic amino acids such as arginine, organic solvents (with a concentration low enough not to precipitate protein), sodium perchlorate and ion pairing agents in the mobile phase used for separation of peptides, proteins and antibodies to prevent silanol interaction. These commonly used solutions are not always successful, as they not only interact with the biologic, but are sometimes, not compatible. The non-ionic cyclodextrin itself does not cause protein aggregation but prevents the nonspecific binding or interaction of protein itself and thereby allowing for improved resolution, and accurate quantification of aggregates in antibodies, and peptides. The data on the separation in presence of cyclodextrin in the mobile phase showed higher peak resolution, improved peak shape, accurate apparent molecular weight, improved efficiency, and less peak tailing for biological products.

Conclusion

Hydroxypropyl ß Cyclodextrin in the mobile phase, resulted improved SEC-HPLC resolution, and quantitation of aggregates in biologics by preventing the interaction of biologics to silanol of the commercial SEC-HPLC columns.

     

Identification of a distinct lineage of aviadenovirus from crane feces

Viruses are believed to be ubiquitous; however, the diversity of viruses is largely unknown because of the bias of previous research toward pathogenic viruses. Deep sequencing is a promising and unbiased approach to detect viruses from animal-derived materials. Although cranes are known to be infected by several viruses such as influenza A viruses, previous studies targeted limited species of viruses, and thus viruses that infect cranes have not been extensively studied. In this study, we collected crane fecal samples in the Izumi plain in Japan, which is an overwintering site for cranes, and performed metagenomic shotgun sequencing analyses. We detected aviadenovirus-like sequences in the fecal samples and tentatively named the discovered virus crane-associated adenovirus 1 (CrAdV-1). We determined that our sequence accounted for approximately three-fourths of the estimated CrAdV-1 genome size (33,245 bp). The GC content of CrAdV-1 genome is 34.1%, which is considerably lower than that of other aviadenoviruses. Phylogenetic analyses revealed that CrAdV-1 clusters with members of the genus Aviadenovirus, but is distantly related to the previously identified aviadenoviruses. The protein sequence divergence between the DNA polymerase of CrAdV-1 and those of other aviadenoviruses is 45.2–46.8%. Based on these results and the species demarcation for the family Adenoviridae, we propose that CrAdV-1 be classified as a new species in the genus Aviadenovirus. Results of this study contribute to a deeper understanding of the diversity and evolution of viruses and provide additional information on viruses that infect cranes, which might lead to protection of the endangered species of cranes.

     

Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase Mps1

Mps1 is a dual specificity protein kinase that is essential for the bipolar attachment of chromosomes to the mitotic spindle and for maintaining the spindle assembly checkpoint until all chromosomes are properly attached. Mps1 is expressed at high levels during mitosis and is abundantly expressed in cancer cells. Disruption of Mps1 function induces aneuploidy and cell death. We report the identification of MPI-0479605, a potent and selective ATP competitive inhibitor of Mps1. Cells treated with MPI-0479605 undergo aberrant mitosis, resulting in aneuploidy and formation of micronuclei. In cells with wild-type p53, this promotes the induction of a postmitotic checkpoint characterized by the ATM- and RAD3-related-dependent activation of the p53-p21 pathway. In both wild-type and p53 mutant cells lines, there is a growth arrest and inhibition of DNA synthesis. Subsequently, cells undergo mitotic catastrophe and/or an apoptotic response. In xenograft models, MPI-0479605 inhibits tumor growth, suggesting that drugs targeting Mps1 may have utility as novel cancer therapeutics.