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Background: Substantial developments in physeal-sparing surgical techniques for anterior cruciate ligament (ACL) reconstruction (ACLR) have demonstrated safety and efficacy in treating skeletally immature patients. However, outcomes using all–soft tissue quadriceps tendon (QT) autograft in this population are unknown. Purpose: To evaluate outcomes including return to sport (RTS) and reinjury risk in skeletally immature patients ≥2 years after undergoing hybrid transepiphyseal ACLR using QT autograft. Study Design: Case series; Level of evidence, 4. Methods: A consecutive series of skeletally immature patients who underwent primary QT autograft ACLR using a hybrid transepiphyseal technique with ≥2 years of follow-up were retrospectively analyzed. Outcomes included RTS (primary), ability to return to preinjury level of competition, and subsequent ipsilateral/contralateral knee injury (secondary). Results: A total of 50 patients were identified and contacted, of which 40 (80.0%) (35 male; mean age, 12.6 years [range, 9.4-16.0 years]) completed the survey at 5.7 ± 2.8 years (range, 2.0-11.5 years) postoperation. Of those, 26 (65.0%) were competitive middle/high school athletes and 18 (45.0%) competed in ≥2 sports. At a mean of 10.6 ± 2.3 months (range, 6-17 months) postoperatively, 37 patients (92.5%) returned to unrestricted sports participation, and 35 patients (87.5%) resumed competition at their preinjury level. Five patients required subsequent ipsilateral knee surgery for ACL revision (n = 2; 5.0%), meniscal injury (n = 2; 5.0%), or symptomatic hardware (n = 1; 2.5%) after a mean of 4.4 ± 1.7 years (range, 2.8-7.1 years). Three patients (7.5%) sustained a subsequent contralateral ACL injury, and 1 patient sustained a contralateral posterior cruciate ligament sprain. Conclusion: Findings of this study suggest that midterm outcomes of patients treated with hybrid transepiphyseal ACLR using QT autograft are promising, with a high and expedited RTS and relatively low graft tear risk.

ObjectiveThe lifetime direct and indirect costs of spinal injury and spinal cord injury (SCI) increase as the severity of injury worsens. Despite the potential for substantial improvement in function with acute rehabilitation, the factors affecting its cost have not yet been evaluated. We used a proprietary hospital database to evaluate the direct costs of rehabilitation after spine injury.MethodsA single-center, retrospective cohort cost analysis of patients with acute, traumatic spine injury treated at a tertiary facility from 2011 to 2017 was performed.ResultsIn the 190 patients (mean age 46.1 ± 18.6 years, 76.3% males) identified, American Spinal Injury Association impairment scores on admission were 32.1% A, 14.7% B, 14.7% C, 33.2% D, and 1.1% E. Surgical treatment was performed in 179 (94.2%) cases. Most injuries were in the cervical spine (53.2%). A mean improvement of Functional Impairment Score of 30.7 ± 16.2 was seen after acute rehabilitation. Costs for care comprised facility (86.5%), pharmacy (9.2%), supplies (2.0%), laboratory (1.5%), and imaging (0.8%) categories. Injury level, injury severity, and prior inpatient surgical treatment did not affect the cost of rehabilitation. Higher injury severity (p = 0.0001, one-way ANOVA) and spinal level of injury (p = 0.001, one-way ANOVA) were associated with higher length of rehabilitation stay in univariate analysis. However, length of rehabilitation stay was the strongest independent predictor of higher-than-median cost (risk ratio = 1.56, 95% CI 1.21-2.0, p = 0.001) after adjusting for other factors.ConclusionsSpine injury has a high upfront cost of care, with greater need for rehabilitation substantially affecting cost. Improving the efficacy of rehabilitation to reduce length of stay may be effective in reducing cost.

\\textcopyright 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016 - several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions.

Delineating cell populations is crucial for understanding immune function in health and disease. Spatial omics technologies offer insights by capturing three complementary domains: single-cell molecular biomarker expression, cellular spatial relationships and tissue architecture. However, current computational methods often fail to fully integrate these multidimensional data, particularly for immune cell populations and intrinsic functional states. We introduce Cell Local Environment and Neighborhood Scan (CellLENS), a self-supervised computational method that learns cellular representations by fusing information across three spatial omics domains (expression, neighborhood and image). CellLENS markedly enhances de novo discovery of biologically relevant immune cell populations at fine granularity by integrating individual cells’ molecular profiles with their neighborhood context and tissue localization. By applying CellLENS to diverse spatial proteomic and transcriptomic datasets across multiple tissue types and disease settings, we uncover unique immune cell populations functionally stratified according to their spatial contexts. Our work demonstrates the power of multi-domain data integration in spatial omics to reveal insights into immune cell heterogeneity and tissue-specific functions. In this Technical Report, the authors present CellLENS, a computational method that enhances immune cell identification and analyses by integrating cross-domain information in spatial multiomics data.

Objective To compare the effects of laparoscopic hysterectomy and abdominal hysterectomy in the abdominal trial, and laparoscopic hysterectomy and vaginal hysterectomy in the vaginal trial. Design Two parallel, multicentre, randomised trials. Setting 28 UK centres and two South African centres. Participants 1380 women were recruited; 1346 had surgery; 937 were followed up at one year. Primary outcome Rate of major complications. Results In the abdominal trial laparoscopic hysterectomy was associated with a higher rate of major complications than abdominal hysterectomy (11.1% v 6.2%, P = 0.02; difference 4.9%, 95% confidence interval 0.9% to 9.1%) and the number needed to treat to harm was 20. Laparoscopic hysterectomy also took longer to perform (84 minutes v 50 minutes) but was less painful (visual analogue scale 3.51 v 3.88, P = 0.01) and resulted in a shorter stay in hospital after the operation (3 days v 4 days). Six weeks after the operation, laparoscopic hysterectomy was associated with less pain and better quality of life than abdominal hysterectomy (SF-12, body image scale, and sexual activity questionnaires). In the vaginal trial we found no evidence of a difference in major complication rates between laparoscopic hysterectomy and vaginal hysterectomy (9.8% v 9.5%, P = 0.92; difference 0.3%, -5.2% to 5.8%), and the number needed to treat to harm was 333. We found no evidence of other differences between laparoscopic hysterectomy and vaginal hysterectomy except that laparoscopic hysterectomy took longer to perform (72 minutes v 39 minutes) and was associated with a higher rate of detecting unexpected pathology (16.4% v 4.8%, P = < 0.01). However, this trial was underpowered. Conclusions Laparoscopic hysterectomy was associated with a significantly higher rate of major complications than abdominal hysterectomy. It also took longer to perform but was associated with less pain, quicker recovery, and better short term quality of life. The trial comparing vaginal hysterectomy with laparoscopic hysterectomy was underpowered and is inconclusive on the rate of major complications; however, vaginal hysterectomy took less time.

The 2013–2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics. Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone. Evolution of an epidemic Understanding how and why viruses spread during epidemics is crucial for planning how to prevent and respond to future threats. Andrew Rambaut and colleagues provide an overview of the genetic epidemiology of the 2013–2016 epidemic caused by Ebola virus in West Africa. By analysing more than 1,600 Ebola virus genomes, the authors determine the factors that were important in the spread of the epidemic and also explain why the virus did not spread into neighbouring countries.

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are the two dominant revascularisation strategies for obstructive coronary artery disease, yet their relative roles continue to shift because they address coronary pathophysiology differently with ever-evolving techniques. PCI has advanced through iterative improvements, including balloon angioplasty, bare-metal stents, and drug-eluting stents, with contemporary outcomes increasingly driven by procedural optimisation using intracoronary imaging and physiology-guided lesion selection rather than device category alone. CABG has progressed through perioperative management, improvements in operative safety, and, critically, conduit durability. Recognition of progressive saphenous vein graft failure has underpinned a conduit-optimisation era in which the left internal mammary artery to left anterior descending artery remains the gold standard. Further, broader arterial grafting (including radial artery use, multiple arterial grafting, and selected total-arterial strategies) has been increasingly applied, albeit with deliverability and competing-risk constraints highlighted in randomised evidence. This perspective review reframes the CABG versus PCI comparison not as a binary contest, but as a context-dependent assessment in which the relative value of each strategy depends on the specific technologies, techniques, and conduits available at the time of comparison. We summarise comparative effectiveness where evidence is most consistent and where it remains sensitive to anatomy, comorbidity, and endpoint definitions. In diabetes with multivessel disease, trial data favour CABG for long-term survival and clinical outcomes despite higher stroke risk. In left main disease, outcomes depend on lesion pattern and overall complexity, with trial-era stent technology and composite endpoint definitions influencing conclusions. In ischaemic left ventricular dysfunction, a long-term survival benefit is established for CABG added to medical therapy, while multi-vessel PCI has not demonstrated comparable prognostic modification in contemporary data. We then examine hybrid coronary revascularisation as territory-specific allocation, highlighting its physiological rationale, program dependence, and limited, adequately powered randomised evidence. Finally, we outline how artificial intelligence (AI) and robotics may accelerate a precision revascularisation paradigm by standardising lesion assessment, supporting procedural planning, improving procedural reproducibility, and enabling more patient-specific selection among PCI, contemporary CABG with optimised conduits, and hybrid pathways.

We develop a method to estimate the seismic moments of deep non‐volcanic tremor bursts observed in northern Cascadia. For each tremor burst, the maximum amplitudes at individual stations within a time window ±5 s around the predicted arrivals of the S phase are measured and compared to the maximum S amplitudes measured from synthetic seismograms. The proposed method is thoroughly calibrated using 464 local earthquakes and the results show excellent consistency between the reported ML and the estimated Mw. We apply the method to northern Cascadia tremors and infer that most bursts have Mw∼1.0–1.7. The corresponding b value appears to be 1, consistent with that of ordinary earthquakes but over a narrower Mw range. Comparison of cumulative tremor Mw and the Mw estimated from the accompanying slow slip suggests that the “seismic efficiency” of the Episodic Tremor and Slip (ETS) is of the order of 0.1% or less.

Abstract Among chlamydial virulence factors are the type III secretion (T3S) system and its effectors. T3S effectors target host proteins to benefit the infecting chlamydiae. The assortment of effectors, each with a unique function, varies between species. This variation likely contributes to differences in host specificity and disease severity. A dozen effectors of Chlamydia trachomatis have been identified; however, estimates suggest that more exist. A T3S prediction algorithm, SVM-based Identification and Evaluation of Virulence Effectors (SIEVE), along with a Yersinia surrogate secretion system helped to identify a new T3S substrate, CT082, which rather than functioning as an effector associates with the chlamydial envelope after secretion. SIEVE was modified to improve/expand effector predictions to include all sequenced genomes. Additional adjustments were made to the existing surrogate system whereby the N terminus of putative effectors was fused to a known effector lacking its own N terminus and was tested for secretion. Expansion of effector predictions by cSIEVE and modification of the surrogate system have also assisted in identifying a new T3S substrate from C. psittaci . The expanded predictions along with modifications to improve the surrogate secretion system have enhanced our ability to identify novel species-specific effectors, which upon characterization should provide insight into the unique pathogenic properties of each species. The manuscript describes the application of new algorithms for computational discovery of type III secretion substrates in Chlamydiae , a group of pathogenic bacteria with limited experimental tools available for virulence gene discovery.

Containment limited the 2014 Nigerian Ebola virus (EBOV) disease outbreak to 20 reported cases and 8 fatalities. We present here clinical data and contact information for at least 19 case patients, and full-length EBOV genome sequences for 12 of the 20. The detailed contact data permits nearly complete reconstruction of the transmission tree for the outbreak. The EBOV genomic data are consistent with that tree. It confirms that there was a single source for the Nigerian infections, shows that the Nigerian EBOV lineage nests within a lineage previously seen in Liberia but is genetically distinct from it, and supports the conclusion that transmission from Nigeria to elsewhere did not occur.