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PURPOSE: To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. METHODS: We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. RESULTS: Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). CONCLUSION: A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.
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Gluteal tendon tears are a common cause of hip pain. Most commonly, tears occur in the gluteus medius and minimus, and there are well-established nonoperative or operative treatment pathways. In this Technical Note, we describe our technique for repair of a full-thickness gluteus maximus tendon tear using anchor fixation.
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BACKGROUND: Approximately 100,000 anterior cruciate ligament (ACL) reconstructions (ACLRs) occur annually in the United States, and postoperative surgical-site infection is a relatively rare but devastating complication, often leading to graft failure or septic arthritis of the knee, necessitating repeat surgery. Wrapping allografts in vancomycin-soaked gauze has been adopted as a common sterilization technique in the operating room to reduce surgical-site infection; however, identifying effective alternatives to vancomycin has not been extensively pursued. HYPOTHESIS: Tobramycin would be as effective as vancomycin in reducing the concentrations of Staphylococcus epidermidis bacteria on tendon allografts. STUDY DESIGN: Controlled laboratory study. METHODS: S. epidermidis strain ATCC 12228 was inoculated onto the human cadaveric gracilis tendon. The tendons were wrapped in sterile gauze saturated with tobramycin or vancomycin at various experimental concentrations. Bacteria remaining on the tendon were dislodged, serially diluted, and plated for colony counting. Statistical analysis was performed utilizing 2-way analysis of variance testing. Results were considered statistically significant when P < .05. RESULTS: Vancomycin (P = .0001) and tobramycin (P < .0001) reduced bacterial concentration. Tobramycin was found to produce a statistically significant reduction in bacterial concentration at concentrations as low as 0.1 mg/mL (P < .0001 and P = .01 at 10 and 20 minutes), while vancomycin produced a statistically significant reduction at a concentration as low as 2.5 mg/mL (P < .0001 at both 10 and 20 minutes). CONCLUSION: This study demonstrates that tobramycin is as effective as vancomycin in bacterial concentration reduction but can achieve this reduction level at lower doses. Further studies clarifying the biomechanical and cytotoxic effects of tobramycin on tendon tissue are indicated to solidify its use as a clinical alternative to vancomycin in ACLR. CLINICAL RELEVANCE: These results will begin establishing tobramycin as an alternative to vancomycin in ACL graft decontamination. Because of relatively frequent shortages of vancomycin, establishing tobramycin as an alternative agent is a useful option for the orthopaedic surgeon.
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Lesiones del Ligamento Cruzado Anterior , Vancomicina , Humanos , Vancomicina/farmacología , Ligamento Cruzado Anterior/cirugía , Tobramicina/farmacología , Descontaminación , Lesiones del Ligamento Cruzado Anterior/cirugía , Infección de la Herida Quirúrgica/prevención & control , AloinjertosRESUMEN
Cancer cells maintain telomeres by upregulating telomerase or alternative lengthening of telomeres (ALT) via homology-directed repair at telomeric DNA breaks. 8-Oxoguanine (8oxoG) is a highly prevalent endogenous DNA lesion in telomeric sequences, altering telomere structure and telomerase activity, but its impact on ALT is unclear. Here, we demonstrate that targeted 8oxoG formation at telomeres stimulates ALT activity and homologous recombination specifically in ALT cancer cells. Mechanistically, an acute 8oxoG induction increases replication stress, as evidenced by increased telomere fragility and ATR kinase activation at ALT telomeres. Furthermore, ALT cells are more sensitive to chronic telomeric 8oxoG damage than telomerase-positive cancer cells, consistent with increased 8oxoG-induced replication stress. However, telomeric 8oxoG production in G2 phase, when ALT telomere elongation occurs, impairs telomeric DNA synthesis. Our study demonstrates that a common oxidative base lesion has a dual role in regulating ALT depending on when the damage arises in the cell cycle.
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Telomerasa , Telomerasa/metabolismo , Homeostasis del Telómero , Telómero/metabolismo , Estrés Oxidativo , GuaninaRESUMEN
PURPOSE: To present a theoretical framework that rigorously defines and analyzes key concepts and quantities for velocity selective arterial spin labeling (VSASL). THEORY AND METHODS: An expression for the VSASL arterial delivery function is derived based on (1) labeling and saturation profiles as a function of velocity and (2) physiologically plausible approximations of changes in acceleration and velocity across the vascular system. The dependence of labeling efficiency on the amplitude and effective bolus width of the arterial delivery function is defined. Factors that affect the effective bolus width are examined, and timing requirements to minimize quantitation errors are derived. RESULTS: The model predicts that a flow-dependent negative bias in the effective bolus width can occur when velocity selective inversion (VSI) is used for the labeling module and velocity selective saturation (VSS) is used for the vascular crushing module. The bias can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal cutoff velocity of the vascular crushing module. CONCLUSION: The elements of the model are specified in a general fashion such that future advances can be readily integrated. The model can facilitate further efforts to understand and characterize the performance of VSASL and provide critical theoretical insights that can be used to design future experiments and develop novel VSASL approaches.
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Arterias , Angiografía por Resonancia Magnética , Marcadores de Spin , Arterias/diagnóstico por imagen , Modelos Teóricos , Aceleración , Circulación Cerebrovascular/fisiología , Velocidad del Flujo Sanguíneo/fisiologíaRESUMEN
Hip arthroscopy is rapidly increasing in case volume annually in the United States. However, it remains a challenging surgery with a steep learning curve. Labral repair is commonly performed to preserve the labrum rather than labral debridement or reconstruction. Many techniques have been described for labral repair. In this technical note, we describe our technique for a modified loop suture technique for arthroscopic labral repair of the hip.
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Radial meniscus tears occur commonly as traumatic tears in younger patients, as well as in association with concomitant degenerative changes. Traditional management of these tears has centered around partial meniscectomy; however, there has been a more recent trend toward preserving the meniscus and attempting repair. Because of the gapping and displacement that frequently occurs with these tears, repair is often challenging and is done under high amounts of tension. The following article describes a technique using a traction suture to aid in maintaining reduction throughout repair. This is followed by the use of a combination of techniques to form a "super-hashtag" configuration of both vertical and horizontal mattress sutures, leading to a secure repair under little tension.
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Horizontal cleavage meniscus tears occur more frequently in older patient populations with degenerative changes within the meniscus. Traditionally, they have been managed with nonsurgical interventions or with partial meniscectomy. As increasing evidence demonstrates the link between partial meniscectomy and progressive osteoarthritis with these types of tears, as well as worse long-term outcomes and reduced cost savings, surgical repair of horizontal cleavage meniscal tears has increased in appropriate patients. This technique article highlights the evaluation, indications, and preferred repair technique for horizontal cleavage tears in appropriately selected patients.
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Meniscus root tears are tears that occur within 1 cm of the meniscus root attachment to the tibia. If not repaired, root tears will lead to altered knee biomechanics and accelerated degenerative changes in the knee. In this surgical technique, we demonstrate repair of a meniscus root tear with an all-inside suture repair of the posterior meniscus that is then passed through 2 transtibial tunnels and then fixed with an anchor. After surgery, patients are non-weightbearing for 4 weeks and can return to activity by 6 months.
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OBJECTIVE: Knee arthrocentesis can be performed by landmark (LM) or ultrasound (US) guidance. The goal of performing knee arthrocentesis is to obtain synovial fluid, however, it is also important to consider the number of attempts required and accidental bone contacts that occur. This study evaluates procedural success without bone contact in knee arthrocentesis and compares both LM and US guided techniques in a cadaver model. METHODS: This was a randomized crossover study comparing US vs LM guidance for arthrocentesis in a single academic center. Volunteers were randomized to perform both LM and US guided knee arthrocentesis on cadavers. The primary outcome was procedural success, defined as first attempt aspiration of synovial fluid without bone contact. Secondary outcomes included number of attempts, number of bone contacts, time to aspiration, and confidence. RESULTS: Sixty-one participants completed the study with a total of 122 procedures performed. Procedural success without bone contact was greater in the US group (84% vs 64% p = 0.02). Time to aspiration was longer for US (38.75 s vs 25.54 s p = 0.004). Participants were more confident with US compared to LM both before the procedure on a Visual Analog Scale from 1 to 100 (29 vs 21 p = 0.03) as well as after the procedure (83 vs 69 p = 0.0001). Participants had a greater median increase in confidence with US following training (44 vs 26 p = 0.01). CONCLUSIONS: Study participants had greater procedural success without bone contact when US guidance was used. The increase in confidence following training was greater for US guidance than the LM method. Use of US guidance may offer a benefit by allowing for better needle control and avoidance of sensitive structures for clinicians performing knee arthrocentesis.
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Artrocentesis , Articulación de la Rodilla , Humanos , Artrocentesis/métodos , Estudios Cruzados , Ultrasonografía , Articulación de la Rodilla/diagnóstico por imagen , Cadáver , Ultrasonografía Intervencional/métodosRESUMEN
Telomeres are prone to formation of the common oxidative lesion 8-oxoguanine (8oxoG), and the acute production of 8oxoG damage at telomeres is sufficient to drive rapid cellular senescence. OGG1 and MUTYH glycosylases initiate base excision repair (BER) at 8oxoG sites to remove the lesion or prevent mutation. Here, we show OGG1 loss or inhibition, or MUTYH loss, partially rescues telomeric 8oxoG-induced senescence, and loss of both glycosylases results in a near complete rescue. Loss of these glycosylases also suppresses 8oxoG-induced telomere fragility and dysfunction, indicating that single-stranded break (SSB) intermediates arising downstream of glycosylase activity impair telomere replication. The failure to initiate BER in glycosylase-deficient cells suppresses PARylation at SSB intermediates and confers resistance to the synergistic effects of PARP inhibitors on damage-induced senescence. Our studies reveal that inefficient completion of 8oxoG BER at telomeres triggers cellular senescence via SSB intermediates which impair telomere replication and stability.
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Telomeres present inherent difficulties to the DNA replication machinery due to their repetitive sequence content, formation of non-B DNA secondary structures, and the presence of the nucleo-protein t-loop. Especially in cancer cells, telomeres are hot spots for replication stress, which can result in a visible phenotype in metaphase cells termed "telomere fragility". A mechanism cells employ to mitigate replication stress, including at telomeres, is DNA synthesis in mitosis (MiDAS). While these phenomena are both observed in mitotic cells, the relationship between them is poorly understood; however, a common link is DNA replication stress. In this review, we will summarize what is known to regulate telomere fragility and telomere MiDAS, paying special attention to the proteins which play a role in these telomere phenotypes.
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Replicación del ADN , ADN , ADN/metabolismo , Mitosis , Fenotipo , Telómero/metabolismoRESUMEN
Subscapularis management and repair are crucial during total shoulder arthroplasty to maximize outcomes. Bioinductive implants have been used to aid in repair of tendons in a variety of surgical techniques. In this surgical technique, we demonstrate our technique of subscapularis repair augmentation with a bioinductive implant during anatomic total shoulder arthroplasty.
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Purpose: To develop a standardized opioid prescribing schedule (SOPS) following anterior cruciate ligament reconstruction (ACLR) and rotator cuff repair (RCR) and evaluate postoperative opioid consumption alongside Patient-Reported Outcome Measurement Information System (PROMIS) pain interference scores. Methods: A prospective observational study was performed on all patients undergoing primary ACLR and RCR from March 2019 to October 2021. Patients taking opioids preoperatively and revision ACLR and RCR were excluded. PROMIS 6B questionnaires were administered before and after implantation of the SOPS initiated on December 15, 2019. Opioid consumption was determined by email surveys. Hypothesis testing was performed with Mann-Whitney U test. Results: A total of 599 patients met inclusion criteria with 188 patients (71 ACLR and 117 RCR) completing surveys. Before the initiation of SOPS, the average number of oxycodone 5-mg tablets prescribed for ACLR was 44.6 (95% confidence interval [CI] 42.4-46.9) and for RCR was 44.7 (95% CI 42.7-46.8). The average usage was 23.1 (95% CI 16.9-29.2) and 22.1 (95% CI 16.2-28.0), respectively. Following SOPS of 30 tablets of oxycodone 5 mg for ACLR and 40 tablets for RCR, the average number of tablets prescribed significantly decreased for both procedures (P < .01 for ACLR and RCR), and the average consumption decreased to 20.5 (95% CI 16.6-24.4) and 18.6 (95% CI 14.6-22.5), respectively. PROMIS 6B responses did not demonstrate statistically significant changes following SOPS. Conclusions: The results of the present study demonstrate that the implementation of a SOPS reduced postoperative opioid prescribing amounts and consumption without significant impacting PROMIS pain interference scores for ACLR and RCR, supporting the possibility to decrease and standardize opioid prescribing following common sports medicine procedures. Level of Evidence: III: Retrospective, comparative, therapeutic study.
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Mitochondrial dysfunction plays an important role in the aging process. However, the mechanism by which this dysfunction causes aging is not fully understood. The accumulation of mutations in the mitochondrial genome (or "mtDNA") has been proposed as a contributor. One compelling piece of evidence in support of this hypothesis comes from the PolgD257A/D257A mutator mouse (Polgmut/mut ). These mice express an error-prone mitochondrial DNA polymerase that results in the accumulation of mtDNA mutations, accelerated aging, and premature death. In this paper, we have used the Polgmut/mut model to investigate whether the age-related biological effects observed in these mice are triggered by oxidative damage to the DNA that compromises the integrity of the genome. Our results show that mutator mouse has significantly higher levels of 8-oxoguanine (8-oxoGua) that are correlated with increased nuclear DNA (nDNA) strand breakage and oxidative nDNA damage, shorter average telomere length, and reduced mtDNA integrity. Based on these results, we propose a model whereby the increased level of reactive oxygen species (ROS) associated with the accumulation of mtDNA mutations in Polgmut/mut mice results in higher levels of 8-oxoGua, which in turn lead to compromised DNA integrity and accelerated aging via increased DNA fragmentation and telomere shortening. These results suggest that mitochondrial play a central role in aging and may guide future research to develop potential therapeutics for mitigating aging process.
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Envejecimiento Prematuro , Envejecimiento/genética , Envejecimiento Prematuro/genética , Animales , Daño del ADN/genética , ADN Polimerasa gamma/genética , ADN Mitocondrial/genética , ADN Polimerasa Dirigida por ADN/genética , Guanina/análogos & derivados , Ratones , Mutación/genéticaRESUMEN
Oxidative stress is a primary cause of cellular senescence and contributes to the etiology of numerous human diseases. Oxidative damage to telomeric DNA has been proposed to cause premature senescence by accelerating telomere shortening. Here, we tested this model directly using a precision chemoptogenetic tool to produce the common lesion 8-oxo-guanine (8oxoG) exclusively at telomeres in human fibroblasts and epithelial cells. A single induction of telomeric 8oxoG is sufficient to trigger multiple hallmarks of p53-dependent senescence. Telomeric 8oxoG activates ATM and ATR signaling, and enriches for markers of telomere dysfunction in replicating, but not quiescent cells. Acute 8oxoG production fails to shorten telomeres, but rather generates fragile sites and mitotic DNA synthesis at telomeres, indicative of impaired replication. Based on our results, we propose that oxidative stress promotes rapid senescence by producing oxidative base lesions that drive replication-dependent telomere fragility and dysfunction in the absence of shortening and shelterin loss.
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Guanina , Acortamiento del Telómero , Senescencia Celular/genética , ADN/metabolismo , Daño del ADN , Humanos , Estrés Oxidativo , Telómero/metabolismoRESUMEN
Background: Postoperative stiffness is a known complication after rotator cuff repair (RCR). Glenohumeral hydrodistension (GH) has been a treatment modality for shoulder pathology but has not been used to treat postoperative stiffness after RCR. Purpose/Hypothesis: The purpose of this study was to identify the risk factors for postoperative stiffness after RCR and review outcomes after treatment with GH. Our hypotheses were that stiffness would be associated with diabetes and hyperlipidemia and correlated with the tendons involved and that patients with stiffness who underwent GH would have significant improvement in range of motion (ROM). Study Design: Case series; Level of evidence, 4. Methods: Included were 388 shoulders of patients who underwent primary RCR by a single surgeon between 2015 and 2019. Shoulders with revision RCRs were excluded. Patient characteristics, medical comorbidities, and perioperative details were collected. A total of 40 shoulders with postoperative stiffness (10.3%) received GH injectate of a 21-mL mixture (15 mL of sterile water, 5 mL of 0.5% ropivacaine, and 1 mL of triamcinolone [10 mg/mL]). The primary outcome measure was ROM in forward flexion, internal rotation, external rotation, and abduction. Statistical tests were performed using analysis of variance. Results: Patients with diabetes had significantly decreased internal rotation at final follow-up after RCR as compared with patients without diabetes. GH to treat stiffness was performed most commonly between 1 and 4 months after RCR (60%), and patients who received GH saw statistically significant improvements in forward flexion, external rotation, and abduction after the procedure. Patients with hyperlipidemia had the most benefit after GH. Among those undergoing concomitant procedures, significantly more patients who had open subpectoral biceps tenodesis underwent GH. Patients who underwent subscapularis repair or concomitant subacromial decompression had significant improvement in ROM after GH. Only 1 patient who received GH underwent secondary surgery for resistant postoperative stiffness. Conclusion: Patients with diabetes had increased stiffness. Patients with a history of hyperlipidemia or concomitant open subpectoral biceps tenodesis were more likely to undergo GH for postoperative stiffness. Patients who underwent subscapularis repair demonstrated the most improvement in ROM after GH. After primary RCR, GH can increase ROM and is a useful adjunct for patients with stiffness to limit secondary surgery.
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Purpose: The purpose of this study was to determine the inter-rater reliability of arthroscopic video quality, determine correlation between surgeon rating and computational image metrics, and facilitate a quantitative methodology for assessing video quality. Methods: Five orthopaedic surgeons reviewed 60 clips from deidentified arthroscopic shoulder videos and rated each on a four-point Likert scale from poor to excellent view. The videos were randomized, and the process was completed a total of three times. Each user rating was averaged to provide a user rating per clip. Each video frame was processed to calculate brightness, local contrast, redness (used to represent bleeding), and image entropy. Each metric was then averaged over each frame per video clip, providing four image quality metrics per clip. Results: Inter-rater reliability for grading video quality had an intraclass correlation of .974. Improved image quality rating was positively correlated with increased entropy (.8142; P < .001), contrast (.8013; P < .001), and brightness (.6120; P < .001), and negatively correlated with redness (-.8626; P < .001). A multiple linear regression model was calculated with the image metrics used as predictors for the image quality ranking, with an R-squared value of .775 and root mean square error of .42. Conclusions: Our study demonstrates strong inter-rater reliability between surgeons when describing image quality and strong correlations between image quality and the computed image metrics. A model based on these metrics enables automatic quantification of image quality. Clinical Relevance: Video quality during arthroscopic cases can impact the ease and duration of the case which could contribute to swelling and complication risk. This pilot study provides a quantitative method to assess video quality. Future works can objectively determine factors that affect visualization during arthroscopy and identify options for improvement.
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BACKGROUND: Optic nerve sheath diameters (ONSD) have been validated as an accurate screening tool to detect elevated intracranial pressure in hypertensive encephalopathy. The neurologic manifestations of preeclampsia and/or eclampsia mimic those of hypertensive encephalopathy. This study was performed to assess the incidence of elevated optic nerve sheath diameters of patients with severe preeclampsia and neurologic criteria compared to non-preeclamptic patients. The secondary objective was to determine baseline optic nerve sheath diameters in patients with severe preeclampsia without neurologic criteria and preeclampsia without severe features. METHODS: Single site cohort study including 62 pregnant women 18 years or older and 20 weeks or further gestation. Patients with preeclampsia without severe features, preeclampsia with severe features by non-neurologic criteria, preeclampsia with severe features with neurologic criteria, and patients without preeclampsia were enrolled via convenience sampling. One blinded reviewer measured sheath diameters; baseline demographics and pregnancy data were collected by chart review. Statistical analysis was completed with STATA/IC 16. Categorical variables were compared by the χ2 test. Continuous variables were presented as mean ± standard deviation, and discrete variables were presented as medians and compared by Kruskal-Wallis testing. Normality was confirmed by Shapiro-Wilk testing. Linear and logistic regression were used to test the association between the preeclampsia groups and optic nerve sheath diameters. Models were presented as unadjusted and adjusted for BMI, gestation, hypertension, diabetes, parity, and gravidity. RESULTS: The incidence of optic nerve sheath diameters > 5.8 mm was 43.8% in the severe preeclampsia with neurologic features cohort, and 42.1% in the control cohort, with a relative risk of 1.04. Patients with severe preeclampsia without neurologic features had sheath diameters of 5.75 mm ± 1.09 mm; non-severe preeclampsia patients had sheath diameters of 5.54 mm ± 1.26 mm. CONCLUSIONS: We did not find a significant elevated optic nerve sheath diameter relative risk between severe preeclampsia patients with neurologic features and non-preeclampsia control patients. This is the first study to assess a North American population utilizing ACOG criteria for severe and non-severe preeclampsia, with severe cohorts additionally stratified by neurologic criteria.
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Nervio Óptico/fisiopatología , Preeclampsia/fisiopatología , Adulto , Estudios de Cohortes , Femenino , Humanos , Hipertensión Intracraneal/fisiopatología , Nervio Óptico/diagnóstico por imagen , Embarazo , Análisis de Regresión , UltrasonografíaRESUMEN
Mammalian telomeres are guanine-rich sequences which cap the ends of linear chromosomes. While recognized as sites sensitive to oxidative stress, studies on the consequences of oxidative damage to telomeres have been primarily limited to experimental conditions which cause oxidative damage throughout the whole genome and cell. We developed a chemoptogenetic tool (FAP-mCER-TRF1) to specifically induce singlet oxygen at telomeres, resulting in the formation of the common oxidative lesion 8-oxo-guanine. Here, we describe this tool and detail how to generate cell lines which express FAP-mCER-TRF1 at telomeres and verify the formation of 8-oxo-guanine.