| 1. |
- Abildgaard, Amanda B., et al.
(författare)
-
HSP70-binding motifs function as protein quality control degrons
- 2023
-
Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 80:1
-
Tidskriftsartikel (refereegranskat)abstract
- Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding.
|
|
| 2. |
- Gunst, Jesper D., et al.
(författare)
-
Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
-
Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
|
|
| 3. |
- Hait, A. S., et al.
(författare)
-
Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans
- 2020
-
Ingår i: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:54
-
Tidskriftsartikel (refereegranskat)abstract
- Recurrent herpesvirus infections can manifest in different forms of disease, including cold sores, genital herpes, and encephalitis. There is an incomplete understanding of the genetic and immunological factors conferring susceptibility to recurrent herpes simplex virus 2 (HSV2) infection in the central nervous system (CNS). Here, we describe two adult patients with recurrent HSV2 lymphocytic Mollaret's meningitis that each carry a rare monoallelic variant in the autophagy proteins ATG4A or LC3B2. HSV2-activated autophagy was abrogated in patient primary fibroblasts, which also exhibited significantly increased viral replication and enhanced cell death. HSV2 antigen was captured in autophagosomes of infected cells, and genetic inhibition of autophagy by disruption of autophagy genes, including ATG4A and LC3B2, led to enhanced viral replication and cell death in primary fibroblasts and a neuroblastoma cell line. Activation of autophagy by HSV2 was sensitive to ultraviolet (UV) irradiation of the virus and inhibited in the presence of acyclovir, but HSV2-induced autophagy was independent of the DNA-activated STING pathway. Reconstitution of wild-type ATG4A and LC3B2 expression using lentiviral gene delivery or electroporation of in vitro transcribed mRNA into patient cells restored virus-induced autophagy and the ability to control HSV2 replication. This study describes a previously unknown link between defective autophagy and an inborn error of immunity that can lead to increased susceptibility to HSV2 infection, suggesting an important role for autophagy in antiviral immunity in the CNS.
|
|
| 4. |
- Hasan, Shaho, et al.
(författare)
-
Late stabilization after initial migration in patients undergoing cemented total knee arthroplasty : a 5-year followup of 2 randomized controlled trials using radiostereometric analysis
- 2022
-
Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 93, s. 271-276
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: In total knee arthroplasty (TKA), metal-backed (MBT) and all-polyethylene (APT) designs have shown comparable implant migration up to 2 years postoperatively using radiostereometric analysis (RSA). However, studies comparing mid-term migration of both designs are lacking. Furthermore, continuously migrating TKAs up to 2 years may continue to migrate or stabilize thereafter. Therefore, we compared 5-year migration of MBT and APT using either cruciate-stabilizing (CS) or posteriorstabilizing (PS) designs and specifically assessed migration profiles of continuously migrating TKAs beyond 2 years. PATIENTS AND METHODS: The present study includes results from 2 randomized trials comparing migration of cemented MBT with APT of either CS (CS study, n = 59) or PS (PS study, n = 56) design. 2 surgeons performed all surgeries. We used a linear mixed model for the analyses. RESULTS: The overall migration between MBT and APT TKAs was similar for either the CS or PS design over a 5-year period. In both studies combined, 9 implants showed continuous migration in the second postoperative year, of which 1 (APT-CS) was revised for instability, 4 (2 MBT-CS, MBT-PS, APT-PS) stabilized, and 4 (2 MBT-CS, APT-CS, MBT-PS) lacked 5-year data. INTERPRETATION: Overall migration was similar between MBT and APT TKAs up to 5 years, for both the CS and PS design. 4 initially migrating TKAs stabilized between 2- and 5-year follow-up, stressing the need for longer-term followup to determine whether second-year continuous migration correctly predicts loosening.
|
|
| 5. |
- Hasan, Shaho, et al.
(författare)
-
The Influence of Postoperative Coronal Alignment on Tibial Migration After Total Knee Arthroplasty in Preoperative Varus and Valgus Knees : A Secondary Analysis of 10 Randomized Controlled Trials Using Radiostereometric Analysis
- 2021
-
Ingår i: The Journal of bone and joint surgery. American volume. - 1535-1386. ; 103:24, s. 2281-2290
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Orthopaedic surgeons aim for mechanical alignment when performing total knee arthroplasty (TKA) as malalignment is associated with loosening. Loosening may be predicted by migration as measured with radiostereometric analysis (RSA), but previous RSA studies on postoperative alignment have shown contradictory results and have been limited to cemented implants and small numbers of patients. Therefore, we performed a secondary analysis of 10 previously published randomized controlled trials (RCTs) to compare migration between postoperative in-range and out-of-range cemented and uncemented TKA implants among patients with a preoperative varus or valgus knee. METHODS: All RCTs involving the use of RSA that had been conducted at 2 centers were included. Alignment was classified, with use of the hip-knee-ankle angle (HKA), as in-range (0° ± 3°) or out-of-range (<-3° or >3°). The fixation methods included cemented, uncemented-coated, and uncemented-uncoated. Migration was measured at 3, 12, and 24 months. A linear mixed model was used, with adjustment for fixation method and clustering of patients within centers. RESULTS: Of 476 TKA implants that had been out-of-range preoperatively, 290 were in-range postoperatively and 186 were out-of-range in either varus (n = 143) or valgus (n = 43) postoperatively. The mean migration at 3, 12, and 24 months was 0.73 mm (95% confidence interval [CI], 0.66 to 0.79 mm), 0.92 mm (95% CI, 0.85 to 1.00 mm), and 0.97 mm (95% CI, 0.90 to 1.05 mm), respectively, for the in-range group and 0.80 mm (95% CI, 0.72 to 0.87 mm), 0.98 (95% CI, 0.90 to 1.07 mm), and 1.04 mm (95% CI, 0.95 to 1.13 mm), respectively, for the out-of-range group (p = 0.07). The fixation method significantly influenced migration, with uncemented-uncoated implants migrating more than cemented and uncemented-coated implants (p < 0.001). CONCLUSIONS: Postoperative alignment did not influence migration of TKAs in the first 2 postoperative years in patients with preoperative varus or valgus alignment of the knee. However, the fixation method significantly influenced migration, with uncemented-uncoated implants showing the greatest migration. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
|
|
| 6. |
- Madsen, Mads, et al.
(författare)
-
Well-Being, Physical Fitness, and Health Profile of 2,203 Danish Girls Aged 10-12 in Relation to Leisure-time Sports Club Activity-With Special Emphasis on the Five Most Popular Sports
- 2022
-
Ingår i: Strength and conditioning journal. - Philadelphia, PA : Lippincott Williams & Wilkins. - 1524-1602 .- 1533-4295. ; 36:8, s. 2283-2290
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigated the relationship between leisure-time sports club activities and well-being as well as physical health parameters in 10-12-year-old Danish girls. Two thousand two hundred three girls took part in the study, which included questionnaires on participation in leisure-time sports clubs, well-being, Yo-Yo intermittent recovery level 1 children's test, long jump, balance tests, body composition, blood pressure (BP), and resting heart rate (RHR). Data were analyzed according to whether the girls participated in leisure-time sport and according to the 5 most frequently reported sports. Girls enrolled in leisure-time sports had higher physical well-being (49.3 ± 8.6 vs. 45.2 ± 8.3), psychological well-being (50.4 ± 9.0 vs. 49.4 ± 9.8), experienced more peer and social support (50.2 ± 10.0 vs. 48.9 ± 10.7), and perceived a more positive school environment (52.5 ± 8.0 vs. 50.5 ± 9.3), as well as showing higher Yo-Yo (+39%), long jump (+10%), and balance performance (+15%) than girls not involved in sport clubs. The girls active in sports clubs had higher relative muscle mass (+5%), lower fat percentage (-11%), body mass index (-5%), RHR (-3.4 b·min-1), and diastolic BP (-1.4 mm Hg) compared with girls not involved in sport (p<0.05). Girls who played soccer showed higher aerobic fitness compared with inactive girls (+67%), dancers (+39%), swimmers (+38%), and gymnasts (+16%). Gymnasts had a lower fat percentage than inactive girls (-19%), team handballers (-10%), swimmers (-12%), and soccer players (-4%). Girls participating in club-based leisure-time sports showed higher well-being and better fitness and health profiles than girls not involved in any sports club activities. Girls involved in soccer had better aerobic fitness and gymnasts a lower fat percentage. Copyright © 2020 National Strength and Conditioning Association.
|
|
| 7. |
- Moslemi, Camous, et al.
(författare)
-
Genetic prediction of 33 blood group phenotypes using an existing genotype dataset
- 2023
-
Ingår i: Transfusion. - 0041-1132. ; 63:12, s. 2297-2310
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate blood type data are essential for blood bank management, but due to costs, few of 43 blood group systems are routinely determined in Danish blood banks. However, a more comprehensive dataset of blood types is useful in scenarios such as rare blood type allocation. We aimed to investigate the viability and accuracy of predicting blood types by leveraging an existing dataset of imputed genotypes for two cohorts of approximately 90,000 each (Danish Blood Donor Study and Copenhagen Biobank) and present a more comprehensive overview of blood types for our Danish donor cohort. Study Design and Methods: Blood types were predicted from genome array data using known variant determinants. Prediction accuracy was confirmed by comparing with preexisting serological blood types. The Vel blood group was used to test the viability of using genetic prediction to narrow down the list of candidate donors with rare blood types. Results: Predicted phenotypes showed a high balanced accuracy >99.5% in most cases: A, B, C/c, Coa/Cob, Doa/Dob, E/e, Jka/Jkb, Kna/Knb, Kpa/Kpb, M/N, S/s, Sda, Se, and Yta/Ytb, while some performed slightly worse: Fya/Fyb, K/k, Lua/Lub, and Vel ~99%–98% and CW and P1 ~96%. Genetic prediction identified 70 potential Vel negatives in our cohort, 64 of whom were confirmed correct using polymerase chain reaction (negative predictive value: 91.5%). Discussion: High genetic prediction accuracy in most blood groups demonstrated the viability of generating blood types using preexisting genotype data at no cost and successfully narrowed the pool of potential individuals with the rare Vel-negative phenotype from 180,000 to 70.
|
|
| 8. |
|
|
| 9. |
- Sheng, Bulei, et al.
(författare)
-
Effects of genetic variants and sialylation on in vitro digestibility of purified κ-casein
- 2022
-
Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302. ; 105:4, s. 2803-2814
-
Tidskriftsartikel (refereegranskat)abstract
- Milk with different κ-casein (CN) phenotypes has previously been found to influence its gastric digestion rate. Therefore, the aim of the present study is to disentangle contributions of genetic variation and its related sialylation on the in vitro digestion process of κ-CN. Accordingly, κ-CN was purified from milk representing homozygous cows with κ-CN phenotypes AA, BB, or EE and used as substrate molecules in model studies using the INFOGEST 2.0 in vitro static digestion model. Furthermore, the effect of removal of the terminal sialic acids present on the O-linked oligosaccharides of the purified κ-CN A, B, and E protein variants were studied by desialylation enzymatic assays. The κ-CN proteins were purified by reducing anion exchange chromatography with purities of variants A, B, and E of 93.0, 97.1, and 90.0%, respectively. Protein degradations of native and desialylated κ-CN isolates in gastric and intestinal phases were investigated by sodium dodecyl sulfate-PAGE, degree of hydrolysis (DH), and liquid chromatography electrospray ionization mass spectrometry. It was shown that after purification, the κ-CN molecules reassembled into multimer states, which then constituted the basis for the digestion studies. As assessed by DH, purified variants A and E were found to exhibit faster in vitro digestion rates in both gastric and intestinal phases compared with variant B. Desialylation increased both gastric and intestinal digestion rates for all variants, as measured by DH. In the gastric phase, desialylation promoted digestion of variant B at a rate comparable with native variants A and E, whereas in the intestinal phase, desialylation of variant B promoted better digestion than native A or E. Taken together, the results confirm that low glycosylation degree of purified κ-CN promotes faster in vitro digestion rates, and that desialylation of the O-linked oligosaccharides further promotes digestion. This finding could be applied to produce dairy products with enhanced digestibility.
|
|
| 10. |
- Sheng, Bulei, et al.
(författare)
-
Influence of genetic variants and sialylation of purified κ-casein on peptide release during in vitro digestion
- 2023
-
Ingår i: Food Chemistry Advances. - 2772-753X. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- In the present study, digestion pattern of purified bovine κ-casein (κ-CN) variants A, B, E as well as desialylated variant B, using INFOGEST 2.0 in vitro gastrointestinal digestion were investigated using peptidomics. Peptide profiles of the digests were identified and quantified using ion abundancies by liquid chromatography electrospray quadropole time of flight mass spectrometry (LC-ESI/Q-TOF MS/MS). Results showed that the κ-CN variants A and E had comparable digestion patterns at most digestion time points. In the in vitro gastric and in the initial intestinal phases fewer peptides and with lower total abundances were identified for variant B compared to variants A and E, indicating a slower digestion rate for κ-CN B. By desialylation, the digestion rate of desialylated variant B in both gastric and initial intestinal phases increased compared to the natural sialylated counterpart. Bioinformatics search revealed nine potential bioactive peptides released from all three variants A, B and E by the in vitro intestinal digestion, with four additional potential bioactive peptides being released after desialylation of κ-CN B.
|
|
| 11. |
- Sheng, Bulei, et al.
(författare)
-
Phosphorylation and glycosylation isoforms of bovine κ-casein variant E in homozygous Swedish Red cow milk by liquid chromatography-electrospray ionization mass spectrometry
- 2022
-
Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302. ; 105:3, s. 1959-1965
-
Tidskriftsartikel (refereegranskat)abstract
- Variations in the phosphorylation and glycosylation patterns of the common κ-casein (CN) variants A and B have been explored, whereas studies on variant E heterogeneity are scarce. This study reports for the first time the detailed phosphorylation and glycosylation pattern of the κ-CN variant E in comparison with variants A and B. Individual cow milk samples representing κ-CN genotype EE (n = 12) were obtained from Swedish Red cows, and the natural posttranslational modifications of its κ-CN were identified and quantified by liquid chromatography-electrospray mass spectrometry. In total, 12 unique isoform masses of κ-CN variant E were identified. In comparison, AA and BB milk consisted of 14 and 17 unique isoform masses, respectively. The most abundant κ-CN E isoform detected in the EE milk was the monophosphorylated, unglycosylated [1P 0G, ∼70%; where P indicates phosphorylation from single to triple phosphorylation (1–3P), and G indicates glycosylation from single to triple glycosylation (1–3G)] form, followed by diphosphorylated, unglycosylated (2P 0G, ∼12%) form, resembling known patterns from variants A and B. However, a clear distinction was the presence of the rare triphosphorylated, nonglycosylated (3P 0G, ∼0.05%) κ-CN isoform in the EE milk. All isoforms detected in variant E were phosphorylated, giving a phosphorylation degree of 100%. This is comparable with the phosphorylation degree of variants A and B, being also almost 100%, though with very small amounts of nonphosphorylated, glycosylated isoforms detected. The glycosylation degree of variant E was found to be around 17%, a bit higher than observed for variant B (around 14%), and higher than variant A (around 7%). Among glycosylation, the glycan e was the most common type identified for all 3 variants, followed by c/d (straight and branched chain trisaccharides, respectively), and b. In contrast to κ-CN variants A and B, no glycan of type a was found in variant E. Taken together, this study shows that the posttranslational modification pattern of variant E resembles that of known variants to a large extent, but with subtle differences.
|
|
| 12. |
|
|
| 13. |
- Svensson, Emma, et al.
(författare)
-
The Effect of Botulinum Toxin Type A Injections on Stricture Formation, Leakage Rates, Esophageal Elongation, and Anastomotic Healing Following Primary Anastomosis in a Long- and Short-Gap Esophageal Atresia Model : A Protocol for a Randomized, Controlled, Blinded Trial in Pigs
- 2021
-
Ingår i: International Journal of Surgery Protocols. - : IJS Press. - 2468-3574. ; 25:1, s. 171-177
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Esophageal atresia (EA) is a congenital malformation affecting 1:3000-4500 newborns. Approximately 15% have a long-gap EA (LGEA), in which case a primary anastomosis is often impossible to achieve. To create continuity of the esophagus patients instead have to undergo lengthening procedures or organ interpositions; methods associated with high morbidity and poor functional outcomes. Esophageal injections of Botulinum Toxin Type A (BTX-A) could enable primary anastomosis and mitigate stricture formation through decreased tissue tension.Methods and Analysis:In this randomized controlled blinded animal trial, 24 pigs are divided into a long- or short-gap EA group (LGEA and SGEA, respectively) and randomized to receive BTX-A or isotonic saline injections. In the LGEA group, injections are given endoscopically in the esophageal musculature. After seven days, a 3 cm esophageal resection and primary anastomosis is performed. In the SGEA group, a 1 cm esophageal resection and primary anastomosis is performed, followed by intraoperative injections of BTX-A or isotonic saline. After 14 days, stricture formation, presence of leakage, and esophageal compliance is assessed using endoscopic and manometric techniques, and in vivo and ex vivo contrast radiography. Tissue elongation is evaluated in a stretch-tension test, and the esophagus is assessed histologically to evaluate anastomotic healing.Ethics and Dissemination:The study complies with the ARRIVE guidelines for animal studies and has been approved by the Danish Animal Experimentation Council. Results will be published in peer-reviewed journals and presented at national and international conferences.
|
|
| 14. |
- Thøgersen, Marie Høgh, et al.
(författare)
-
The Danish Trauma Database for Refugees (DTD) : A Multicenter Database Collaboration—Overcoming the Challenges and Enhancing Mental Health Treatment and Research for Refugees
- 2023
-
Ingår i: International Journal of Environmental Research and Public Health. - 1661-7827. ; 20:16
-
Tidskriftsartikel (refereegranskat)abstract
- Mental health of trauma-affected refugees is an understudied area, resulting in inadequate and poorer treatment outcomes. To address this, more high-quality treatment studies that include predictive analyses, long-term evaluations, cultural adaptations, and take account for comorbidities, are needed. Moreover, given the complex intertwining of refugees’ health with post-migration stressors and other social factors, it is crucial to examine the social determinants of refugee mental health. The Danish Trauma Database for Refugees (DTD) is a multicenter research database uniting six national centers that provide outpatient treatment for trauma-affected refugees. Through the database, we collect clinical and sociodemographic data from approximately 1200 refugees annually and will merge the database with Danish population register data. The purpose of the DTD is two-fold; clinical and research. The DTD offers data-driven guidance for routine clinical treatment planning of the individual patient, as well as exceptional research opportunities for testing treatment interventions in clinical settings, with larger sample sizes, and more representative heterogeneity of the population. Complex analyses of risk and protective factors, barriers, access to treatment, and societal and transgenerational aspects of trauma are possible with the DTD. This conceptual paper introduces the DTD, the historical background, the development process and implementation strategy, and the associated challenges with developing and running a multicenter database. Most importantly, it highlights the clinical and research potential of the DTD for advancing the understanding and treatment of trauma-affected refugees.
|
|
| 15. |
- van der Lelij, Thies J.N., et al.
(författare)
-
Continued Stabilization of a Cementless 3D-Printed Total Knee Arthroplasty : Five-Year Results of a Randomized Controlled Trial Using Radiostereometric Analysis
- 2023
-
Ingår i: The Journal of bone and joint surgery. American volume. - 1535-1386. ; 105:21, s. 1686-1694
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Three-dimensional (3D) printing of highly porous orthopaedic implants aims to promote better osseointegration, thus preventing aseptic loosening. However, short-term radiostereometric analysis (RSA) after total knee arthroplasty (TKA) has shown higher initial migration of cementless 3D-printed tibial components compared with their cemented counterparts. Therefore, critical evaluation of longer-term tibial component migration is needed. We investigated migration of a cementless 3D-printed and a cemented tibial component with otherwise similar TKA design during 5 years of follow-up, particularly the progression in migration beyond 2 years postoperatively. METHODS: Seventy-two patients were randomized to a cementless 3D-printed Triathlon Tritanium (Stryker) cruciate-retaining (CR) TKA or a cemented Triathlon CR (Stryker) TKA implant. Implant migration was evaluated with RSA at baseline and postoperatively at 3 months and at 1, 2, and 5 years. The maximum total point motion (MTPM) of the tibial component was compared between the groups at 5 years, and progression in migration was assessed between 2 and 5 years. Individual implants were classified as continuously migrating if the MTPM was ≥0.1 mm/year beyond 2 years postoperatively. Clinical scores were evaluated, and a linear mixed-effects model was used to analyze repeated measurements. RESULTS: At 5 years, the mean MTPM was 0.66 mm (95% confidence interval [CI], 0.56 to 0.78 mm) for the cementless group and 0.53 mm (95% CI, 0.43 to 0.64 mm) for the cemented group (p = 0.09). Between 2 and 5 years, there was no progression in mean MTPM for the cementless group (0.02 mm; 95% CI, -0.06 to 0.10 mm) versus 0.07 mm (95% CI, 0.00 to 0.14) for the cemented group. One implant was continuously migrating in the cementless group, and 4 were continuously migrating in the cemented group. The clinical scores were comparable between the groups across the entire time of follow-up. CONCLUSIONS: No significant difference in mean migration was found at 5 years between the cementless and cemented TKA implants. Progression of tibial component migration was present beyond 2 years for the cemented implant, whereas the cementless implant remained stable after initial early migration. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.
|
|
| 16. |
- VAN DER LELIJ, Thies J.N., et al.
(författare)
-
Influence of marker-selection method in radiostereometric analysis of total knee arthroplasty on tibial baseplate migration patterns : a secondary analysis of a randomized controlled trial with 5-year follow-up
- 2024
-
Ingår i: Acta Orthopaedica. - 1745-3674. ; 95, s. 157-165
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — Different marker-selection methods are applied to represent implant and tibial seg-ments in radiostereometric analysis (RSA) studies of total knee arthroplasty (TKA). Either a consistent set of markers throughout subsequent RSA examinations (“consistent-marker method”) is used or all available markers at each follow-up (“all-marker method”). The aim of this secondary analysis was to compare marker-selection methods on individual and group level TKA migration results. Methods — Data from a randomized RSA study with 72 patients was included. Tibial baseplate migration was evalu-ated at 3 months, 1, 2, and 5 years postoperatively with both marker-selection methods. Additionally, migration was calculated using 5 fictive points, either plotted based on the consistent set of markers or all available markers. Results — Migration could be calculated with both marker-selection methods for 248 examinations. The same prosthesis and bone markers (n = 136), different prosthesis markers (n = 71), different bone markers (n = 21), or different prosthesis and bone markers (n = 20) were used. The mean difference in maximum total point motion (MTPM) between all examinations was 0.02 mm, 95% confidence interval –0.26 to 0.31 mm. 5 implants were classified as continuously migrating with the consistent-marker method versus 6 implants (same 5 plus one additional implant) with the all-marker method. Using fictive points, fewer implants were classified as continuously migrating in both marker-selection methods. Differences between TKA groups in mean MTPM were comparable with both marker-selection methods, also when fictive points were used. Conclusion — Estimated group differences in mean MTPM were similar between marker-selection methods, but individual migration results differed. The latter has implications when classifying implants for estimated risk of future loosening.
|
|
| 17. |
- van Hamersveld, Koen T., et al.
(författare)
-
Risk Factors for Tibial Component Loosening : A Meta-Analysis of Long-Term Follow-up Radiostereometric Analysis Data
- 2021
-
Ingår i: Journal of Bone and Joint Surgery. American volume. - : NLM. - 0021-9355 .- 1535-1386. ; 103:12, s. 1115-1124
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Radiostereometric analysis (RSA) is a highly accurate tool to detect implant migration and predict loosening following total knee arthroplasty (TKA). However, little is known about the predisposing risk factors for implant migration, nor which migration profile should be considered physiological (i.e., merely part of an implant-settling phase) and which should be considered pathological (i.e., having a high probability for implant loosening). By pooling individual participant data from long-term follow-up RSA studies, we aimed to identify predisposing risk factors for tibial component loosening.METHODS: Individual data were collected for 630 patients from 11 RSA studies. The repeated measurements were analyzed with use of a linear mixed-effects model, determining the effect of age, sex, body mass index, diagnosis, preoperative and postoperative limb alignment, and prosthesis characteristics on tibial component migration over time, taking into account the clustering of patients within studies.RESULTS: High initial migration was found to result in early mechanical loosening in 18 cases (2.9%) and septic loosening in 2 cases (0.3%), whereas stabilization of high initial migration occurred in 17 cases (2.7%). Late loosening occurred in 13 cases (2.1%). All other 580 cases (92.1%) showed early stabilization and remained stable over time. Mixed-effects model analyses showed that for cemented prostheses, sex, diagnosis, and posterior cruciate ligament type had an effect on migration, but these differences were nonsignificant when analyzing migration from 3 months onwards. Uncemented prostheses aligned in varus showed more migration than neutrally and valgus-aligned TKAs (p = 0.031), and this difference increased over time (p < 0.001). Significantly higher migration was observed following uncemented TKA without an osseointegration-promoting surface (p < 0.001).CONCLUSIONS: For cemented prostheses, increased migration during the first 3 postoperative months was observed for female patients, patients with rheumatoid arthritis, and patients who underwent a posterior-stabilized TKA. For uncemented prostheses, both postoperative varus alignment of the lower limb and the absence of an osseointegration-promoting surface significantly increased postoperative tibial component migration.LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
|
|
| 18. |
- Zhang, Jie, et al.
(författare)
-
Modeling coupled nitrification-denitrification in soil with an organic hotspot
- 2023
-
Ingår i: Biogeosciences. - 1726-4170. ; 20:18, s. 3895-3917
-
Tidskriftsartikel (refereegranskat)abstract
- The emission of nitrous oxide (N2O) from agricultural soils to the atmosphere is a significant contributor to anthropogenic greenhouse gas emissions. The recycling of organic nitrogen (N) in manure and crop residues may result in spatiotemporal variability in N2O production and soil efflux which is difficult to capture by process-based models. We propose a multi-species, reactive transport model to provide detailed insight into the spatiotemporal variability in nitrogen (N) transformations around such N2O hotspots, which consists of kinetic reactions of soil respiration, nitrification, nitrifier denitrification, and denitrification represented by a system of coupled partial differential equations. The model was tested with results from an incubation experiment at two different soil moisture levels (-30 and -100 hPa) and was shown to reproduce the recorded N2O and dinitrogen (N2) emissions and the dynamics of important carbon (C) and N components in soil reasonably well. The simulation indicated that the four different microbial populations developed in closely connected but separate layers, with denitrifying bacteria growing within the manure-dominated zone and nitrifying bacteria in the well-aerated soil outside the manure zone and with time also within the manure layer. The modeled N2O production within the manure zone was greatly enhanced by the combined effect of oxygen deficit, abundant carbon source, and supply of nitrogenous substrates. In the wetter soil treatment with a water potential of -30 hPa, the diffusive flux of nitrate (NO3-) across the manure-soil interface was the main source of NO3- for denitrification in the manure zone, while at a soil water potential of -100 hPa, diffusion became less dominant and overtaken by the co-occurrence of nitrification and denitrification in the manure zone. Scenarios were analyzed where the diffusive transport of dissolved organic carbon or different mineral N species was switched off, and they showed that the simultaneous diffusion of NO3-, ammonium (NH4+), and nitrite (NO2-) was crucial to simulate the dynamics of N transformations and N2O emissions in the model. Without considering solute diffusion in process-based N2O models, the rapid turnover of C and N associated with organic hotspots can not be accounted for, and it may result in the underestimation of N2O emissions from soil after manure application. The model and its parameters allow for new detailed insights into the interactions between transport and microbial transformations associated with N2O emissions in heterogeneous soil environments.
|
|
