A CUC1/auxin genetic module links cell polarity to patterned tissue growth and leaf shape diversity in crucifer plants.

How tissue-level information encoded by fields of regulatory gene activity is translated into the patterns of cell polarity and growth that generate the diverse shapes of different species remains poorly understood. Here, we investigate this problem in the case of leaf shape differences between Arabidopsis thaliana, which has simple leaves, and its relative Cardamine hirsuta that has complex leaves divided into leaflets. We show that patterned expression of the transcription factor CUP-SHAPED COTYLEDON1 in C. hirsuta (ChCUC1) is a key determinant of leaf shape differences between the two species. Through inducible genetic perturbations, time-lapse imaging of growth, and computational modeling, we find that ChCUC1 provides instructive input into auxin-based leaf margin patterning. This input arises via transcriptional regulation of multiple auxin homeostasis components, including direct activation of WAG kinases that are known to regulate the polarity of PIN-FORMED auxin transporters. Thus, we have uncovered a mechanism that bridges biological scales by linking spatially distributed and species-specific transcription factor expression to cell-level polarity and growth, to shape diverse leaf forms.

New techniques to identify the tissue of origin for cancer of unknown primary in the era of precision medicine: progress and challenges.

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.

Single-Molecule Analysis Reveals Linked Cycles of RSC Chromatin Remodeling and Ace1p Transcription Factor Binding in Yeast.

It is unknown how the dynamic binding of transcription factors (TFs) is molecularly linked to chromatin remodeling and transcription. Using single-molecule tracking (SMT), we show that the chromatin remodeler RSC speeds up the search process of the TF Ace1p for its response elements (REs) at the CUP1 promoter. We quantified smFISH mRNA data using a gene bursting model and demonstrated that RSC regulates transcription bursts of CUP1 only by modulating TF occupancy but does not affect initiation and elongation rates. We show by SMT that RSC binds to activated promoters transiently, and based on MNase-seq data, that RSC does not affect the nucleosomal occupancy at CUP1. Therefore, transient binding of Ace1p and rapid bursts of transcription at CUP1 may be dependent on short repetitive cycles of nucleosome mobilization. This type of regulation reduces the transcriptional noise and ensures a homogeneous response of the cell population to heavy metal stress.

Synergic activity of FGFR2 and MEK inhibitors in the treatment of FGFR2-amplified cancers of unknown primary.

Patients with cancer of unknown primary (CUP) carry the double burden of an aggressive disease and reduced access to therapies. Experimental models are pivotal for CUP biology investigation and drug testing. We derived two CUP cell lines (CUP#55 and #96) and corresponding patient-derived xenografts (PDXs), from ascites tumor cells. CUP cell lines and PDXs underwent histological, immune-phenotypical, molecular, and genomic characterization confirming the features of the original tumor. The tissue-of-origin prediction was obtained from the tumor microRNA expression profile and confirmed by single-cell transcriptomics. Genomic testing and fluorescence in situ hybridization analysis identified FGFR2 gene amplification in both models, in the form of homogeneously staining region (HSR) in CUP#55 and double minutes in CUP#96. FGFR2 was recognized as the main oncogenic driver and therapeutic target. FGFR2-targeting drug BGJ398 (infigratinib) in combination with the MEK inhibitor trametinib proved to be synergic and exceptionally active, both in vitro and in vivo. The effects of the combined treatment by single-cell gene expression analysis revealed a remarkable plasticity of tumor cells and the greater sensitivity of cells with epithelial phenotype. This study brings personalized therapy closer to CUP patients and provides the rationale for FGFR2 and MEK targeting in metastatic tumors with FGFR2 pathway activation.

Discovery of an unusual copper homeostatic mechanism in yeast cells respiring on minimal medium and an unexpectedly diverse labile copper pool.

Copper is essential for all eukaryotic cells but many details of how it is trafficked within the cell and how it is homeostatically regulated remain uncertain. Here, we characterized the copper content of cytosol and mitochondria using liquid chromatography with ICP-MS detection. Chromatograms of cytosol exhibited over two dozen peaks due to copper proteins and coordination complexes. Yeast cells respiring on minimal media did not regulate copper import as media copper concentration increased; rather, they imported copper at increasing rates while simultaneously increasing the expression of metallothionein CUP1 which then sequestered most of the excessive imported copper. Peak intensities due to superoxide dismutase SOD1, other copper proteins, and numerous coordination complexes also increased, but not as drastically. The labile copper pool was unexpectedly diverse and divided into two groups. One group approximately comigrated with copper-glutathione, -cysteine, and -histidine standards; the other developed only at high media copper concentrations and at greater elution volumes. Most cytosolic copper arose from copper-bound proteins, especially CUP1. Cytosol contained an unexpectedly high percentage of apo-copper proteins and apo-coordination complexes. Copper-bound forms of non-CUP1 proteins and complexes coexisted with apo-CUP1 and with the chelator BCS. Both experiments suggest unexpectedly stable-binding copper proteins and coordination complexes in cytosol. COX17Δ cytosol chromatograms were like those of WT cells. Chromatograms of soluble mitochondrial extracts were obtained, and mitoplasting helped distinguish copper species in the intermembrane space versus in the matrix/inner membrane. Issues involving the yeast copperome, copper homeostasis, labile copper pool, and copper trafficking are discussed.

GhSBI1, a CUP-SHAPED COTYLEDON 2 homologue, modulates branch internode elongation in cotton.

Branch length is an important plant architecture trait in cotton (Gossypium) breeding. Development of cultivars with short branch has been proposed as a main object to enhance cotton yield potential, because they are suitable for high planting density. Here, we report the molecular cloning and characterization of a semi-dominant quantitative trait locus, Short Branch Internode 1(GhSBI1), which encodes a NAC transcription factor homologous to CUP-SHAPED COTYLEDON 2 (CUC2) and is regulated by microRNA ghr-miR164. We demonstrate that a point mutation found in sbi1 mutants perturbs ghr-miR164-directed regulation of GhSBI1, resulting in an increased expression level of GhSBI1. The sbi1 mutant was sensitive to exogenous gibberellic acid (GA) treatments. Overexpression of GhSBI1 inhibited branch internode elongation and led to the decreased levels of bioactive GAs. In addition, gene knockout analysis showed that GhSBI1 is required for the maintenance of the boundaries of multiple tissues in cotton. Transcriptome analysis revealed that overexpression of GhSBI1 affects the expression of plant hormone signalling-, axillary meristems initiation-, and abiotic stress response-related genes. GhSBI1 interacted with GAIs, the DELLA repressors of GA signalling. GhSBI1 represses expression of GA signalling- and cell elongation-related genes by directly targeting their promoters. Our work thus provides new insights into the molecular mechanisms for branch length and paves the way for the development of elite cultivars with suitable plant architecture in cotton.

Combatting ageing in dermal papilla cells and promoting hair follicle regeneration using exosomes from human hair follicle dermal sheath cup cells.

Dermal papilla cells (DPCs) undergo premature ageing in androgenetic alopecia and senescent alopecia. As critical components of hair follicle reconstruction, DPCs are also prone to senescence in vitro, resulting in a diminished hair follicle inductivity capacity. Dermal sheath cup cells (DSCCs), a specific subset of hair follicle mesenchymal stem cells, intimately linked to the function of DPCs. The primary objective of this research is to investigate the anti-ageing effect of exosomes derived from DSCCs (ExoDSCCs ) on DPCs. Exosomes were utilized to treat H2 O2 -induced DPCs or long-generation DPCs(P10). Our findings demonstrate that ExoDSCCs(P3) promote the proliferation, viability and migration of senescent DPCs while inhibiting cell apoptosis. The expression of senescence marker SA-ß-Gal were significantly downregulated in senescent DPCs. When treated with ExoDSCCs(P3) , expression of inducibility related markers alkaline phosphatase and Versican were significantly upregulated. Additionally, ExoDSCCs(P3) activated the Wnt/ß-catenin signalling in vitro. In patch assay, ExoDSCCs(P3) significantly promoted hair follicle reconstruction in senescent DPCs. In summary, our work highlights that ExoDSCCs(P3) may restore the biological functions and improve the hair follicle induction ability of senescent DPCs. Therefore, ExoDSCCs(P3) may represent a new strategy for intervening in the ageing process of DPCs, contributing to the prevention of senile alopecia.

Development and characterization of a chronic high intraocular pressure model in New Zealand white rabbits for glaucoma research.

Glaucoma is a neurodegenerative disease characterized by visual field loss associated with optic nerve damage and ocular hypertension. The biological basis for the elevated intraocular pressure (IOP) is largely unknown, such that lowering the IOP is currently the only established treatment. Several animal models have been developed to elucidate the mechanism underlying the increased IOP and for use in drug discovery research, but their utility is often limited by the occurrence of severe intraocular inflammation and by technical challenges. In this study, we developed a rabbit glaucoma model that does not require experimental disease induction. Rabbits were chosen as the model because their eyeballs are similar in size to those of humans, and they are easy to breed. By crossing rabbit strains with inherited glaucoma, as indicated by obvious buphthalmos, we produced a strain that exhibits ocular hypertension. The IOP of the Ocular Hypertension (OH) rabbits was significantly higher than that of the wild type (WT; normal New Zealand white rabbits) from the age of 3 weeks to at least 22 weeks. The significantly larger corneal diameter of the OH rabbits indicated ocular enlargement, whereas there was no significant difference in corneal thickness compared with WT rabbits. Anterior segment ocular coherence tomography and gonioscopic observations revealed an open angle in the OH rabbits. Hematoxylin and eosin (HE) staining together with Masson's trichrome staining showed abnormal collagen accumulation in the angle of the OH rabbit's eyes. Furthermore, aqueous humor (AH) outflow imaging following an intravitreal injection of a fluorescent probe into the anterior chamber for tissue-section analysis revealed retention of the probe in the area of collagen deposition in the OH eyes. The OH rabbits also had a time-dependent increase in the cup/disc ratio. In conclusion, investigations using our newly developed rabbit model of open-angle ocular hypertension showed that abnormal accumulation of extracellular matrix at the angle increased AH outflow resistance in the conventional outflow pathway, leading to a high IOP. Furthermore, the OH rabbits exhibited glaucomatous optic disc cupping over time. These findings suggest the utility of the OH rabbits as a model for open-angle glaucoma (OAG).

Self-supervised pre-training for joint optic disc and cup segmentation via attention-aware network.

Image segmentation is a fundamental task in deep learning, which is able to analyse the essence of the images for further development. However, for the supervised learning segmentation method, collecting pixel-level labels is very time-consuming and labour-intensive. In the medical image processing area for optic disc and cup segmentation, we consider there are two challenging problems that remain unsolved. One is how to design an efficient network to capture the global field of the medical image and execute fast in real applications. The other is how to train the deep segmentation network using a few training data due to some medical privacy issues. In this paper, to conquer such issues, we first design a novel attention-aware segmentation model equipped with the multi-scale attention module in the pyramid structure-like encoder-decoder network, which can efficiently learn the global semantics and the long-range dependencies of the input images. Furthermore, we also inject the prior knowledge that the optic cup lies inside the optic disc by a novel loss function. Then, we propose a self-supervised contrastive learning method for optic disc and cup segmentation. The unsupervised feature representation is learned by matching an encoded query to a dictionary of encoded keys using a contrastive technique. Finetuning the pre-trained model using the proposed loss function can help achieve good performance for the task. To validate the effectiveness of the proposed method, extensive systemic evaluations on different public challenging optic disc and cup benchmarks, including DRISHTI-GS and REFUGE datasets demonstrate the superiority of the proposed method, which can achieve new state-of-the-art performance approaching 0.9801 and 0.9087 F1 score respectively while gaining 0.9657 D C disc and 0.8976 D C cup . The code will be made publicly available.

Enhancing the notification system for surveillance of infectious diseases in Qatar during the FIFA World Cup 2022: project overview.

BACKGROUND: In 2022, the Surveillance Department of the Ministry of Public Health in Qatar adopted an integrated project called the Notification Enhancement Project (NEP) to enhance the infectious disease notification system. Efficient surveillance and notification promote early alerts and allow immediate interference in reducing morbidity and mortality from outbreaks. The project was designed to improve the knowledge, attitudes, practices, and notification processes of healthcare workers in Qatar by increasing their reporting rates. METHODS: The strategy for comprehensively enhancing notifications was based on the observation and evaluation of the current notification system, the implementation of interventions, and post-evaluation follow-up. To implement the project, we relied on three aspects: effective methods used in previous relevant studies through a literature review, feedback received from healthcare workers, and suggestions from public health surveillance experts from the Ministry of Public Health, Qatar. A preassessment was conducted through an online survey by the Ministry of Public Health. The effectiveness of the different interventions was assessed by analyzing the data of notified patients reported through the Disease Surveillance and Reporting Electronic System. Pre- and postintervention assessments were performed by comparing the percentage of patients notified by healthcare providers with that of patients confirmed by healthcare providers in the laboratory to compare the notification rates over three time periods between January and December 2022. RESULTS: There was significant improvement in the infectious disease notification process. A comparison before and after the implementation of the interventions revealed an increase in the communicable disease notification rate among healthcare workers. Pre- and postintervention data were compared. Infectious disease notification activities by healthcare workers increased from 2.5% between January and May 2022 to 41.4% between November and December 2022. CONCLUSION: This study highlights the efficiency of different interventions in correcting the underreporting of infectious diseases. Our findings suggest that implementing the Notification Enhancement Project significantly improves notification rates. We recommend continuing interventions through constant education and training, maintaining solid communication with HCWs through regular reminder emails and feedback, periodic assessment of the electronic notification system, and engagement of healthcare workers and other stakeholders to sustain and expand progress achieved through continuous evaluation.

Association between cup orientation and low back pain after total hip arthroplasty in patients with osteonecrosis of the femoral head.

BACKGROUND: Postoperative low back pain (LBP) following total hip arthroplasty (THA) is classified as secondary hip-spine syndrome. The purpose of this study was to explore the correlations between cup orientation of THA and postoperative LBP in patients with osteonecrosis of the femoral head (ONFH). METHODS: A retrospective cohort study included 364 ONFH patients who underwent bilateral THA between January 2011 and December 2020. Among them, 53 patients (14.6%) experienced postoperative LBP at the end of follow-up and were designated as pain group (PG). A control group (CG) consisting of 106 patients with similar age, sex, and body mass index (BMI) to those in the PG was selected. Postoperative LBP in the PG was assessed using the visual analogue scale (VAS). Demographic data, clinical information, and radiographic criteria were evaluated as potential predictors of LBP. RESULTS: Patients in PG (mean age, 47.3 years [range, 27 to 75 years]; 42 [79%] male) had a mean VAS score of 4.6 (range, 1 to 9) compared with 0 for the patients in CG (mean age, 47.6 years [range, 19 to 77 years]; 84 [79%] male). There were no significant differences in clinical data between the two groups (p > 0.05). Preoperative radiographic variables also showed no significant differences between the PG and CG (p > 0.05). However, the postoperative inclination, anteversion, and standing ante-inclination (AI) were significantly lower in the PG compared to the CG, whereas the sitting and standing sacral slope (SS) were significantly higher (p < 0.05). Moreover, the variations in standing AI, standing and sitting pelvic tilt (PT) were significantly lower in the PG compared to the CG, while the variations in standing and sitting SS and lumbar lordosis (LL) were significantly higher (p < 0.05). The variation in standing AI in the PG showed a significantly correlation with the variation of standing SS, standing PT, and LL (p < 0.05). CONCLUSION: Postoperative LBP in ONFH patients after bilateral THA is significantly associated with the intraoperative cup orientation. The variation in standing AI is correlated with the variations in standing SS, standing PT, and LL, potentially contributing to the development of postoperative LBP.

Satisfactory mid-term clinical outcomes of endoscopic tenotomy for iliopsoas tendinopathy following total hip arthroplasty.

PURPOSE: To report 5-year outcomes of endoscopic iliopsoas tenotomy in patients with iliopsoas tendinopathy following total hip arthroplasty (THA) and determine whether clinical scores are associated with cup position. METHODS: Patients who underwent endoscopic iliopsoas tenotomy for iliopsoas tendinopathy following THA (2014-2017) were contacted. Indications for endoscopic iliopsoas tenotomy after THA were groin pain during active hip flexion, exclusion of other causes of groin pain, and no pain relief after 6 months of conservative treatment. Pretenotomy cup inclination and anteversion were measured on radiographs; axial and sagittal cup overhang were measured on computed tomography (CT) scans. Oxford hip score (OHS), modified Harris hip score (mHHS), and groin pain were assessed. RESULTS: The initial cohort comprised 16 men (17 hips) and 31 women (32 hips), aged 60.7 ± 10.6 years. Cup inclination and anteversion were, respectively, 46.2 ± 6.2° and 14.6 ± 8.4°, while axial and sagittal cup overhang were, respectively, 4.4 ± 4.0 mm and 6.9 ± 4.5 mm. At ≥5 years follow-up, four hips underwent cup and stem revision, two underwent isolated cup revision and one underwent secondary iliopsoas tenotomy. OHS improved by 23 ± 10 and mHHS improved by 31 ± 16. Posttenotomy groin pain was slight in 20.0%, mild in 17.5% and moderate in 12.5%. Regression analyses revealed that net change in mHHS decreased with sagittal cup overhang (ß = -3.1; 95% confidence interval [CI] = -4.6 to -1.7; p < 0.001), but that there were no associations between cup position and net change in OHS. CONCLUSIONS: Endoscopic iliopsoas tenotomy provides good mid-term clinical outcomes in patients with iliopsoas tendinopathy following THA. Furthermore, improvements in mHHS were found to decrease with increasing sagittal cup overhang, in cases for which adequate preoperative imaging was available. LEVEL OF EVIDENCE: Level IV.

Cup-Cage Construct for Treatment of Severe Acetabular Bone Loss in Revision Total Hip Arthroplasty: Clinical and Radiographic Outcomes at a Mean Follow-Up of 7.7 Years.

BACKGROUND: Acetabular reconstruction in the context of massive acetabular bone loss is challenging. Achieving implant stability in these situations requires special considerations. The cup-cage construct is a treatment option that addresses this issue. This study evaluates survivorship, complications, and functional outcomes using the cup-cage construct. METHODS: A total of 131 cup-cage implants (129 patients) were identified from our retrospective review of revision total hip arthroplasties from January 2003 to January 2022. Among these cases, 100 (76.3%) were women, the mean age at the time of surgery was 68 years (range, 29 to 92; SD [SD], 12.4), and the mean follow-up was 7.7 years (range, 0.02 to 20.3; SD, 5.1). Kaplan-Meier survivorship analysis was conducted with failure defined as revision surgery and/or failure of the cup-cage reconstruction. RESULTS: At a mean follow-up of 7.7 years, the cup-cage construct survivorship due to all-cause failure was 83.9% (95% CI [confidence interval]: 77.6 to 90.2) at 5 years with 88 hips at risk, 74.8% (95% CI: 66.2 to 83.4) at 10 years with 38 hips at risk, and 69.8% (95% CI: 59.4 to 80.2) at 15 years with 11 hips at risk. The survivorship due to failure from aseptic loosening was 96.7% (95% CI: 93.6 to 99.8) at 5 years with 88 hips at risk and 95.5% (95% CI: 91.6 to 99.4) at 10 and 15 years with 38 and 11 hips at risk, respectively. The revision rate for aseptic loosening of the cup and/or cage, infection, dislocation, and aseptic loosening of the femoral stem was 5 of 131 (3.8%), 12 of 131 (9.1%), 10 of 131 (7.6%), and 2 of 131 (1.5%). CONCLUSIONS: The cup-cage construct is a reliable treatment option for the treatment of various acetabular defects. There are favorable survivorship, clinical, and radiographic outcomes, with a satisfactory complication rate.

A Registry Study On Acetabular Revisions Using Jumbo Cups: Do We Really Need A More Complex Revision Strategy?

BACKGROUND: The increasing global performance of total hip arthroplasty (THA) has led to a corresponding rise in revision surgeries, primarily due to cup implant failure, with aseptic loosening and periprosthetic infection being common causes. Various techniques and implants, including jumbo cups (JCs), are employed to manage residual bone loss post-cup removal, facilitating enhanced surface area for improved host bone contact and biological osteointegration. The purpose of the present study was to determine the outcomes of acetabular revision arthroplasty using JC implants over a 20-year follow-up period by reporting overall survival, complications leading to re-revision surgery, and surgical strategy in the case of re-revision. METHODS: A cohort study based on a large regional registry was conducted, examining revision THA surgeries utilizing JCs between 2000 and 2020. The study included all the revision acetabular procedures performed with cementless JCs, identified with a diameter ≥ 62 mm in women or ≥ 66 mm in men. All iliac fixation cups were excluded. Data on demographics, revision surgery indications, components, fixation types, causes of failure, and reintervention strategies were collected and analyzed. A total of 541 JCs implanted from January 2000 to December 2020 were evaluated. The most common revision indications were "cup aseptic loosening" (54.5%) and "total aseptic loosening," which included both the cup and stem (32%). RESULTS: Jumbo cup survival rates were 92.5% at 5 years, 85.8% at 10 years, and 81.5% at 15 years. Among the 70 failures, the main causes were "cup aseptic loosening" (40%), "total aseptic loosening" (17.1%), and "septic loosening" (12.8%). Revisions primarily involved acetabular cup revision surgery (54 cases), component explantation (11 cases), or insert/head revision (5 cases). CONCLUSIONS: This registry-based study of JCs in revision THA demonstrates excellent 15-year survival rates and acceptable failure rates. It supports JCs as a viable option, offering relative surgical simplicity compared to alternatives like anti-protrusion cages, bone grafts, and augments.

Aseptic Acetabular Revisions ≤90 Days, 91 Days to 2 Years, and >2 Years After Total Hip Arthroplasty: Comparing Etiologies, Complications, and Postoperative Outcomes.

BACKGROUND: Isolated acetabular component revision is an effective treatment for revision total hip arthroplasty patients who have well-fixed femoral implants. We aimed to evaluate the modes of acetabular failure following primary total hip arthroplasty and to identify factors associated with increased morbidities and postoperative outcomes. METHODS: We conducted a retrospective analysis and identified 318 isolated aseptic acetabular revisions. We separated patients by ≤90 days, 91 days to 2 years, and >2 years for acetabular revisions and compared demographics, reasons for revision, 90-day readmissions, rerevisions, and postrevision infections. Revisions ≤90 days, 91 days to 2 years, and >2 years accounted for 10.7, 19.2, and 70.1% of revisions, respectively. Revisions ≤90 days, 91 days to 2 years, and >2 years had their primary total hip arthroplasty at a mean age of 66, 63, and 55 years (P < .001), respectively. RESULTS: Revisions within 90 days were mainly indicated for dislocation/instability (58.8%) or periprosthetic fracture (23.5%) while revisions over 2 years were indicated for polyethylene wear/osteolysis (37.2%). Patients with revisions past 90 days were more likely to require rerevision compared to patients with revisions within 90 days (P < .001). There were no differences in readmissions (P = .28) or infection rates (P = .37). CONCLUSIONS: Acetabular revisions within 90 days were more commonly indicated for instability and periprosthetic fracture, while those over 2 years were indicated for polyethylene wear. Revisions past 90 days were more likely to require subsequent rerevisions without increased 90-day readmissions or infections. LEVEL III EVIDENCE: Retrospective cohort study.

Can Dual Mobility Cups Reduce Revision and Dislocation Risks? An Analysis of 107,528 Primary Total Hip Arthroplasties in the United States.

BACKGROUND: Dual mobility acetabular cups (DMC) were designed to increase the effective femoral head size and improve stability with the goal of reducing revision risk at the potential cost of polyethylene thickness. We sought to evaluate revision risk following primary elective total hip arthroplasty with DMC compared to highly cross-linked polyethylene (XLPE). METHODS: A cohort study was conducted using data from a Kaiser Permanente's total joint arthroplasty registry. Patients ≥18 years who underwent primary elective total hip arthroplasty using DMC, unipolar Metal-on-XLPE (MoXLPE), or unipolar Ceramic-on-XLPE (CoXLPE) were identified (2010 to 2021). The final sample comprised 2,219 DMC, 48,251 MoXLPE, and 57,058 CoXLPE. Multiple Cox proportional hazard regressions were used to evaluate aseptic revision and any dislocation regardless of revision within 6 years follow-up. RESULTS: In adjusted analyses, no differences in aseptic revision risk were observed for MoXLPE (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.72 to 1.51) or CoXLPE (HR = 0.98, 95% CI = 0.69 to 1.40) compared to DMC. No differences in dislocation risk were observed for MoXLPE (HR = 1.42, 95% CI = 0.93 to 2.15) or CoXLPE (HR = 1.25, 95% CI = 0.84 to 1.87) compared to DMC. CONCLUSIONS: In a US-based cohort, 6-year aseptic revision risk of DMC was similar to metal or ceramic femoral head unipolar constructs. Furthermore, no difference in dislocation risk was observed. Continued longer-term follow-up may reveal if there is a reduced risk of dislocation that comes at the cost of increased late revision. LEVEL OF EVIDENCE: Level III.

Outcomes of a Double-Cup Construct to Treat Paprosky 3A and 3B Acetabular Defects at a Mean of 39 Months.

BACKGROUND: Modular reconstruction systems based on porous tantalum (PT) prosthetic components have been increasingly used for the treatment of complex acetabular bone defects in revision total hip arthroplasty. We report a novel technique that applies a revision cup as a "super-augment" to form a "double-cup" construct for Paprosky type III defects. METHODS: A retrospective review was conducted on revision total hip arthroplasty cases, comparing those treated with double-cup constructs (DC group, n = 48) to those treated with PT shells and augments (PT group, n = 48). All procedures were performed at the same institute between 2017 and 2022. Clinical outcome evaluation utilized the Harris Hip Score, Oxford Hip Score, and the 36-Item Short Form Survey. Preoperative and postoperative radiographic assessments measured hip center of rotation (COR) position and leg length discrepancy. Additionally, postoperative complications and implant survivorship were monitored during the follow-up period. RESULTS: The clinical outcomes improved substantially in both groups, which showed no significant difference in the Harris Hip Score (P = .786), the Oxford Hip Score (P = .570), and the 36-Item Short Form Survey (P = .691). Compared to the PT group, the reconstruction COR was significantly closer to the anatomic COR (vertical distance: 2.630 versus 7.355 mm, P = .0034; horizontal distance: 1.881 versus -6.413 mm, P < .0001) in Paprosky 3B type defects. Additionally, postoperative leg length discrepancy was less in the DC group (-8.252 versus -1.821 mm, P = .0008). Dislocation was the main complication in the DC group, and only 1 patient received re-revision due to repeated dislocation. The cumulative survival rate of the DC group (100%; 95% confidence interval 100) was better than the PT group (83.4%; 95% confidence interval 70.5 to 98.6) when re-revisions for aseptic loosening were the endpoint (P = .046). CONCLUSIONS: The DC is a reliable revision technique for the reconstruction of Paprosky type III bone defects. Although dislocation remains challenging, the biomechanically superior restoration achieved by this technique lowers the risk of aseptic loosening.

Measurement of the Acetabular Cup Orientation After Total Hip Arthroplasty Based on 3-Dimensional Reconstruction From a Single X-Ray Image Using Generative Adversarial Networks.

BACKGROUND: The purpose of this study was to reconstruct 3-dimensional (3D) computed tomography (CT) images from single anteroposterior (AP) postoperative total hip arthroplasty (THA) X-ray images using a deep learning algorithm known as generative adversarial networks (GANs) and to validate the accuracy of cup angle measurement on GAN-generated CT. METHODS: We used 2 GAN-based models, CycleGAN and X2CT-GAN, to generate 3D CT images from X-ray images of 386 patients who underwent primary THAs using a cementless cup. The training dataset consisted of 522 CT images and 2,282 X-ray images. The image quality was validated using the peak signal-to-noise ratio and the structural similarity index measure. The cup anteversion and inclination measurements on the GAN-generated CT images were compared with the actual CT measurements. Statistical analyses of absolute measurement errors were performed using Mann-Whitney U tests and nonlinear regression analyses. RESULTS: The study successfully achieved 3D reconstruction from single AP postoperative THA X-ray images using GANs, exhibiting excellent peak signal-to-noise ratio (37.40) and structural similarity index measure (0.74). The median absolute difference in radiographic anteversion was 3.45° and the median absolute difference in radiographic inclination was 3.25°, respectively. Absolute measurement errors tended to be larger in cases with cup malposition than in those with optimal cup orientation. CONCLUSIONS: This study demonstrates the potential of GANs for 3D reconstruction from single AP postoperative THA X-ray images to evaluate cup orientation. Further investigation and refinement of this model are required to improve its performance.

Highly Porous Acetabular Cup and Augment Constructs in Complex Revision Total Hip Arthroplasty: What Predicts 10-Year Implant Survivorship?

BACKGROUND: Porous tantalum acetabular cup and augment constructs have demonstrated favorable outcomes up to 5 years postsurgery despite severe bone loss during revision total hip arthroplasty (THA). Prior literature lacks long-term studies with substantial case numbers. This study aims to assess long-term clinical and radiographic outcomes 10 years postsurgery in patients undergoing revision THA with porous tantalum acetabular cup-augment constructs and determine factors associated with long-term survivorship. METHODS: Between 2000 and 2012, 157 revision THAs were performed in cases with major acetabular defects (mainly Paprosky type IIIA and IIIB) utilizing porous tantalum cup-augment constructs. Pelvic discontinuity was noted intraoperatively in 17 hips (11%). Postoperative radiographs were evaluated at regular intervals for implant stability and radiolucent lines. There were 49 patients who had complete radiographic follow-up at 10 years or longer postsurgery. RESULTS: The 10-year survivorship free of revision of the cup-augment construct for aseptic loosening was 93%, free of any acetabular construct revision was 91%, free of any hip rerevision was 77%, and free of any reoperation was 75%. Pelvic discontinuity was associated with increased risk of reoperation (hazard ratio [HR] = 2.8), any hip rerevision (HR = 3.2), any cup-augment construct revision (HR = 11.8), and aseptic construct revision (HR = 10.0). Of unrevised cases with radiographs at 10 years, 4 hips showed radiographic loosening. Mean Harris hip scores improved from 47 preoperatively to 79 at 10 years. CONCLUSIONS: Porous tantalum acetabular cup-augment constructs used in revision THA with severe acetabular bone loss provide excellent implant survivorship at 10 years when the acetabulum is intact. Due to lower survivorship of cup-augment constructs in cases of pelvic discontinuity, additional construct fixation or stabilization methods are recommended, when a discontinuity is present. LEVEL OF EVIDENCE: IV.

Menstrual cup adoption among reproductive age women in India: a systematic review and meta-analysis.

This systematic review and meta-analysis aim to synthesize the information on menstrual cup adoption among reproductive-age women in India. A comprehensive search was conducted in four databases following PRISMA 2020 guidelines. A total of 18 articles were included in this review. The findings of the studies were described narratively, and meta-analysis and sensitivity analysis were also performed. The pooled prevalence of knowledge regarding menstrual cups among women in the included studies was 35 percent (CI: 0.23-.49). Just 5 percent (CI: 0.02-0.12) of women use menstrual cups. Only 24 percent (CI: 0.17-0.33) of the women who used menstrual cups reported leakage as one of the key barriers or issues to menstrual cup use. Nevertheless, 62 percent (CI: 0.42-0.78) of non-users have a pooled prevalence expressing willingness to use in the future. The price was found to be both a motivating and discouraging factor for using menstruation cups. Currently, menstrual cup use among Indian women and girls is very low. However, user reviews suggest that menstrual cups are an appealing and safer replacement for conventional period supplies. To fully realize the potential of menstruation cups, significant education, and awareness efforts are required to ensure proper usage. Furthermore, initiatives to lower the initial cost of menstruation cups are critical.