Nevin Manimala

J Bone Joint Surg Am. 2023 Sep 21. doi: 10.2106/JBJS.22.01302. Online ahead of print.

ABSTRACT

BACKGROUND: Periprosthetic fractures are rare but devastating complications of knee replacement, often requiring complex surgery with substantial morbidity and mortality. It is not known how the fracture rates after total knee replacement (TKR) and unicompartmental knee replacement (UKR) compare. We performed the first matched study comparing TKR and UKR periprosthetic fracture rates.

METHODS: This study involved 54,215 UKRs and 54,215 TKRs, identified in the National Joint Registry and Hospital Episodes Statistics database, which were propensity score-matched on patient and surgical factors. The International Classification of Diseases, Tenth Revision, (ICD-10) code M96.6 was used to identify periprosthetic fractures at ≤3 and >3 months postoperatively, as well as estimate rates at up to 10 years. Subgroup analyses were performed in different age groups (<55, 55 to 64, 65 to 74, and ≥75 years), body mass index (BMI) categories (normal, 18.5 to <25 kg/m2; overweight, 25 to <30 kg/m2; obese, 30 to <40 kg/m2; and morbidly obese, ≥40 kg/m2), and sexes.

RESULTS: The 3-month fracture rate was 0.09% (n = 50) in the UKR group and 0.05% (n = 25) in the TKR group, with this difference being significant (odds ratio [OR], 2.0; p = 0.004). The rate of fractures occurring at >3 months was 0.32% (n = 171) in the UKR group and 0.61% (n = 329) in the TKR group (OR, 0.51; p < 0.001). At 10 years, the cumulative incidence of fractures was 0.6% after UKR versus 1% after TKR (OR, 0.68; p < 0.001). Fracture rates increased with increasing age, decreasing BMI, and female sex for both UKRs and TKRs.

CONCLUSIONS: The fracture risk was small after both UKR and TKR, with small absolute differences between implant types. During the first 3 postoperative months, the fracture rate after UKR was 0.1% and was about twice as high as that after TKR. However, over the first 10 years, the cumulative fracture rate after TKR was 1% and was almost twice as high as that after UKR. Fracture rates after both UKR and TKR were higher in women, patients ≥75 years of age, and patients with normal weight.

LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

PMID:37733918 | DOI:10.2106/JBJS.22.01302

J Bone Joint Surg Am. 2023 Sep 21. doi: 10.2106/JBJS.23.00252. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the fact that many synovial fluid biomarkers have found application in the routine diagnosis of periprosthetic joint infection (PJI), this process still remains a challenge for orthopaedic surgeons. To simplify this process, fast point-of-care (POC) tests can be used during ambulatory visits and in operating room conditions. However, before such tests can be routinely used in clinical practice, they require validation. The purpose of the present study was to evaluate the diagnostic accuracy of different fast POC tests for detecting C-reactive protein (CRP) in synovial fluid for the diagnosis of PJI.

METHODS: Synovial fluid samples were collected from 120 consecutive patients who underwent revision total joint arthroplasty (TJA). The patients were divided into 2 groups. The first group included 76 patients who underwent revision for reasons other than infection (the aseptic revision TJA [arTJA] group), and the second group included 44 patients who underwent revision because of periprosthetic joint infection (PJI). The diagnosis of infection was made according to the International Consensus Meeting (ICM) 2018 criteria. All patients were operatively treated at a single orthopaedic center from January 2022 to February 2023. Four fast CRP tests with different cutoff values (1 and 3 mg/L, ≥8 mg/L, ≥10 mg/L [cassette], ≥10 mg/L [strip]) were used off-label for synovial fluid testing. Tests were performed on the same synovial fluid samples, and the results of these tests were compared with those obtained with the laboratory method.

RESULTS: The cassette test with a minimum cutoff value of ≥8 mg/L demonstrated the best accuracy for the diagnosis of chronic PJI, with a sensitivity and specificity of 90.9% and 90.8%, respectively. For the cassette test with a cutoff value of >3 mg/L, the sensitivity and specificity were 68.2% and 77.6%, respectively. For the tests with a minimum cutoff value of ≥10 mg/L, the sensitivity and specificity were 77.3% and 94.7%, respectively, for the cassette test and 77.3% and 96.1%, respectively, for the strip test. The laboratory method with the statistically calculated threshold (2.7 mg/L) revealed the highest AUC (area under the receiver operating characteristic curve) value (0.95), with 90.9% sensitivity and 94.7% specificity.

CONCLUSIONS: The cassette POC test with the minimum cutoff value of ≥8 mg/L had very good accuracy for the diagnosis of chronic PJI. This test had comparable sensitivity and slightly lower specificity in comparison with the laboratory method with the calculated threshold of 2.7 mg/L.

LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

PMID:37733911 | DOI:10.2106/JBJS.23.00252

Science. 2023 Sep 22;381(6664):eadg7492. doi: 10.1126/science.adg7492. Epub 2023 Sep 22.

ABSTRACT

The vast majority of missense variants observed in the human genome are of unknown clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on human and primate variant population frequency databases to predict missense variant pathogenicity. By combining structural context and evolutionary conservation, our model achieves state-of-the-art results across a wide range of genetic and experimental benchmarks, all without explicitly training on such data. The average pathogenicity score of genes is also predictive for their cell essentiality, capable of identifying short essential genes that existing statistical approaches are underpowered to detect. As a resource to the community, we provide a database of predictions for all possible human single amino acid substitutions and classify 89% of missense variants as either likely benign or likely pathogenic.

PMID:37733863 | DOI:10.1126/science.adg7492

Science. 2023 Sep 22;381(6664):eadd1250. doi: 10.1126/science.add1250. Epub 2023 Sep 22.

ABSTRACT

Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)-DNA affinities and apparent on-rates by about 70-fold by directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. STRs maximize the number of weakly preferred microstates near target sites, thereby increasing TF density, with impacts well predicted by statistical mechanics. Confirming that STRs also affect TF binding in cells, neural networks trained only on in vivo occupancies predicted effects identical to those observed in vitro. Approximately 90% of TFs preferentially bound STRs that need not resemble known motifs, providing a cis-regulatory mechanism to target TFs to genomic sites.

PMID:37733848 | DOI:10.1126/science.add1250

PLoS Comput Biol. 2023 Sep 21;19(9):e1011396. doi: 10.1371/journal.pcbi.1011396. Online ahead of print.

ABSTRACT

Personalized prediction of chronic diseases is crucial for reducing the disease burden. However, previous studies on chronic diseases have not adequately considered the relationship between chronic diseases. To explore the patient-wise risk of multiple chronic diseases, we developed a multitask learning Cox (MTL-Cox) model for personalized prediction of nine typical chronic diseases on the UK Biobank dataset. MTL-Cox employs a multitask learning framework to train semiparametric multivariable Cox models. To comprehensively estimate the performance of the MTL-Cox model, we measured it via five commonly used survival analysis metrics: concordance index, area under the curve (AUC), specificity, sensitivity, and Youden index. In addition, we verified the validity of the MTL-Cox model framework in the Weihai physical examination dataset, from Shandong province, China. The MTL-Cox model achieved a statistically significant (p<0.05) improvement in results compared with competing methods in the evaluation metrics of the concordance index, AUC, sensitivity, and Youden index using the paired-sample Wilcoxon signed-rank test. In particular, the MTL-Cox model improved prediction accuracy by up to 12% compared to other models. We also applied the MTL-Cox model to rank the absolute risk of nine chronic diseases in patients on the UK Biobank dataset. This was the first known study to use the multitask learning-based Cox model to predict the personalized risk of the nine chronic diseases. The study can contribute to early screening, personalized risk ranking, and diagnosing of chronic diseases.

PMID:37733837 | DOI:10.1371/journal.pcbi.1011396

Stapp Car Crash J. 2022 Nov;66:31-68. doi: 10.4271/2022-22-0002.

ABSTRACT

The American population is getting heavier and automated vehicles will accommodate unconventional postures. While studies replicating mid-size and upright fore-aft seated occupants are numerous, experiments with post-mortem human subjects (PMHS) with obese and reclined occupants are sparse. The objective of this study was to compare the kinematics of the head-neck, torso and pelvis, and document injuries and injury patterns in frontal impacts. Six PMHS with a mean body mass index of 38.2 ± 5.3 kg/m2 were equally divided between upright and reclined groups (seatback: 23°, 45°), restrained by a three-point integrated belt, positioned on a semi-rigid seat, and exposed to low and moderate velocities (15, 32 km/h). Data included belt loads, spinal accelerations, kinematics, and injuries from x-rays, computed tomography, and necropsy. At 15 km/h speed, no significant difference in the occupant kinematics and evidence of orthopedic failure was observed. At 32 km/h speed, the primary difference between the cohorts was significantly larger Z displacements in the reclined occupant at the head (190 ± 32 mm, vs. 105 ± 33 mm p < 0.05) and femur (52 ± 18 mm vs. 30 ± 10 mm, p < 0.05). All the moderate-speed tests produced at least one thorax injury. Rib fractures were scattered around the circumference of the rib-cage in the upright, while they were primarily concentrated on the anterior aspect of the rib-cage in two reclined specimens. Although MAIS was the same in both groups, the reclined specimens had more bi-cortical rib fractures, suggesting the potential for pneumothorax. While not statistical, these results suggest enhanced injuries with reclined obese occupants. These results could serve as a data set for validating the response of restrained obese anthropometric test device (ATDs) and computational human body models.

PMID:37733821 | DOI:10.4271/2022-22-0002

PLoS Comput Biol. 2023 Sep 21;19(9):e1010704. doi: 10.1371/journal.pcbi.1010704. Online ahead of print.

ABSTRACT

In many organisms, interactions among genes lead to multiple functional states, and changes to interactions can lead to transitions into new states. These transitions can be related to bifurcations (or critical points) in dynamical systems theory. Characterizing these collective transitions is a major challenge for systems biology. Here, we develop a statistical method for identifying bistability near a continuous transition directly from high-dimensional gene expression data. We apply the method to data from honey bees, where a known developmental transition occurs between bees performing tasks in the nest and leaving the nest to forage. Our method, which makes use of the expected shape of the distribution of gene expression levels near a transition, successfully identifies the emergence of bistability and links it to genes that are known to be involved in the behavioral transition. This proof of concept demonstrates that going beyond correlative analysis to infer the shape of gene expression distributions might be used more generally to identify collective transitions from gene expression data.

PMID:37733808 | DOI:10.1371/journal.pcbi.1010704

PLoS One. 2023 Sep 21;18(9):e0278428. doi: 10.1371/journal.pone.0278428. eCollection 2023.

ABSTRACT

Football (soccer) is a very popular team sport among African women and girls, with player numbers continuing to rise at all levels of the sport. Whereas the participation in football and associated injuries are on the rise, there are not enough sports and exercise medicine (SEM) personnel to attend to these women football players. While Africa may not currently have enough SEM trained medical doctors and/or physiotherapists, it has relatively higher numbers of other healthcare workers; for example, nurses, who lead healthcare services provision from community to tertiary levels. The primary objective of this study will be to compare sports medicine practices; injury prevention behaviours; injury risk parameters; incidence and prevalence of injuries and illnesses in teams with and without a Football Nurse during one competitive season in Malawi’s Women’s football league. This study will be a cluster randomised control trial will recruit 24 teams from the Women’s Football League in Malawi, which will be randomised to either the intervention group or the control group. A cohort of 12 nurses will receive training in basic football medicine; after which they will be attached to a total of 12 women’s football teams (intervention group) during one competitive season. The Football Nurses will be directly report to a physiotherapist or doctor in their district to whom they will refer serious injuries for investigations, or further management. The teams with Football Nurses will be compared to other teams that will not have Football Nurses. We expect to develop a low cost, sustainable and context relevant solution to manage the treatment gap of football injuries/illnesses in underserved communities such as women’s football. Trial registration number: Pan African Clinical Trial Registry (PACTR202205481965514).

PMID:37733774 | DOI:10.1371/journal.pone.0278428

Acta Med Litu. 2022;29(2):225-235. doi: 10.15388/Amed.2022.29.2.9. Epub 2022 Jun 29.

ABSTRACT

BACKGROUND AND OBJECTIVES: The most effective treatment of infertility is in vitro fertilization (IVF). IVF with Preimplantation Genetic Testing (PGT) allows to identify embryos with a genetic abnormality associated with a specific medical disorder and to select the most optimal embryos for the transfer. PGT is divided into structural rearrangement testing (PGT-SR), monogenetic disorder testing (PGT-M), and aneuploidy testing (PGT-A). This study mostly analyzes PGT-SR, also describes a few cases of PGT-M. The aim of this study was to implement PGT procedure at Vilnius University Hospital Santaros Klinikos (VUHSK) Santaros Fertility Centre (SFC) and to perform retrospective analysis of PGT procedures after the implementation.

MATERIALS AND METHODS: A single-center retrospective analysis was carried out. The study population included infertile couples who underwent PGT at SFC, VUHSK from January 01st, 2017 to December 31st, 2020. Ion PGM platform (Life Technologies, USA) and Ion ReproSeq PGS View Kit (Life Technologies, USA) were used for the whole genome amplification. Results were assessed using descriptive statistics.

RESULTS: PGT was successfully implemented in VUHSK in 2017. During the analyzed time period, thirty-four PGT procedures were performed for 26 couples. Two procedures were performed in 2017, 7 procedures – in 2018, 13 – in 2019, and 12 – in 2020. In comparison with all IVF procedures, 2.5% procedures were IVF with PGT, a highest percentage was in 2020 (3.8% of all procedures). The main indication for PGT was balanced chromosomal rearrangements (in 85.3% cases). In all 34 cases 515 oocytes were aspirated in total, 309 oocytes were fertilized, oocytes fertilization rate exceeded 60%. A normal diploid karyotype was found in 46 (16.8%) biopsied embryos. Out of all PGT procedures, 9 (26.5%) resulted in a clinical pregnancy. Six (66.7%) pregnancies were confirmed in 2019, and 3 (33.3%) – in 2020. Three (33.3%) pregnancies resulted in spontaneous abortion, 6 (66.7%) – in delivery.

CONCLUSIONS: The implementation of PGT in VUHSK was successful. The most common indication for PGT was a reciprocal translocation. Oocytes fertilization rate exceeded 60%, a normal karyotype was found less than in one-fifth of biopsied embryos. A highest clinical pregnancy rate was achieved in 2019 when almost half of women conceived, which is probably related to the experience gained by the multidisciplinary team. This is the first study analyzing IVF with PGT in Lithuania, however, the results should be interpreted with caution due to a low number of total procedures performed.

PMID:37733426 | PMC:PMC9799000 | DOI:10.15388/Amed.2022.29.2.9

Neurol Res. 2023 Sep 21:1-9. doi: 10.1080/01616412.2023.2257439. Online ahead of print.

ABSTRACT

AIM: The Dubousset Functional Test (DFT) ia a practical four-component assessment test to assess the physical function and balance capacities. The study aimed to examine the reliability, validity, responsiveness of the DFT in stroke survivors.

METHODS: This study included a total of 57 post-stroke patients (age 60.16 ± 15.08 years). The participants were divided into two groups according to the duration of stroke (6-12 months, 12 months and more). Reliability of DFT test was evaluated with Intraclass Correlation Coefficient (ICC). The correlation between the DFT and The Timed Up and Go test (TUG), dual-task TUG, Functional Reach Test (FRT), 3-meter backward walk test (3MBWT), Tinetti Performance Oriented Mobility Assessment (POMA) was used for the validity.

RESULTS: For total post-stroke patients, ICC values were between 0.899 and 0.984 (excellent agreement). For stroke patients have 6-12 months stroke duration ICC values were between 0.831 and 0.988 (excellent agreement). For post-stroke patients have 6-12 months stroke duration ICC values were between 0.858 and 0.992 (excellent agreement). For total stroke post-patients the correlation with four component of DFT and TUG, dual-task TUG, FRT, 3MBWT and POMA was found to be statistically significant (p < 0.001).

CONCLUSION: The DFT has excellent reliability and validity in post-stroke patients. Therefore, it may be a clinically suitable test for detecting balance and physical function.

PMID:37733422 | DOI:10.1080/01616412.2023.2257439