Group B Streptococcus transcriptome when interacting with brain endothelial cells.

Bacterial meningitis is a life-threatening infection of the central nervous system (CNS) that occurs when bacteria are able to cross the blood-brain barrier (BBB) or the meningeal-cerebrospinal fluid barrier (mBCSFB). The BBB and mBCSFB comprise highly specialized brain endothelial cells (BECs) that typically restrict pathogen entry. Group B Streptococcus (GBS or Streptococcus agalactiae) is the leading cause of neonatal meningitis. Until recently, identification of GBS virulence factors has relied on genetic screening approaches. Instead, we here conducted RNA-seq analysis on GBS when interacting with induced pluripotent stem cell-derived BECs (iBECs) to pinpoint virulence-associated genes. Of the 2,068 annotated protein-coding genes of GBS, 430 transcripts displayed significant changes in expression after interacting with BECs. Notably, we found that the majority of differentially expressed GBS transcripts were downregulated (360 genes) during infection of iBECs. Interestingly, codY, encoding a pleiotropic transcriptional repressor in low-G + C Gram-positive bacteria, was identified as being highly downregulated. We conducted qPCR to confirm the codY downregulation observed via RNA-seq during the GBS-iBEC interaction and obtained codY mutants in three different GBS background parental strains. As anticipated from the RNA-seq results, the [Formula: see text]codY strains were more adherent and invasive in two in vitro BEC models. Together, this demonstrates the utility of RNA-seq during the BEC interaction to identify GBS virulence modulators. IMPORTANCE: Group B Streptococcus (GBS) meningitis remains the leading cause of neonatal meningitis. Research work has identified surface factors and two-component systems that contribute to GBS disruption of the blood-brain barrier (BBB). These discoveries often relied on genetic screening approaches. Here, we provide transcriptomic data describing how GBS changes its transcriptome when interacting with brain endothelial cells. Additionally, we have phenotypically validated these data by obtaining mutants of a select regulator that is highly down-regulated during infection and testing on our BBB model. This work provides the research field with a validated data set that can provide an insight into potential pathways that GBS requires to interact with the BBB and open the door to new discoveries.

The Number of Patients Lost to Follow-up May Exceed the Fragility Index of a Randomized Controlled Trial Without Reversing Statistical Significance: A Systematic Review and Statistical Model.

PURPOSE: To 1) analyze trends in the publishing of statistical fragility index (FI)-based systematic reviews in the orthopaedic literature, including the prevalence of misleading or inaccurate statements related to the statistical fragility of randomized controlled trials (RCTs) and patients lost to follow-up (LTF) and 2) determine whether RCTs with relatively "low" FIs are truly as sensitive to patients LTF as previously portrayed in the literature. METHODS: All FI-based studies published in the orthopaedic literature were identified using the Cochrane Database of Systematic Reviews, Web of Science Core Collection, PubMed, and MEDLINE databases. All articles involving application of the FI or reverse FI (RFI) to study the statistical fragility of studies in orthopaedics were eligible for inclusion in the study. Study characteristics, median FIs and sample sizes, and misleading or inaccurate statements related to the FI and patients LTF were recorded. Misleading or inaccurate statements were defined as those basing conclusions of trial fragility on the false assumption that adding patients LTF back to a trial has the same statistical effect as existing patients in a trial experiencing the opposite outcome and were determined by two authors. A theoretical RCT with a sample size of 100, p-value of 0.006, and an FI of 4 was used to evaluate the difference in effect on statistical significance between flipping outcome events of patients already included in the trial (the FI) vs. adding patients LTF back to the trial to demonstrate the true sensitivity of RCTs to patients LTF. RESULTS: Of the 39 FI-based studies, 37 (95%) directly compared the FI to the number of patients lost to follow-up. Of these, 22 (59%) included a statement regarding the FI and patients LTF that was determined to be inaccurate or misleading. In the theoretical RCT, a reversal of significance was not observed until 7 patients LTF (nearly twice the FI) were added to the trial in the distribution of maximal significance reversal. CONCLUSIONS: The claim that any RCT in which the number of patients LTF exceeds the FI could potentially have its significance reversed simply by maintaining study follow-ups is commonly inaccurate and prevalent in orthopaedic studies applying the FI. Patients LTF and the FI are not equivalent. The minimum number of patients LTF required to flip the significance of a typical RCT was demonstrated to be greater than the FI, suggesting RCTs with relatively "low" FIs may not be as sensitive to patients LTF as previously portrayed in the literature; however, only a holistic approach that considers the context in which the trial was conducted, potential biases, and study results can determine the merits of any particular RCT.

What Patients Say About Their Orthopaedic Hand and Wrist Surgeons: A Qualitative Analysis of Negative Reviews on Yelp.

Background Patients often turn to online reviews as a source of information to inform their decisions regarding care. Existing literature has analyzed factors associated with positive online patient ratings among hand and wrist surgeons. However, there is limited in-depth analysis of factors associated with low patient satisfaction for hand and wrist surgeons. The focus of this study is to examine and characterize extremely negative reviews of hand and wrist surgeons on Yelp.com. Methods A search was performed using the keywords "hand surgery" on Yelp.com for eight major metropolitan areas including Washington DC, Dallas, New York, Phoenix, Los Angeles, San Francisco, Boston, and Seattle. Only single-star reviews (out of a possible 5 stars) of hand and wrist surgeons were included. The complaints in the 1-star reviews were then categorized into clinical and nonclinical categories. Result A total of 233 single-star reviews were included for analysis, which resulted in 468 total complaints. Of these complaints, 81 (18.8%) were clinically related and 351 (81.3%) were nonclinical in nature. The most common clinical complaints were for complication (24 complaints, 6%), misdiagnosis (16 complaints, 4%), unclear treatment plan (16 complaints, 4%), and uncontrolled pain (15 complaints, 3%). The most common nonclinical complaints were for physician bedside manner (93 complaints, 22%), financially related (80 complaints, 19%), unprofessional nonclinical staff (61 complaints, 14%), and wait time (46 complaints, 11%). The difference in the number of complaints for surgical and nonsurgical patients was statistically significant ( p < 0.05) for complication and uncontrolled pain. Clinical Relevance Patient satisfaction is dependent on a multitude of clinical and nonclinical factors. An awareness of online physician ratings is essential for hand and wrist surgeons to maintain and improve patient care and patient satisfaction. We believe the results of our study could be used to further improve the quality of care provided by hand and wrist surgeons.

On-Chip Quantum Information Processing with Distinguishable Photons.

Multiphoton interference is at the heart of photonic quantum technologies. Arrays of integrated cavities can support bright sources of single photons with high purity and small footprint, but the inevitable spectral distinguishability between photons generated from nonidentical cavities is an obstacle to scaling. In principle, this problem can be alleviated by measuring photons with high timing resolution, which erases spectral information through the time-energy uncertainty relation. Here, we experimentally demonstrate that detection can be implemented with a temporal resolution sufficient to interfere photons detuned on the scales necessary for cavity-based integrated photon sources. By increasing the effective timing resolution of the system from 200 to 20 ps, we observe a 20% increase in the visibility of quantum interference between independent photons from integrated microring resonator sources that are detuned by 6.8 GHz. We go on to show how time-resolved detection of nonideal photons can be used to improve the fidelity of an entangling operation and to mitigate the reduction of computational complexity in boson sampling experiments. These results pave the way for photonic quantum information processing with many photon sources without the need for active alignment.

Full-dose whole-body PET synthesis from low-dose PET using high-efficiency denoising diffusion probabilistic model: PET consistency model.

PURPOSE: Positron Emission Tomography (PET) has been a commonly used imaging modality in broad clinical applications. One of the most important tradeoffs in PET imaging is between image quality and radiation dose: high image quality comes with high radiation exposure. Improving image quality is desirable for all clinical applications while minimizing radiation exposure is needed to reduce risk to patients. METHODS: We introduce PET Consistency Model (PET-CM), an efficient diffusion-based method for generating high-quality full-dose PET images from low-dose PET images. It employs a two-step process, adding Gaussian noise to full-dose PET images in the forward diffusion, and then denoising them using a PET Shifted-window Vision Transformer (PET-VIT) network in the reverse diffusion. The PET-VIT network learns a consistency function that enables direct denoising of Gaussian noise into clean full-dose PET images. PET-CM achieves state-of-the-art image quality while requiring significantly less computation time than other methods. Evaluation with normalized mean absolute error (NMAE), peak signal-to-noise ratio (PSNR), multi-scale structure similarity index (SSIM), normalized cross-correlation (NCC), and clinical evaluation including Human Ranking Score (HRS) and Standardized Uptake Value (SUV) Error analysis shows its superiority in synthesizing full-dose PET images from low-dose inputs. RESULTS: In experiments comparing eighth-dose to full-dose images, PET-CM demonstrated impressive performance with NMAE of 1.278 ± 0.122%, PSNR of 33.783 ± 0.824 dB, SSIM of 0.964 ± 0.009, NCC of 0.968 ± 0.011, HRS of 4.543, and SUV Error of 0.255 ± 0.318%, with an average generation time of 62 s per patient. This is a significant improvement compared to the state-of-the-art diffusion-based model with PET-CM reaching this result 12× faster. Similarly, in the quarter-dose to full-dose image experiments, PET-CM delivered competitive outcomes, achieving an NMAE of 0.973 ± 0.066%, PSNR of 36.172 ± 0.801 dB, SSIM of 0.984 ± 0.004, NCC of 0.990 ± 0.005, HRS of 4.428, and SUV Error of 0.151 ± 0.192% using the same generation process, which underlining its high quantitative and clinical precision in both denoising scenario. CONCLUSIONS: We propose PET-CM, the first efficient diffusion-model-based method, for estimating full-dose PET images from low-dose images. PET-CM provides comparable quality to the state-of-the-art diffusion model with higher efficiency. By utilizing this approach, it becomes possible to maintain high-quality PET images suitable for clinical use while mitigating the risks associated with radiation. The code is availble at https://github.com/shaoyanpan/Full-dose-Whole-body-PET-Synthesis-from-Low-dose-PET-Using-Consistency-Model.

Advances in the understanding and exploitation of carbohydrate-active enzymes.

Carbohydrate-active enzymes (CAZymes) are responsible for the biosynthesis, modification and degradation of all glycans in Nature. Advances in genomic and metagenomic methodologies, in conjunction with lower cost gene synthesis, have provided access to a steady stream of new CAZymes with both well-established and novel mechanisms. At the same time, increasing access to cryo-EM has resulted in exciting new structures, particularly of transmembrane glycosyltransferases of various sorts. This improved understanding has resulted in widespread progress in applications of CAZymes across diverse fields, including therapeutics, organ transplantation, foods, and biofuels. Herein, we highlight a few of the many important advances that have recently been made in the understanding and applications of CAZymes.

Sphingomyelinase-responsive nanomicelles for targeting atherosclerosis.

Atherosclerosis, a leading cause of cardiovascular diseases requires approaches to enhance disease monitoring and treatment. Nanoparticles offer promising potential in this area by being customisable to target components or molecular processes within plaques, while carrying diagnostic and therapeutic agents. However, the number of biomarkers available to target this disease is limited. This study investigated the use of sphingomyelin-based nanomicelles triggered by sphingomyelinase (SMase) in atherosclerotic plaques. Accumulation of iron oxide-based nanomicelles in the plaque was demonstrated by fluorescence, MR imaging and electron microscopy. These findings demonstrate the possibility of utilising SMase as a mechanism to retain nanoprobes within plaques, thus opening up possibilities for future therapeutic interventions.

Diagnostic Performance of Artificial Intelligence for Detection of Scaphoid and Distal Radius Fractures: A Systematic Review.

PURPOSE: To review the existing literature to (1) determine the diagnostic efficacy of artificial intelligence (AI) models for detecting scaphoid and distal radius fractures and (2) compare the efficacy to human clinical experts. METHODS: PubMed, OVID/Medline, and Cochrane libraries were queried for studies investigating the development, validation, and analysis of AI for the detection of scaphoid or distal radius fractures. Data regarding study design, AI model development and architecture, prediction accuracy/area under the receiver operator characteristic curve (AUROC), and imaging modalities were recorded. RESULTS: A total of 21 studies were identified, of which 12 (57.1%) used AI to detect fractures of the distal radius, and nine (42.9%) used AI to detect fractures of the scaphoid. AI models demonstrated good diagnostic performance on average, with AUROC values ranging from 0.77 to 0.96 for scaphoid fractures and from 0.90 to 0.99 for distal radius fractures. Accuracy of AI models ranged between 72.0% to 90.3% and 89.0% to 98.0% for scaphoid and distal radius fractures, respectively. When compared to clinical experts, 13 of 14 (92.9%) studies reported that AI models demonstrated comparable or better performance. The type of fracture influenced model performance, with worse overall performance on occult scaphoid fractures; however, models trained specifically on occult fractures demonstrated substantially improved performance when compared to humans. CONCLUSIONS: AI models demonstrated excellent performance for detecting scaphoid and distal radius fractures, with the majority demonstrating comparable or better performance compared with human experts. Worse performance was demonstrated on occult fractures. However, when trained specifically on difficult fracture patterns, AI models demonstrated improved performance. CLINICAL RELEVANCE: AI models can help detect commonly missed occult fractures while enhancing workflow efficiency for distal radius and scaphoid fracture diagnoses. As performance varies based on fracture type, future studies focused on wrist fracture detection should clearly define whether the goal is to (1) identify difficult-to-detect fractures or (2) improve workflow efficiency by assisting in routine tasks.

Microsurgical Resection of Brainstem Cavernous Malformations in Older Adults: A Multicenter, 30-Year Experience.

BACKGROUND AND OBJECTIVES: Microsurgical resection is the only curative intervention for symptomatic brainstem cavernous malformations (BSCMs), but the management of these lesions in older adults (≥65 years) is not well described. This study sought to address this gap by examining the safety and efficacy of BSCM resection in a cohort of older adults. METHODS: Records of patients who underwent BSCM resection over a 30-year period were reviewed retrospectively. Baseline characteristics and outcomes were compared between older (≥65 years) and younger (<65 years) patients. RESULTS: Of 550 patients with BSCM who met inclusion criteria, 41 (7.5%) were older than 65 years. Midbrain (43.9% vs 26.1%) and medullary lesions (19.5% vs 13.6%) were more common in the older cohort than in the younger cohort (P = .01). Components of the Lawton BSCM grading system (ie, lesion size, crossing axial midpoint, developmental venous anomaly, and timing of hemorrhage) were not significantly different between cohorts (P ≥ .11). Mean (SD) Elixhauser comorbidity score was significantly higher in older patients (1.86 [1.06]) than in younger patients (0.66 [0.95]; P < .001). Older patients were significantly more likely than younger patients to have poor outcomes at final follow-up (28.9% vs 13.8%, P = .01; mean follow-up duration, 28.7 [39.1] months). However, regarding relative neurological outcome (preoperative modified Rankin Scale to final modified Rankin Scale), rate of worsening was not significantly different between older and younger patients (23.7% vs 14.9%, P = .15). CONCLUSION: BSCMs can be safely resected in older patients, and when each patient's unique health status and life expectancy are taken into account, these patients can have outcomes similar to younger patients.

A practical guide to the development and deployment of deep learning models for the orthopaedic surgeon: Part III, focus on registry creation, diagnosis, and data privacy.

Deep learning is a subset of artificial intelligence (AI) with enormous potential to transform orthopaedic surgery. As has already become evident with the deployment of Large Language Models (LLMs) like ChatGPT (OpenAI Inc.), deep learning can rapidly enter clinical and surgical practices. As such, it is imperative that orthopaedic surgeons acquire a deeper understanding of the technical terminology, capabilities and limitations associated with deep learning models. The focus of this series thus far has been providing surgeons with an overview of the steps needed to implement a deep learning-based pipeline, emphasizing some of the important technical details for surgeons to understand as they encounter, evaluate or lead deep learning projects. However, this series would be remiss without providing practical examples of how deep learning models have begun to be deployed and highlighting the areas where the authors feel deep learning may have the most profound potential. While computer vision applications of deep learning were the focus of Parts I and II, due to the enormous impact that natural language processing (NLP) has had in recent months, NLP-based deep learning models are also discussed in this final part of the series. In this review, three applications that the authors believe can be impacted the most by deep learning but with which many surgeons may not be familiar are discussed: (1) registry construction, (2) diagnostic AI and (3) data privacy. Deep learning-based registry construction will be essential for the development of more impactful clinical applications, with diagnostic AI being one of those applications likely to augment clinical decision-making in the near future. As the applications of deep learning continue to grow, the protection of patient information will become increasingly essential; as such, applications of deep learning to enhance data privacy are likely to become more important than ever before. Level of Evidence: Level IV.

Microsurgical Resection of a Lateral Pontine Arteriovenous Malformation Masquerading as a Cavernous Malformation: 2-Dimensional Operative Video.

Although cavernous malformations (CMs) often demonstrate characteristic T2 heterogeneity and gadolinium enhancement, whereas arteriovenous malformations (AVMs) appear as tangles of T2 hypointense flow voids, small lesions in deep locations may have equivocal features on preoperative imaging.1-4 This video presents an unusual case of a lateral pontine AVM masquerading as a CM. The patient presented with sudden-onset headache, dizziness, double vision, and left facial numbness. Diagnostic imaging findings suggested a hemorrhagic left lateral pontine mass lesion, most consistent with brainstem CM. Resection through a left extended retrosigmoid craniotomy was recommended. Patient consent was obtained. During dissection, a prominent petrosal vein tributary was noted to be arterialized, which was concerning for AVM. Indocyanine green videoangiography (ICG-VA) was performed to confirm the diagnosis, and the intraoperative plan was dynamically adjusted in accordance with the principles of AVM resection. The small superficial feeding arteries were identified and disconnected, and the nidus was dissected circumferentially with the pial resection technique. After dearterialization, the draining petrosal vein was noted to darken, and repeat ICG-VA confirmed complete occlusion of the AVM without residual shunting. The patient recovered well, with no neurological deficits, and postoperative angiography confirmed complete resection of the Spetzler-Martin grade III AVM. Key learning points for this unusual case include the importance of dynamic interpretation of intraoperative findings, openness to alterations of the surgical plan when integrating new diagnostic information, and the integration of ICG-VA as a critical tool for differentiating CMs and AVMs during microsurgical resection. Images in Surgical Video © 2024 Barrow Neurological Institute. Used with permission.

Sex differences in patients with and without high-risk factors associated with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Controversy remains regarding the appropriate screening for intracranial aneurysms or for the treatment of aneurysmal subarachnoid hemorrhage (aSAH) for patients without known high-risk factors for rupture. This study aimed to assess how sex affects both aSAH presentation and outcomes for aSAH treatment. METHOD: A retrospective cohort study was conducted of all patients treated at a single institution for an aSAH during a 12-year period (August 1, 2007-July 31, 2019). An analysis of women with and without high-risk factors was performed, including a propensity adjustment for a poor neurologic outcome (modified Rankin Scale [mRS] score > 2) at follow-up. RESULTS: Data from 1014 patients were analyzed (69% [n = 703] women). Women were significantly older than men (mean ± SD, 56.6 ± 14.1 years vs 53.4 ± 14.2 years, p < 0.001). A significantly lower percentage of women than men had a history of tobacco use (36.6% [n = 257] vs 46% [n = 143], p = 0.005). A significantly higher percentage of women than men had no high-risk factors for aSAH (10% [n = 70] vs 5% [n = 16], p = 0.01). The percentage of women with an mRS score > 2 at the last follow-up was significantly lower among those without high-risk factors (34%, 24/70) versus those with high-risk factors (53%, 334/633) (p = 0.004). Subsequent propensity-adjusted analysis (adjusted for age, Hunt and Hess grade, and Fisher grade) found no statistically significant difference in the odds of a poor outcome for women with or without high-risk factors for aSAH (OR = 0.7, 95% CI = 0.4-1.2, p = 0.18). CONCLUSIONS: A higher percentage of women versus men with aSAH had no known high-risk factors for rupture, supporting more aggressive screening and management of women with unruptured aneurysms.

Costs of revision operations for distal junctional kyphosis following thoracic posterior spinal fusion for adolescent idiopathic scoliosis.

PURPOSE: To assess direct costs and risks associated with revision operations for distal junctional kyphosis/failure (DJK) following thoracic posterior spinal instrumented fusions (TPSF) for adolescent idiopathic scoliosis (AIS). METHODS: Children who underwent TPSF for AIS by a single surgeon (2014-2020) were reviewed. Inclusion criteria were minimum follow-up of 2 years, thoracolumbar posterior instrumented fusion with a lower instrumented vertebra (LIV) cranial to L2. Patients who developed DJK requiring revision operations were identified and compared with those who did not develop DJK. RESULTS: Seventy-nine children were included for analysis. Of these, 6.3% developed DJK. Average time to revision was 20.8 ± 16.2 months. Comparing index operations, children who developed DJK had significantly greater BMIs, significantly lower thoracic kyphosis postoperatively, greater post-operative lumbar Cobb angles, and significantly more LIVs cranial to the sagittal stable vertebrae (SSV), despite having statistically similar pre-operative coronal and sagittal alignment parameters and operative details compared with non-DJK patients. Revision operations for DJK, when compared with index operations, involved significantly fewer levels, longer operative times, greater blood loss, and longer hospital lengths of stay. These factors resulted in significantly greater direct costs for revision operations for DJK ($76,883 v. $46,595; p < 0.01). CONCLUSIONS: In this single-center experience, risk factors for development of DJK were greater BMI, lower post-operative thoracic kyphosis, and LIV cranial to SSV. As revision operations for DJK were significantly more costly than index operations, all efforts should be aimed at strategies to prevent DJK in the AIS population.

Modafinil Therapy and Mental Status Following Aneurysmal Subarachnoid Hemorrhage: Comprehensive Stroke Center Analysis.

BACKGROUND: Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. METHODS: Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. RESULTS: Modafinil (100-200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4-16) days and initiated 14 (7-17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. -0.2 [6.32], P = 0.003). CONCLUSIONS: A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting.

High-temperature Josephson diode.

Many superconducting systems with broken time-reversal and inversion symmetry show a superconducting diode effect, a non-reciprocal phenomenon analogous to semiconducting p-n-junction diodes. While the superconducting diode effect lays the foundation for realizing ultralow dissipative circuits, Josephson-phenomena-based diode effect (JDE) can enable the realization of protected qubits. The superconducting diode effect and JDE reported thus far are at low temperatures (~4 K), limiting their applications. Here we demonstrate JDE persisting up to 77 K using an artificial Josephson junction of twisted layers of Bi2Sr2CaCu2O8+δ. JDE manifests as an asymmetry in the magnitude and distributions of switching currents, attaining the maximum at 45° twist. The asymmetry is induced by and tunable with a very small magnetic field applied perpendicular to the junction and arises due to interaction between Josephson and Abrikosov vortices. We report a large asymmetry of 60% at 20 K. Our results provide a path towards realizing superconducting Josephson circuits at liquid-nitrogen temperature.

Does Combining Drilling and Curettage to Percutaneous Trans-epiphyseal Screws Improve Correction of Limb Length Discrepancy? A Comparative Study.

Objectives: Physeal drilling and curettage (PDC) and percutaneous epiphysiodesis using transphyseal screws (PETS) are among the most widely used techniques to treat leg-length discrepancy (LLD). This study compared the efficacy and outcomes between PETS alone and PETS combined with PDC (PETS + PDC). Methods: Retrospective study of children who underwent epiphysiodesis of the proximal tibia or distal femur with either PETS or PETS + PDC between 2008 and 2018 at a single institution. Radiographic parameters and complications were reviewed at completion of treatment and most recent follow-up. Results: A total of 23 epiphysiodeses in 15 patients, average age 13.1 years, with either PETS (13 femur/tibias) or PETS + PDC (10 femur/tibias) were included. PETS patients were treated for a longer time (median: 24 months vs 11 months, p = 0.004), however, follow-up time was similar between groups (p = 0.577), on average 2.7 years. In the PETS group, LLD decreased from 2.55 to 0.84 cm at most recent follow-up (p = 0.010), and in the PETS + PDC group from 3.01 to 1.2 cm (p = 0.005), achieving a correction of 1.71 cm for PETS and 1.83 cm for PETS + PDC (p = 0.871). A correction of LLD to ≤ 2 cm was achieved in 8 PETS (89%) and 4 PETS + PDC cases (67%) (p = 0.525). Two PETS patients (22%) and 1 PETS + PDC (17%) patient returned to the OR for further correction due to persistent LLD (p = 1.000). No differences existed in total number of complications, angular deformity or return to physical activity between groups (p ≥ 0.05 for each comparison). Conclusions: This study showed equal efficiency in resolving LLD between the PETS and PETS + PDC procedures with minimal operative complications.Level of Evidence III.

Platelet-Rich Plasma Versus Alternative Injections for Osteoarthritis of the Knee: A Systematic Review and Statistical Fragility Index-Based Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown. PURPOSE: To evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 2. METHODS: All RCTs comparing PRP with alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse FI were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from ≥1 trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect. RESULTS: In total, this analysis included outcomes from 1993 patients with a mean ± SD age of 58.0 ± 3.8 years. The mean number of events required to reverse significance of individual RCTs (FI) was 4.57 ± 5.85. Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared with hyaluronic acid (P = .002; odds ratio [OR], 2.19; 95% CI, 1.33-3.62), as well as higher rates of patient-reported symptom relief (P = .019; OR, 1.55; 95% CI, 1.07-2.24), not requiring a reintervention after the initial injection treatment (P = .002; OR, 2.17; 95% CI, 1.33-3.53), and achieving the minimal clinically important difference (MCID) for pain improvement (P = .007; OR, 6.19; 95% CI, 1.63-23.42) when compared with all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50. CONCLUSION: Conclusions drawn from individual RCTs evaluating PRP for knee OA demonstrated slight robustness. On meta-analysis, PRP demonstrated a significant advantage over hyaluronic acid as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared with alternative nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and health care. Future RCTs and meta-analyses should consider reporting FIs and fragility quotients to facilitate interpretation of results in their proper context.

From trenches to technology: a narrative review of sleep medicine in the military.

Diagnoses of military-relevant sleep disorders have increased substantially since the terrorist attacks of 9-11. The cause of this increase appears to be complicated and multifactorial, with military and civilian populations clearly differing with respect to both the nature and distribution of sleep disorders diagnoses. In part, these differences may be attributable to the fact that a majority of service members (SMs) are chronically sleep restricted - an unavoidable consequence of continuous and sustained military operations that 'set the stage' for development of specific sleep disorders. The purpose of this narrative review is to describe the military relevance of several common sleep disorders, assess the extent to which these disorders currently constitute a burden on the military healthcare system, and suggest strategies to alleviate that burden. The military healthcare system does not have enough sleep providers to address the immediate and long-term consequences of sleep disorders in military personnel. Digital technologies and education packages can be leveraged to improve access to care.