Decline in use of high-risk agents for tight glucose control among older adults with diabetes in New York City: 2017-2022.

BACKGROUND: This study aimed to examine the prevalence of inappropriate tight glycemic control in older adults with type 2 diabetes and other chronic conditions in New York City, and to identify factors associated with this practice. METHODS: We conducted a retrospective cohort study using the INSIGHT Clinical Research Network. The study population included 11,728 and 15,196 older adults in New York City (age ≥ 75 years) with a diagnosis of type 2 diabetes, and at least one other chronic medical condition, in 2017 and 2022, respectively. The main outcome of interest was inappropriate tight glycemic control, defined as HbA1c <7.0% (<53 mmol/mol) with prescription of at least one high-risk agent (insulin or insulin secretagogue). RESULTS: The proportion of older adults with inappropriate tight glycemic control decreased by nearly 19% over a five-year period (19.4% in 2017 to 15.8% in 2022). There was a significant decrease in insulin (27.8% in 2017; 24.3% in 2022) and sulfonylurea (29.4% in 2017; 21.7% in 2022) medication prescription, and increase in use of GLP-1 agonists (1.8% in 2017; 11.4% in 2022) and SGLT-2 inhibitors (5.8% in 2017; 25.1% in 2022), among the total population. Factors associated with inappropriate tight glycemic control in 2022 included history of heart failure (adjusted odds ratio [aOR] 1.38), chronic kidney disease ([aOR] 1.93), colorectal cancer ([aOR] 1.38), acute myocardial infarction ([aOR] 1.28), "other" ([aOR] 0.72) or "unknown" ([aOR] 0.72) race, and a point increase in BMI ([aOR] 0.98). CONCLUSIONS: We found an encouraging trend toward less use of high-risk medication strategies for older adults with type 2 diabetes and multiple chronic conditions. However, one in six patients in 2022 still had inappropriate tight glycemic control, indicating a need for continued efforts to optimize diabetes management in this population.

Cervical Diastematomyelia: A Case Presentation and Systematic Review.

Diastematomyelia is a rare congenital disorder characterized by the separation of the spinal cord by an osseocartilaginous or fibrous septum. While diastematomyelia has been reported to be more common in the thoracic and lumbar regions, the true incidence of cervical diastematomyelia is currently unknown. In this study, we conducted the most comprehensive systematic review to date of all other case reports of diastematomyelia to better characterize the incidence of cervical diastematomyelia and provide comprehensive statistics on the clinical characteristics of diastematomyelia generally. Ninety-one articles were included in our study, which comprised 252 males (27.9%) and 651 females (72.0%) (and one patient with unspecified gender). In 507 cases, the vertebral level of the diastematomyelia was described, and we recorded those levels as either cervical ( n = 8, 1.6%), thoracic ( n = 220, 43.4%), lumbar ( n = 277, 54.6%), or sacral ( n = 2, 0.4%). In 719 cases, the type of diastematomyelia was specified as either Type I ( n = 482, 67.0%) or Type II ( n = 237, 33.0%). Our study found that diastematomyelia has been reported in the cervical region in only 1.6% of cases, and we provide comprehensive data that this disorder occurs in female-to-male ratio of approximately 2.6:1 and Type I versus Type II diastematomyelia in an estimated ratio of 2:1.

Bevacizumab and gamma knife radiosurgery for first-recurrence glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common central nervous system malignancy in adults. Despite decades of developments in surgical management, radiation treatment, chemotherapy, and tumor treating field therapy, GBM remains an ultimately fatal disease. There is currently no definitive standard of care for patients with recurrent glioblastoma (rGBM) following failure of initial management. OBJECTIVE: In this retrospective cohort study, we set out to examine the relative effects of bevacizumab and Gamma Knife radiosurgery on progression-free survival (PFS) and overall survival (OS) in patients with GBM at first-recurrence. METHODS: We conducted a retrospective review of all patients with rGBM who underwent treatment with bevacizumab and/or Gamma Knife radiosurgery at Roswell Park Comprehensive Cancer Center between 2012 and 2022. Mean PFS and OS were determined for each of our three treatment groups: Bevacizumab Only, Bevacizumab Plus Gamma Knife, and Gamma Knife Only. RESULTS: Patients in the combined treatment group demonstrated longer post-recurrence median PFS (7.7 months) and median OS (11.5 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total PFS (p=0.015), total OS (p=0.0050), post-recurrence PFS (p=0.018), and post-recurrence OS (p=0.0082) compared to patients who received either bevacizumab or Gamma Knife as monotherapy. CONCLUSION: This study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice.

The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV. Here we describe a vaccine formulation based on a lymph node targeting Amphiphile vaccine adjuvant, Amphiphile-CpG, admixed with EBV gp350 glycoprotein and an engineered EBV polyepitope protein that includes 20 CD8+ T cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses are induced in mice with titers >100,000 in Amphiphile-CpG vaccinated mice. Immunization including Amphiphile-CpG also induces high frequencies of polyfunctional gp350-specific CD4+ T cells and EBV-specific CD8+ T cells that are 2-fold greater than soluble CpG and are maintained for >7 months post immunization. This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases.

Cervical spine flexion-extension radiography versus magnetic resonance imaging in pediatric patients following blunt traumatic injury.

Background: In pediatric trauma patients, 60-80% of spinal cord injuries involve the cervical vertebrae. While the American College of Radiology offers guidelines for best imaging practices in the setting of acute pediatric trauma, there is a lack of uniformity in imaging-decision protocols across institutions. MRI has been shown to demonstrate high sensitivity for both bony and ligamentous injuries while also avoiding unnecessary radiation exposure in the pediatric patient population. However, the efficacy of flexion-extension (FE) radiography following initial MRI has not been evaluated in children. Our hypothesis is that FE radiography conducted following an initial MRI does not contribute significant diagnostic information or reduce time to cervical collar removal and thus can be removed from institutional protocols in order to avoid unnecessary testing and reduce pediatric radiation exposure. Methods: Trauma data were collected for pediatric patients presenting with suspected acute cervical spine injury from 2014 to 2021. A total of 108 patients were subdivided into 41 patients who received "MRI Only" and 67 patients who received both "MRI and FE" diagnostic cervical spine imaging. Chi-square testing and t-tests were performed to determine differences between MRI and FE radiographic detection rates of bony and ligamentous injuries in the subgroups. Results: In patients for whom FE did not find any injury, MRI detected bony and ligamentous injuries in 9/63 and 12/65 cases, respectively. In 3/21 (14.3%) cases in which MRI detected a bony and/or ligamentous injury and FE did not, patients eventually required surgical intervention for c-spine stabilization. No patients required surgical fixation when FE radiography showed an abnormality and MRI was normal. Addition of follow-up FE radiography after initial MRI did not have a significant effect on overall hospital length of stay (MRI Only vs MRI+FE: 9.2±12.0 days vs 8.6±13.5 days, p=0.816) or on rates of collar removal at discharge or greater than 48 hours after imaging (MRI Only vs MRI+FE: 41.5% vs 56.7%, p=0.124). Conclusions: FE radiography following initial MRI did not have a significant effect on reducing time to cervical collar removal or overall hospital length of stay. In addition, in 3 of 6 cases (50.0%) in which surgical fixation was required, MRI detected ligamentous and/or bony injury while FE radiography was normal. Level of Evidence: This study contributes Level 2b scientific evidence consistent with a well-designed cohort or case-control analytic study.

Postoperative Morbidity and Mortality in Lumbar Spine Surgery Patients With Chronic Kidney Disease and Chronic Steroid Use.

BACKGROUND: Perioperative steroids have traditionally been administered during lumbar spine surgery in order to decrease local inflammation and prevent scar tissue formation, which can otherwise contribute to significant, long-lasting postoperative pain due to the formation of epidural fibrosis around lumbar nerve roots. However, the use of steroids in lumbar spine patients has raised concerns of postoperative wound complications caused by corticosteroid-induced immunomodulatory effects and changes in collagen synthesis. Patients with chronic kidney disease (CKD) undergoing spine surgery are at a particularly elevated risk of various complications due to chronic CKD-related systemic inflammation and endothelial dysfunction. It is currently uncertain whether chronic steroid use in CKD patients exerts a protective effect postoperatively due to decreased systemic inflammation or instead is correlated with increased rates of wound complications. RESULTS: Using adjusted odds ratios to control for CKD-related comorbidities, our study of lumbar spine fusion patients who were chronic steroid users vs nonusers found no significant differences in rates of postoperative wound infections in later stage CKD patients. However, we also did not observe statistically significant reductions in hospital length of stay or rates of 30-day mortality, sepsis, or cardiac, pulmonary, and renal events. CONCLUSIONS: Our results indicate chronic steroid use neither contributes significantly to rates of wound infections nor exerts a protective effect against postoperative inflammatory complications in lumbar spine patients with CKD. CLINICAL RELEVANCE: Our findings do not support the practice of holding steroids in chronic users prior to lumbar spine surgery. Perioperative steroids do not appear to increase the risk of postoperative complications, but neither do they improve lumbar spine patient outcomes.

Pan-Cancer Characterization of Intratumoral Autonomic Innervation in 32 Cancer Types in the Cancer Genome Atlas.

Over the past two decades, multiple studies have demonstrated the important role that the autonomic nervous system (ANS) plays in tumorigenesis and cancer progression. However, the mechanisms by which this process occurs have only recently begun to be elucidated. Further, the extent of autonomic innervation in various cancer types and its effects on tumor molecular, immunological, and histopathological features, as well as on patient outcomes, are not yet fully characterized. In this study, we analyzed intratumoral ANS gene expression signatures, including overall intratumoral neuron growth and sympathetic and parasympathetic markers, across 32 cancer types using tumor transcriptomic and clinical annotation data available from The Cancer Genome Atlas (TCGA). Our analysis revealed wide variations in intratumoral ANS expression both within and across cancer types. The association of ANS signatures with tumor histopathological characteristics and survival outcomes also varied by cancer type. We found intratumoral ANS expression to be commonly correlated with angiogenesis, TGF-ß signaling, and immunosuppression in the tumor microenvironment of many cancer types, which provide mechanistic insights into the involvement of intratumoral innervation in cancer development and progression. Our findings suggest that the potential benefits of cancer therapies targeting ß-adrenergic receptor-mediated stress signaling pathways are likely dependent on cancer type.

Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies.

Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and in cell differentiation, and alteration of PRC2 activity has been associated with cancer. On a molecular level, PRC2 catalyzes methylation of histone H3 lysine 27 (H3K27), resulting in mono-, di-, or trimethylated forms of H3K27, of which the trimethylated form H3K27me3 leads to transcriptional repression of polycomb target genes. Previously, we have shown that binding of the low-molecular-weight compound EED226 to the H3K27me3 binding pocket of the regulatory subunit EED can effectively inhibit PRC2 activity in cells and reduce tumor growth in mouse xenograft models. Here, we report the stepwise optimization of the tool compound EED226 toward the potent and selective EED inhibitor MAK683 (compound 22) and its subsequent preclinical characterization. Based on a balanced PK/PD profile, efficacy, and mitigated risk of forming reactive metabolites, MAK683 has been selected for clinical development.

Radial first or patient first: a case series and meta-analysis of transradial versus transfemoral access for acute ischemic stroke intervention.

BACKGROUND: Few studies have compared technical success and effectiveness of transradial access (TRA) versus transfemoral access (TFA) for mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We compared the two approaches for technical success, effectiveness, and outcomes. METHODS: We retrospectively compared TRA with TFA for AIS MT at our institute. We additionally performed a systematic review and meta-analysis of studies describing the use of TRA alone or in comparison with TFA for MT. Primary outcomes included rate of successful reperfusion (thrombolysis in cerebral infarction (TICI) >2b), number of passes, access-site complications, and 3- month mortality and favorable functional outcomes (modified Rankin Scale (mRS) score 0-2). RESULTS: A total of 222 consecutive patients (TRA=93, TFA=129) were included in our case series. The rate of successful reperfusion was significantly higher for the TFA cohort (91.4% vs 79.6%, P=0.01) with lower mean number of passes (1.8±1.2 vs 2.4±1.6, P=0.014). Three-month mortality in the TFA group was lower (22.1% vs 40.9% for the TRA cohort (P=0.004), with a higher rate of favorable functional outcomes (51.3% vs 34.1%, P=0.015). A meta-analysis of 10 studies showed significant heterogeneity in rates of successful reperfusion (57.1% to 95.6%, heterogeneity=67.55%, P=0.001). None of the previous comparative studies reported 3-month mortality and functional outcomes. CONCLUSIONS: This case series demonstrate a higher successful reperfusion rate, fewer passes, lower 3-month mortality, and improved 3-month functional outcomes with TFA. The systematic review highlights the inadequacy of existing evidence. Prospective comparative studies are needed before a 'radial-first' approach can be adopted for stroke intervention.

Exercise-induced calf muscle hyperemia: Rapid mapping of magnetic resonance imaging using deep learning approach.

Exercise-induced hyperemia in calf muscles was recently shown to be quantifiable with high-resolution magnetic resonance imaging (MRI). However, processing of the MRI data to obtain muscle-perfusion maps is time-consuming. This study proposes to substantially accelerate the mapping of muscle perfusion using a deep-learning method called artificial neural network (NN). Forty-eight MRI scans were acquired from 21 healthy subjects and patients with peripheral artery disease (PAD). For optimal training of NN, different training-data sets were compared, investigating the effect of data diversity and reference perfusion accuracy. Reference perfusion was estimated by tracer kinetic model fitting initialized with multiple values (multigrid model fitting). Result: The NN method was much faster than tracer kinetic model fitting. To generate a perfusion map of matrix 128 × 128 on a same computer, multigrid model fitting took about 80 min, single-grid or regular model fitting about 3 min, while the NN method took about 1 s. Compared to the reference values, NN trained with a diverse group gave estimates with mean absolute error (MAE) of 15.9 ml/min/100g and correlation coefficient (R) of 0.949, significantly more accurate than regular model fitting (MAE 22.3 ml/min/100g, R 0.889, p < .001). Conclusion: the NN method enables rapid perfusion mapping, and if properly trained, estimates perfusion with accuracy comparable to multigrid model fitting.

Renal perfusion imaging by MRI.

Renal perfusion can be quantitatively assessed by multiple magnetic resonance imaging (MRI) methods, including dynamic contrast enhanced (DCE), arterial spin labeling (ASL), and diffusion-weighted imaging with intravoxel incoherent motion (IVIM) analysis. In this review we summarize the advances in the field of renal-perfusion MRI over the past 5 years. The review starts with a brief introduction of relevant MRI methods, followed by a discussion of recent technical developments. In the main section of the review, we examine the clinical and preclinical applications for three disease populations: chronic kidney disease, renal transplant, and renal tumors. The DCE method has been routinely used for assessing renal tumors but not other renal diseases. As a noncontrast alternative, ASL was extensively explored in both preclinical and clinical applications and showed much promise. Protocol standardization for the methods is desperately needed, and then large-scale clinical trials for the methods can be initiated prior to their broad clinical use. Level of Evidence: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;52:369-379.

Vasoactive Intestinal Polypeptide-Expressing Interneurons in the Hippocampus Support Goal-Oriented Spatial Learning.

Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP+), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands. Optogenetic manipulations of VIP+ INs and computational modeling further showed that VIP+ disinhibition is necessary for goal-directed learning and related reorganization of hippocampal pyramidal cell population dynamics. Our results demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial learning. VIDEO ABSTRACT.

Quantitative characterization of glomerular fibrosis with magnetic resonance imaging: a feasibility study in a rat glomerulonephritis model.

Glomerular fibrosis occurs in the early stages of multiple renal diseases, including hypertensive and diabetic nephropathy. Conventional assessment of glomerular fibrosis relies on kidney biopsy, which is invasive and does not reflect physiological aspects such as blood perfusion. In this study, we sought to assess potential changes of cortical perfusion and microstructure at different degrees of glomerular fibrosis using magnetic resonance imaging (MRI). A rat model of glomerular fibrosis was induced by injecting anti-Thy-1 monoclonal antibody OX-7 to promote mesangial extracellular matrix proliferation. For six rats on day 5 and five rats on day 12 after the induction, we measured renal cortical perfusion and spin-spin relaxation time (T2) in a 3-Tesla MRI scanner. T2 reflects tissue microstructural changes. Glomerular fibrosis severity was evaluated by histological analysis and proteinuria. Four rats without fibrosis were included as controls. In the control rats, the periodic acid-Schiff (PAS)-positive area was 22 ± 1% of total glomerular tuft, which increased significantly to 56 ± 12% and 45 ± 10% in the day 5 and day 12 fibrotic groups, respectively ( P < 0.01). For the three groups (control, day 5, and day 12 after OX-7 injection), cortical perfusion was 7.27 ± 2.54, 3.78 ± 2.17, and 3.32 ± 2.62 ml·min-1·g-1, respectively, decreasing with fibrosis severity ( P < 0.01), and cortical T2 was 75.2 ± 4.6, 84.1 ± 3.0, and 87.9 ± 5.6 ms, respectively ( P < 0.01). In conclusion, extracellular matrix proliferation in glomerular mesangial cells severely diminished blood flow through the glomeruli and also altered cortical microstructure to increase cortical T2. The MRI-measured parameters are proven to be sensitive markers for characterizing glomerular fibrosis.

Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy.

Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective, and orally bioavailable EED inhibitor compound 43 (EED226). Guided by X-ray crystallography, compound 43 was discovered by fragmentation and regrowth of compound 7, a PRC2 HTS hit that directly binds EED. The ensuing scaffold hopping followed by multiparameter optimization led to the discovery of 43. Compound 43 induces robust and sustained tumor regression in EZH2MUT preclinical DLBCL model. For the first time we demonstrate that specific and direct inhibition of EED can be effective as an anticancer strategy.

An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED.

Polycomb repressive complex 2 (PRC2) consists of three core subunits, EZH2, EED and SUZ12, and plays pivotal roles in transcriptional regulation. The catalytic subunit EZH2 methylates histone H3 lysine 27 (H3K27), and its activity is further enhanced by the binding of EED to trimethylated H3K27 (H3K27me3). Small-molecule inhibitors that compete with the cofactor S-adenosylmethionine (SAM) have been reported. Here we report the discovery of EED226, a potent and selective PRC2 inhibitor that directly binds to the H3K27me3 binding pocket of EED. EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity. EED226 shows similar activity to SAM-competitive inhibitors in blocking H3K27 methylation of PRC2 target genes and inducing regression of human lymphoma xenograft tumors. Interestingly, EED226 also effectively inhibits PRC2 containing a mutant EZH2 protein resistant to SAM-competitive inhibitors. Together, we show that EED226 inhibits PRC2 activity via an allosteric mechanism and offers an opportunity for treatment of PRC2-dependent cancers.

Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach.

Oncogenic MLL fusion proteins aberrantly recruit Dot1L, a histone methyltransferase, to ectopic loci, leading to local hypermethylation of H3K79 and misexpression of HoxA genes driving MLL-rearranged leukemias. Inhibition of the methyltransferase activity of Dot1L in this setting is predicted to reverse aberrant H3K79 methylation, leading to repression of leukemogenic genes and tumor growth inhibition. In the context of our Dot1L drug discovery program, high-throughput screening led to the identification of 2, a weak Dot1L inhibitor with an unprecedented, induced pocket binding mode. A medicinal chemistry campaign, strongly guided by structure-based consideration and ligand-based morphing, enabled the discovery of 12 and 13, potent, selective, and structurally completely novel Dot1L inhibitors.

Comparison of fitting methods and b-value sampling strategies for intravoxel incoherent motion in breast cancer.

PURPOSE: To compare fitting methods and sampling strategies, including the implementation of an optimized b-value selection for improved estimation of intravoxel incoherent motion (IVIM) parameters in breast cancer. METHODS: Fourteen patients (age, 48.4 ± 14.27 years) with cancerous lesions underwent 3 Tesla breast MRI examination for a HIPAA-compliant, institutional review board approved diffusion MR study. IVIM biomarkers were calculated using "free" versus "segmented" fitting for conventional or optimized (repetitions of key b-values) b-value selection. Monte Carlo simulations were performed over a range of IVIM parameters to evaluate methods of analysis. Relative bias values, relative error, and coefficients of variation (CV) were obtained for assessment of methods. Statistical paired t-tests were used for comparison of experimental mean values and errors from each fitting and sampling method. RESULTS: Comparison of the different analysis/sampling methods in simulations and experiments showed that the "segmented" analysis and the optimized method have higher precision and accuracy, in general, compared with "free" fitting of conventional sampling when considering all parameters. Regarding relative bias, IVIM parameters fp and Dt differed significantly between "segmented" and "free" fitting methods. CONCLUSION: IVIM analysis may improve using optimized selection and "segmented" analysis, potentially enabling better differentiation of breast cancer subtypes and monitoring of treatment.

New magnetic resonance imaging methods in nephrology.

Established as a method to study anatomic changes, such as renal tumors or atherosclerotic vascular disease, magnetic resonance imaging (MRI) to interrogate renal function has only recently begun to come of age. In this review, we briefly introduce some of the most important MRI techniques for renal functional imaging, and then review current findings on their use for diagnosis and monitoring of major kidney diseases. Specific applications include renovascular disease, diabetic nephropathy, renal transplants, renal masses, acute kidney injury, and pediatric anomalies. With this review, we hope to encourage more collaboration between nephrologists and radiologists to accelerate the development and application of modern MRI tools in nephrology clinics.

Long-term Outcomes After Anterior Cruciate Ligament Reconstruction in Patients 60 Years and Older.

BACKGROUND: Studies evaluating the benefit of surgical reconstruction of the anterior cruciate ligament (ACL) in middle-aged patients have shown promising results, but study populations were limited primarily to patients who were 40 to 60 years old. Some authors have suggested that surgery may benefit these older patients. HYPOTHESIS: Patients aged ≥60 years with functional instability after ACL injury would benefit from ACL reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Medical records from 1984 through 2010 were searched for patients aged ≥60 years who had undergone primary arthroscopic ACL reconstruction at a single institution. Fifteen patients (15 knees) were identified as meeting the above criteria. All patients were contacted for a telephone interview, and they completed Short Form-36 and modified Cincinnati Knee Score forms. One patient was deceased, and 1 had undergone revision to total knee arthroplasty. Among the remaining 13 patients, the mean age at surgery was 63.5 years (range, 60-73 years), and the mean patient age at the time of follow-up was 73 years (range, 65-85 years). Preoperative radiographs showed no obvious evidence of arthritis in 10 (77%) of the 13 patients; small osteophytes without loss of joint space were seen in 3 (23%) patients. The mean length of follow up was 115.7 months (range, 53-193 months). RESULTS: At their last clinic visits, all 13 patients had regained full range of motion and returned to sports or exercise, such as tennis, golf, gym exercise, and yoga. Twelve patients reported no joint laxity. CONCLUSION: Patients aged ≥60 years with symptomatic instability from ACL injury can have good to excellent subjective outcomes with surgical reconstruction. CLINICAL RELEVANCE: Physicians who treat active patients older than 60 years should not exclude ACL reconstruction based on the patient's age alone.

Dynamic contrast-enhanced magnetic resonance imaging measurement of renal function in patients undergoing partial nephrectomy: preliminary experience.

OBJECTIVES: To evaluate changes in single-kidney glomerular filtration rate (SK-GFR) using low-dose dynamic contrast-enhanced magnetic resonance (MR) renography (MRR) in patients undergoing partial nephrectomy for renal masses. MATERIALS AND METHODS: In this Health Information Patient Protection Act-compliant prospective study, 18 patients with renal masses underwent preoperative MR imaging at 1.5 T for renal mass evaluation and low-dose gadolinium-enhanced MRR. Magnetic resonance renography was repeated approximately 48 to 72 hours and 6 months after partial nephrectomy. Single-kidney glomerular filtration rate was calculated from the MRR images, and the right and left kidney values were summed for total MR-GFR. Postoperative changes in SK-GFR and MR-GFR were compared with changes in estimated glomerular filtration rate calculated using modification of diet in renal disease formula, renal lesion characteristics, ischemia type (warm vs cold), and ischemia time. RESULTS: A decrease in the operated kidney SK-GFR was seen in 15 of the 18 patients, with a mean (SD) loss of 31% (23%), whereas estimated glomerular filtration rate decreased in 13 of the 18 patients with mean (SD) decrease of 19% (14%). Decrease in SK-GFR was greatest in the patients with warm ischemia time greater than 40 minutes and least in the patients with cold ischemia. In the immediate postoperative period, 6 of 7 patients (86%) with preoperative MR-GFR less than 60 mL/min per 1.73 m failed to demonstrate compensatory increase in SK-GFR in the nonoperated kidney, whereas 5 of 11 patients with baseline MR-GFR more than 60 mL/min per 1.73 m showed compensatory increase in nonoperated kidney SK-GFR. CONCLUSIONS: Magnetic resonance renography can demonstrate functional loss in the operated kidney and compensatory increase in the function of the contralateral kidney, thus enabling evaluation of various surgical techniques on kidney function.