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Purpose: The hypothesis of this study was that single-legged horizontal hop test ratios would correlate with IKDC, KOOS, and Marx activity level scores in patients 2 years after primary ACL reconstruction.Methods: Individual patient-reported outcome tools and hop test ratios on 69 ACL reconstructed patients were compared using correlations and multivariable modeling. Correlations between specific questions on the IKDC and KOOS concerning the ability to jump and hop ratios were also performed.Results: The triple-hop ratio was moderately but significantly correlated with the IKDC, KOOS Sports and Recreation subscale, and the KOOS Knee Related Quality of Life subscale, as well as with the specific questions related to jumping. Similar but weaker relationship patterns were found for the single-hop ratio and timed hop. No significant correlations were found for the Marx activity level or crossover-hop ratio. Multivariable modeling showed almost no significant additional contribution to predictability of the IKDC or KOOS subscores by gender, BMI, or the number of faults on either leg.Conclusions: The triple-hop test is most significantly correlated with patient-reported outcome scores. Multivariable modeling indicates that less than a quarter of the variability in outcome scores can be explained by hop test results. This indicates that neither test can serve as a direct proxy for the other; however, assessment of patient physical function by either direct report using validated outcome tools or by the hop test will provide relatively comparable data. [ABSTRACT FROM AUTHOR]

Rationale: Early in life, lung growth can occur by alveolarization, an increase in the number of alveoli, as well as expansion. We hypothesized that if lung growth early in life occurred primarily by alveolarization, then the ratio of pulmonary diffusion capacity of carbon monoxide (Dl(CO)) to alveolar volume (V(A)) would remain constant; however, if lung growth occurred primarily by alveolar expansion, then Dl(CO)/V(A) would decline with increasing age, as observed in older children and adolescents.Objectives: To evaluate the relationship between alveolar volume and pulmonary diffusion capacity early in life.Methods: In 50 sleeping infants and toddlers, with equal number of males and females between the ages of 3 and 23 months, we measured Dl(CO) and V(A) using single breath-hold maneuvers at elevated lung volumes.Measurements and Main Results: Dl(CO) and V(A) increased with increasing age and body length. Males had higher Dl(CO) and V(A) when adjusted for age, but not when adjusted for length. Dl(CO) increased with V(A); there was no gender difference when Dl(CO) was adjusted for V(A). The ratio of Dl(CO)/V(A) remained constant with age and body length.Conclusions: Our results suggest that surface area for diffusion increases proportionally with alveolar volume in the first 2 years of life. Larger Dl(CO) and V(A) for males than females when adjusted for age, but not when adjusted for length, is primarily related to greater body length in boys. The constant ratio for Dl(CO)/V(A) in infants and toddlers is consistent with lung growth in this age occurring primarily by the addition of alveoli rather than the expansion of alveoli. [ABSTRACT FROM AUTHOR]

The extant literature on the social functioning of students with learning disabilities (LD) has indicated that whereas a majority belong to peer groups, a higher proportion are isolated and most have lower social status among peers in general than their typically achieving classmates. Although some work has examined these issues over short-term longitudinal studies, none to date have examined them over extensive time periods. Toward this end, the current study examined a sample of 1,361 students (678 girls and 683 boys; 55 with LD) using multiple measures of peer social functioning assessed each semester from spring of third grade through fall of sixth grade. The results indicated that whereas students with LD were similar to their typically achieving peers in terms of group functioning and characteristics, they were viewed as lower in social standing among their classmates as a whole. These effects were maintained over time, indicating that long-term inclusion may not substantially affect peer social functioning among students with LD. [ABSTRACT FROM AUTHOR]

RATIONALE: Preterm delivery has been associated with a higher incidence of respiratory morbidity even in infants that do not have significant respiratory disease during the neonatal period. Reduced flows have been reported in children and adolescents born prematurely. OBJECTIVE: The aim of this study was to assess lung function in healthy preterm infants in the first months of life. METHODS: Preterm infants with less than 48 h of supplemental oxygen were recruited. Lung function was assessed by the raised-volume rapid thoracic compression in the first months of life. The control group consisted of full-term infants without a history of respiratory diseases. MEASUREMENTS AND MAIN RESULTS: Sixty-two preterm (29 male) and 27 full-term (10 male) infants were tested. Adjusting for length, age, and sex, we found a mean significant reduction of 92 ml/s (22%) in FEF(50), 73 ml/s (21%) in FEF(25-75), and 19 ml (28%) in FEV(0.5) in the preterm group. These differences in expiratory flows remained significant using another model that adjusts for lung volume (p < 0.01 for FEF(50), FEF(25-75), and FEV(0.5), and p < 0.05 for FEF(75)). In the preterm group, after adjusting for length, male sex, lower gestational age, and increased weight were significantly and independently associated with reduced flows. CONCLUSIONS: Our findings confirm that prematurity is independently associated with reduced lung function and that this is detectable in the first months of life. Male sex, lower gestational age, and weight are important predictors for reduced expiratory flows in this group. [ABSTRACT FROM AUTHOR]

Mycobacterium ulcerans disease (Buruli ulcer) is an important health problem in several west African countries. It is prevalent in scattered foci around the world, predominantly in riverine areas with a humid, hot climate. We review the epidomiology, bacteriology, transmission, immunology, pathology, diagnosis and treatment of infection. M. ulcerans is an ubiquitous micro-organism and is harboured by fish, snails, and water insects.The mode of transmission is unknown. Lesions are most common on exposed parts of the body, particularly on the limbs. Spontaneous healing may occur. Many patients in endemic areas present late with advanced, severe lesions. BCG vaccination yields a limited, relatively short-lived, immune protection. Recommended treatment consists of surgical debridement, followed by skin grafting if necessary. Many patients have functional limitations after healing. better understanding of disease transmission and pathogenesis is needed for improved control and prevention of buruli uncler. [ABSTRACT FROM AUTHOR]

Background: As machine learning becomes increasingly utilized in orthopaedic clinical research, the application of machine learning methodology to cohort data from the Multicenter ACL Revision Study (MARS) presents a valuable opportunity to translate data into patient-specific insights., Purpose: To apply novel machine learning methodology to MARS cohort data to determine a predictive model of revision anterior cruciate ligament reconstruction (rACLR) graft failure and features most predictive of failure., Study Design: Cohort study; Level of evidence, 3., Methods: The authors prospectively recruited patients undergoing rACLR from the MARS cohort and obtained preoperative radiographs, surgeon-reported intraoperative findings, and 2- and 6-year follow-up data on patient-reported outcomes, additional surgeries, and graft failure. Machine learning models including logistic regression (LR), XGBoost, gradient boosting (GB), random forest (RF), and a validated ensemble algorithm (AutoPrognosis) were built to predict graft failure by 6 years postoperatively. Validated performance metrics and feature importance measures were used to evaluate model performance., Results: The cohort included 960 patients who completed 6-year follow-up, with 5.7% (n = 55) experiencing graft failure. AutoPrognosis demonstrated the highest discriminative power (model area under the receiver operating characteristic curve: AutoPrognosis, 0.703; RF, 0.618; GB, 0.660; XGBoost, 0.680; LR, 0.592), with well-calibrated scores (model Brier score: AutoPrognosis, 0.053; RF, 0.054; GB, 0.057; XGBoost, 0.058; LR, 0.111). The most important features for AutoPrognosis model performance were prior compromised femoral and tibial tunnels (placement and size) and allograft graft type used in current rACLR., Conclusion: The present study demonstrated the ability of the novel AutoPrognosis machine learning model to best predict the risk of graft failure in patients undergoing rACLR at 6 years postoperatively with moderate predictive ability. Femoral and tibial tunnel size and position in prior ACLR and allograft use in current rACLR were all risk factors for rACLR failure in the context of the AutoPrognosis model. This study describes a unique model that can be externally validated with larger data sets and contribute toward the creation of a robust rACLR bedside risk calculator in future studies., Registration: NCT00625885 (ClinicalTrials.gov identifier)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant 5R01-AR060846). See Supplemental Material for individual disclosures. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Background: Revision anterior cruciate ligament (ACL) reconstruction has been documented to have inferior outcomes compared with primary ACL reconstruction. The reasons why remain unknown., Purpose: To determine whether surgical factors performed at the time of revision ACL reconstruction can influence a patient's outcome at 6-year follow-up., Study Design: Cohort study; Level of evidence, 2., Methods: Patients who underwent revision ACL reconstruction were identified and prospectively enrolled between 2006 and 2011. Data collected included baseline patient characteristics, surgical technique and pathology, and a series of validated patient-reported outcome instruments: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) subjective form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx activity rating score. Patients were followed up for 6 years and asked to complete the identical set of outcome instruments. Regression analysis was used to control for baseline patient characteristics and surgical variables to assess the surgical risk factors for clinical outcomes 6 years after surgery., Results: A total of 1234 patients were enrolled (716 men, 58%; median age, 26 years), and 6-year follow-up was obtained on 79% of patients (980/1234). Using an interference screw for femoral fixation compared with a cross-pin resulted in significantly better outcomes in 6-year IKDC scores (odds ratio [OR], 2.2; 95% CI, 1.2-3.9; P = .008) and KOOS sports/recreation and quality of life subscale scores (OR range, 2.2-2.7; 95% CI, 1.2-4.8; P < .01). Use of an interference screw compared with a cross-pin resulted in a 2.6 times less likely chance of having a subsequent surgery within 6 years. Use of an interference screw for tibial fixation compared with any combination of tibial fixation techniques resulted in significantly improved scores for IKDC (OR, 1.96; 95% CI, 1.3-2.9; P = .001); KOOS pain, activities of daily living, and sports/recreation subscales (OR range, 1.5-1.6; 95% CI, 1.0-2.4; P < .05); and WOMAC pain and activities of daily living subscales (OR range, 1.5-1.8; 95% CI, 1.0-2.7; P < .05). Use of a transtibial surgical approach compared with an anteromedial portal approach resulted in significantly improved KOOS pain and quality of life subscale scores at 6 years (OR, 1.5; 95% CI, 1.02-2.2; P ≤ .04)., Conclusion: There are surgical variables at the time of ACL revision that can modify clinical outcomes at 6 years. Opting for a transtibial surgical approach and choosing an interference screw for femoral and tibial fixation improved patients' odds of having a significantly better 6-year clinical outcome in this cohort., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This project was funded by grant No. 5R01-AR060846 from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. All author disclosures are listed in the Appendix (available in the online version of this article). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Kinesin-5 motors play an essential role during mitotic spindle assembly in many organisms 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 : they crosslink antiparallel spindle microtubules, step toward plus ends, and slide the microtubules apart. 12 , 13 , 14 , 15 , 16 , 17 This activity separates the spindle poles and chromosomes. Kinesin-5s are not only plus-end-directed but can walk or be carried toward MT minus ends, 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 where they show enhanced localization. 3 , 5 , 7 , 27 , 29 , 32 The kinesin-5 C-terminal tail interacts with and regulates the motor, affecting structure, motility, and sliding force of purified kinesin-5 35 , 36 , 37 along with motility and spindle assembly in cells. 27 , 38 , 39 The tail contains phosphorylation sites, particularly in the conserved BimC box. 6 , 7 , 40 , 41 , 42 , 43 , 44 Nine mitotic tail phosphorylation sites were identified in the kinesin-5 motor of the fission yeast Schizosaccharomyces pombe, 45 , 46 , 47 , 48 suggesting that multi-site phosphorylation may regulate kinesin-5s. Here, we show that mutating all nine sites to either alanine or glutamate causes temperature-sensitive lethality due to a failure of bipolar spindle assembly. We characterize kinesin-5 localization and sliding force in the spindle based on Cut7-dependent microtubule minus-end protrusions in cells lacking kinesin-14 motors. 39 , 49 , 50 , 51 , 52 Imaging and computational modeling show that Cut7p simultaneously moves toward the minus ends of protrusion MTs and the plus ends of spindle midzone MTs. Phosphorylation mutants show dramatic decreases in protrusions and sliding force. Comparison to a model of force to create protrusions suggests that tail truncation and phosphorylation mutants decrease Cut7p sliding force similarly to tail-truncated human Eg5. 36 Our results show that C-terminal tail phosphorylation is required for kinesin-5/Cut7 sliding force and bipolar spindle assembly in fission yeast., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Radiographs are frequently obtained for patients with knee osteoarthritis (KOA), with magnetic resonance imaging (MRI) reserved for those with complex KOA. There are few data on how often subsequent MRI reveals clinically actionable but unanticipated findings. The purpose of this study is to estimate the prevalence of these findings on MRI for patients managed nonoperatively for suspected meniscal tears., Methods: The Treatment of Meniscal Problems and Osteoarthritis (TeMPO) study enrolled patients aged 45 to 85 years with knee pain, osteoarthritis (Kellgren-Lawrence [KL] grades 0-3), and suspected meniscal tear. We reviewed baseline MRI and recorded notable findings, including subchondral insufficiency fractures of the knee (SIFKs), avascular necrosis (AVN), tumors, and nonsubchondral fractures. Other baseline data included demographic characteristics, Knee Injury and Osteoarthritis Outcome Score, duration of knee symptoms, and KL grade., Results: Study-ordered MRI was performed on 760 patients, with 61 concerning findings identified (8.03%, 95% confidence interval 6.09%-9.96%). A total of 25 participants had SIFKs, 10 had nonsubchondral fractures, 4 had AVN, 8 had benign tumors, and 14 had other clinically relevant findings., Conclusion: We estimated the prevalence of clinically relevant incidental findings on MRI to be 8.03% in middle-aged adults with mild to moderate KOA and suspected meniscal tear. These data may prompt clinicians to be more aware of the range of findings that can underlie knee symptoms, some of which could change management but may require different modalities of imaging to detect. Future research is needed to pinpoint factors associated with these concerning findings so that patients who are at risk can be identified and referred for advanced imaging., (© 2024 American College of Rheumatology.)

Objective: To evaluate the seasonality of acute bronchiolitis in Brazil during the 2020-2022 season and compare it with the previous seasons., Methods: Data from the incidence of hospitalizations due to acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2022. These data were also analyzed by macro-regions of Brazil (North, Northeast, Southeast, South, and Midwest). To describe seasonal and trend characteristics over time, we used the Seasonal Autoregressive Integrated Moving Averages Model., Results: Compared to the pre-COVID-19 period, the incidence of hospitalizations related to acute bronchiolitis decreased by 97% during non-pharmacological interventions (March 2020 - August 2021) but increased by 95% after non-pharmacological interventions relaxation (September 2021 - December 2022), resulting in a 16% overall increase. During the pre-COVID-19 period, hospitalizations for acute bronchiolitis followed a seasonal pattern, which was disrupted in 2020-2021 but recovered in 2022, with a peak occurring in May, approximately 4% higher than the pre-COVID-19 peak., Conclusions: This study underscores the significant influence of COVID-19 interventions on acute bronchiolitis hospitalizations in Brazil. The restoration of a seasonal pattern in 2022 highlights the interplay between public health measures and respiratory illness dynamics in young children.

Objective: Musculoskeletal (MSK) disorders affect ~50% of US adults and 75% of those over the age of 65, representing a sizable economic and disability burden. Outcome measures, both objective and subjective, help clinicians and investigators determine whether interventions to treat MSK conditions are effective. This narrative review qualitatively compared the responsiveness of different types of outcome measures, a key measurement characteristic that assesses an outcome measure's ability to detect change in patient status., Methods: We evaluated elective orthopedic interventions as a model for assessing responsiveness because the great majority of patients improves following surgery. We searched for articles reporting responsiveness (quantified as effect size [ES]) of subjective and objective outcome measures after orthopedic surgery and included 16 articles reporting 17 interventions in this review., Results: In 14 of 17 interventions, subjective function measures had an ES 10% greater than that of objective function measures. Two reported a difference in ES of <10%. The sole intervention that demonstrated higher ES of objective function used a composite measure. Sixteen interventions reported measures of subjective pain and/or mixed measures and subjective function. In nine interventions, subjective pain had a higher ES than subjective function by >10%, in three, subjective function had a higher ES than subjective pain by >10%, and in the remaining four, the difference between pain and function was <10%., Conclusion: These findings reinforce the clinical observation that subjective pain generally changes more than function following elective orthopedic surgery. They also suggest that subjective function measures are more responsive than objective function measures, and composite scores may be more responsive than individual performance tests., (© 2024 American College of Rheumatology.)

Background: Surgeon performance has been investigated as a factor affecting patient outcomes after orthopaedic procedures to improve transparency between patients and providers., Purpose/hypothesis: The purpose of this study was to identify whether surgeon performance influenced patient-reported outcomes (PROMs) 1 year after arthroscopic partial meniscectomy (APM). It was hypothesized that there would be no significant difference in PROMs between patients who underwent APM from various surgeons., Study Design: Case-control study; Level of evidence, 3., Methods: A prospective cohort of 794 patients who underwent APM between 2018 and 2019 were included in the analysis. A total of 34 surgeons from a large multicenter health care center were included. Three multivariable models were built to determine whether the surgeon-among demographic and meniscal pathology factors-was a significant variable for predicting the Knee injury and Osteoarthritis Outcome Score (KOOS)-Pain subscale, the Patient Acceptable Symptom State (PASS), and a 10-point improvement in the KOOS-Pain at 1 year after APM. Likelihood ratio (LR) tests were used to determine the significance of the surgeon variable in the models., Results: The 794 patients were identified from the multicenter hospital system. The baseline KOOS-Pain score was a significant predictor of outcome in the 1-year KOOS-Pain model (odds ratio [OR], 2.1 [95% CI, 1.77-2.48]; P < .001), the KOOS-Pain 10-point improvement model (OR, 0.57 [95% CI, 0.44-0.73), and the 1-year PASS model (OR, 1.42 [95% CI, 1.15-1.76]; P = .002) among articular cartilage pathology (bipolar medial cartilage) and patient-factor variables, including body mass index, Veterans RAND 12-Item Health Survey-Mental Component Score, and Area Deprivation Index. The individual surgeon significantly impacted outcomes in the 1-year KOOS-Pain mixed model in the LR test ( P = .004)., Conclusion: Patient factors and characteristics are better predictors for patient outcomes 1 year after APM than surgeon characteristics, specifically baseline KOOS-Pain, although an individual surgeon influenced the 1-Year KOOS-Pain mixed model in the LR test. This finding has key clinical implications; surgeons who wish to improve patient outcomes after APM should focus on improving patient selection rather than improving the surgical technique. Future research is needed to determine whether surgeon variability has an impact on longer-term patient outcomes., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Funding was received from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants AR053684, R01 AR074131, AR053684, and AR075422). M.H.J. has received research support from Flexion Therapeutics and consulting fees from Biosplice and Regeneron. K.P.S. has received research support from DJO and Smith & Nephew; consulting fees from Flexion Therapeutics, National Football League, and NovoPedics; royalties from Oberd; and honoraria from NovoPedics. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Background: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation., Methods: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742., Findings: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23)., Interpretation: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants., Funding: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe., Competing Interests: Declaration of interests YM and ES were affiliated with the University of Edinburgh when this work was conducted. YM is currently affiliated to the School of Public Health, Wuhan University, Wuhan, China and ES is employed by University College Hospital, University College Hospitals NHS Foundation Trust, London, UK. XW reports grants from GSK to their institution and personal fees from Pfizer, outside the submitted work. YL reports grants from Wellcome Trust, WHO, and GSK paid to their institution, and personal fees from Pfizer, outside the submitted work. TS reports grants from Royal Society of Edinburgh outside the submitted work. LJB reports regular interactions with AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, AstraZeneca, MSD, Sanofi, Genzyme, MeMed Diagnostics, and Janssen but has not received personal fees or other personal benefits; being the founding chairman of the ReSViNET Foundation; their affiliation (University Medical Centre Utrecht) has received major funding (>€100 000 per industrial partner) for investigator-initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD, and MeMed Diagnostics; major funding for the RSV GOLD study from the Bill & Melinda Gates Foundation; major funding as part of the public private partnership IMI-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi; major funding by Julius Clinical for participating in clinical studies sponsored by MedImmune and Pfizer; and minor funding (€1000–€25 000 per industrial partner) for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, AstraZeneca, MSD, Sanofi, and Janssen. HYC reports consulting for Ellume, Pfizer, and the Gates Foundation; serving on advisory boards for Vir, Merck, and AbbVie; conducting continuing medical education teaching with Medscape, Vindico, Cataylst CME, and Clinical Care Options; research funding from Gates Ventures; and receiving support and reagents from Ellume and Cepheid, all outside of the submitted work. HJZ reports grants from the Gates Foundation, AstraZeneca, MSD, and Pfizer paid to their institution outside the submitted work, and serving on advisory boards for MSD. TH reports personal fees from Janssen, Sanofi, Enanta, MSD, and Moderna, all outside of the submitted work. MHJ reports personal fees from AstraZeneca, OM-Pharma, Chiesi, GSK, and Boehringer Ingelheim, outside the submitted work. MCN reports grants from the Gates Foundation, European & Developing Countries Clinical Trials Partnership, Pfizer, AstraZeneca, and Sanofi; and serving on advisory boards for Sanofi, all outside the submitted work. BR received honoraria due to lectures from AbbVie, Germania, Sanofi, AstraZeneca, Milupa, Nestle, and Fresenius, outside the submitted work; and travel support from AbbVie, Chiesi, AstraZeneca, Sanofi, and Nestle. HN reports grants from the Innovative Medicines Initiative related to the submitted work; grants from WHO, the National Institute for Health Research, Pfizer, and Icosavax; and personal fees from the Gates Foundation, Pfizer, ReViral, GSK, Merck, Icosavax, Sanofi, Novavax, and AbbVie, outside the submitted work. CFY reports grants from National Medical Research Council Singapore and Wellcome Trust, and funding to attend conferences and honorarium from Sanofi, Pfizer, and Takeda, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Biomarkers collected in synovial tissue and fluid have been identified as potential predictors of outcomes after arthroscopy., Purpose: To provide a narrative review of the current literature that assesses the associations between preoperative biomarkers in the synovial fluid or synovial tissue and patient outcomes after knee arthroscopy., Study Design: Narrative review., Methods: We searched the PubMed database with keywords, "biomarkers AND arthroscopy," "biomarkers AND anterior cruciate ligament reconstruction," and "biomarkers AND meniscectomy." To be included, studies must have collected synovial fluid or synovial tissue from patients before or during arthroscopic knee surgery and analyzed the relationship of biomarkers to postoperative patient outcomes. Biomarkers were classified into 4 main categories: metabolism of aggrecan in cartilage, metabolism of collagen in cartilage (type II collagen), noncollagenous proteins in the knee, and other. When biomarker levels and outcomes were expressed with continuous variables, we abstracted the Pearson or Spearman correlation coefficients as the effect measure. If the biomarker values were continuous and the outcomes binary, we abstracted the mean or median biomarker values in those with favorable versus unfavorable outcomes. We calculated effect sizes as the difference between means of both groups divided by the standard deviation from the mean in the group with better outcomes., Results: Eight studies were included in the review. Each study reported different patient outcomes. Biomarkers associated with metabolism of aggrecan, type II collagen metabolism, and noncollagenous proteins as well as inflammatory biomarkers had statistically significant associations with a range of patient outcomes after knee arthroscopy. Difference across studies in sample size and outcome measures precluded choosing a single biomarker that best predicted patient outcomes., Conclusion: The findings suggest that biomarkers associated with metabolism of aggrecan, type II collagen metabolism, noncollagenous proteins, as well as inflammatory biomarkers may help surgeons and their patients anticipate surgical outcomes., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: J.N.K. has received honoraria from Pfizer. M.H.J. has received research support from Flexion Therapeutics (now Pacira) and consulting fees from Regeneron Pharmaceuticals and Samumed (now Biosplice). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Background: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight., Results: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56 + CD16 - ) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56 + CD16 + ), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4 + CD38 + cells than controls. Contrasting changes were reported in CD25 + CD127 low/neg regulatory T cells, with increased and decreased proportions found in CD4 + and CD8 + T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4 + and CD8 + ) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8 + CD57 + NKG2A + cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19., Conclusions: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight., (© 2024. The Author(s).)

Objective: To compare lung function between adolescents with and without substance use disorder (SUD)., Methods: This was an observational, cross-sectional exploratory study. The sample consisted of 16 adolescents with SUD and 24 age-matched healthy controls. The adolescents in the clinical group were recruited from a psychiatric inpatient unit for detoxification and rehabilitation; their primary diagnosis was SUD related to marijuana, cocaine, or polysubstance use. Questionnaires and pulmonary function tests were applied for clinical evaluation., Results: We found that FVC, FEV1, and their percentages of the predicted values were significantly lower in the adolescents with SUD than in those without. Those differences remained significant after adjustment for BMI and the effects of high levels of physical activity. The largest effect size (Cohen's d = 1.82) was found for FVC as a percentage of the predicted value (FVC%), which was, on average, 17.95% lower in the SUD group. In addition, the years of regular use of smoked substances (tobacco, marijuana, and crack cocaine) correlated negatively with the FVC%., Conclusions: This exploratory study is innovative in that it demonstrates the early consequences of smoked substance use for the lung health of adolescents with SUD.

Background: Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control., Results: Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21 WAF1/Cip1 ) up-regulation. We also observed increased senescence-associated β-galactosidase (SA-β-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16 INK4A ) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli., Conclusions: Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Kinesin-5 motor proteins play essential roles during mitosis in most organisms. Their tetrameric structure and plus-end-directed motility allow them to bind to and move along antiparallel microtubules, thereby pushing spindle poles apart to assemble a bipolar spindle. Recent work has shown that the C-terminal tail is particularly important to kinesin-5 function: The tail affects motor domain structure, ATP hydrolysis, motility, clustering, and sliding force measured for purified motors, as well as motility, clustering, and spindle assembly in cells. Because previous work has focused on presence or absence of the entire tail, the functionally important regions of the tail remain to be identified. We have therefore characterized a series of kinesin-5/Cut7 tail truncation alleles in fission yeast. Partial truncation causes mitotic defects and temperature-sensitive growth, while further truncation that removes the conserved BimC motif is lethal. We compared the sliding force generated by cut7 mutants using a kinesin-14 mutant background in which some microtubules detach from the spindle poles and are pushed into the nuclear envelope. These Cut7-driven protrusions decreased as more of the tail was truncated, and the most severe truncations produced no observable protrusions. Our observations suggest that the C-terminal tail of Cut7p contributes to both sliding force and midzone localization. In the context of sequential tail truncation, the BimC motif and adjacent C-terminal amino acids are particularly important for sliding force. In addition, moderate tail truncation increases midzone localization, but further truncation of residues N-terminal to the BimC motif decreases midzone localization.

Patellar tendon (PT) and quadriceps tendon (QT) ruptures represent significant injuries and warrant surgical intervention in most patients. Outcome data are predominantly retrospective analyses with low sample sizes. There are also minimal data comparing QT and PT repairs and the variables impacting patient outcomes. The level of evidence of the study is level II (prognosis). From the prospective OME cohort, 189 PT or QT repairs were performed between February 2015 and October 2019. Of these, 178 were successfully enrolled (94.2%) with 1-year follow-up on 141 (79.2%). Baseline demographic data included age, sex, race, BMI, years of education, smoking status, and baseline VR-12 MCS score. Surgical and follow-up data included surgeon volume, fixation technique, baseline, and 1-year Knee Injury and Osteoarthritis Outcome Score-Pain (KOOS-Pain), Knee Injury and Osteoarthritis Outcome Score-Physical Function (KOOS-PS), and 1-year Patient Acceptable Symptom State (PASS) scores and complications. Multivariable regression analysis was utilized to identify prognosis and significant risk factors for outcomes-specifically, whether KOOS-Pain or KOOS-PS were different between QT versus PT repairs. There were 59 patients in the PT cohort and 82 patients in QT cohort. Baseline demographic data demonstrated that PT cohort was younger (45.1 vs. 59.5 years, p <0.001), included significantly fewer patients of White race (51.7 vs. 80.0%, p  = 0.001), lesser number of years of education (13.9 vs. 15.2 years, p  = 0.020), a higher percentage of "high" surgeon volume (72.9% vs. 43.9%, p  = 0.001) and 25.4% of PT repairs had supplemental fixation (QT had zero, p <0.001). Multivariable analysis identified gender (female-worse, p  = 0.001), years of education (higher-better, p  = 0.02), and baseline KOOS-Pain score (higher-better, p <0.001) as the risk factors that significantly predicted KOOS-Pain score. The risk factors that significantly predicted KOOS-PS were gender (female worse, p  = 0.033), race (non-White-worse, p <0.001), baseline VR-12 MCS score (higher-better, p <0.001), and baseline KOOS-PS score (higher better, p  = 0.029). KOOS-Pain and KOOS-PS scores improved after both QT and PT repairs. Patient reported pain and function at 1 year were similar between PT and QT repairs after adjusting for known risk factors. Multivariable analysis identified female gender and low baseline KOOS scores as predictors for worse outcomes., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Inflammation is a potential pain generator and treatment target in knee osteoarthritis (OA). Inflammation can be detected on magnetic resonance imaging (MRI) and by synovial fluid white blood cell count (WBC). However, the performance characteristics of synovial fluid WBC for the detection of synovitis have not been established. This study was undertaken to determine the sensitivity and specificity of synovial fluid WBC in identifying inflammation in knee OA using MRI effusion-synovitis as the gold standard., Methods: We identified records of patients seen at an academic center with a diagnosis code for knee OA, a procedural code for knee aspiration, and a laboratory order for synovial fluid WBC in the same encounter, as well as an MRI within 12 months of the aspiration. MRIs were read for effusion-synovitis using the MRI OA Knee Score (MOAKS). We dichotomized effusion-synovitis as 1) none or small, or 2) medium or large. We calculated the sensitivity and specificity of synovial fluid WBC using MRI effusion-synovitis (medium/large) as the gold standard. We used the Youden index to identify the best cut point., Results: We included 75 patients. Mean ± SD age was 63 ± 12 years, and 69% were female. The synovial fluid WBC was higher in the medium/large effusion-synovitis group (median 335 [interquartile range (IQR) 312]) than in the none/small group (median 194 [IQR 272]). The optimal cut point was 242, yielding a sensitivity of 71% (95% confidence interval [95% CI] 56-83%) and specificity of 63% (95% CI 41-81%)., Conclusion: The sensitivity and specificity of synovial fluid WBC in identifying effusion-synovitis on MRI were limited. Further research is needed to better understand the association between MRI and effusion-synovitis measured by synovial fluid and to determine which measure more strongly relates to synovial histopathology and patient outcomes., (© 2022 American College of Rheumatology.)

Objective: Meniscal tear in persons aged ≥45 years is typically managed with physical therapy (PT), and arthroscopic partial meniscectomy (APM) is offered to those who do not respond. Prior studies suggest APM may be associated with greater progression of radiographic changes., Methods: We assessed changes between baseline and 60 months in the Kellgren-Lawrence (KL) grade and OARSI radiographic score (including subscores for joint space narrowing and osteophytes) in subjects aged 45-85 years enrolled into a seven-center randomized trial comparing outcomes of APM with PT for meniscal tear, osteoarthritis changes, and knee pain. The primary analysis classified subjects according to treatment received. To balance APM and PT groups, we developed a propensity score and used inverse probability weighting (IPW). We imputed a 60-month change in the OARSI score for subjects who underwent total knee replacement (TKR). In a sensitivity analysis, we classified subjects by randomization group., Results: We analyzed data from 142 subjects (100 APM, 42 PT). The mean ± SD weighted baseline OARSI radiographic score was 3.8 ± 3.5 in the APM group and 4.0 ± 4.9 in the PT group. OARSI scores increased by a mean of 4.1 (95% confidence interval [95% CI] 3.5-4.7) in the APM group and 2.4 (95% CI 1.7-3.2) in the PT group (P < 0.001) due to changes in the osteophyte component. We did not observe statistically significant differences in the KL grade. Sensitivity analyses yielded similar findings to the primary analysis., Conclusion: Subjects treated with APM had greater progression in the OARSI score because of osteophyte progression but not in the KL grade. The clinical implications of these findings require investigation., (© 2023 American College of Rheumatology.)

Thermosetting materials generated by photopolymerization frequently suffer from significant shrinkage stress, are often brittle, and have a limited range of mechanical properties. Various classes of chain transfer agents (CTAs) have been investigated and developed to reduce the cross-linking density of photopolymers by terminating chains and initiating new chains in situ . Although CTAs are successful in manipulating the mechanical properties of photopolymers, they are traditionally consumed during the polymerization and are therefore required in high loadings (up to 20 wt % of the total formulation). Moreover, traditional CTAs frequently contain sulfur, which is malodorous and can create unstable formulations. Presented here is a catalytic, sulfur-free CTA that can be added in ppm quantities to existing commercial monomer feedstocks to create photopolymers similar to those prepared using traditional CTAs, but at 10 000-fold lower loadings. These catalysts, which are based on macrocyclic cobaloximes, were found to tunably reduce the molecular weight of the chain proportional to catalyst loading. It was shown, using only commercial monomers, that this catalyst could reduce the glass-transition temperature ( T g ), rubbery modulus ( E ' rubbery ), and stiffness of a cross-linked photopolymer while utilizing identical processing conditions and keeping 99.99 wt % of the formulation the same.