Unveiling triglyceride levels in preterm neonates: a study to guide targeted monitoring.

BACKGROUND: Mixed lipid emulsion (MLE), most commonly soybean, medium chain triglycerides, olive, and fish oils (SMOF), has replaced soybean-based lipid emulsions in many neonatal intensive care units. Only a few studies report the triglyceride (TG) trajectory in neonates receiving MLE. We designed a study to compare TG levels in neonates receiving MLE stratified by gestational age (GA), birth weight (BW), and growth restriction status. METHODS: We included neonates born at <32 weeks GA or with BW <1500 gm. SMOF is started on admission, and plasma TG levels are measured 24 hours after 2 gm/kg/day and 24 hours after 3 gm/kg/day. TG levels were compared across groups defined by GA (<28 weeks vs. 328 weeks), BW (<1000 gm vs. 31000 gm), and small for GA (SGA) vs. appropriate plus large for GA groups using the Wilcoxon rank sum test. RESULTS: From 2018 to 2021, 427 infants met the inclusion criteria. TG levels were significantly higher in neonates with GA <28 weeks, BW <1000 grams, and SGA with a notable broad distribution of TG levels. Logistic regression analysis confirmed SGA and BW as significant independent predictors of hypertriglyceridemia after SMOF at 2 gm/kg/day and 3 gm/kg/day, respectively. CONCLUSIONS: The study emphasizes the importance of TG monitoring for neonates with GA <28 weeks, BW <1000 grams, and SGA. Conversely, it is advisable to individualize TG monitoring for infants with GA>28 weeks, BW>1000 grams, and non-SGA status. Prospective studies with larger sample sizes are warranted to validate our findings.

A Improving Birth-dose Hepatitis-B Vaccination in a Tertiary Level IV Neonatal Intensive Care Unit.

Background: Perinatal hepatitis B is a global public health concern. To reduce perinatal hepatitis B and its complications, the Hepatitis B vaccine (HBV) is recommended by the New York State Department of Health and Advisory Committee on Immunization Practices within 24 hours of life for infants born with a birth weight ≥2000 g. Infants admitted to the neonatal intensive care unit (NICU) weighing over 2000 g missed their birth dose HBV frequently, which prompted the implementation of a quality improvement initiative to increase birth dose HBV immunization in a level IV NICU in New York. Methods: May 2019 to April 2021 baseline data showed the birth dose HBV rate of infants born ≥2000 g at 24% and 31% within 12 and 24 hours, respectively. The multidisciplinary QI team identified barriers using an Ishikawa cause-and-effect diagram. Our interventions included multidisciplinary collaboration, electronic medical record reminders, education, posters, and improved communication between staff and parents. We aimed to achieve a 25% improvement from the baseline. Results: After 19 months of QI interventions (four Plan-Do-Study-Act cycles), the rate of administering birth dose HBV within 12 hours of life increased from 24% to 56% and within 24 hours from 31% to 64%. Process measure compliance improved, exceeding the 25% target, and showed sustained improvement. Conclusion: This QI initiative improved the rate of eligible infants receiving HBV within the first 24 hours of life in the NICU. This work can serve as a model for other healthcare institutions to improve HBV immunization rates in NICUs.

A platform for modular assembly and feeding of micro-organoids on standard Petri dishes.

Organoids grow in vitro to reproduce structures and functions of corresponding organs in vivo. As diffusion delivers nutrients over only ∼200 µm, refreshing flows through organoids are required to avoid necrosis at their cores; achieving this is a central challenge in the field. Our general aim is to develop a platform for culturing micro-organoids fed by appropriate flows that is accessible to bioscientists. As organs develop from layers of several cell types, our strategy is to seed different cells in thin modules (i.e. extra-cellular matrices in stronger scaffolds) in standard Petri dishes, stack modules in the required order, and overlay an immiscible fluorocarbon (FC40) to prevent evaporation. As FC40 is denser than medium, one might expect medium to float on FC40, but interfacial forces can be stronger than buoyancy ones; then, stacks remain attached to the bottom of dishes. After manually pipetting medium into the base of stacks, refreshing upward flows occur automatically (without the need for external pumps), driven mainly by differences in hydrostatic pressure. Proof-of-concept experiments show that such flows support clonal growth of human embryonic kidney cells at expected rates, even though cells may lie hundreds of microns away from surrounding fluid walls of the two immiscible liquids.

Pacsin2 is required for endocytosis in the zebrafish pronephric tubule.

Endocytosis mediates the cellular uptake of numerous molecules from the extracellular space and is a fundamentally important process. In the renal proximal tubule, the scavenger receptor megalin and its co-receptor cubilin mediate endocytosis of low molecular weight proteins from the renal filtrate. However, the extent to which megalin endocytosis relies on different components of the trafficking machinery remains relatively poorly defined in vivo. In this study, we identify a functional requirement for the F-BAR protein pacsin2 in endocytosis in the renal proximal tubule of zebrafish larvae. Pacsin2 is expressed throughout development and in all zebrafish tissues, similar to the mammalian orthologue. Within renal tubular epithelial cells, pacsin2 is enriched at the apical pole where it is localised to endocytic structures. Loss of pacsin2 results in reduced endocytosis within the proximal tubule, which is accompanied by a reduction in the abundance of megalin and endocytic organelles. Our results indicate that pacsin2 is required for efficient endocytosis in the proximal tubule, where it likely cooperates with other trafficking machinery to maintain endocytic uptake and recycling of megalin.

Psychoactive Drugs Like Cannabis -Induce Hypodopaminergic Anhedonia and Neuropsychological Dysfunction in Humans: Putative Induction of Dopamine Homeostasis via Coupling of Genetic Addiction Risk Severity (GARS) testing and Precision Pro-dopamine Regulation (KB220).

Many US states now embrace the medical and recreational use of Cannabis. Changes in the laws have heightened interest and encouraged research into both cannabinoid products and the potential harms of Cannabis use, addiction and intoxication. The major active ingredient of Cannabis sativa (marijuana), Δ9-tetrahydrocannabinol (THC) and it powerfully stimulates the type-1 cannabinoid (CB1) receptor. When used in the form of the plant marijuana, because of the many compounds that exist in the plant form they could inhibit the activity of the CB1 receptor thereby reducing many of the effects of THC. While this mechanism seems correct, in our opinion, Vallee., et al. incorrectly suggest that blocking CB1 receptors could open unforeseen approaches to the treatment of cannabis intoxication and addiction. We caution the scientific community that, other CB1 receptor blockers, such as, Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB1 receptor blockers were rejected by the FDA due to mood changes including suicide ideation. We argue that one issue facing the scientific community, has to do with the increasing legalization of Cannabis products in many states across America. We are in favor of some reform in terms of either decriminalization or restrictive legalization especially in control of legal limits of THC. Like other psychoactive compounds at high doses, it is our hypothesis that chronic use of these drugs including high THC content in its various forms (wax, smoke or vapor) resulting in brain reward dysfunction induces an imbalance of neurotransmission and subsequent hypodopaminergia and lead to aberrant substance and non-substance (behavioral) addictions. It is further proposed that in order to overcome THC and even other psychoactive drugs of abuse induced anhedonia the coupling of genetic risk testing and pro dopamine regulation is warranted.

Incidence of Complications Associated with Parenteral Nutrition in Preterm Infants < 32 Weeks with a Mixed Oil Lipid Emulsion vs a Soybean Oil Lipid Emulsion in a Level IV Neonatal Intensive Care Unit.

BACKGROUND: Parenteral nutrition (PN) is crucial for the improvement of long-term outcomes in very low birth weight (VLBW) neonates. Lipid injectable emulsions are a key component of PN, as they contain essential fatty acids and provide energy critical for brain growth. Prolonged administration increases risk of intestinal failure-associated liver disease, including cholestasis, and other complications. METHODS: This is a retrospective, quasi-experimental cohort study of 215 VLBW neonates. The primary outcome was a change in direct bilirubin concentration. Secondary outcomes included change in total bilirubin concentration and incidences of cholestasis and other disease states associated with PN and prematurity. Cholestasis was defined as direct bilirubin ≥ 1.0 mg/dL with total bilirubin < 5.0 mg/dL or direct bilirubin > 20% of total bilirubin with total bilirubin > 5.0 mg/dL. RESULTS: Change in direct bilirubin concentration was not different between groups. Incidence of cholestasis was not different between groups per charted diagnosis or per study definition. Non-stage-0 retinopathy of prematurity, bronchopulmonary dysplasia, sepsis, and necrotizing enterocolitis were all lower in the mixed oil lipid emulsion group, which remained significant after adjustment for differences in gestational age, birth weight, and PN duration. CONCLUSIONS: Although mixed oil lipid emulsion was not found to be associated with a lower risk of cholestasis, it may decrease risks of other disease states associated with PN therapy.

Low Operating Voltage Carbon-Graphene Hybrid E-textile for Temperature Sensing.

Graphene-coated polypropylene (PP) textile fibers are presented for their use as temperature sensors. These temperature sensors show a negative thermal coefficient of resistance (TCR) in a range between 30 and 45 °C with good sensitivity and reliability and can operate at voltages as low as 1 V. The analysis of the transient response of the temperature on resistance of different types of graphene produced by chemical vapor deposition (CVD) and shear exfoliation of graphite (SEG) shows that trilayer graphene (TLG) grown on copper by CVD displays better sensitivity due to the better thickness uniformity of the film and that carbon paste provides good contact for the measurements. Along with high sensitivity, TLG on PP shows not only the best response but also better transparency, mechanical stability, and washability compared to SEG. Temperature-dependent Raman analysis reveals that the temperature has no significant effect on the peak frequency of PP and expected effect on graphene in the demonstrated temperature range. The presented results demonstrate that these flexible, lightweight temperature sensors based on TLG with a negative TCR can be easily integrated in fabrics.

Withings Body Cardio versus Gold Standards of Pulse-Wave Velocity and Body Composition.

Home blood pressure monitors are widely used by consumers yet cardiovascular health may be better defined by pulse-wave velocity (PWV). So far, the Withings Body Cardio scale is the only consumer device that has been designed to measure PWV and body composition, including fat mass (FM) and fat-free mass (FFM), in the home setting. While one study has demonstrated that this device meets the acceptable accuracy standards of the ARTERY Society, no study has accounted for the gravitational effect of standing on a scale on aortic-leg PWV. PURPOSE: The purpose of this study was to assess the accuracy of PWV and body composition as determined by the Body Cardio scale. METHODS: Measurements of PWV and body composition in healthy, young males and females (n = 20) using the Body Cardio device were compared to PWV assessed by applanation tonometry (SphygmoCor) and body composition analysis determined by air displacement plethysmography (Bod Pod). Bland-Altman analysis and mean absolute percent error (MAPE) were used to assess accuracy. RESULTS: Data are reported as the mean bias (95% confidence interval). The Body Cardio overestimated PWV by 0.68 m/s (-0.16, 1.51) and FM by 2.91 kg (-2.91, 8.73). Body Cardio PWV and FM estimations had a MAPE of 9.7% and 25.8%, respectively. The Body Cardio underestimated body mass (BM) and FFM by 0.11 kg (-0.41, 0.18) and 2.87 kg (-9.04, 3.30), respectively. Body Cardio BM and FFM estimations had a MAPE of 0.15% and 5.6%, respectively. CONCLUSIONS: The Body Cardio scale provides accurate measures of BM and PWV; however, it should be used cautiously for measures of FM and FFM.

Fine Sediment Removal Influences Biogeochemical Processes in a Gravel-bottomed Stream.

The transport and processing of nutrients and organic matter in streams are important functions that influence the condition of watersheds and downstream ecosystems. In this study, we investigated the effects of streambed sediment removal on biogeochemical cycling in Fawn River, a gravel-bottomed river in Indiana, U.S.A. We measured stream metabolism as well as nitrogen (N) and phosphorus (P) retention in both restored and unrestored reaches of Fawn River to examine how sediment removal affected multiple biogeochemical functions at the reach scale. We also assessed the properties of restored and unrestored streambed sediments to elucidate potential mechanisms driving observed reach-scale differences. We found that sediment removal led to lower rates of primary productivity and ecosystem respiration in the restored reach, likely due to macrophyte removal and potentially due to changes to sediment organic matter quality. We found minimal differences in N and P retention, suggesting that these processes are controlled at larger spatial or temporal scales than were examined in this study. Denitrification enzyme activity was lower in sediments from the restored reach compared to the unrestored reach, suggesting that restoration may have decreased N removal. Our results indicate that most near-term changes in biogeochemical function following restoration could be attributed to macrophyte removal, although effects from sediment removal may emerge over longer timescales.

The renin angiotensin system and the brain: New developments.

The traditional renin-angiotensin system (RAS) is indispensable system in adjusting sodium homeostasis, body fluid volume, and controlling arterial blood pressure. The key elements are renin splitting inactive angiotensinogen to yield angiotensin (Ang-I). Ang-1 is then changed by angiotensin-1 converting enzyme (ACE) into angiotensin II (Ang-II). Using PubMed, Google Scholar, and other means, we searched the peer-reviewed literature from 1990 to 2013 for articles on newly discovered findings related to the RAS, especially focusing on how the system influences the central nervous system (CNS). The classical RAS is now considered to be only part of the picture; the discovery of additional RAS pathways in the brain and elsewhere has yielded a vastly improved understanding of how the RAS influences the CNS. Newly discovered effects of the RAS on brain tissue include neuroprotection, cognition, and cerebral vasodilation. A number of brain biochemical pathways are influenced by the brain RAS. Within various pathways, there are potential opportunities for classical pharmacologic interventions as well as the possibility of controlling gene expression.

Cystinosis (ctns) zebrafish mutant shows pronephric glomerular and tubular dysfunction.

The human ubiquitous protein cystinosin is responsible for transporting the disulphide amino acid cystine from the lysosomal compartment into the cytosol. In humans, Pathogenic mutations of CTNS lead to defective cystinosin function, intralysosomal cystine accumulation and the development of cystinosis. Kidneys are initially affected with generalized proximal tubular dysfunction (renal Fanconi syndrome), then the disease rapidly affects glomeruli and progresses towards end stage renal failure and multiple organ dysfunction. Animal models of cystinosis are limited, with only a Ctns knockout mouse reported, showing cystine accumulation and late signs of tubular dysfunction but lacking the glomerular phenotype. We established and characterized a mutant zebrafish model with a homozygous nonsense mutation (c.706 C > T; p.Q236X) in exon 8 of ctns. Cystinotic mutant larvae showed cystine accumulation, delayed development, and signs of pronephric glomerular and tubular dysfunction mimicking the early phenotype of human cystinotic patients. Furthermore, cystinotic larvae showed a significantly increased rate of apoptosis that could be ameliorated with cysteamine, the human cystine depleting therapy. Our data demonstrate that, ctns gene is essential for zebrafish pronephric podocyte and proximal tubular function and that the ctns-mutant can be used for studying the disease pathogenic mechanisms and for testing novel therapies for cystinosis.

Asymmetrical lumbosacral transitional vertebrae in dogs may promote asymmetrical hip joint development.

OBJECTIVES: This study examines the relationship between the morphology of the lumbosacral transitional vertebra (LTV) and asymmetrical development of the hip joints in dogs. METHODS: A total of 4000 dogs which had been consecutively scored for canine hip dysplasia were checked for the presence of a LTV. A LTV was noted in 138 dogs and classified depending on the morphology of the transverse processes and the degree of contact with the ilium. RESULTS: In dogs with an asymmetrical LTV, the hip joint was significantly more predisposed to subluxation and malformation on the side of the intermediate or sacral-like transverse process (p <0.01), on the side of the elevated pelvis (p <0.01), or when an asymmetrical LTV resulted in pelvic rotation on its long axis (p <0.01), whereas hip joint conformation was less affected on the side featuring a free transverse process (p <0.01). CLINICAL SIGNIFICANCE: The results support our hypothesis that an asymmetrical LTV favours pelvic rotation over its long axis, resulting in inadequate femoral head coverage by the acetabulum on one side. Inadequate coverage of the femoral head favours subluxation, malformation of the hip joint, and secondary osteoarthritis. Asymmetrical hip conformation may therefore be the sequela of a LTV and mask or aggravate genetically induced canine hip dysplasia.

Translational bioinformatics in the era of real-time biomedical, health care and wellness data streams.

Monitoring and modeling biomedical, health care and wellness data from individuals and converging data on a population scale have tremendous potential to improve understanding of the transition to the healthy state of human physiology to disease setting. Wellness monitoring devices and companion software applications capable of generating alerts and sharing data with health care providers or social networks are now available. The accessibility and clinical utility of such data for disease or wellness research are currently limited. Designing methods for streaming data capture, real-time data aggregation, machine learning, predictive analytics and visualization solutions to integrate wellness or health monitoring data elements with the electronic medical records (EMRs) maintained by health care providers permits better utilization. Integration of population-scale biomedical, health care and wellness data would help to stratify patients for active health management and to understand clinically asymptomatic patients and underlying illness trajectories. In this article, we discuss various health-monitoring devices, their ability to capture the unique state of health represented in a patient and their application in individualized diagnostics, prognosis, clinical or wellness intervention. We also discuss examples of translational bioinformatics approaches to integrating patient-generated data with existing EMRs, personal health records, patient portals and clinical data repositories. Briefly, translational bioinformatics methods, tools and resources are at the center of these advances in implementing real-time biomedical and health care analytics in the clinical setting. Furthermore, these advances are poised to play a significant role in clinical decision-making and implementation of data-driven medicine and wellness care.

Evaluation of direct-to-consumer low-volume lab tests in healthy adults.

BACKGROUND: Clinical laboratory tests are now being prescribed and made directly available to consumers through retail outlets in the USA. Concerns with these test have been raised regarding the uncertainty of testing methods used in these venues and a lack of open, scientific validation of the technical accuracy and clinical equivalency of results obtained through these services. METHODS: We conducted a cohort study of 60 healthy adults to compare the uncertainty and accuracy in 22 common clinical lab tests between one company offering blood tests obtained from finger prick (Theranos) and 2 major clinical testing services that require standard venipuncture draws (Quest and LabCorp). Samples were collected in Phoenix, Arizona, at an ambulatory clinic and at retail outlets with point-of-care services. RESULTS: Theranos flagged tests outside their normal range 1.6× more often than other testing services (P < 0.0001). Of the 22 lab measurements evaluated, 15 (68%) showed significant interservice variability (P < 0.002). We found nonequivalent lipid panel test results between Theranos and other clinical services. Variability in testing services, sample collection times, and subjects markedly influenced lab results. CONCLUSION: While laboratory practice standards exist to control this variability, the disparities between testing services we observed could potentially alter clinical interpretation and health care utilization. Greater transparency and evaluation of testing technologies would increase their utility in personalized health management. FUNDING: This work was supported by the Icahn Institute for Genomics and Multiscale Biology, a gift from the Harris Family Charitable Foundation (to J.T. Dudley), and grants from the NIH (R01 DK098242 and U54 CA189201, to J.T. Dudley, and R01 AG046170 and U01 AI111598, to E.E. Schadt).

The Effect of Cartilage Injury After Arthroscopic Stabilization for Shoulder Instability.

This study was undertaken to (1) determine the incidence of articular cartilage injuries in patients with instability of the glenohumeral joint, (2) determine whether recurrent dislocations increased the risk of articular damage, and (3) correlate these injuries with postoperative clinical outcomes. A cohort was identified of consecutive patients who underwent diagnostic magnetic resonance imaging and shoulder arthroscopy for glenohumeral instability with documented dislocation or subluxation between 1997 and 2006 at a single institution. Patients with moderate or severe osteoarthritis were excluded. Arthroscopic findings were recorded, including lesion location and Outerbridge grade. The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) was used to assess outcome in 61 patients who were available for follow-up. Outcomes were compared between shoulders with and without articular lesions. A total of 87 shoulders (83 patients) met the inclusion criteria, with 69 (83%) men and 14 (17%) women. Mean age was 26.1 years (range, 18-64 years), and mean follow-up was 36 months (range, 33-39 months). Cartilage injuries were found in 56 shoulders (64%). Previously documented shoulder dislocation requiring closed reduction (P=.046) and the number of discrete dislocations (P=.032) were significant for glenoid injury. A greater number of dislocations was associated with higher-grade lesions of the glenohumeral joint (P<.001). Overall, mean ASES score was 89.6 (range, 37-100). In patients with an articular cartilage lesion, mean ASES score was 90.4 (range, 58-100) compared with 88.1 (range, 37-100) in those without this injury (P=.75). Although clinical outcomes were not significantly affected, further investigation is warranted to establish a relationship between these injuries and longer-term outcomes.

Incidence and Risk Factor Analysis of Symptomatic Venous Thromboembolism After Knee Arthroscopy.

PURPOSE: To (1) determine the incidence of symptomatic venous thromboembolic events (VTEs) after knee arthroscopy and arthroscopy-assisted procedures at a single institution and (2) determine associated risk factors for VTEs in these patients. METHODS: The records of patients who underwent knee arthroscopy at a single institution between 1988 and 2008 were reviewed. Chemoprophylaxis was not routinely used. Confirmed VTEs occurring within 4 weeks after the index arthroscopy procedure were included. A 2:1 matched control group was generated to include patients in whom knee arthroscopy was performed by the same surgeon either on the same day or immediately before each case resulting in a VTE. Preoperative and perioperative data were collected with respect to demographic data, medical history, medications, and surgical and anesthesia data. Univariate and multivariate analyses were performed. RESULTS: During the study period, 12,595 patients underwent knee arthroscopy. Among these patients, 43 cases of VTEs (35 deep venous thromboses [DVTs], 5 pulmonary embolisms [PEs], and 3 DVTs that progressed to PEs) occurred, resulting in an incidence of 0.30% (95% confidence interval [CI], 0.22% to 0.41%) for DVT, 0.06% (95% CI, 0.03% to 0.12%) for PE, and 0.34% (95% CI, 0.25% to 0.46%) for VTEs overall. Factors associated with an elevated risk of symptomatic postoperative VTEs included a history of malignancy (P = .01; odds ratio [OR], 6.3), a history of VTEs (P = .02; OR, 5.2), or the presence of more than 2 classic risk factors for VTEs (P = .01; OR, 13.6). CONCLUSIONS: In this study, symptomatic VTEs were rare and occurred infrequently, with an incidence of 0.34% (95% CI, 0.25% to 0.46%), after knee arthroscopy and arthroscopy-assisted cases in the absence of routine chemoprophylaxis. Patients with a history of VTEs, a history of malignancy, or 2 or more classic risk factors are at increased risk of VTEs after knee arthroscopy, and chemoprophylaxis should be considered in these select patients. LEVEL OF EVIDENCE: Level III, case-control study.

An update of the role of renin angiotensin in cardiovascular homeostasis.

The renin angiotensin system (RAS) is thought to be the body's main vasoconstrictor system, with physiological effects mediated via the interaction of angiotensin II with angiotensin I receptors (the "classic" RAS model). However, since the discovery of the heptapeptide angiotensin 1-7 and the development of the concept of the "alternate" RAS system, with its ability to reduce arterial blood pressure, our understanding of this physiologic system has changed dramatically. In this review, we focus on the newly discovered functions of the RAS, particularly the potential clinical significance of these developments, especially in the realm of new pharmacologic interventions for treating cardiovascular disease.

Factors associated with excellent 6-month functional and isokinetic test results following ACL reconstruction.

PURPOSE: To identify patient concomitant injury and surgical characteristics associated with 6-month excellent functional and isokinetic testing results following anterior cruciate ligament (ACL) reconstruction. METHODS: Patients that underwent ACL reconstruction by a single surgeon had isokinetic and functional testing performed with excellent 6-month outcome defined as greater than 85 % in isokinetic strength and 90 % in functional tests (excellent 6-month group vs. delayed 6-month group). Patient concomitant injury and surgical factors were then analysed in univariate and multivariate statistical models to assess which characteristics predicted the excellent 6-month group. RESULTS: The 224 patients included 93 males and 131 females, with median age of 22 (range 12-59) years, body mass index (BMI) of 25.4 (range 17-44), and median Tegner activity score of 6 (range 2-10). Fifty-two patients (23 %) were included in the excellent 6-month group, while 172 patients (77 %) were in the delayed 6-month group. In univariate analysis, favourable factors with the excellent 6-month outcome group were younger age (24 vs. 27; p = 0.01), lower BMI (24.5 vs. 26.2; p = 0.03), and minimal articular cartilage damage (71 vs. 56 %; p = 0.048). In multivariate analysis, a negative effect was observed for patients older than 30 years that had ACL reconstruction with autograft (p = 0.0004). CONCLUSION: Factors significantly associated with excellent 6-month functional and isokinetic test results following ACL reconstruction included younger age, lower BMI, and minimal cartilage degeneration. The use of allograft was associated with improved functional and strength testing after ACL reconstruction in patients over 30 years of age. LEVEL OF EVIDENCE: Prognostic/therapeutic study, Level III.